bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Holding Calipers: A Modification of the Bone Holding Forceps to Aid in Depth Measurement: A Technical Tip
Authors: Jain Gunjar , Chandra Manas , Trikha Vivek
Published: January 2021

One of the critical steps in plate osteosynthesis is the determination of screw length. The depth gauge is not a reliable instrument. It is inconvenient and may cause soft tissue damage. We have shared a simple and economical solution to this problem wherein a little modification in a bone holding forceps increases the accuracy of a depth gauge. We have referred to this modified instrument as a bone holding caliper. It has a dial that indicates the gap between the center of the jaws of the forceps. We have found this instrument to not only reduce the number of screws wasted but also help in containing the radiation exposure.
Three-Dimensional Correction of Hallux Valgus Deformity: A Novel Technique
Authors: Zein Abo Bakr , Elhalawany Ahmed S. , Nagy Mohamed , Kholeif Ahmed , El Barbary Hassan , Hegazy Mohamed , Afifi Ahmed
Published: January 2021

Background:

Minimally invasive techniques for forefoot surgery are increasingly used nowadays with short operative time and smaller incisions allowing early rehabilitation. Consequently, the purpose of this study was to evaluate a novel technique for 3-dimensional correction of hallux valgus deformity using small incisions.

Materials and methods:

A single-center, prospective study was conducted from February 2016 to February 2019. The study included a total of 36 feet in 34 patients with hallux valgus deformity treated with soft tissue release combined with osteotomy of the first metatarsal base with correction of angular, rotational deformities of the hallux and fixation by transverse pinning to the second metatarsal. Patients were assessed radiographically for union and measurements as well as clinically using the “The American Orthopedic Foot and Ankle Society (AOFAS)” for functional assessment.

Results:

Union was achieved in all cases. Hallux valgus angle improved from a mean of 40±5.9 degrees to a mean of 9.1±2.3 degrees (P<0.001). Intermetatarsal angle improved from a mean of 17.5±2.1 degrees to a mean of 6.1±1.5 degrees (P<0.001). At the final follow-up period (2 y), the mean hallux valgus angle was 10.9±2.8 degrees (P<0.001) and the mean intermetatarsal angle was 7±1.7 degrees (P<0.001).

Conclusion:

This technique yielded good radiographic and functional outcomes and can be a viable option in management of mild, moderate, and severe cases of hallux valgus deformity.

Level of Evidence:

Level IV, Therapeutic study.
A Simple Corrective Strategy for Adolescent Hallux Valgus by Ilizarov Method
Authors: Subramanyam Koushik N. , Mundargi Abhishek V.
Published: January 2021

Background:

Management of adolescent hallux valgus is controversial. There is no one procedure that is described for this condition.

Materials and Methods:

The authors report for the first time a simple surgical strategy in a 14-year-old patient presenting with painful hallux valgus using the Ilizarov approach. It uses small cosmetic incisions and involves soft tissue procedures, 2-level osteotomy of the metatarsal and fixation with a novel fixator assembled with Ilizarov components.

Results:

The patient was made to weight bear with the fixator immediately after the surgery and the fixator was removed in 8 weeks. At a follow-up of 3 years, the patient has a painless plantigrade foot with acceptable deformity parameters.

Conclusion:

The authors recommend this technique in adolescent hallux valgus and propose that this technique will work equally well in adults.
Does Calculated Prognostic Estimation Lead to Different Outcomes Compared With Experience-Based Prognostication in the ICU? A Systematic Review
Authors: Basile Melissa , Press Anne , Adia Alexander C. , Wang Jason J. , Herman Saori Wendy , Lester Janice , Parikh Nisha , Hajizadeh Negin
Published: January 2021

Objectives:

Little is known about the impact of providing calculator/guideline based versus clinical experiential-based prognostic estimates to patients/caregivers in the ICU. We sought to determine whether studies have compared types of prognostic estimation in the ICU and associations with outcomes.

Data Sources:

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases searched were PubMed, Embase, Web of Science, and Cochrane Library. The search was run on January 4, 2016, and April 12, 2017. References for included articles were searched.

Study Selection:

Studies meeting the following criteria were included in the analysis: communication of prognostic estimates, a comparator group, and in the adult ICU setting.

Data Extraction:

Titles/abstracts were reviewed by two researchers. We identified 10,704 articles of which 10 met inclusion criteria. Seven of the studies included estimates obtained from calculators/guidelines and three were based on subjective estimation wherein clinicians were asked to estimate prognosis based on experience. Only the seven using calculated/guideline based estimation were used for pooled analysis. Of these, one was a randomized trial, and six were nonrandomized before/after studies. All of the studies communicated the calculated/guideline-based estimates to the clinician. Two studies involved the communication of calculated prognostic estimates to the ICU physicians for all ICU patients. Four included identification of high-risk patients based on guidelines or review of historical local data which triggered a palliative care/ethics consultation, and one study included communication to physicians about guideline based likely outcomes for neurologic recovery for patients with out-of-hospital cardiac arrest survivors. The comparator arm in all studies was usual care without protocolized prognostication.

Data Synthesis:

Included studies were assessed for risk of bias. The most common outcomes measured were hospital mortality; do-not-resuscitate status; and medical ICU length of stay. In pooled analyses, there was an association between calculated/guideline based prognostic estimation and decreased medical ICU length of stay as well as increased do-not-resuscitate status, but no difference in hospital mortality.

Conclusions:

Protocolized assessment of calculator/guideline based prognosis in ICU patients is associated with decreased medical ICU length of stay and increased do-not-resuscitate status but does not have a significant effect on mortality. Future studies should explore how communicating these estimates to physicians changes behaviors including communication to patients/families and whether calculator/guideline based prognostication is associated with improved patient and family rated outcomes.
STRUCTURAL PATHOLOGY AFTER RETINAL DETACHMENT
Authors: Thomseth Vilde M. , Ushakova Anastasia , Krohn Jørgen , Utheim Tor P. , Austeng Dordi , Fossen Kristian , Varhaug Pål , Malmin Agni , Skeiseid Liliane , Tharaldsen Ane , Lindtjørn Birger , Johannesen Henrik , Juul Jens , Forsaa Vegard A.
Published: January 2021

Purpose:

To compare pathology detection using multicolor confocal scanning laser ophthalmoscopy with color fundus photography following macula-off rhegmatogenous retinal detachment.

Methods:

Postsurgery multicolor confocal scanning laser ophthalmoscopy and color fundus photography images from 30 rhegmatogenous retinal detachment patients were examined by 10 masked graders. Imaging was performed with the Heidelberg Spectralis HRA and the digital retinal camera Basler acA2500-14gc GigE. Swept-source optical coherence tomography was used as verification modality. Detection rates of ellipsoid zone disruption, foveal ellipsoid zone rosette, outer retinal folds, intraretinal cysts, subretinal fluid layer, subretinal fluid blebs, retinal striae, and retinal detachment line were compared. Intermodality and intergrader agreement were estimated.

Results:

Overall pathology detection was significantly higher for multicolor confocal scanning laser ophthalmoscopy multicolor confocal scanning laser ophthalmoscopy (adjusted odds ratio = 7.39; 95% confidence interval, 1.64–33.30; P = 0.009). The intermodality and intergrader agreement on overall pathology detection were moderate. The intermodality agreement was 0.49 (95% confidence interval, 0.48–0.51; P < 0.0001) (Gwet's AC1). Intergrader agreement was 0.53 (95% confidence interval, 0.52–0.54; P < 0.0001) for multicolor confocal scanning laser ophthalmoscopy and 0.58 (95% confidence interval, 0.57–0.59; P < 0.0001) (Fleiss kappa) for color fundus photography.

Conclusion:

Multicolor confocal scanning laser ophthalmoscopy imaging is superior to color fundus photography in detecting and delineating structural retinal abnormalities following rhegmatogenous retinal detachment and can be a helpful tool in the visualization of retinal remodeling processes in patients recovering from rhegmatogenous retinal detachment surgery.
ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR DOSING AND EXPECTED ACUITY OUTCOME AT 1 YEAR
Authors: Spaide Richard F.
Published: January 2021

Purpose:

To determine the dose–response characteristics of the antivascular endothelial growth factor agents ranibizumab and aflibercept in neovascular age-related macular degeneration using published randomized trials and observational series.

Methods:

Literature review of published series from 2006 to 2018 as determined from electronic searches of PubMed and the Cochrane Library. Data extracted included treatment strategy, frequency, and first year visual acuity response. Monthly or bimonthly treatment schedules were classified as Fixed, pro re nata studies as PRN, treat and extend as TE, and when no strategy was listed, as Variable.

Results:

Of 2062 citations retrieved, 96 were deemed eligible; these 96 citations provided 120 data points of dose frequency versus visual acuity change in Year 1 of treatment. The dose–response curve was nonlinear, but a log transform of the number of injections per year yielded a linear relationship defined by the expression, Letters of Improvement = −6.66 + 15.7*log (number of injections Year 1). After accounting for the number of injections neither the drug used (ranibizumab or aflibercept) nor the strategy used (Fixed, pro re nata, treat and extend, or Variable) were significant predictors of acuity change. As a group, studies using the pro re nata approach had the lowest number of injections and the worst acuity improvements as a treatment strategy.

Conclusion:

There seems to be a predictable, mathematically defined relationship between dose frequency and visual acuity change at 1 year in neovascular age-related macular degeneration. The performance of current treatment efforts, as suggested by reported series and Medicare claims data, seems to be substandard.
Clinically Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion Associated with Rhinovirus
Authors: Soma Noriko , Aizawa Yuta , Matsunaga Masamichi , Saitoh Akihiko
Published: January 2021

A 2-year-old girl with fever and seizures was diagnosed as having clinically mild encephalitis/encephalopathy with a reversible splenial lesion, as indicated by magnetic resonance imaging. Virologic analysis identified human rhinovirus A49 in her serum. Although human rhinovirus rarely involves the central nervous system, such involvement could result in mild encephalitis/encephalopathy with a reversible splenial lesion.
Toxic Shock Syndrome in Patients Younger than 21 Years of Age, United States, 2006–2018
Authors: Leung Jessica , Abrams Joseph Y. , Maddox Ryan A. , Godfred-Cato Shana , Schonberger Lawrence B. , Belay Ermias D.
Published: January 2021

We examined the incidence of toxic shock syndrome in the United States during 2006–2018 among persons <21 years old with commercial or Medicaid-insurance using administrative data. There were 1008 commercially-insured and 481 Medicaid-insured toxic shock syndrome cases. The annual rate was 1 per 100,000 and stable over time. Rates were even lower in children <5 years old and stable over time.
Risk Factors and Clinical Profile of Sapovirus-associated Acute Gastroenteritis in Early Childhood
Authors: Vielot Nadja A. , González Fredman , Reyes Yaoska , Zepeda Omar , Blette Bryan , Paniagua Margarita , Toval-Ruíz Christian , Diez-Valcarce Marta , Hudgens Michael G. , Gutiérrez Lester , Blandón Patricia , Herrera Roberto , Cuadra Edwing Centeno , Bowman Natalie , Vilchez Samuel , Vinjé Jan , Becker-Dreps Sylvia , Bucardo Filemón
Published: January 2021

Background:

Sapovirus is increasingly recognized as an important cause of acute gastroenteritis (AGE) in children. We identified risk factors and characterized the clinical profile of sapovirus AGE in a birth cohort in León, Nicaragua.

Methods:

We conducted a case-control study nested within a birth cohort (n = 444). Fieldworkers conducted weekly household AGE surveillance. AGE stools were tested for sapovirus by reverse transcriptase quantitative polymerase chain reaction. For each first sapovirus episode, we selected 2 healthy age-matched controls and estimated independent risk factors of sapovirus AGE using conditional logistic regression. We compared clinical characteristics of sapovirus AGE episodes with episodes associated with other etiologies and identified co-infections with other enteric pathogens.

Results:

From June 2017 to July 2019, we identified 63 first sapovirus AGE episodes and selected 126 controls. Having contact with an individual with AGE symptoms and vaginal delivery were independent risk factors for sapovirus AGE. All cases experienced diarrhea, lasting a median 6 days; 23% experienced vomiting. Compared with children with AGE due to another etiology, sapovirus AGE was similar in severity, with less reported fever. Most cases experienced co-infections and were more likely than controls to be infected with diarrheagenic Escherichia coli or astrovirus.

Conclusions:

Sapovirus was a commonly identified AGE etiology in this Central American setting, and symptoms were similar to AGE associated with other etiologies. The association between vaginal delivery and sapovirus is a novel finding. Gut microbiome composition might mediate this relationship, or vaginal delivery might be a proxy for other risk factors. Further investigation into more specific biological mechanisms is warranted.
Awareness of and Attitudes Toward Pre-exposure Prophylaxis Among Predominantly Heterosexual Black Adolescents and Young Adults and Their Guardians in an Urban Area With HIV Epidemic in the United States
Authors: Koay Wei Li Adeline , Fortuna Gabriella , Griffith Caleb , Ellenberger Nicole , Ferrer Kathleen , Madati Jamil P. , Rakhmanina Natella
Published: January 2021

Among 185 Black, cis-gender, predominantly heterosexual adolescents and young adults (AYA) and 35 guardians surveyed in Washington, DC, the majority of AYA (96.8%) and guardians (94.3%) were unaware of pre-exposure prophylaxis (PrEP); 62.2% of AYA were uncertain if PrEP was safe or effective against HIV. Of 41.6% of AYA willing to use PrEP, 24.9% reported concern about PrEP-related social stigma.
COVID-19-Related Potential Multisystem Inflammatory Syndrome in Childhood in a Neonate Presenting as Persistent Pulmonary Hypertension of the Newborn
Authors: Khaund Borkotoky Rekha , Banerjee Barua Puja , Paul Siba Prosad , Heaton Paul Anthony
Published: January 2021

A term infant with persistent pulmonary hypertension of newborn developed clinical and laboratory features of multisystem inflammatory syndrome in childhood (MIS-C) between days 12 and 14. Mother and baby were anti-SARS-Coronavirus-2 (SARS-CoV-2) IgG positive and anti-SARS-CoV-2 IgM negative on day 18, with negative COVID-19 PCR on repeated testing; possible first documentation of neonatal MIS-C following passive transfer of maternal antibodies.
Cardiovascular disease in children with chronic kidney disease
Authors: Kouri Anne M. , Rheault Michelle N.
Published: January 2021

Purpose of review

Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in children with chronic kidney disease (CKD). The cause of CVD in children with CKD is multifactorial and there are new and emerging data regarding prevalence and risk factors for CVD in this population.

Recent findings

A number of recent publications from longitudinal cohort studies of children with CKD have greatly increased our knowledge about the prevalence and risk factors for CVD including hypertension, obesity and dyslipidaemia. Masked hypertension and isolated nocturnal hypertension both correlate with surrogate markers of CVD in children. Obesity and adiposity are associated with an increased risk of CVD. Markers other than BMI such as waist to height ratio and fat-free tissue to fat tissue ratio better correlate with the presence of CVD in children. Dyslipidaemia is extremely prevalent in the paediatric CKD population, but there is a lack of consensus on treatment. More data on the relationship between bone mineral disease and CVD continue to emerge including an association between hyperparathyroidism and isolated nocturnal hypertension.

Children with CKD have multiple potentially modifiable risk factors for CVD. Research focused on CVD outcomes in children is needed.
Disparities in chronic kidney disease-the state of the evidence
Authors: Clark-Cutaia Maya N. , Rivera Eleanor , Iroegbu Christin , Squires Allison
Published: January 2021

Purpose of review

The purpose of this review was to assess the prevalence of United States chronic kidney disease (CKD) health disparities, focusing on racial/ethnic groups, immigrants and refugees, sex or gender, and older adults.

Recent findings

There are major racial/ethnic disparities in CKD, with possible contributions from the social determinants of health, socioeconomics, and racial discrimination. Racial/ethnic minority patients experience faster progression to end-stage kidney disease (ESKD) and higher mortality predialysis, however, once on dialysis, appear to live longer. Similarly, men are quicker to progress to ESKD than women, with potential biological, behavioral, and measurement error factors. There is a lack of substantial evidence for intersex, nonbinary, or transgender patients. There are also strikingly few studies about US immigrants or older adults with CKD despite the fact that they are at high risk for CKD due to a variety of factors.

As providers and scientists, we must combat both conscious and unconscious biases, advocate for minority patient populations, and be inclusive and diverse in our treatment regimens and provision of care. We need to acknowledge that sufficient evidence exists to change treatment guidelines, and that more is required to support the diversity of our patient population.
Novel developments in chronic myeloid leukaemia
Authors: Harrington Patrick , de Lavallade Hugues
Published: January 2021

Purpose of review

Despite unprecedented challenges during the preceding year, there have been a wide range of significant advances in the field of chronic myeloid leukaemia. In this review article we highlight papers reporting on some of the most important developments over the last year, both with regards to the clinical management of patients with chronic myeloid leukaemia, as well as studies that help to increase our understanding of the pathophysiology of the disease. We have performed a PubMed search to identify important papers and abstracts listed over the last year and have included additional papers published prior to this, where relevant, to provide context.

Recent findings

We comment on novel biomarkers for treatment free remission as well as recent results from second generation Tyrosine Kinase Inhibitor (TKI) discontinuation studies. We discuss new techniques that are being used to assess TKI resistance as well as reviewing novel and emerging approaches to the management of resistant patients, including the use of combination therapies.

This review highlights some of the most important research to have been reported over the last year in the field of chronic myeloid leukaemia, encompassing emerging diagnostic techniques, biomarkers and novel therapeutic options.
Direct visualization of the syndesmosis for evaluation of syndesmotic disruption
Authors: Gosselin-Papadopoulos Nayla , Hébert-Davies Jonah , Laflamme G. Yves , Ménard Jérémie , Leduc Stéphane , Rouleau Dominique M. , Nault Marie-Lyne
Published: January 2021

Objectives:

Radiologic criteria for syndesmosis instability evaluation remain controversial and direct visualization (DV) of the distal tibiofibular articulation is an alternative diagnostic method worthy of further investigation. We speculate that DV is a more accurate way to evaluate syndesmosis instability than fluoroscopy. The purpose of this study is to determine whether syndesmosis instability can accurately be recognized through DV and if this new intraoperative diagnostic method is more sensitive than fluoroscopy in detecting syndesmosis instability.

Methods:

Ten cadaveric ankles were tested using a sequential iatrogenic syndesmosis injury model. Specimens were tested incrementally with the lateral stress test (LST) and the external rotation stress test (ERT). The resulting instability was measured directly and fluoroscopically with a true mortise view by using medial clear space (MCS) and tibiofibular clear space (TFCS).

Results:

DV detected a 2-ligaments injury at a mean diastasis of 3.02 mm (P = 0.0077) and 3.19 mm (P = 0.0077) with the LST and ERT, respectively. Fluoroscopically, TFCS showed a significant diastasis only with a complete syndesmosis rupture while MCS did not show any significant differences.

Conclusions:

DV of the syndesmosis in a cadaver injury model appears to be more sensitive than fluoroscopy in identifying injury, especially incomplete syndesmotic disruption.
Accurate bulk quantitation of droplet digital PCR
Authors: Sun Chen , Liu Leqian , Vasudevan Harish N. , Chang Kai-Chun , Abate Adam R.
Published: January 2021

Droplet digital PCR provides superior accuracy in nucleic acid quantitation. The requirement of microfluidics to generate and analyze the emulsions, however, is a barrier to its adoption, particularly in low resource or clinical settings. Here, we report a novel method to prepare ddPCR droplets by vortexing and readout the results by bulk analysis of recovered amplicons. We demonstrate the approach by accurately quantitating SARS-CoV-2 sequences using entirely bulk processing and no microfluidics. Our approach for quantitating reactions should extend to all digital assays that generate amplicons, including digital PCR and LAMP conducted in droplets, microchambers, or nanoliter wells. More broadly, our approach combines important attributes of ddPCR, including enhanced accuracy and robustness to inhibition, with the high-volume sample processing ability of quantitative PCR.
Controlling one’s world: identification of sub-regions of primate PFC underlying goal-directed behavior
Authors: Duan Lisa Y. , Horst Nicole K. , Cranmore Stacey A.W. , Horiguchi Naotaka , Cardinal Rudolf N. , Roberts Angela C. , Robbins Trevor W.
Published: January 2021

Impaired detection of causal relationships between actions and their outcomes can lead to maladaptive behavior. However, causal roles of specific prefrontal cortex (PFC) sub-regions and the caudate nucleus in mediating such relationships in primates are unclear. We inactivated and over-activated five PFC sub-regions, reversibly and pharmacologically: areas 24 (perigenual anterior cingulate cortex), 32 (medial PFC), 11 (anterior orbitofrontal cortex, OFC), 14 (rostral ventromedial PFC/medial OFC) and 14-25 (caudal ventromedial PFC), and the anteromedial caudate, to examine their role in expressing learned action-outcome contingencies using a contingency degradation paradigm in marmosets. Area 24 or caudate inactivation impaired the response to contingency change, while area 11 inactivation enhanced it, and inactivation of areas 14, 32 or 14-25 had no effect. Over-activation of areas 11 and 24 impaired this response. These findings demonstrate distinct roles of PFC sub-regions in goal-directed behavior and illuminate the candidate neurobehavioral substrates of psychiatric disorders including obsessive-compulsive disorder.
The impact of C-Tactile Low threshold mechanoreceptors on affective touch and social interactions in mice
Authors: Bourinet Emmanuel , Martin Miquel , Huzard Damien , Jeanneteau Freddy , Mery Pierre-Francois , François Amaury
Published: January 2021

Affective touch is necessary for proper neurodevelopment and sociability. However, it is still unclear how the neurons innervating the skin detect affective and social behaviours. To clarify this matter, we targeted a specific population of somatosensory neurons in mice, named C-low threshold mechanoreceptors (C-LTMRs), that appears particularly well suited physiologically and anatomically to perceive affective and social touch but whose contribution to these processes has not yet been resolved. Our observations revealed that C-LTMRs functional deficiency from birth induced social isolation and reduced tactile interactions in adults. Conversely, transient increase in C-LTMRs excitability in adults using chemogenetics was rewarding, temporally promoted touch seeking behaviours and thus had pro-social effects on group dynamics. This work provides the first empirical evidence that specific peripheral inputs alone can drive complex social behaviour, demonstrating the existence of a specialised neuronal circuit originating from the skin wired to promote interaction with other individuals.
Comprehensive mapping of local and diaspora scientists: a database and analysis of 63951 Greek scientists
Authors: Ioannidis John P.A. , Koutsioumpa Chara , Vakka Angeliki , Agoranos Georgios , Mantsiou Chrysanthi , Drekolia Maria Kyriaki , Avramidis Nikos , Contopoulos-Ioannidis Despina G. , Drosatos Konstantinos , Baas Jeroen
Published: January 2021

Research policy and planning for a given country may benefit from reliable data on both its scientific workforce as well as the diaspora of scientists for countries with substantial brain drain. Here we use a systematic approach using Scopus to generate a comprehensive country-level database of all scientists in Greece. Moreover, we expand that database to include also Greek diaspora scientists. The database that we have compiled includes 63951 scientists who have published at least 5 papers indexed in Scopus. Of those, 35116 have an affiliation in Greece. We validate the sensitivity and specificity of the database against different control sets of scientists. We also analyze the scientific disciplines of these scientists according to the Science Metrix classification (174 subfield disciplines) and provide detailed data on each of the 63951 scientists using multiple citation indicators and a composite thereof. These analyses demonstrate differential concentrations in specific subfields for the local versus the diaspora cohorts, as well as an advantage of the diaspora cohort in terms of citation indicators especially among top-impact researchers. The approach that we have taken can be applied to map also the scientific workforce of other countries and nations for evaluation, planning and policy purposes.
MoTSE: an interpretable task similarity estimator for small molecular property prediction tasks
Authors: Li Han , Zhao Xinyi , Li Shuya , Wan Fangping , Zhao Dan , Zeng Jianyang
Published: January 2021

Understanding the molecular properties (e.g., physical, chemical or physiological characteristics and biological activities) of small molecules plays essential roles in biomedical researches. The accumulating amount of datasets has enabled the development of data-driven computational methods, especially the machine learning based methods, to address the molecular property prediction tasks. Due to the high cost of obtaining experimental labels, the datasets of individual tasks generally contain limited amount of data, which inspired the application of transfer learning to boost the performance of the molecular property prediction tasks. Our analyses revealed that simultaneously considering similar tasks, rather than randomly chosen ones, can significantly improve the performance of transfer learning in this field. To provide accurate estimation of task similarity, we proposed an effective and interpretable computational tool, named Molecular Tasks Similarity Estimator (MoTSE). By extracting task-related local and global knowledge from pretrained graph neural networks (GNNs), MoTSE projects individual tasks into a latent space and measures the distance between the embedded vectors to derive the task similarity estimation and thus enhance the molecular prediction results. We have validated that the task similarity estimated by MoTSE can serve as a useful guidance to design a more accurate transfer learning strategy for molecular property prediction. Experimental results showed that such a strategy greatly outperformed baseline methods including training from scratch and multitask learning. Moreover, MoTSE can provide interpretability for the estimated task similarity, through visualizing the important loci in the molecules attributed by the attribution method employed in MoTSE. In summary, MoTSE can provide an accurate method for estimating the molecular property task similarity for effective transfer learning, with good interpretability for the learned chemical or biological insights underlying the intrinsic principles of the task similarity.
Robust T1 MRI cortical surface pipeline for neonatal brain and systematic evaluation using multi-site MRI datasets
Authors: Liu Mengting , Lepage Claude , Kim Sharon Y. , Jeon Seun , Kim Sun Hyung , Simon Julia Pia , Tanaka Nina , Yuan Shiyu , Islam Tasfiya , Peng Bailin , Arutyunyan Knarik , Surento Wesley , Kim Justin , Jahanshad Neda , Styner Martin A. , Toga Arthur W. , Barkovich A. James , Xu Duan , Evans Alan C. , Kim Hosung
Published: January 2021

The human brain grows the most dramatically during the perinatal and early postnatal periods, during which preterm birth or perinatal injury that may alter brain structure and lead to developmental anomalies. Thus, characterizing cortical thickness of developing brains remains an important goal. However, this task is often complicated by inaccurate cortical surface extraction due to small-size brains. Here, we propose a novel complex framework for the reconstruction of neonatal WM and pial surfaces, accounting for large partial volumes due to small-size brains. The proposed approach relies only on T1-weighted images unlike previous T2-weighted image-based approaches while only T1-weighted images are sometimes available under the different clinical/research setting. Deep neural networks are first introduced to the neonatal MRI pipeline to address the mis-segmentation of brain tissues. Furthermore, this pipeline enhances cortical boundary delineation using combined models of the CSF/GM boundary detection with edge gradient information and a new skeletonization of sulcal folding where no CSF voxels are seen due to the limited resolution. We also proposed a systematic evaluation using three independent datasets comprising 736 preterm and 97 term neonates. Qualitative assessment for reconstructed cortical surfaces shows that 86.9% are rated as accurate across the three site datasets. In addition, our landmark-based evaluation shows that the mean displacement of the cortical surfaces from the true boundaries was less than a voxel size (0.532±0.035mm). Evaluating the proposed pipeline (namely NEOCIVET 2.0) shows the robustness and reproducibility across different sites and different age-groups. The mean cortical thickness measured positively correlated with postmenstrual age (PMA) at scan (p<0.0001); Cingulate cortical areas grew the most rapidly whereas the inferior temporal cortex grew the least rapidly. The range of the cortical thickness measured was biologically congruent (1.3mm at 28 weeks of PMA to 1.8mm at term equivalent). Cortical thickness measured on T1 MRI using NEOCIVET 2.0 was compared with that on T2 using the established dHCP pipeline. It was difficult to conclude that either T1 or T2 imaging is more ideal to construct cortical surfaces. NEOCIVET 2.0 has been open to the public through CBRAIN (https://mcin-cnim.ca/technology/cbrain/), a web-based platform for processing brain imaging data.
Manduca sextaexperience high parasitoid pressures in the field but minor fitness costs of consuming plant secondary compounds
Authors: Jacobsen Deidra J.
Published: January 2021

Plant-herbivore co-evolutionary interactions have led to a range of plant defenses that minimize insect damage and a suite of counter-adaptations that allow herbivores to feed on defended plants. Consuming plant secondary compounds results in herbivore growth and developmental costs but can have beneficial effects such as deterrence or harm of parasitoid enemies. Therefore, the role of secondary compounds on herbivore fitness must be considered in the context of the abundance and level of harm from natural enemies and the costs herbivores incur feeding on plant secondary compounds.

In this study, I combined field measurements ofCotesia congregatawasp parasitism pressure with detailed measurements of the costs of plant secondary compounds across developmental stages in the herbivore host,Manduca sexta.

I show thatC. congregataparasitoids exert large negative selective pressures, killing 31-57% ofM. sextalarvae in the field.Manduca sextadeveloped fastest during instars most at risk for parasitoid oviposition but growth was slowed by consumption of plant secondary compounds. The negative effects of consuming plant secondary compounds as larvae influenced adult size traits but there were no immune, survival, or fecundity costs.

These results suggest that developmental costs experienced byM. sextaherbivores consuming defensive compounds are minor in comparison to the strong negative survival pressures from abundant parasitoid enemies.
Structural characterization of cocktail-like targeting polysaccharides fromEcklonia kuromeOkam and their anti-SARS-CoV-2 activitiesinvitro
Authors: Zhang Shihai , Pei Rongjuan , Li Meixia , Sun Hao , Su Minbo , Ding Yaqi , Chen Xia , Du Zhenyun , Jin Can , Huang Chunfan , Zang Yi , Li Jia , Xu Yechun , Chen Xinwen , Zhang Bo , Ding Kan
Published: January 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent responsible for the worldwide coronavirus disease 2019 (COVID-19) outbreak. Investigation has confirmed that polysaccharide heparan sulfate can bind to the spike protein and block SARS-CoV-2 infection. Theoretically, similar structure of nature polysaccharides may also have the impact on the virus. Indeed, some marine polysaccharide has been reported to inhibit SARS-Cov-2 infectionin vitro, however the convinced targets and mechanism are still vague. By high throughput screening to target 3CLpro enzyme, a key enzyme that plays a pivotal role in the viral replication and transcription using nature polysaccharides library, we discover the mixture polysaccharide 375 from seaweedEcklonia kuromeOkam completely block 3Clpro enzymatic activity (IC50, 0.48 µM). Further, the homogeneous polysaccharide 37502 from the 375 may bind to 3CLpro molecule well (kD value : 4.23 × 10−6). Very interestingly, 37502 also can potently disturb spike protein binding to ACE2 receptor (EC50, 2.01 µM). Importantly, polysaccharide 375 shows good anti-SARS-CoV-2 infection activity in cell culture with EC50values of 27 nM (99.9% inhibiting rate at the concentration of 20 µg/mL), low toxicity (LD50: 136 mg/Kg on mice). By DEAE ion-exchange chromatography, 37501, 37502 and 37503 polysaccharides are purified from native 375. Bioactivity test show that 37501 and 37503 may impede SARS-Cov-2 infection and virus replication, however their individual impact on the virus is significantly less that of 375. Surprisingly, polysaccharide 37502 has no inhibition effect on SARS-Cov-2. The structure study based on monosaccharide composition, methylation, NMR spectrum analysis suggest that 375 contains guluronic acid, mannuronic acid, mannose, rhamnose, glucouronic acid, galacturonic acid, glucose, galactose, xylose and fucose with ratio of 1.86 : 9.56 : 6.81 : 1.69 : 1.00 : 1.75 : 1.19 : 11.06 : 4.31 : 23.06. However, polysaccharide 37502 is an aginate which composed of mannuronic acid (89.3 %) and guluronic acid (10.7 %), with the molecular weight (Mw) of 27.9 kDa. These results imply that mixture polysaccharides 375 works better than the individual polysaccharide on SARS-Cov-2 may be the cocktail-like polysaccharide synergistic function through targeting multiple key molecules implicated in the virus infection and replication. The results also suggest that 375 may be a potential drug candidate against SARS-CoV-2.
Enhanced Cholesterol-dependent Hemifusion by Internal Fusion Peptide 1 of SARS Coronavirus-2 Compared to its N-terminal Counterpart
Authors: Pattnaik Gourab Prasad , Bhattacharjya Surajit , Chakraborty Hirak
Published: January 2021

Membrane fusion is an important step for the entry of the lipid-sheathed viruses into the host cells. The fusion process is being carried out by fusion proteins present in the viral envelope. The class I viruses contains a 20-25 amino acid sequence at its N-terminal of the fusion domain, which is instrumental in fusion, and is termed as ‘fusion peptide’. However, Severe Acute Respiratory Syndrome Coronavirus (SARS) coronaviruses contain more than one fusion peptide sequences. We have shown that the internal fusion peptide 1 (IFP1) of SARS-CoV is far more efficient than its N-terminal counterpart (FP) to induce hemifusion between small unilamellar vesicles. Moreover, the ability of IFP1 to induce hemifusion formation increases dramatically with growing cholesterol content in the membrane. Interestingly, IFP1 is capable of inducing hemifusion, but fails to open pore.
Atrioventricular Nodal Function, Atrial Fibrillation And Ventricular Tachycardia in Giraffes
Authors: Shivkumar Tejas E. , Hadaya Joseph , Bertelsen Mads Frost , Aalkjær Christian , Smerup Morten H. , Wang Tobias , Ajijola Olujimi A. , Horowitz Barbara N.
Published: January 2021

Unique cardiovascular adaptations in giraffes (Giraffa Camelopardalis reticulata) have been the focus of numerous investigations for almost a century. The vertical distance between the heart and brain impose high pressure on the giraffe left ventricle leading to thickening that exceeds heart in other mammals. Yet, cardiovascular function appears to be unimpacted by these morphologic differences. Physiologically adapted atrioventricular conduction may contribute to these unique cardiovascular characteristics. Atrioventricular (AV) function was assessed to determine whether physiologically adapted AV intervals might optimize the delay between atrial and ventricular contractions. Using ambulatory and intracardiac recordings, we report a longer PR interval in giraffes than predicted by allometric scaling. Slow ventricular response during atrial fibrillation further supports species-specific atrioventricular adaptations.
Human urine alters methicillin-resistantStaphylococcus aureusvirulence and transcriptome
Authors: Paudel Santosh , Bagale Kamal , Patel Swapnil , Kooyers Nicholas J. , Kulkarni Ritwij
Published: January 2021

Gram-positive methicillin-resistantStaphylococcus aureus(MRSA) is an emerging cause of hospital-associated urinary tract infections, especially in catheterized individuals. Despite being rare, MRSA-UTI are prone to potentially life-threatening exacerbations such as bacteremia that can be refractory to routine antibiotic therapy. Hence, MRSA-UTI is an important of research topic. To delineate molecular mechanisms governing MRSA urinary pathogenesis, we exposed threeS. aureusstrains, of which two were MRSA, to human urine and analyzed virulence characteristics and gene expression. We also analyzed MRSA-1369 transcriptome following cultivation in human urine for 2h. Our results reveal that human urine induces global changes in MRSA transcriptome, marked by changes in genes encoding proteins involved in metabolic pathways, virulence, and transcriptional regulators. In addition,in vitroassays also showed that human urine alters, in a strain-specific manner, adherence to human bladder epithelial cells and fibronectin, hemolysis of sheep RBCs, and surface hydrophobicity. In summary, our results provide first important insights into how the urine may specifically alter MRSA physiology in turn facilitating MRSA survival in the nutrient-limiting and hostile urinary microenvironment.

Importance

Methicillin-resistantStaphylococcus aureus(MRSA) is an uncommon cause of urinary tract infections (UTI) in the general population. However, it is important to understand MRSA pathophysiology in the urinary tract because isolation of MRSA in urine samples is often secondary to potentially life-threatening MRSA bacteremia. In this report, we describe that cultivation in human urine alters MRSA global gene expression and virulence. We hypothesize that these alterations may aid MRSA adapt to the nutrient-limiting, immunologically hostile conditions within the urinary tract.
Correlation of Computerized Tomography (CT) Severity Score for COVID-19 pneumonia with Clinical Outcomes
Authors: Hilal Kiran , Shahid Jehanzeb , Ameen Abdullah , Martins Russell , Nankani Avinash , Arshad Ainan
Published: January 2021

Introduction

Various CT severity scores have already been described in literature since the start of this pandemic. One pertinent issue with all of the previously described severity scores is their relative challenging calculation and variance in inter-observer agreement. The severity score proposed in our study is relatively simpler, easier to calculate and apart from a trained radiologist, can easily be calculated even by physicians with good inter-observer agreement. Therefore, a rapid CT severity score calculation can give a clue to physician about possible clinical outcome without being dependent on radiologist who may not be readily available especially in third world countries.

Objective

The objective of this study is to develop a simple CT severity score (CT-SS) with good inter-observer agreement and access its correlation with clinical outcome.

Methods

This retrospective study was conducted by the Department of Radiology and Internal Medicine, at the Aga Khan University Hospital Karachi, from April 2020 to August 2020. Non-probability consecutive sampling was used to include all patients who were positive for COVID-19 on PCR, and underwent CT chest examination at AKUH. Severity of disease was calculated in each lobe on the basis of following proposed CT severity scoring system (CT-SS). For each lobe the percentage of involvement by disease was scored – 0% involvement was scored 0, <50% involvement was scored 1 and >50% involvement was scored 2. Maximum score for one lobe was 2 and hence total maximum overall score for all lobes was 10. Continuous data was represented using mean and standard deviation, and compared using independent sample t-tests. Categorical data was represented using frequencies and percentages, and compared using Chi-squared tests. Inter-observer reliability between radiologist and COVID intensivist for the 10 point CT-SS rated on 0-10 was assessed using the Kappa statistic. A p-value < 0.05 was considered significant for all analyses.

Results

A total of 73 patients were included, the majority male (58.9%) with mean age 55.8 ± 13.93 years. The CT-SS rated on 0-10 showed substantial inter-observer reliability between radiologist and intensivist with a Kappa statistic of 0.78. Patients with CT-SS 8-10 had a significantly higher ICU admission & intubation rate (53.8% vs. 23.5%) and mortality rate (35.9% vs. 11.8%; p = 0.017), as compared to those with CT-SS 0-7.

Conclusion

We conclude that the described CT severity score (CT-SS) is a quick, effective and easily reproducible tool for prediction of adverse clinical outcome in patients with COVID 19 pneumonia. The tool shows good inter-observer agreement when calculated by radiologist and physician independently.
Anterior insula-associated social novelty recognition: orchestrated regulation by a local retinoic acid cascade and oxytocin signaling
Authors: Kim Sun-Hong , An Kyongman , Namkung Ho , Rannals Matthew D. , Moore James R. , Cash-Padgett Tyler , Mihaljevic Marina , Saha Sneha , Oh Lina S. , Kondo Mari A. , Yang Kun , Maher Brady J. , Niwa Minae , Sawa Akira
Published: January 2021

Background

Deficits in social cognition consistently underlie functional disabilities in a wide range of psychiatric disorders. Neuroimaging studies have suggested that the anterior insula is a ‘common core’ brain region that is impaired across neurological and psychiatric disorders, which include social cognition deficits. Nevertheless, neurobiological mechanisms of the anterior insula for social cognition remain elusive.

Methods

To determine the role of anterior insula in social cognition, we manipulated expression of Cyp26B1, an anterior insula-enriched molecule that is crucial for retinoic acid degradation and involved in the pathology of neuropsychiatric conditions. Social cognition was mainly assayed using the three-chamber social interaction test. We conducted multimodal analyses at the molecular, cellular, circuitry, and behavioral levels.

Results

At the molecular/cellular level, anterior insula-mediated social novelty recognition is maintained by proper activity of the layer 5 pyramidal neurons, for which retinoic acid-mediated gene transcription can play a role. We also demonstrate that oxytocin influences the anterior insula-mediated social novelty recognition, not by direct projection of oxytocin neurons, nor by direct diffusion of oxytocin to the anterior insula, which contrasts the modes of oxytocin regulation onto the posterior insula. Instead, oxytocin affects oxytocin receptor-expressing neurons in the dorsal raphe nucleus where serotonergic neurons are projected to the anterior insula. Furthermore, we show that serotonin 5HT2C receptor expressed in the anterior insula influences social novelty recognition.

Conclusions

Anterior insula plays a pivotal role in social novelty recognition that is partly regulated by a local retinoic acid cascade, but also remotely regulated by oxytocin via a non-classic mechanism.
Incremental Urban and Dwelling Proposals in Guanajuato, Mexico
Authors: Martin-Chavez Andrea , Andrade Jorge
Published: January 2021

An International Competition of Architecture, Urban Development and Sustainable Housing, was held in Mexico in 2001. The aim of the contest was to create a vanguard and imaginative urban and architectural design that could accommodate the local regulation, the concept of sustainability and bioclimatic design. The proposed site is located within Guanajuato city’s periphery

From a critic review of the finalist projects we concluded that although they were very innovative in bioclimatic design they maintained the concept of prototype at the unit level and groups of prototypes layout in the plot at the urban level. We decided to take the same theme as an academic exercise for the following reasons:

• The opportunity to design under the same rules but changing the concept of a traditional mass housing complex to a slice of city that transforms itself in time with incremental dwellings.

• The city of Guanajuato is a colonial city very important for its history, cultural activity and architecture. The urban layout adapts to its rugged surface, which is very similar to the one of the given site.

• The contest program had a similar objective to that of the academic program of the last year of architecture in our University.

From the analysis of Guanajuato City thematic and non thematic elements of the urban tissue and with the aid of the Tissue Model method, students made the urban proposals. The unit proposals were designed with Open Building in mind instead of designing the required prototypes.

This article will focus on the tissue model methodology applied, first to formulate the tissue characteristics of downtown Guanajuato, then to develop the urban layout of the new housing complex and finally to develop the agreement documents for the urban design. Some examples of different final urban and support design will be given.