bluuebunny/crossref_metadata_2025 huggingface dataset:
Similar Frequency and Inducibility of Intact Human Immunodeficiency Virus-1 Proviruses in Blood and Lymph Nodes
Authors: Martin Alyssa R , Bender Alexandra M , Hackman Jada , Kwon Kyungyoon J , Lynch Briana A , Bruno Daniel , Martens Craig , Beg Subul , Florman Sander S , Desai Niraj , Segev Dorry , Laird Gregory M , Siliciano Janet D , Quinn Thomas C , Tobian Aaron A R , Durand Christine M , Siliciano Robert F , Redd Andrew D
Published: November 2020

Background

The human immunodeficiency virus (HIV)-1 latent reservoir (LR) in resting CD4+ T cells is a barrier to cure. LR measurements are commonly performed on blood samples and therefore may miss latently infected cells residing in tissues, including lymph nodes.

Methods

We determined the frequency of intact HIV-1 proviruses and proviral inducibility in matched peripheral blood (PB) and lymph node (LN) samples from 10 HIV-1-infected patients on antiretroviral therapy (ART) using the intact proviral DNA assay and a novel quantitative viral induction assay. Prominent viral sequences from induced viral RNA were characterized using a next-generation sequencing assay.

Results

The frequencies of CD4+ T cells with intact proviruses were not significantly different in PB versus LN (61/106 vs 104/106 CD4+ cells), and they were substantially lower than frequencies of CD4+ T cells with defective proviruses. The frequencies of CD4+ T cells induced to produce high levels of viral RNA were not significantly different in PB versus LN (4.3/106 vs 7.9/106), but they were 14-fold lower than the frequencies of cells with intact proviruses. Sequencing of HIV-1 RNA from induced proviruses revealed comparable sequences in paired PB and LN samples.

Conclusions

These results further support the use of PB as an appropriate proxy for the HIV-1 LR in secondary lymphoid organs.
Malaria Is Associated With Kaposi Sarcoma-Associated Herpesvirus Seroconversion in a Cohort of Western Kenyan Children
Authors: Sabourin Katherine R , Daud Ibrahim , Ogolla Sidney , Labo Nazzarena , Miley Wendell , Lamb Molly , Newton Robert , Whitby Denise , Rochford Rosemary
Published: November 2020

Background

We aimed to determine whether Plasmodium falciparum infection affects age of Kaposi sarcoma-associated herpesvirus (KSHV) seroconversion in Kenyan children.

Methods

Kenyan children (n = 144) enrolled at age 1 month, from 2 sites with different levels of malaria transmission (stable/high vs unstable/low) were followed to age 24 months. Plasma was tested for KSHV antibodies using enzyme-linked immunosorbent assay (ELISA; K8.1 and LANA) and a multiplex bead-based assay (K8.1, K10.5, ORF38, ORF50, and LANA) and whole blood tested for P. falciparum DNA using quantitative PCR. Cox proportional hazards models were used to assess associations between P. falciparum DNA detection, malaria annualized rate (P. falciparum detections/person-years), and enrollment site (malaria-high vs malaria-low) with time to KSHV seroconversion.

Results

KSHV seroprevalence was 63% by age 2 years when assessed by multiplex assay. Children with P. falciparum were at increased hazards of earlier KSHV seroconversion and, among children with malaria, the hazard of becoming KSHV seropositive increased significantly with increasing malaria annualized rate. Children from the malaria-high transmission region had no significant difference in hazards of KSHV seroconversion at 12 months but were more likely to become KSHV seropositive by age 24 months.

Discussion

Malaria exposure increases the risk for KSHV seroconversion early in life.
Levels of Soluble CD14 and Tumor Necrosis Factor Receptors 1 and 2 May Be Predictive of Death in Severe Coronavirus Disease 2019
Authors: Bowman Emily R , Cameron Cheryl M Ainslie , Avery Ann , Gabriel Janelle , Kettelhut Aaren , Hecker Michelle , Sontich Claudia Ute , Tamilselvan Banumathi , Nichols Carmen N , Richardson Brian , Cartwright Michael , Funderburg Nicholas T , Cameron Mark J
Published: November 2020

People infected with severe acute respiratory syndrome coronavirus 2 display a wide range of illness, from asymptomatic infection to severe respiratory distress resulting in death. We measured serum biomarkers in uninfected individuals and in individuals with mild, moderate, or critical coronavirus disease 2019 (COVID-19) disease. Levels of monocyte activation (soluble CD14 and fatty acid–binding protein 4) and inflammation (tumor necrosis factor receptors 1 and 2 [TNFR1 and TNFR2]) were increased in COVID-19 individuals, regardless of disease severity. Among patients with critical disease, individuals who recovered from COVID-19 had lower levels of TNFR1 and TNFR2 at hospital admission compared to these levels in patients with critical disease who ultimately died.
Validation of the EQUAL Aspergillosis Score by analysing guideline-adherent management of invasive pulmonary aspergillosis
Authors: Budin Sofia , Salmanton-García Jon , Koehler Philipp , Stemler Jannik , Cornely Oliver A , Mellinghoff Sibylle C
Published: November 2020

Objectives

To investigate the diagnosis and treatment standards at the University Hospital of Cologne, Germany, by applying the EQUAL Aspergillosis Score to invasive pulmonary aspergillosis (IPA) patients.

Methods

The charts of 103 patients with probable or proven IPA at the University Hospital of Cologne were reviewed and the score retrospectively applied to all patients.

Results

Patients were stratified into two groups according to the underlying disease: a haematology group (n = 76, 73.8%) and a non-haematology group (n = 27, 26.2%). While the haematology group attained 67.8% of achievable score points (median: 15; IQR: 13–18; range: 8–25), the non-haematology group reached 48.4% (median: 12 points; IQR: 9–14; range: 4–18) (P < 0.001). Regarding diagnostics, haematological patients achieved 81.3% of achievable points (median: 7; IQR: 8–10; range: 3–13) and non-haematological 56.3% (median: 7; IQR: 5–9; range: 3–11). Concerning treatment, haematological patients gained 86.3% (median: 5; IQR: 5–5; range: 0–5) and non-haematological 68.1% (median: 5; IQR: 0–5; range: 0–5) of achievable points. Among the haematological patients with versus those without mould-active prophylaxis, 90 day mortality was 46.0% and 59.3% (P = 0.004), respectively. Guideline adherent management of IPA was observed in 31.1% of cases (39.5% in haematological patients and 7.4% in non-haematological).

Conclusions

The EQUAL Aspergillosis Score is more suitable for evaluation of management of haematological patients compared with those without such underlying disease. In both groups there was no correlation between score points and survival. Larger prospective studies may be suitable to correlate outcome and score. A revision of the score should be considered based on the data presented.
The N2N3 domains of ClfA, FnbpA and FnbpB in Staphylococcus aureus bind to human complement factor H, and their antibodies enhance the bactericidal capability of human blood
Authors: Mao Xinrui , Kim Junghyun , Zhang QingFeng , Jiang TingTing , Ahn Dong Ho , Jung Yunjin , Matsushita Misao , Bae Taeok , Lee Bok Luel
Published: November 2020

In the complement system, the opsonin C3b binds to the bacterial cell surface and mediates the opsonophagocytosis. However, the cell-wall protein SdrE of Staphylococcus aureus inhibits the C3b activity by recruiting the complement regulatory protein factor H (fH). SdrE binds to fH via its N-terminal N2N3 domain, which are also found in six other staphylococcal cell-wall proteins. In this study, we report that not only the N2N3 domain of SdrE but also those of ClfA, FnbpA and FnbpB can bind to fH. When immobilized on a microplate, the N2N3 domains recruited fH and enhanced the factor I (fI)-mediated cleavage of C3b. When mixed with fH and S. aureus cells, the N2N3 domains inhibited the fH binding to S. aureus cells and reduced the fI-mediated C3b cleavage on the bacterial cell surface. The F(ab)′2 fragments of the rabbit N2N3 antibodies also inhibited the fH binding to the S. aureus cell surface. When added to human blood, the N2N3 antibodies or the N2N3 domain proteins significantly increased the bactericidal activity. Based on these results, we conclude that, in S. aureus, not only SdrE but also ClfA, FnbpA and FnbpB can contribute to the inhibition of C3b-mediated opsonophagocytosis.
Comparisons of Efficiency of Two Formulations of Verbenone (4, 6, 6-trimethylbicyclo [3.1.1] hept-3-en-2-one) for Protecting Whitebark Pine, Pinus albicaulis (Pinales: Pinaceae) From Mountain Pine Beetle (Colopetera: Curculionidae)
Authors: Progar Robert A , Fettig Christopher J , Munson A Steven , Mortenson Leif A , Snyder Cynthia L , Kegley Sandra J , Cluck Daniel R , Steed Brytten E , Mafra-Neto Agenor , Rinella Matthew J
Published: November 2020

Whitebark pine, Pinus albicaulis Engelm., is a subalpine tree endemic to western North America. This species provides multiple ecosystem services and is suffering widespread mortality from mountain pine beetle, Dendroctonus ponderosae Hopkins. Verbenone is a pheromone produced as D. ponderosae feed, and high air concentrations of verbenone deter D. ponderosae from colonizing trees. Synthetic verbenone has been formulated into products used to prevent D. ponderosae from colonizing trees. We compared the ability of verbenone pouches and SPLAT Verb to protect individuals and small stands of P. albicaulis. With individual trees in Montana, all treated trees survived regardless of verbenone formulation and rate, whereas untreated trees suffered 70 and 90% mortality in 2015 and 2016. In plot experiments in California from 2015 to 2017, and Oregon from 2015 to 2018, verbenone was applied to trees spaced ~10 m apart, and survival of small (12.7–23 cm DBH = diameter at 1.37 m height), medium (23.1–33 cm DBH) and large (>33 cm DBH) trees was compared. In California, where >80% of untreated trees survived, pouches increased survival ~2 to 3% and SPLAT Verb increased survival ~4 to 7% regardless of tree size. In Oregon, verbenone pouches and SPLAT Verb performed similarly on medium and small trees, but large trees had greater survival when treated with SPLAT Verb (~93%) than pouches (~82%). Compared to verbenone pouches, SPLAT Verb appears to better protect P. albicaulis from D. ponderosae.
The effect of temperature changes and K supply on the reproduction and growth of Bolboschoenus planiculmis
Authors: Liu Ying , Bachofen Christoph , Lou Yanjing , Ding Zhi , Jiang Ming , Lü Xianguo , Buchmann Nina
Published: November 2020

Aims

Climate warming and agricultural non-point source pollution both resulting from anthropogenic activities have been projected to affect plant reproduction and growth in wetlands worldwide. In order to predict and mitigate impacts of these anthropogenic activities, it is important to investigate how marsh plants respond to such environmental changes.

Methods

In this study, Bolboschoenus planiculmis, a tuberous sedge with a wide distribution range in Eurasia, was selected to examine the effect of air temperature changes (15, 20 and 25 °C over 24 h; 20/10 and 30/15 °C, day/night) and K supply (0, 1, 3, 9 and 18 mmol/L) on its reproductive and growth traits in climate chambers.

Important Findings

We found that high constant temperatures (20 and 25 °C) were more beneficial for tuberization of B. planiculmis than high alternating temperatures (30/15 °C), whereas aboveground biomass and shoot height were generally largest at high temperatures (30/15 and 25 °C). Both reproductive and growth traits of B. planiculmis showed hump-shaped relationships with K supply, with an optimum K concentration of around 1–3 mmol/L. The combination of high constant temperatures and optimal K concentrations promoted reproductive traits the most, whereas the combination of higher temperatures (30/15 and 25 °C) and K concentrations up to 9 mmol/L increased growth traits only. We therefore conclude that population abundance of B. planiculmis might benefit from global warming and the additional K supply.
Correction of lateral response artifacts from flatbed scanners for dual-channel radiochromic film dosimetry
Authors: Akino Yuichi , Shiomi Hiroya , Isohashi Fumiaki , Suzuki Osamu , Seo Yuji , Tamari Keisuke , Hirata Takero , Mizuno Hirokazu , Ogawa Kazuhiko
Published: November 2020

In this study, we evaluated the inter-unit variability of the lateral response artifact for multiple flatbed scanners, focusing on the dual-channel method, and investigated the correction method of the lateral non-uniformity. Four scanners with A3+ paper-size and five scanners with A4 paper-size were evaluated. To generate the dose–response curves, small pieces of the Gafchromic EBT3 and EBT-XD films were irradiated, and five of the pieces were repeatedly scanned by moving them on the scanner to evaluate the lateral non-uniformity. To calculate the dose distribution accounting for the lateral non-uniformity, linear functions of the correction factor, representing the difference between the pixel values at offset position and the scanner midline, were calculated for red and blue color channels at each lateral position. Large variations of the lateral non-uniformity among the scanners were observed, even for the same model of scanner. For high dose, red color showed pixel value profiles similar to symmetric curves, whereas the profiles for low dose were asymmetric. The peak positions changed with dose. With correction of the lateral non-uniformity, the dose profiles of the pyramidal dose distribution measured at various scanner positions and that calculated with a treatment planning system showed almost identical profile shapes at all high-, middle- and low-dose levels. The dual-channel method used in this study showed almost identical dose profiles measured with all A3+ and A4 paper-size scanners at any positions when the corrections were applied for each color channel.
A Blighted History
Authors: Alison Laurence J. , Shortland Neil D. , Surmon-Böhr Frances , Alison Emily K.
Published: November 2020

This chapter outlines the history of “harsh” interrogation methods based on coercion and torture. This includes discussion of the US “Enhanced Interrogation” Program and the British military’s development and use of the “Five Techniques,” along with real-world examples, including the interrogation of two detainees thought to be associated with the 2001 9/11 terrorist attacks on the United States. The chapter discusses the underlying theory behind the use of torture and coercion and explains why these interrogation methods are ineffective at obtaining reliable information from detainees. It also describes the reasons why torture continues to be used. Such reasons relate to revenge, dehumanization, and hatred.
The Interpersonal Management of Difficult Behavior
Authors: Alison Laurence J. , Alison Emily K. , Surmon-Böhr Frances , Shortland Neil D.
Published: November 2020

This chapter discusses the ORBIT approach to managing difficult interpersonal behavior. It outlines the history and evolution of theories of interpersonal relating, which informed the ORBIT interpersonal circumplex. The ORBIT circumplex organizes behaviors across two axes: the power axis (ranging from controlling to capitulating behaviors) and the intimacy axis (ranging from cooperative to confrontational behaviors). The model consists of eight octants of behavior based on combinations of these two axes (e.g., controlling, controlling–cooperative, controlling–confrontational). The chapter includes the ORBIT coding framework for identifying each of these groups of behavior and their adaptive and maladaptive variants. Real-world examples of interrogations with convicted terrorist Anders Breivik and Parkland School shooter Nikolas Cruz are used to highlight the complexities of different suspect behaviors and how they would be assessed using the ORBIT interpersonal wheels.
Impact on Counter-Interrogation and Yield
Authors: Shortland Neil D. , Surmon-Böhr Frances , Alison Laurence J. , Alison Emily K. , Christiansen Paul
Published: November 2020

This chapter outlines the initial research conducted into the efficacy of the ORBIT model on detainees’ use of counter-interrogation tactics and the amount of evidentially useful information gained from detainees. Counter-interrogation tactics have been defined as a deliberate strategy adopted by a suspect to resist cooperating and may be consciously self-generated or learned from instructions or in training. This chapter outlines the research showing the use of counter-interrogation tactics with individuals from different terrorist groups and the effects of rapport-based strategies in reducing them. The chapter uses a real-world example of an interrogation with Saddam Hussein.
Under Pressure
Authors: Surmon-Böhr Frances , Alison Laurence J. , Shortland Neil D. , Alison Emily K.
Published: November 2020

This chapter discusses the concept and potential issues surrounding “urgent safety” or “imminent threat” interviews. It also summarizes a series of observations of law enforcement officers’ performance during simulated urgent interviews across a series of training exercises. The authors’ observations (both from psychologists as trainers and police facilitators) include the following: (1) safety interviewing appears to require a different skill set from evidential interviewing; (2) officers struggled to communicate a sense of intensity, gravity, and urgency required of an interview that aims to obtain information very quickly to preserve life and maintain public safety; (3) in order to improve, interviewers must practice these sorts of interactions more often (they require deliberate practice and feedback with guidance); and (4) elements of interviewing and time-sensitive questioning in the military may offer a useful template of the intensity and urgency required in police safety interviews.
ORBIT Outside the Room
Authors: Alison Laurence J. , Noone Geraldine , Surmon-Böhr Frances , Shortland Neil D. , Alison Emily K. , Christiansen Paul
Published: November 2020

This chapter is concerned with individual and social factors that may influence suspects’ decision-making during police interviews, as well as with the procedural and contextual landscape in which the interviews take place. The focus is on presenting descriptive data on a sample of 20 terrorist organization and organized criminal gang suspects and data regarding individual and contextual factors relating to each suspect in the sample. These factors include fear, status and relationship, criminal background, legal advice, strength of evidence, timing of arrest, type or circumstances of arrest or detention, and duration between offense and arrest. Using these outside-the-room factors as a framework, this chapter provides descriptive data on these factors as it pertained to the 20 suspects in the sample as well as data on the outcome of the process. The interviews with the suspects are also examined to identify and present instances of these factors arising in interactions between police interviewers and the suspects.
Moral Criticism and Structural Injustice
Authors: Zheng Robin
Published: November 2020

Moral agency is limited, imperfect, and structurally constrained. This is evident in the many ways we all unwittingly participate in widespread injustice through our everyday actions, which I call ‘structural wrongs’. To do justice to these facts, I argue that we should distinguish between summative and formative moral criticism. While summative criticism functions to conclusively assess an agent's performance relative to some benchmark, formative criticism aims only to improve performance in an ongoing way. I show that the negative sanctions associated with summative responses are only justifiably imposed under certain conditions when persons exercise their agency wrongly — conditions that do not always hold for structural wrongs. Yet even in such cases we can still use formative responses, which are warranted whenever agents fall short of moral ideals. Expanding our repertoire of moral criticism to include both summative and formative responses enables us to better appreciate both the powers and limitations of our agency, and the complexity of moral life.
Radio light curves and imaging of the helium nova V445 Puppis reveal seven years of synchrotron emission
Authors: Nyamai M M , Chomiuk L , Ribeiro V A R M , Woudt P A , Strader J , Sokolovsky K V
Published: November 2020

V445 Puppis is the only helium nova observed to date; its eruption in late 2000 showed high velocities up to 8500 km s−1, and a remarkable bipolar morphology cinched by an equatorial dust disc. Here we present multifrequency radio observations of V445 Pup obtained with the Very Large Array (VLA) spanning 1.5–43.3 GHz, and between 2001 January and 2008 March (days ∼89–2700 after eruption). The radio light curve is dominated by synchrotron emission over these 7 yr, and shows four distinct radio flares. Resolved radio images obtained in the VLA’s A configuration show that the synchrotron emission hugs the equatorial disc, and comparisons to near-IR images of the nova clearly demonstrate that it is the densest ejecta – not the fastest ejecta – that are the sites of the synchrotron emission in V445 Pup. The data are consistent with a model where the synchrotron emission is produced by a wind from the white dwarf impacting the dense equatorial disc, resulting in shocks and particle acceleration. The individual synchrotron flares may be associated with density enhancements in the equatorial disc and/or velocity variations in the wind from the white dwarf. This overall scenario is similar to a common picture of shock production in hydrogen-rich classical novae, but V445 Pup is remarkable in that these shocks persist for almost a decade, much longer than the weeks or months for which shocks are typically observed in classical novae.
A New Catalog of Structural Variants in 1,301 A. thaliana Lines from Africa, Eurasia, and North America Reveals a Signature of Balancing Selection at Defense Response Genes
Authors: Göktay Mehmet , Fulgione Andrea , Hancock Angela M
Published: November 2020

Genomic variation in the model plant Arabidopsis thaliana has been extensively used to understand evolutionary processes in natural populations, mainly focusing on single-nucleotide polymorphisms. Conversely, structural variation has been largely ignored in spite of its potential to dramatically affect phenotype. Here, we identify 155,440 indels and structural variants ranging in size from 1 bp to 10 kb, including presence/absence variants (PAVs), inversions, and tandem duplications in 1,301 A. thaliana natural accessions from Morocco, Madeira, Europe, Asia, and North America. We show evidence for strong purifying selection on PAVs in genes, in particular for housekeeping genes and homeobox genes, and we find that PAVs are concentrated in defense-related genes (R-genes, secondary metabolites) and F-box genes. This implies the presence of a “core” genome underlying basic cellular processes and a “flexible” genome that includes genes that may be important in spatially or temporally varying selection. Further, we find an excess of intermediate frequency PAVs in defense response genes in nearly all populations studied, consistent with a history of balancing selection on this class of genes. Finally, we find that PAVs in genes involved in the cold requirement for flowering (vernalization) and drought response are strongly associated with temperature at the sites of origin.
CoolMPS: evaluation of antibody labeling based massively parallel non-coding RNA sequencing
Authors: Li Yongping , Fehlmann Tobias , Borcherding Adam , Drmanac Snezana , Liu Sophie , Groeger Laura , Xu Chongjun , Callow Matthew , Villarosa Christian , Jorjorian Alexander , Kern Fabian , Grammes Nadja , Meese Eckart , Jiang Hui , Drmanac Radoje , Ludwig Nicole , Keller Andreas
Published: November 2020

Results of massive parallel sequencing-by-synthesis vary depending on the sequencing approach. CoolMPS™ is a new sequencing chemistry that incorporates bases by labeled antibodies. To evaluate the performance, we sequenced 240 human non-coding RNA samples (dementia patients and controls) with and without CoolMPS. The Q30 value as indicator of the per base sequencing quality increased from 91.8 to 94%. The higher quality was reached across the whole read length. Likewise, the percentage of reads mapping to the human genome increased from 84.9 to 86.2%. For both technologies, we computed similar distributions between different RNA classes (miRNA, piRNA, tRNA, snoRNA and yRNA) and within the classes. While standard sequencing-by-synthesis allowed to recover more annotated miRNAs, CoolMPS yielded more novel miRNAs. The correlation between the two methods was 0.97. Evaluating the diagnostic performance, we observed lower minimal P-values for CoolMPS (adjusted P-value of 0.0006 versus 0.0004) and larger effect sizes (Cohen's d of 0.878 versus 0.9). Validating 19 miRNAs resulted in a correlation of 0.852 between CoolMPS and reverse transcriptase-quantitative polymerase chain reaction. Comparison to data generated with Illumina technology confirmed a known shift in the overall RNA composition. With CoolMPS we evaluated a novel sequencing-by-synthesis technology showing high performance for the analysis of non-coding RNAs.
Asymptomatic Spinal Cord Compression: Is Surgery Necessary to Return to Play
Authors: Lee Yunsoo , Selverian Stephen , Hsu Wellington K , Watkins Robert G , Vaccaro Alexander R , Hecht Andrew C
Published: November 2020

Advising athletes with asymptomatic cervical canal stenosis on their return to active play is a topic of considerable debate, with no definitive guidelines in place. Once cervical canal stenosis is identified, often through imaging following other injuries, it is difficult to predict the risk of future injury upon return to play in both contact and collision sports. Consequently, the decision can be a complicated one for the athlete, family, and physician alike. In this article, we identify radiographical and magnetic resonance imaging (MRI)-based criteria that may distinguish athletes “at-risk” for more severe consequences due to asymptomatic cervical canal stenosis from those who are safe to return to play. Using a Torg-Pavlov ratio <0.7 and MRI metrics, namely a minimal disc-level canal diameter <8 mm, a cord-to-canal area ratio >0.8, or space available for the cord <1.2 mm, can help when making these difficult decisions. Counseling can be a critical asset to patients with cervical stenosis who have had a previous episode of cervical cord neuropraxia, especially when they are involved in high-risk sports such as American football and rugby. We believe that while this remains an area of continued concern and controversy, improved MRI criteria will be a useful springboard for further studies, especially in the elite athlete population.
Cerebrospinal Fluid-Venous Fistulas: A Systematic Review and Examination of Individual Patient Data
Authors: Shlobin Nathan A , Shah Vinil N , Chin Cynthia T , Dillon William P , Tan Lee A
Published: November 2020

BACKGROUND

Spontaneous intracranial hypotension (SIH) is usually caused by a spinal cerebrospinal fluid (CSF) leak. CSF-venous fistula is an underdiagnosed cause of spinal CSF leak, as it is challenging to identify on myelography.

OBJECTIVE

To review existing literature to summarize common presentations, diagnostic imaging modalities, and current treatment strategies for CSF-venous fistulas.

METHODS

We conducted a systematic review using PubMed, Embase, Scopus, and Web of Science databases to identify studies discussing CSF-venous fistulas. Titles and abstracts were screened. Studies meeting prespecified inclusion criteria were reviewed in full.

RESULTS

Of 180 articles identified, 16 articles met inclusion criteria. Individual patient data was acquired from 7 studies reporting on 18 patients. CSF-venous fistula most frequently presented as positional headache. Digital subtraction myelography provided greatest detection of CSF-venous fistula in the lateral decubitus position and detected CSF-venous fistula in all individual patient cases. Dynamic computed tomography (CT) myelogram enabled detection and differentiation of CSF-venous fistulas from low-flow epidural leaks. The majority of fistulas were in the thoracic spine and slightly more common on the right. Epidural blood patch (EBP) provided temporary or no relief in all individual patients. Resolution or improvement of clinical symptoms and radiologic normalization were observed in all surgically treated patients.

CONCLUSION

Although rare, CSF-venous fistula is an important cause of spinal CSF leak contributing to SIH. Dynamic CT myelogram and digital subtraction myelography, particularly in the lateral decubitus position, are the most accurate and effective diagnostic imaging modalities. EBPs often provide only transient relief, while surgical management is preferred.
More is different: how aggregation turns on the light
Authors: Ball Philip
Published: November 2020

The reductionist approach to science seeks to understand the behaviour of systems by studying their individual components. It has been an enormously productive approach, but it is also widely acknowledged now that in some systems the behaviour of interest is an emergent property that cannot be discerned in the separate parts. Biology is replete with such examples, from the flocking of birds to the way metabolic processes in cells rely on a dynamic interplay of proteins and other components.

Yet molecular systems do not have to be particularly complex before their properties become more than the sum of the parts. A classic example is the appearance of bulk-like metallic behaviour in small clusters of metal atoms only once they exceed a certain critical size. One of the most striking instances became apparent in 2001, when Ben Zhong Tang of the Hong Kong University of Science and Technology and his co-workers found that heterocyclic silicon-containing molecules called siloles become luminescent as nanoscopic aggregates even though the individual molecules in dilute solution do not emit light [1]. This looked like the opposite of the well-known phenomenon of concentration quenching, in which energy transfer between fluorescent (generally organic) molecules quenches the emission, an effect explained in 1955 [2]. Aggregation-induced ‘switching off’ is intuitively understandable, but ‘switching on’ due to aggregation was more surprising.

Yet this effect of ‘aggregation-induced emission’ (AIE), as Tang and colleagues called it, was apparently seen, but not understood, much earlier [3]. In the 1850s, George Stokes noted that some inorganic complexes were fluorescent in the condensed, solid state but not in solution. At first, AIE was seen as a curiosity and deemed likely to be rare. However, subsequent research has shown not only that it is a rather common effect but also that it can be considered just one manifestation of a wide range of behaviours that arise from aggregation—leading to the proposed field of ‘aggregate science’, manifesting at the supramolecular level of small clusters or groups of molecules held together by relatively weak interactions. The field might be considered to illustrate George Whitesides’ notion of a chemistry ‘beyond the molecule’ [4], which bridges disciplines ranging from colloid science to crystal growth, nanotechnology, liquid crystals, photochemistry and molecular biology. At the same time, it echoes the famous insight of physicist Philip Anderson about emergent phenomena and the hierarchical nature of science: ‘More is different’ [5]. An ability to switch properties on and off by controlling intermolecular interactions and aggregation suggests various applications, from optical device technologies to targeted drugs for cancer therapy [6].

NSR spoke to Ben Zhong Tang about the origins and possibilities of the field.
Cure of Limb-Threatening XDR Pseudomonas aeruginosa Infection: Combining Genome Sequencing, Therapeutic Drug Level Monitoring, and Surgical Debridement
Authors: Narayanasamy Shanti , Nation Roger L , Mahony Andrew A , Grayson M Lindsay , Kwong Jason C , Sherry Norelle L , Khumra Sharmila , Ellis Andrew G , Frauman Albert G , Holmes Natasha E
Published: November 2020

We describe a case of limb-threatening osteomyelitis and metalware infection with carbapenemase-producing extensively drug-resistant Pseudomonas aeruginosa successfully cured with aggressive surgical debridement and combined intravenous fosfomycin and colistin. Real-time therapeutic drug monitoring was used to maximize probability of efficacy and minimize potential for toxicity.
Diagnostic and Prognostic Utility Compared Among Different Sepsis Scoring Systems in Adult Patients With Sepsis in Thailand: A Prospective Cohort Study
Authors: Pairattanakorn Prat , Angkasekwinai Nasikarn , Sirijatuphat Rujipas , Wangchinda Walaiporn , Tancharoen Lalita , Thamlikitkul Visanu
Published: November 2020

Background

The diagnostic and prognostic utility of various sepsis scores varied among different cohorts and settings.

Methods

A prospective cohort study in adult patients with sepsis at Siriraj Hospital (Bangkok, Thailand) was conducted during January to July 2019. The performance of sepsis assessments, including systemic inflammatory response syndrome (SIRS) score, sequential organ failure assessment (SOFA) score, quick sepsis-related organ failure assessment (qSOFA) score, modified early warning score (MEWS), and national early warning score (NEWS), for sepsis detection and mortality prediction were compared with agreement between 2 infectious disease (ID) specialists to determine their sepsis and septic shock status as the reference standard.

Results

Among the 470 subjects included in this study, 206 patients (43.8%) were determined by 2 ID specialists to have sepsis. Systemic inflammatory response syndrome ≥2, qSOFA ≥2, and NEWS ≥5 yielded the highest sensitivity (93.2%), specificity (81.3%), and accuracy (72.6%), respectively, for detecting sepsis. The SIRS ≥2 had the highest sensitivity (97.8%), whereas qSOFA ≥2 had the highest specificity (61%) and accuracy (69.7%) for predicting mortality among sepsis patients. Receiver operating characteristic (ROC) curve showed MEWS to have the highest discriminatory power for sepsis detection (area under the ROC curve [AUROC], 0.79; 95% confidence interval [CI], 0.74–0.83), whereas SOFA had the highest discriminatory power for predicting hospital mortality (AUROC, 0.76; 95% CI, 0.69–0.79).

Conclusions

The NEWS ≥5 and qSOFA ≥2 were the most accurate scoring systems for sepsis detection and mortality prediction, respectively. Each scoring system is useful for different specific purposes relative to early detection and mortality prediction in sepsis patients.
Clinical Symptoms Among Ambulatory Patients Tested for SARS-CoV-2
Authors: Chung Jessie R , Kim Sara S , Jackson Michael L , Jackson Lisa A , Belongia Edward A , King Jennifer P , Zimmerman Richard K , Nowalk Mary Patricia , Martin Emily T , Monto Arnold S , Gaglani Manjusha , Smith Michael E , Patel Manish , Flannery Brendan
Published: November 2020

We compared symptoms and characteristics of 4961 ambulatory patients with and without laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Findings indicate that clinical symptoms alone would be insufficient to distinguish between coronavirus disease 2019 and other respiratory infections (eg, influenza) and/or to evaluate the effects of preventive interventions (eg, vaccinations).
High-resolution mapping and characterization of epitopes in COVID-19 patients
Authors: Haynes Winston A. , Kamath Kathy , Bozekowski Joel , Baum-Jones Elisabeth , Campbell Melissa , Casanovas-Massana Arnau , Daugherty Patrick S. , Dela Cruz Charles S. , Dhal Abhilash , Farhadian Shelli F. , Fitzgibbons Lynn , Fournier John , Jhatro Michael , Jordan Gregory , Kessler Debra , Klein Jon , Lucas Carolina , Luchsinger Larry L. , Martinez Brian , Muenker Mary C. , Pischel Lauren , Reifert Jack , Sawyer Jaymie R. , Waitz Rebecca , Wunder Elsio A. , Zhang Minlu ,   Yale IMPACT Team, Iwasaki Akiko , Ko Albert I. , Shon John C.
Published: November 2020

Fine scale delineation of epitopes recognized by the antibody response to SARS-CoV-2 infection will be critical to understanding disease heterogeneity and informing development of safe and effective vaccines and therapeutics. The Serum Epitope Repertoire Analysis (SERA) platform leverages a high diversity random bacterial display library to identify epitope binding specificities with single amino acid resolution. We applied SERA broadly, across human, viral and viral strain proteomes in multiple cohorts with a wide range of outcomes from SARS-CoV-2 infection. We identify dominant epitope motifs and profiles which effectively classify COVID-19, distinguish mild from severe disease, and relate to neutralization activity. We identify a repertoire of epitopes shared by SARS-CoV-2 and endemic human coronaviruses and determine that a region of amino acid sequence identity shared by the SARS-CoV-2 furin cleavage site and the host protein ENaC-alpha is a potential cross-reactive epitope. Finally, we observe decreased epitope signal for mutant strains which points to reduced antibody response to mutant SARS-CoV-2. Together, these findings indicate that SERA enables high resolution of antibody epitopes that can inform data-driven design and target selection for COVID-19 diagnostics, therapeutics and vaccines.
Skin Lesion Classification Using Convolutional Neural Network for Melanoma Recognition
Authors: Dutta Aishwariya , Hasan Md. Kamrul , Ahmad Mohiuddin
Published: November 2020

Skin cancer, also known as melanoma, is generally diagnosed visually from the dermoscopic images, which is a tedious and time-consuming task for the dermatologist. Such a visual assessment, via the naked eye for skin cancers, is a challenging and arduous due to different artifacts such as low contrast, various noise, presence of hair, fiber, and air bubbles, etc. This article proposes a robust and automatic framework for the Skin Lesion Classification (SLC), where we have integrated image augmentation, Deep Convolutional Neural Network (DCNN), and transfer learning. The proposed framework was trained and tested on publicly available IEEE International Symposium on Biomedical Imaging (ISBI)-2017 dataset. The obtained average area under the receiver operating characteristic curve (AUC), recall, precision, and F1-score are respectively 0.87, 0.73, 0.76, and 0.74 for the SLC. Our experimental studies for lesion classification demonstrate that the proposed approach can successfully distinguish skin cancer with a high degree of accuracy, which has the capability of skin lesion identification for melanoma recognition.
Translatomic profiling of the acute stress response: It’s a TRAP
Authors: von Ziegler Lukas , Bohacek Johannes , Germain Pierre-Luc
Published: November 2020

The impact of stress on gene expression in different cell types of the brain remains poorly characterized. Three pioneering studies have recently used translating ribosome affinity purification followed by RNA sequencing (TRAP-seq) to assess the response to stress in CA3 pyramidal neurons of the hippocampus. The results suggest that acute stress alters the translation of thousands of genes in CA3 pyramidal neurons, and that this response is strongly modulated by factors such as sex, genotype and a history of early life stress. However, our reanalysis of these datasets leads to different conclusions. We confirm that acute stress induces robust translational changes in a small set of genes. However, we found no evidence that either early life stress or sex have an effect on gene translation induced by acute stress. Our findings highlight the need for additional studies with adequate sample sizes and proper methods of analysis to assess the impact of stress across cell types in the brain.
Optimization of Spectral Library Size Improves DIA-MS Proteome Coverage
Authors: Ge Weigang , Liang Xiao , Zhang Fangfei , Xu Luang , Xiang Nan , Sun Rui , Liu Wei , Xue Zhangzhi , Yi Xiao , Wang Bo , Zhu Jiang , Lu Cong , Zhan Xiaolu , Chen Lirong , Wu Yan , Zheng Zhiguo , Gong Wangang , Wu Qijun , Yu Jiekai , Ye Zhaoming , Teng Xiaodong , Huang Shiang , Zheng Shu , Liu Tong , Yuan Chunhui , Guo Tiannan
Published: November 2020

Efficient peptide and protein identification from data-independent acquisition mass spectrometric (DIA-MS) data typically rely on an experiment-specific spectral library with a suitable size. Here, we report a computational strategy for optimizing the spectral library for a specific DIA dataset based on a comprehensive spectral library, which is accomplished bya priorianalysis of the DIA dataset. This strategy achieved up to 44.7% increase in peptide identification and 38.1% increase in protein identification in the test dataset of six colorectal tumor samples compared with the comprehensive pan-human library strategy. We further applied this strategy to 389 carcinoma samples from 15 tumor datasets and observed up to 39.2% increase in peptide identification and 19.0% increase in protein identification. In summary, we present a computational strategy for spectral library size optimization to achieve deeper proteome coverage of DIA-MS data.
SequenceBouncer: A method to remove outlier entries from a multiple sequence alignment
Authors: Dunn Cory D.
Published: November 2020

Phylogenetic analyses can take advantage of multiple sequence alignments as input. These alignments typically consist of homologous nucleic acid or protein sequences, and the inclusion of outlier or aberrant sequences can compromise downstream analyses. Here, I describe a program, SequenceBouncer, that uses the Shannon entropy values of alignment columns to identify and remove outlier entries in a manner responsive to overall alignment context. I demonstrate the utility of this software using alignments of mammalian reference mitochondrial genomes, bird cytochromecoxidase-derived sequence barcodes, and COVID-19 sequences.
Using seasonal genomic changes to understand historical adaptation: parallel selection on stickleback in highly-variable estuaries
Authors: Garcia-Elfring Alan , Paccard Antoine , Thurman Timothy J. , Wasserman Ben A. , Palkovacs Eric P. , Hendry Andrew P. , Barrett Rowan D. H.
Published: November 2020

Parallel evolution is considered strong evidence for natural selection. However, few studies have investigated the process of parallel selection as it plays out in real time. The common approach is to study historical signatures of selection in populations already well adapted to different environments. Here, to document selection in action under natural conditions, we study six populations of threespine stickleback (Gasterosteus aculeatus) inhabiting bar-built estuaries that undergo seasonal cycles of environmental changes. Estuaries are periodically isolated from the ocean due to sandbar formation during dry summer months, with concurrent environmental shifts that resemble the long-term changes associated with postglacial colonization of freshwater habitats by marine populations. We used pooled whole-genome sequencing (Pool-WGS) to track seasonal allele frequency changes in these populations and search for signatures of natural selection. We found consistent changes in allele frequency across estuaries, suggesting a potential role for parallel selection. Functional enrichment among candidate genes included transmembrane ion transport and calcium binding, which are important for osmoregulation and ion balance. The genomic changes that occur in threespine stickleback from bar-built estuaries could provide a glimpse into the early stages of adaptation that have occurred in many historical marine to freshwater transitions.
SABRE populates ER domains essential for cell plate maturation and cell expansion influencing cell and tissue patterning
Authors: Cheng Xiaohang , Bezanilla Magdalena
Published: November 2020

The SABRE protein, originally identified in plants, is found throughout eukaryotes. In plants, SABRE has been implicated in cell expansion, division plane orientation and planar polarity. However, how SABRE mediates these processes remains an open question. Here, we have taken advantage of the fact that the bryophytePhyscomitrium patenshas a single copy ofSABRE, is an excellent model for cell biology and is readily amenable to precise genetic alterations to investigate SABRE’s mechanism of action. We discovered that SABRE null mutants were stunted in both polarized growing and diffusely growing tissues, similar to reported phenotypes in seed plants. However, in polarized growing cells, we observed significant delays in cell plate formation and sometimes catastrophic failures in cell division. We generated a functional SABRE fluorescent fusion protein and determined that it forms dynamic puncta on regions of the endoplasmic reticulum (ER) both in the cytoplasm during interphase and at the new cell plate during division. In the absence ofSABRE, ER morphology was severely compromised with large aggregates accumulating in the cytoplasm and abnormal buckling along the developing cell plate late in cytokinesis. In fact, SABRE and the ER maximally accumulated on the developing plate specifically during cell plate maturation, coincident with the timing of the onset of failures in cell plate formation in cells lacking SABRE. Further we discovered that callose deposition is delayed inΔsabrecells, and in cells that failed to divide, abnormal callose accumulations formed at the cell plate. Our findings demonstrated that SABRE functions by influencing the ER and callose deposition, revealing a surprising and essential role for the ER in cell plate maturation. Given that SABRE is conserved, understanding how SABRE influences cell and tissue patterning has profound significance across eukaryotes.
An Evaluation of Phylogenetic Workflows in Viral Molecular Epidemiology
Authors: Young Colin , Meng Sarah , Moshiri Niema
Published: November 2020

The use of computational techniques to analyze viral sequence data and ultimately inform public health intervention has become increasingly common in the realm of epidemiology. These methods typically attempt to make epidemiological inferences based on multiple sequence alignments and phylogenies estimated from the raw sequence data. Like all estimation techniques, multiple sequence alignment and phylogenetic inference tools are error-prone, and the impacts of such imperfections on downstream epidemiological inferences are poorly understood. To address this, we executed multiple commonly-used workflows for conducting viral phylogenetic analyses on simulated viral sequence data modeling HIV, HCV, and Ebola, and we computed multiple methods of accuracy motivated by transmission clustering techniques. For multiple sequence alignment, MAFFT consistently outperformed MUSCLE and Clustal Omega in both accuracy and runtime. For phylogenetic inference, FastTree 2, IQ-TREE, RAxML-NG, and PhyML had similar topological accuracies, but branch lengths and pairwise distances were consistently most accurate in phylogenies inferred by RAxML-NG. However, FastTree 2 was orders of magnitude faster than the other tools, and when the other tools were used to optimize branch lengths along a fixed topology provided by FastTree 2 (i.e., no tree search), the resulting phylogenies had accuracies that were indistinguishable from their original counterparts, but with a fraction of the runtime. Our results indicate that an ideal workflow for viral phylogenetic inference is to (1) use MAFFT to perform MSA, (2) use FastTree 2 under the GTR model with discrete gamma-distributed site-rate heterogeneity to quickly obtain a reasonable tree topology, and (3) use RAxML-NG to optimize branch lengths along the fixed FastTree 2 topology.