bluuebunny/crossref_metadata_2025 huggingface dataset:
Homoeologous recombination is recurrent in the nascent synthetic allotetraploidArachis ipaënsis×Arachis correntina4x and its derivatives
Authors: Chu Ye , Bertioli David , Levinson Chandler M , Stalker H Thomas , Holbrook C Corley , Ozias-Akins Peggy
Published: March 2021

Genome instability in newly synthesized allotetraploids of peanut has breeding implications that have not been fully appreciated. Synthesis of wild species-derived neo-tetraploids offers the opportunity to broaden the gene pool of peanut; however, the dynamics among the newly merged genomes creates predictable and unpredictable variation. Selfed progenies from the neo-tetraploid Arachis ipaënsis × Arachis correntina (A. ipaënsis × A. correntina)4x and F1 hybrids and F2 progenies from crosses between A. hypogaea × [A. ipaënsis × A. correntina]4x were genotyped by the Axiom Arachis 48 K SNP array. Homoeologous recombination between the A. ipaënsis and A. correntina derived subgenomes was observed in the S0 generation. Among the S1 progenies, these recombined segments segregated and new events of homoeologous recombination emerged. The genomic regions undergoing homoeologous recombination segregated mostly disomically in the F2 progenies from A. hypogaea × [A. ipaënsis × A. correntina]4x crosses. New homoeologous recombination events also occurred in the F2 population, mostly found on chromosomes 03, 04, 05, and 06. From the breeding perspective, these phenomena offer both possibilities and perils; recombination between genomes increases genetic diversity, but genome instability could lead to instability of traits or even loss of viability within lineages.
Stability analysis of quasi one-sided Lipschitz non-linear multi-agent system via sampled data control subject to directed switching topology
Authors: Ali M Syed , Agalya R , Priya Banadana , Kumar Thakur Ganesh , Shekher Vineet
Published: March 2021

This paper is concerned with the problem of stability and consensus of non-linear multi-agent system by utilizing the sampled-data control. The innovative part of this paper is that the nonlinearity of this class of nonlinear systems is considered to satisfy a quasi one-sided Lipschitz condition. Communication among agents are assumed to be a switching directed graph. The principle target of this paper is to design a sampled data controller such that for all permissible uncertainties, the resulting closed-loop system is stable in the sense of mean square. For this reason, through the development of an appropriate Lyapunov–Krasovskii functional with dual integral terms and usage of Kronecker product properties alongside the matrix inequality techniques, a new set of stability and consensus conditions for the prescribed system is obtained in the form of a linear matrix inequality, which can be easily solved by the well-known effective numerical programming. Finally numerical examples are given to show the validity of the proposed hypothetical results.
Impact of the COVID-19 Pandemic on Breast Imaging Education
Authors: Chalfant James S , Pittman Sarah M , Kothari Pranay D , Chong Alice , Grimm Lars J , Sohlich Rita E , Leung Jessica W T , Downey John R , Cohen Ethan O , Ojeda-Fournier Haydee , Hoyt Anne C , Joe Bonnie N , Feig Stephen A , Trinh Long , Rosen Eric L , Aminololama-Shakeri Shadi , Ikeda Debra M
Published: March 2021

Objective

To determine the impact of the COVID-19 pandemic on breast imaging education.

Methods

A 22-item survey addressing four themes during the early pandemic (time on service, structured education, clinical training, future plans) was emailed to Society of Breast Imaging members and members-in-training in July 2020. Responses were compared using McNemar’s and Mann-Whitney U tests; a general linear model was used for multivariate analysis.

Results

Of 136 responses (136/2824, 4.8%), 96 U.S. responses from radiologists with trainees, residents, and fellows were included. Clinical exposure declined during the early pandemic, with almost no medical students on service (66/67, 99%) and fewer clinical days for residents (78/89, 88%) and fellows (48/68, 71%). Conferences shifted to remote live format (57/78, 73%), with some canceled (15/78, 19%). Compared to pre-pandemic, resident diagnostic (75/78, 96% vs 26/78, 33%) (P < 0.001) and procedural (73/78, 94% vs 21/78, 27%) (P < 0.001) participation fell, as did fellow diagnostic (60/61, 98% vs 47/61, 77%) (P = 0.001) and procedural (60/61, 98% vs 43/61, 70%) (P < 0.001) participation. Most thought that the pandemic negatively influenced resident and fellow screening (64/77, 83% and 43/60, 72%, respectively), diagnostic (66/77, 86% and 37/60, 62%), and procedural (71/77, 92% and 37/61, 61%) education. However, a majority thought that decreased time on service (36/67, 54%) and patient contact (46/79, 58%) would not change residents’ pursuit of a breast imaging fellowship.

Conclusion

The pandemic has had a largely negative impact on breast imaging education, with reduction in exposure to all aspects of breast imaging. However, this may not affect career decisions.
The Moment of Worldwide Renewal: Hillel Zeitlin and the Theosophical Activity in Warsaw 1917–1924
Authors: Bluman Oz
Published: March 2021

This article examines the idiosyncratic conduct of the philosopher, journalist and mystic, Hillel Zeitlin (1871–1942). Both Zeitlin's writings and activities are unique or even strange when viewed against the backdrop of the Jewish streets of Warsaw during those years, even when considering other “neo-Hasidic” projects. He published poem-prayers and a personal-mystical diary, founded journals, called for religious and spiritual awakening and tried to start mystical study and prayer groups. Zeitlin's work had a messianic fervor that was lacking in the activity of other Jewish figures. Despite an expansion of scholarly interest in Zeitlin's writings and activities, no satisfactory explanation of his behavior has yet been proposed. This article contextualizes Zeitlin's writing and activities in light of those of various spiritual and esoteric movements that flourished in early twentieth century Poland, Russia and Germany, in particular, those of the Theosophical Societies in Warsaw. He was aware and deeply sympathetic to the various movements of spiritual awakening, and these affected his work profoundly.
Asexual Experimental Evolution of Yeast Does Not Curtail Transposable Elements
Authors: Chen Piaopiao , Zhang Jianzhi
Published: March 2021

Compared with asexual reproduction, sex facilitates the transmission of transposable elements (TEs) from one genome to another, but boosts the efficacy of selection against deleterious TEs. Thus, theoretically, it is unclear whether sex has a positive net effect on TE’s proliferation. An empirical study concluded that sex is at the root of TE’s evolutionary success because the yeast TE load was found to decrease rapidly in approximately 1,000 generations of asexual but not sexual experimental evolution. However, this finding contradicts the maintenance of TEs in natural yeast populations where sexual reproduction occurs extremely infrequently. Here, we show that the purported TE load reduction during asexual experimental evolution is likely an artifact of low genomic sequencing coverages. We observe stable TE loads in both sexual and asexual experimental evolution from multiple yeast data sets with sufficient coverages. To understand the evolutionary dynamics of yeast TEs, we turn to asexual mutation accumulation lines that have been under virtually no selection. We find that both TE transposition and excision rates per generation, but not their difference, tend to be higher in environments where yeast grows more slowly. However, the transposition rate is not significantly higher than the excision rate and the variance of the TE number among natural strains is close to its neutral expectation, suggesting that selection against TEs is at best weak in yeast. We conclude that the yeast TE load is maintained largely by a transposition–excision balance and that the influence of sex remains unclear.
Factors affecting time to brain metastases for stage 2 and 3 breast cancer patients: A large single-institutional analysis with potential screening implications
Authors: Cao Toni Q , Dixit Karan , Santa-Maria Cesar , Kumthekar Priya
Published: March 2021

Background

Breast cancer is the second most common cancer associated with brain metastases. The purpose of this study was to identify factors that impact the time to brain metastases in breast cancer patients at a single institution.

Methods

Single institution retrospective study that captured all consecutive stage 2 and stage 3 breast cancer patients from 2003 to 2010. Patient characteristics analyzed included age, hormone status, HER2 receptor status, grade, stage, and time from breast cancer diagnosis to brain metastasis.

Results

A total of 1218 patients were eligible for the final analysis. 849 (69.7%) patients were ER+/HER2−, 90 (7.4%) were HER2+, and 279 (22.9%) were triple-negative (TN). Overall, 74 patients (6.1%) developed brain metastases over a median follow up time of 92 months. Median times to brain metastases for HER2+, TN, and ER+/HER2− patients were 20, 26, and 57 months, respectively. Multivariate analysis demonstrated that TN disease (HR = 2.043, P = .015), grade (HR = 1.667, P = .024) and stage (HR = 3.851, P < .001) were independent risk factors for earlier brain metastases. Median times to brain metastases were 34 and 52 months for stage 3 and 2 patients, and 30, 49, and 71 months for grade 3, 2, and 1 tumors, respectively.

Conclusions

This single-institutional case series demonstrates that TN breast cancer, higher stage, and higher histologic grade are associated with earlier brain metastases in multivariate analysis. Additional prospective studies are warranted to investigate the impact of brain metastases screening on survival outcome in this high-risk defined group.
Human immunodeficiency virus infection with multiple opportunistic infections: lessons learnt from a non-adherent patient
Authors: Soneja Manish , Aggarwal Anivita , Kodan Parul , Gupta Nitin
Published: March 2021

We report a case of advanced human immunodeficiency virus (HIV) infection with multiple opportunistic infections (Pneumocystis carinii pneumonia, cryptosporidiosis, oesophagal candidiasis and cytomegalovirus infection). The patient was presumed to be adherent on antiretroviral therapy (ART) and was initiated on respective treatments for the opportunistic infections but continued to deteriorate. On further reviewing, he was found to be poorly adherent to ART and was advised enhanced adherence counselling after which his condition improved. We report this case to emphasize the importance of adherence to ART medications in the management of patients with HIV.
STEMI associated with SARS-CoV-2 infection and the use of ECMO as a potential therapeutic approach in addition to the PCI
Authors: Rahman Tanvir , Alayo Quazim A , Chaudhary Sibgha G , Moghadam Reihaneh C , German Matthew L , Ettinger Neil A , Leidenfrost Jeremy E , Cranston-D'amato Hope A , Rinder Morton R , Donnelly Julianne E
Published: March 2021

A 55-year-old male presented to the emergency department with the complaints of chest pain that started 4 h before presentation. Pain was located over the anterior chest, 5 out of 10 intensity, with radiation to the left arm. Chest x-ray on admission showed severe diffuse bilateral pulmonary infiltrates concerning for COVID-19 pneumonia. Electrocardiogram showed inferior and lateral ST-segment elevation compatible with acute inferolateral myocardial infarction. Successful percutaneous coronary intervention (PCI) of the proximal and mid-right coronary artery using the balloon angioplasty and drug-eluting stent was performed. Post-PCI stenosis was 0% with a thrombolysis in myocardial infarction (TIMI) flow of 3. Five-day course of azithromycin and hydroxychloroquine was completed with no improvement overall. Patient received two doses of 400 mg of tocilizumab intravenously on hospital days 5 (HD#5) and #6. The patient was proned, on FiO2 100%, PEEP 15 cm H2O, on epoprostenol sodium and paralytics and eventually received venovenous ECMO, which improved outcome.
Heparin-induced thrombocytopenia during IgA vasculitis: a case report
Authors: Yamasaki Kaisei , Kyotani Moe , Urase Yasuyo , Goto Yoichi , Kenzaka Tsuneaki
Published: March 2021

Immunoglobulin A (IgA) vasculitis is characterized by small vessel vasculitis involving immune complexes and IgA deposition. The development of heparin-induced thrombocytopenia (HIT) during IgA vasculitis is extremely rare. An 87-year-old man presented with general fatigue, leg edema, purpura, arthritis and renal disease. He was diagnosed with IgA vasculitis and was admitted to our hospital. Hemodialysis with heparin was initiated thrice a week on post-admission Day 11. On Day 21, during hemodialysis, the pressure in the dialysis circuit increased and the dialysis was interrupted. On Day 24, the platelet count rapidly decreased to 18 000/μl. The patient was diagnosed with HIT after testing positive for HIT antibodies; heparin was discontinued at this time. Precautions must be taken against the onset of HIT when initiating hemodialysis in patients with IgA vasculitis.
Why Ethics Matter in Psychotherapy
Authors: Trachsel Manuel , Gaab Jens , Tekin Şerife , Biller-Andorno Nikola , Sadler John Z.
Published: March 2021

The clinical practice of psychotherapy is saturated with ethics and moralities. Having an Oxford Handbook of Psychotherapy Ethics seems a necessity in a contemporary world where visions of the good seem up for grabs; subject to whomever shouts the loudest and the most often. The quiet exchanges behind (typically) closed doors, which consider what the good is for the patient, what it means, and how to secure it, seem more crucial than ever. The Oxford Handbook of Psychotherapy Ethics aims to provide the most comprehensive reference textbook of psychotherapy ethics; to offer benchmark chapters as go-to guides for a wide variety of practitioners, scholars, policymakers, and patients; to address conceptual, philosophical, cultural, and religious perspectives while also addressing everyday practice concerns; and to identify areas of ethical consensus and convention, while identifying unresolved issues as well as identifying new, problematic areas needing further analysis and research.
The microbiome in obstructive sleep apnea
Authors: Cai Yi , Juszczak Hailey M , Cope Emily K , Goldberg Andrew N
Published: March 2021

Recent evidence has highlighted important associations between obstructive sleep apnea and the microbiome. Although the intricacies of the pathophysiologic mechanisms are not well understood, available evidence suggests a bidirectional relationship between obstructive sleep apnea and microbiota composition. Sleep fragmentation, intermittent hypoxia, and intermittent hypercapnia all play significant roles in altering the microbiome, and initial evidence has shown that alterations of the microbiota affect sleep patterns. Animal model evidence strongly supports the idea that the microbiome mediates disease states associated with obstructive sleep apnea including hypertension, atherosclerosis, and obesity. While evidence is limited, several studies suggest there may be a role for treatment of obstructive sleep apnea and obstructive sleep apnea-related comorbidities through alteration of the microbiome with probiotics, prebiotics, and microbiota transplantation.
Ventral–Dorsal Subregions in the Posterior Cingulate Cortex Represent Pay and Interest, Two Key Attributes of Job Value
Authors: Matsuura Shunsui , Suzuki Shinsuke , Motoki Kosuke , Yamazaki Shohei , Kawashima Ryuta , Sugiura Motoaki
Published: March 2021

Career choices affect not only our financial status but also our future well-being. When making these choices, individuals evaluate their willingness to obtain a job (i.e., job values), primarily driven by simulation of future pay and interest. Despite the importance of these decisions, their underlying neural mechanisms remain unclear. In this study, we examined the neural representation of pay and interest. Forty students were presented with 80 job names and asked to evaluate their job values while undergoing functional magnetic resonance imaging (fMRI). Following fMRI, participants rated the jobs in terms of pay and interest. The fMRI data revealed that the ventromedial prefrontal cortex (vmPFC) was associated with job value representation, and the ventral and dorsal regions of the posterior cingulate cortex (PCC) were associated with pay and interest representations, respectively. These findings suggest that the neural computations underlying job valuation conform to a multi-attribute decision-making framework, with overall value signals represented in the vmPFC and the attribute values (i.e., pay and interest) represented in specific regions outside the vmPFC, in the PCC. Furthermore, anatomically distinct representations of pay and interest in the PCC may reflect the differing roles of the two subregions in future simulations.
You Want It Extra CRISPERY? Legal Disruption through New Plant Breeding Technologies in the EU
Authors: Purnhagen Kai P
Published: March 2021

I will illustrate how the ‘old’ European Union (EU) legal regime on genetically modified organisms (GMOs) is applied to regulate new plant breeding technologies (NPBT). I will discuss why and how this results in what elsewhere had been called ‘legal disruption’. Legal disruption will occur once legal rules which were initially confined to a specific identified issue start to be applied beyond their original target. Such legal disruption may be found in the example of NPBT interacting with the precautionary principle, the use of scientific evidence in preliminary ruling proceedings, and the enforcement of labelling and traceability requirements. In the case of NPBT, legal disruption took place because policy makers were unwilling to adopt legislation designed to meet the demands of the technology. Consequently, they shuffled the responsibility for regulatory decision to the Court of Justice of the EU (CJEU). The CJEU, in its current design, represents an ill-suited institution to decide on such complex technology questions. I will explain why. I will end with a plea for a regulation of NPBT, which likewise enables and protects, following the eight principles developed by Michéle Finck on the example of the governance of blockchain technology.
Double Discrimination, the Pay Gap in Gynecologic Surgery, and Its Association With Quality of Care
Authors: Watson Katie L. , King Louise P.
Published: March 2021

In this commentary, we describe historical and other influences that drive “double discrimination” in gynecologic surgery—lower pay in the area of surgery that boasts the largest proportion of female surgeons and is focused on female patients and explore how it results in potentially lower quality care. Insurers reimburse procedures for women at a lower rate than similar procedures for men, although there is no medically justifiable reason for this disparity. The wage gap created by lower reimbursement rates disproportionately affects female surgeons, who are disproportionately represented among gynecologic surgeons. This contributes to a large wage gap in surgery for women. Finally, poor reimbursement for gynecologic surgery pushes many obstetrics and gynecology surgeons to preferentially perform obstetric services, resulting in a high prevalence of low-volume gynecologic surgeons, a metric that is closely tied to higher complication rates. Creating equity in reimbursement for gynecologic surgery is one important and ethically required step forward to gender equity in medicine for patients and surgeons.
Next-generation Sequencing in Bone Marrow Failure Syndromes and Isolated Cytopenias: Experience of the Spanish Network on Bone Marrow Failure Syndromes
Authors: Gálvez Eva , Vallespín Elena , Arias-Salgado Elena G. , Sánchez-Valdepeñas Carmen , Giménez Yari , Navarro Susana , Río Paula , Bogliolo Massimo , Pujol Roser , Peiró Montserrat , Nevado Julián , Zubicaray Josune , Sebastián Elena , Catalá Albert , Beléndez Cristina , Díaz de Heredia Cristina , Galera Ana , Badell Isabel , Madero Luis , Perona Rosario , Sastre Leandro , Surrallés Jordi , Bueren Juan , Lapunzina Pablo , Sevilla Julián
Published: March 2021

Inherited bone marrow failure syndromes (IBMFSs) are a group of congenital rare diseases characterized by bone marrow failure, congenital anomalies, high genetic heterogeneity, and predisposition to cancer. Appropriate treatment and cancer surveillance ideally depend on the identification of the mutated gene. A next-generation sequencing (NGS) panel of genes could be 1 initial genetic screening test to be carried out in a comprehensive study of IBMFSs, allowing molecular detection in affected patients. We designed 2 NGS panels of IBMFS genes: version 1 included 129 genes and version 2 involved 145 genes. The cohort included a total of 204 patients with suspected IBMFSs without molecular diagnosis. Capture-based targeted sequencing covered > 99% of the target regions of 145 genes, with more than 20 independent reads. No differences were seen between the 2 versions of the panel. The NGS tool allowed a total of 91 patients to be diagnosed, with an overall molecular diagnostic rate of 44%. Among the 167 patients with classified IBMFSs, 81 patients (48%) were diagnosed. Unclassified IBMFSs involved a total of 37 patients, of whom 9 patients (24%) were diagnosed. The preexisting diagnosis of 6 clinically classified patients (6%) was amended, implying a change of therapy for some of them. Our NGS IBMFS gene panel assay is a useful tool in the molecular diagnosis of IBMFSs and a reasonable option as the first tier genetic test in these disorders.
Role of microglia and P2X4 receptors in chronic pain
Authors: Kohno Keita , Tsuda Makoto
Published: March 2021

Pain plays an indispensable role as an alarm system to protect us from dangers or injuries. However, neuropathic pain, a debilitating pain condition caused by damage to the nervous system, persists for a long period even in the absence of dangerous stimuli or after injuries have healed. In this condition, pain becomes a disease itself rather than the alarm system and is often resistant to currently available medications. A growing body of evidence indicates that microglia, a type of macrophages residing in the central nervous system, play a crucial role in the pathogenesis of neuropathic pain. Whenever microglia in the spinal cord detect a damaging signal within the nervous system, they become activated and cause diverse alterations that change neural excitability, leading to the development of neuropathic pain. For over a decade, several lines of molecular and cellular mechanisms that define microglial activation and subsequently altered pain transmission have been proposed. In particular, P2X4 receptors (a subtype of purinergic receptors) expressed by microglia have been investigated as an essential molecule for neuropathic pain. In this review article, we describe our understanding of the mechanisms by which activated microglia cause neuropathic pain through P2X4 receptors, their involvement in several pathological contexts, and recent efforts to develop new drugs targeting microglia and P2X4 receptors.
The mitochondrial intermembrane space: the most constricted mitochondrial sub-compartment with the largest variety of protein import pathways
Authors: Edwards Ruairidh , Eaglesfield Ross , Tokatlidis Kostas
Published: March 2021

The mitochondrial intermembrane space (IMS) is the most constricted sub-mitochondrial compartment, housing only about 5% of the mitochondrial proteome, and yet is endowed with the largest variability of protein import mechanisms. In this review, we summarize our current knowledge of the major IMS import pathway based on the oxidative protein folding pathway and discuss the stunning variability of other IMS protein import pathways. As IMS-localized proteins only have to cross the outer mitochondrial membrane, they do not require energy sources like ATP hydrolysis in the mitochondrial matrix or the inner membrane electrochemical potential which are critical for import into the matrix or insertion into the inner membrane. We also explore several atypical IMS import pathways that are still not very well understood and are guided by poorly defined or completely unknown targeting peptides. Importantly, many of the IMS proteins are linked to several human diseases, and it is therefore crucial to understand how they reach their normal site of function in the IMS. In the final part of this review, we discuss current understanding of how such IMS protein underpin a large spectrum of human disorders.
Enhancement of signal-to-noise ratio for fluorescence endoscope image based on fast digital lock-in algorithm
Authors: Wang Huiquan , Hu Meng , Xia Fang , Guo Meng , Zhang Shengzhao , Zhao Zhe , Han Guang , Wang Jinhai
Published: March 2021

In this paper, the signal-to-noise ratios (SNR) of two image channels were enhanced with the fast digital lock-in algorithm. In order to simultaneously improve the quality of white and fluorescence images obtained by fluorescence endoscope, and improve the SNR to achieve a better image processing effect, two sources of white light and near-infrared light of a fluorescence endoscope were modulated, then the acquired images were demodulated into white and fluorescence images. A fluorescent endoscope experimental platform was setup to acquire endoscopic images of a target dyed by indocyanine green. The experimental results showed that the SNR of white and fluorescent images without the lock-in algorithm were 36.56 dB and 33.47 dB, respectively. However, with the lock-in algorithm, the SNR of white and fluorescent images were 39.54 dB and 35.70 dB, respectively. The SNR of white and fluorescent images was increased by 8.2% and 6.7%, respectively, by appling the digital lock-in algorithm. Therefore, this novel fluorescence endoscope based on the fast digital lock-in algorithm can rapidly and simultaneously obtain two-channel images of white light and fluorescence, effectively enhance the SNR of white and fluorescent images, and improve the imaging quality.
Nanostructured metal oxide semiconductor-based sensors for greenhouse gas detection: progress and challenges
Authors: Gautam Yogendra K. , Sharma Kavita , Tyagi Shrestha , Ambedkar Anit K. , Chaudhary Manika , Pal Singh Beer
Published: March 2021

Climate change and global warming have been two massive concerns for the scientific community during the last few decades. Anthropogenic emissions of greenhouse gases (GHGs) have greatly amplified the level of greenhouse gases in the Earth's atmosphere which results in the gradual heating of the atmosphere. The precise measurement and reliable quantification of GHGs emission in the environment are of the utmost priority for the study of climate change. The detection of GHGs such as carbon dioxide, methane, nitrous oxide and ozone is the first and foremost step in finding the solution to manage and reduce the concentration of these gases in the Earth's atmosphere. The nanostructured metal oxide semiconductor (NMOS) based technologies for sensing GHGs emission have been found most reliable and accurate. Owing to their fascinating structural and morphological properties metal oxide semiconductors become an important class of materials for GHGs emission sensing technology. In this review article, the current concentration of GHGs in the Earth's environment, dominant sources of anthropogenic emissions of these gases and consequently their possible impacts on human life have been described briefly. Further, the different available technologies for GHG sensors along with their principle of operation have been largely discussed. The advantages and disadvantages of each sensor technology have also been highlighted. In particular, this article presents a comprehensive study on the development of various NMOS-based GHGs sensors and their performance analysis in order to establish a strong detection technology for the anthropogenic GHGs. In the last, the scope for improved sensitivity, selectivity and response time for these sensors, their future trends and outlook for researchers are suggested in the conclusion of this article.
Sustainability issues in a tropical mega trail
Authors: Grelle Carlos E. V. , Niemeyer Julia , Viveiros de Castro Ernesto B. , Lanna André M. , Uzeda Mariella , Vieira Marcus Vinicius
Published: March 2021

Sustainability is a target that involves many socio-ecological questions, depends on opportunities and combines different initiatives. This can be especially difficult in regions with high biodiversity scores, mega cities, high level of human populations and an intense and long-standing land use. Here, we show how a mega trail, named Atlantic Forest Trail, within the Brazilian Atlantic Forest can join the protection of biodiversity and sustainable tourism through a 4270 km corridor connecting protected areas and crossing a variety of landscapes. Further, we show some initiatives of ongoing biodiversity monitoring, and an analysis of ecological restoration in private lands that can be applied in many regions to improve habitat connectivity for both biodiversity and human use.
An electronic circular dichroism spectroscopy method for the quantification of L- and D-amino acids in enantiomeric mixtures
Authors: Ding Ruiwen , Ying Jianxi , Zhao Yufen
Published: March 2021

Rapid quantitative analysis of single chiral amino acid (aa) was achieved using circular dichroism (CD) with data analysis by standard calibration curve. The absolute concentrations of D- and L-aas in enantiomeric mixtures were determined by CD and achiral liquid chromatography (LC) method. It is worth noting that CD and LC were used independently, not online LC/CD in this study. The errors of the experimental results were less than 10%. The method is also applicable to the quantification of non-aa chiral molecules, such as chiral nucleoside and chiral quinine. With this study, we provide a new method for the chiral quantitative analysis of enantiomeric aas mixtures.
A brief review on Group A Streptococcus pathogenesis and vaccine development
Authors: Castro Sowmya Ajay , Dorfmueller Helge C.
Published: March 2021

Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is a Gram-positive human-exclusive pathogen, responsible for more than 500 000 deaths annually worldwide. Upon infection, GAS commonly triggers mild symptoms such as pharyngitis, pyoderma and fever. However, recurrent infections or prolonged exposure to GAS might lead to life-threatening conditions. Necrotizing fasciitis, streptococcal toxic shock syndrome and post-immune mediated diseases, such as poststreptococcal glomerulonephritis, acute rheumatic fever and rheumatic heart disease, contribute to very high mortality rates in non-industrialized countries. Though an initial reduction in GAS infections was observed in high-income countries, global outbreaks of GAS, causing rheumatic fever and acute poststreptococcal glomerulonephritis, have been reported over the last decade. At the same time, our understanding of GAS pathogenesis and transmission has vastly increased, with detailed insight into the various stages of infection, beginning with adhesion, colonization and evasion of the host immune system. Despite deeper knowledge of the impact of GAS on the human body, the development of a successful vaccine for prophylaxis of GAS remains outstanding. In this review, we discuss the challenges involved in identifying a universal GAS vaccine and describe several potential vaccine candidates that we believe warrant pursuit.
Investigation of EDTA concentration on the size of carbonated flowerlike hydroxyapatite microspheres
Authors: Yao Shengkun , Qi Mei-li , Qi Liang , Ding Yongling , Chen Min , Wang Yanmin
Published: March 2021

Ethylenediamine tetraacetic acid (EDTA) is considered an effective crystal growth modifier for template-assisted hydrothermal synthesis of hydroxyapatite (HA) materials. In this work, flowerlike-carbonated HA (CHA) microspheres were synthesized using EDTA via a one-step hydrothermal route. The phase, functional groups, morphology and particle size distribution of the products were examined by X-ray diffraction, Fourier transform infrared spectrometer, field emission scanning electron microscopy as well as laser diffraction particle size analysis. Results show that the morphology of the products can be well controlled by adjusting the EDTA concentration. With an increase of the EDTA concentration, the particle size of flowerlike microspheres decreased from tens of microns down to a few microns. The underlying mechanism for the morphological transition of CHA microspheres with different concentrations of EDTA under hydrothermal conditions is proposed. This work provides a simple way to controllably fabricate CHA microspheres with various sizes using the same synthesis system for biomedical applications, such as cell carriers and drug delivery.
High levels of common cold coronavirus antibodies in convalescent plasma are associated with improved survival in COVID-19 patients
Authors: Greenbaum Uri , Klein Kimberly , Martinez Fernando , Song Juhee , Thall Peter F. , Ramdial Jeremy L. , Knape Cristina , Aung Fleur M. , Scroggins Jamie , Knopfelmacher Adriana , Mulanovich Victor , Borjan Jovan , Adachi Javier , Muthu Mayoora , Leung Cerena , Medina Mayrin Correa , Champlin Richard , Olson Amanda , Alousi Amin , Rezvani Katayoun , Shpall Elizabeth J.
Published: March 2021

Background

COVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP.

Patients and Methods

Patients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed.

Results

CCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex.

Conclusions

Common cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.
Factors influencing COVID rates at local authority level and contribution of variation in vaccine coverage
Authors: Cullum Rachel , Badrinath Padmanabhan
Published: March 2021

We have undertaken a piece of rapid analysis of the most recent COVID-19 weekly rates to examine commonalities across areas with rates exceeding twice the national average. Our preliminary findings point towards an association between higher case rates and deprivation with implications for health inequalities. Furthermore, we also observed an association between higher case rates and lower rates of vaccination. More analysis is needed to further explore these linkages and help fuel what should be an urgent narrative around the need to tackle health inequalities in the COVID era.
The Prognostic Value of PD-1/PD-L1 Expression on Tumor Cells and Tumor-Infiltrating Immune Cells in Patients with Colorectal Cancer: a Systematic Review and Meta-Analysis Protocol
Authors: Abedini Fateme , Salehi Saeedeh , Janani Leila , Mohsenzadegan Monireh
Published: March 2021

Aim

Colorectal cancer (CRC) is one of the most common cancers in the world. However, the role of immune checkpoint molecules, especially Programmed cell death protein 1 (PD-1) and Programmed cell death-ligand 1 (PD-L1), in the progression of CRC remains unclear. This systematic review and meta-analysis will investigate the prognostic significance of PD-1/PD-L1 expression on tumor-infiltrating immune cells and tumor cells in patients with colorectal cancer.

Methods

This protocol has been prospectively registered in the PROSPERO (registration NO. CRD42020156233). A comprehensive electronic search on PubMed/MEDLINE, Scopus, Web of Science (WOS), Embase and ProQuest will be conducted using a combination of MeSH terms of “programmed cell death 1”, “programmed cell death ligand 1”, “colorectal” and “cancer” between 1 January 1990 and 31 March 2021 with no language limitation. Two independent reviewers will perform study selection, data extraction, and risk of bias assessment. The Newcastle-Ottawa Scale (NOS) for cohort studies will be used to assess the risk of bias. In the case of sufficient data, either random or fixed-effect models, will be used for meta-analysis. Statistical heterogeneity will be evaluated by 𝒳2 test with the I2 statistic. “Funnel plot”, “Begg’s statistical test”, and “Egger’s statistical test and graph” will be used to assess publication bias. Stata V.13 software will be employed for meta-analysis.

Results and conclusion

According to the meta-analysis of the aggregated data from the relevant primary studies, the relationship between expression of PD-1/PD-L1 and prognostic parameters, including progression-free survival and overall survival, will be reported. The results of the current study will be published in a peer-reviewed journal.
Flow cytometry allows rapid detection of protein aggregates in cell culture and zebrafish models of spinocerebellar ataxia-3
Authors: Robinson Katherine J , Tym Madelaine C. , Hogan Alison , Watchon Maxinne , Yuan Kristy C , Plenderleith Stuart K , Don Emily K , Laird Angela S
Published: March 2021

Spinocerebellar ataxia-3 (SCA3, also known as Machado Joseph Disease), is a neurodegenerative disease caused by inheritance of aATXN3gene containing a CAG repeat expansion, resulting in presence of a polyglutamine (polyQ) repeat expansion within the encoded human ataxin-3 protein. SCA3 is characterized by the formation of ataxin-3 protein aggregates within neurons, neurodegeneration, and impaired movement. In this study we have identified protein aggregates in both neuronal-like (SHSY5Y) cells andin vivo(transgenic zebrafish) models expressing human ataxin-3 protein containing polyQ expansion. We have adapted a flow cytometric methodology, allowing rapid quantification of detergent insoluble forms of ataxin-3 fused to a green fluorescent protein. Flow cytometric analysis revealed an increased number of detergent-insoluble ataxin-3 particles in cells and zebrafish expressing polyQ expanded ataxin-3 when compared to cells and zebrafish expressing wildtype human ataxin-3. Interestingly, a protein aggregation phenotype could be detected as early as two days of age in transgenic zebrafish, prior to the onset of a detectable movement impairment at 6 days of age, suggesting protein aggregation may be an early disease phenotype in SCA3. Further, treatment of SCA3 cells and transgenic zebrafish with compounds known to modulate the activity of the autophagy protein quality control pathway altered the number of detergent-insoluble ataxin-3 particles detected by flow cytometry. We conclude that flow cytometry is a powerful tool that can be harnessed to rapidly quantify ataxin-3 aggregates, bothin vitroandin vivo, and can be utilised to screen and compare potential protein aggregate targeting therapies.
GRAMMAR-Lambda: An Extreme Simplification for Genome-wide Mixed Model Association Analysis
Authors: Yang Runqing , Gao Jin , Song Yuxin , Hao Zhiyu , Xu Pao
Published: March 2021

A highly efficient genome-wide association method, GRAMMAR-Lambda is proposed to make simple genomic control for the test statistics deflated by GRAMMAR, producing statistical power as high as exact mixed model association method. Using the simulated and real phenotypes, we show that at a moderate or above genomic heritability, polygenic effects can be estimated using a small number of randomly selected markers, which extremely simplify genome-wide association analysis with an approximate computational complexity to naïve method in large-scale complex population. Upon a test at once, joint association analysis offers significant increase in statistical power over existing methods.
Phylogeography, codon usages, and DNA barcoding of lesser short nosed fruit bat (Cynopterus brachyotisMuller, 1838) populations in Indonesia
Authors: Wibowo Andri
Published: March 2021

Fruit bat (Pteropodidae) is one of the mammals that is common in environments and widely distributed from subtropical to tropical Asia. Whereas the information on phylogeography of fruit batCynopterus brachyotisis still limited. From this situation, this paper aims to assess the phylogeography, codon usage, and DNA barcoding ofC. brachyotispopulations in Indonesia. Phylogeography was developed based on 657 bp of the mtDNA COI gene for all bat individuals and Bayesian inference to construct the phylogeny tree. TheC. brachyotispopulations in Indonesia are different to the populations from the Asia’s continent. The results show thatC. brachyotispopulations in Indonesia were divided into 3 distinct clades. A putative geographical barrier, recent, and rapid range expansion in the Sunda lineage associated with changes in sea levels, possibly coupled with related ecological differences, may have driven population divergence, allopatric, and sympatric speciation. Codon usage and high frequency were also contributing to the dispersal ofC. brachyotisforming a distinct population.
Hierarchical Generalized Linear Mixed Model for Genome-wide Association Analysis
Authors: Zhang Hengyu , Yang Li’ang , Xu Yanan , Zhou Xiaojing , Song Yuxin , Li Shuling , Yang Runqing
Published: March 2021

In genome-wide association analysis (GWAS) for binary traits, we stratified the genomic generalized linear mixed model (GLMM) into two hierarchies—the GLMM regarding genomic breeding values (GBVs) and a generalized linear regression of the normally distributed GBVs to the tested marker effects. In the first hierarchy, the GBVs were predicted by solving for the genomic best linear unbiased prediction for GLMM with the estimated variance components or genomic heritability in advance, and in the second hierarchy, association tests were performed using the generalized least square (GLS) method for the GBVs. Like the Hi-LMM for regular quantitative traits, the so-called Hi-GLMM method exhibited higher statistical power to detect quantitative trait nucleotides (QTNs) with better genomic control for complex population structure than existing methods, especially when the GBVs were estimated precisely and using joint association analysis for QTN candidates obtained from a test at once. Application of the Hi-GLMM to re-analyze maize kernel colors and six human diseases illustrated its advantage over existing GLMM-based association methods in terms of computing efficiency and statistical power.
Beyond residence time: quantifying factors that drive the spatially explicit filtration services of a “pristine” oyster population
Authors: Gray M.W. , Pinton D. , Canestrelli A. , Dix N. , Marcum P. , Kimbro D. , Grizzle R.
Published: March 2021

The Guana-Tolomato-Matanzas (GTM) system is a relatively pristine and well-flushed estuary in Northeastern Florida, USA and characterized as having an extraordinarily high abundance of oysters. Historically, dense populations of oysters, such as those found in GTM, are believed to play an important role in water filtration; however, few biofiltration studies have had access to such pristine populations. To quantify the filtration service(FS)of Eastern oysters(Crassostrea virginica)in GTM at several spatial scales (i.e. reef, watershed, estuary), we implemented a model that solves for the hydrodynamics and depletion of particulate matter passing over model oyster populations, the latter of which were derived from detailed bay-wide surveys. The model results suggested that oyster reefs populating the GTM play an important role in water quality by filtering ~60% of the estuary’s volume within its residence time. Our approach teases apart the role of reef size, residence time, particle concentration, and other physical factors on the generation ofFSat different spatial scales. Downstream effects were found to be very important for estuaryFS, which depend on the spatial distribution of the reefs in the GTM and local and estuarine-scale hydrodynamics. Therefore, the difference between “realized”FSand the “potential”FSof a given reef may be substantial when considering the complex hydrodynamic and connectivity among populations at several scales. Our model results provide clear and actionable information for management of these oyster populations and conservation of their ecosystem services.
SARS-CoV-2 comprehensive receptor profiling: mechanistic insight to drive new therapeutic strategies
Authors: Brockbank Sarah MV , Soden Jo , Faba-Rodriguez Raquel , Ribeiro Lyn Rosenbrier , Geh Catherine , Thomas Helen , Delight Jenni , Coverley Lucy , Abbott W Mark , Freeth Jim
Published: March 2021

Here we describe a hypothesis free approach to screen for interactions of SARS-CoV-2 spike (S) protein with human cell surface receptors. We used a library screening approach to detect binding interactions across one of the largest known panels of membrane-bound and soluble receptors, comprising 5845 targets, expressed recombinantly in human cells. We were able confirm and replicate SARS-CoV-2 binding to ACE2 and other putative coreceptors such as CD209 and CLEC4M. More significantly, we identified interactions with a number of novel SARS-CoV-2 S binding proteins. Three of these novel receptors, NID1, CNTN1 and APOA4 were specific to SARS-CoV-2, and not SARS-COV, with APOA4 binding the S-protein with equal affinity as ACE2. With this knowledge we may further understand the disease pathogenesis of COVID-19 patients and how infection by SARS-CoV-2 may lead to differences in pathology in specific organs or indeed the virulence observed in different ethnicities. Importantly we illustrate a methodology which can be used for rapid, unbiassed identification of cell surface receptors, to support drug screening and drug repurposing approaches for this and future pandemics.