bluuebunny/crossref_metadata_2025 huggingface dataset:
Transgender and Gender-nonbinary Patient Satisfaction after Transmasculine Chest Surgery
Authors: Bustos Valeria P. , Bustos Samyd S. , Mascaro Andres , Del Corral Gabriel , Forte Antonio J. , Ciudad Pedro , Kim Esther A. , Langstein Howard N. , Manrique Oscar J.
Published: March 2021

Background:

Transmasculine chest surgery is the most common surgery performed in transmasculine patients, with high overall acceptance and low postoperative complication rates. Trends have shown clear improvement in quality of life and satisfaction. However, to the best of our knowledge, overall patient satisfaction after transmasculine chest surgery and associated factors are largely unknown. The aim of this study is to estimate the overall patient satisfaction in transgender men and nonbinary population after transmasculine chest surgery and to assess associated factors.

Methods:

A systematic review was conducted by searching literature in several databases. Meta-analyses of prevalence with a random-effect model for overall and subgroup prevalence were performed. Meta-regression, publication bias, and sensitivity analyses were conducted.

Results:

A total of 1052 transmasculine patients underwent any type of transmasculine chest surgery. The pooled overall postoperative satisfaction was 92% [95% confidence interval (CI) 88–96%]. In the subgroup metanalysis, patient satisfaction after periareolar mastectomy was 93% (CI 88%–97%) and after mastectomy with or without free nipple grafting was 90% (CI 84%–95%). Patient satisfaction for studies with mean follow-up >1 year was 91% (CI 83%–97%) and for mean follow-up of 1 year or less was 93% (CI 89%–96%).

Conclusions:

This study shows a high level of satisfaction in transmasculine chest surgery for both techniques, which remain stable over time. Also, our results show that this procedure impacts patient satisfaction beyond chest appearance and surgical outcomes. This corroborates its broad acceptance and the improvements in the standard of care, and decision-making approach.
A Case Report of Reconstruction of the Great Toe with a Homodigital Island Flap
Authors: Rekatsinas Spyridon , Fotiou Antonia , Kassos Christos
Published: March 2021

Homodigital flaps are frequently used in the reconstruction of defects in the fingers. Their use in the coverage of defects of the toes is not commonly reported because such defects are usually treated with skin grafts, proximally based local flaps, or even amputation and shortening of the toe. We describe the implementation of a homodigital island flap of the great toe for reconstruction of a traumatic defect of the dorsal aspect of its distal phalanx.
A Novel Technique for Preventive Lymphovenous Anastomosis: Anastomosing a Ligated Lymphatic Vessel
Authors: Depypere Bernard , Vyncke Tom , Dhooghe Nicolas , Claes Karel , Blondeel Phillip , Van Landuyt Koenraad
Published: March 2021

Background:

Lymphedema is defined as a chronic condition, caused by lymphostasis. A major part in the Western world consists of iatrogenic lymphedema caused by surgery to the lymph nodes of the axilla or groin. Prophylactic lymphovenous anastomosis (LVA) could be beneficial in the prevention of lymphedema of the extremities. These procedures require experienced supramicrosurgeons and can be time consuming, which might be the reasons why prophylactic LVA has not yet been widely implemented in the treatment of cancer. Due to the small diameter of lymphatic vessels, it remains challenging to identify the lumen, and therefore, anastomoses are prone to back wall stitching. Different inventive procedures have been described making use of stents or monofilament sutures.

Methods:

In this article, we describe a newly developed and straightforward technique for LVA in 4 patients who underwent an axilla dissection and 1 patient who underwent a dissection of the groin lymph nodes. This latter approach makes use of clipping of the lymphatic vessel during lymph node dissection, and remains ligated during anastomosis. The candidate vein was the V. thoracodorsalis for the axilla and the V. circumflexa superficialis for the groin. We describe the feasibility, average duration, and complications.

Results:

Performing an end-to-side anastomosis on a clipped lymphatic vessel minimizes the problem of back wall stitching as well as the trouble of finding the lumen due to collapsing of the vessel. The turgor of the lymphatic vessel is maintained and makes anastomosing easy. Average time for LVA was 33.4 minutes and 1 minor complication was seen.

Conclusion:

We believe that this approach might be of value in popularizing LVA in the treatment or prevention of different conditions such as breast cancer-related lymphedema.
Effects of easing shelter-in-place restrictions and the lingering COVID-19 pandemic on orthopaedic trauma at a community level 2 trauma center
Authors: Best Jacob , Stoker Steven , McDaniel Dalton , Lerew Shawn , Jawanda Gurkirat , Krentz Neal , Speicher Mark , Siwiec Ryan
Published: March 2021

Objectives:

Evaluate the effect of easing “shelter-in-place” restrictions and coronavirus-2019 (COVID-19) cases on orthopaedic trauma encounters (OTEs) at a community level II trauma center.

Methods:

A retrospective analysis was conducted of OTEs from March-June of 2016 to 2020. Injuries were classified by high or low severity. Admission and surgical intervention rates were also compared year to year. Data were statistically analyzed and compared with external data for traffic counts near the hospital and COVID-19 cases in Michigan as well as a timeline for enacting and easing of shelter-in-place orders in the state of Michigan.

Results:

There was no difference in the number of OTEs May to June, 2020 compared with the average of those same months 2016 to 2019. March to June, 2020 showed no change in proportion of injury severity, admissions, or surgical interventions when compared with the average of March-June, 2016 to 2019, although the overall quantity of each was decreased in March and April. A significant negative correlation was found between the daily number of COVID-19 cases in Michigan and OTEs.

Conclusions:

The quantity of OTEs normalized to pre-COVID-19 levels in May and June of 2020 compared with 2016 to 2019 despite a previously documented 45.1% drop in March and April. A negative correlation was noted between the number of reported Michigan COVID-19 cases and volume of OTEs. There were no significant changes noted to admission rates or rates of surgical intervention on OTEs throughout the time period studied.
Pilot Study of a Brief Sleep Intervention for Suicidal Ideation in Bipolar Disorder
Authors: SYLVIA LOUISA G. , JANOS JESSICA A. , PEGG SAMANTHA L. , MONTANA REBECCA E. , GOLD ALEXANDRA K. , BIANCHI MATT , NIERENBERG ANDREW A.
Published: March 2021

Objective:

We investigated the feasibility and acceptability of a brief sleep intervention and sleep monitoring device in bipolar disorder (BD), as well as the intervention’s effectiveness in reducing suicidal ideation through improved sleep quality and duration.

Methods:

Participants (N=13) with BD received 4 sessions of cognitive-behavioral therapy for sleep disturbance and completed assessments of the intervention and sleep device acceptability, mood, suicidal ideation, and sleep at pretreatment and posttreatment.

Results:

Feasibility and acceptability of the intervention were high at both pretreatment and posttreatment and did not significantly change by the intervention’s conclusion, although participants reported being significantly more likely to recommend the intervention to others at posttreatment. The sleep device was easy to understand, wear, and did not interfere with participants’ sleep. Suicidal ideation and depressive symptoms significantly decreased from pretreatment to posttreatment (P<0.05). There were small, but not significant, improvements in the percentage of time spent in stable sleep and total average nightly sleep.

Conclusion:

The potential of this intervention for reducing suicidal ideation and improving sleep is promising, but future research is warranted.
Moving Forward While Standing Still: A Case of Mental Health Advocacy Evolving in the Time of COVID-19
Authors: VILLELA RENATA M. , LAZAR SUSAN G.
Published: March 2021

There have been shifts over time in the value placed on long-term psychotherapeutic modalities even though they can be life-saving. For example, the province of Ontario in Canada has been dealing with a government proposal put forward in 2019 to limit the length of psychotherapy treatment. In response, stakeholders from numerous groups came together to advocate for the importance of continuing unrestricted access to long-term psychotherapy. Approaches to this advocacy then had to unexpectedly adapt to the Coronavirus Disease 2019 (COVID-19) pandemic that came to the forefront in 2020 and will continue to develop in response to this changing landscape.
Optimal Dosing of Prophylactic Enoxaparin after Surgical Procedures: Results of the Double-Blind, Randomized, Controlled FIxed or Variable Enoxaparin (FIVE) Trial
Authors: Pannucci Christopher J. , Fleming Kory I. , Bertolaccini Corinne , Agarwal Jayant , Rockwell W. Bradford , Mendenhall Shaun D. , Kwok Alvin , Goodwin Isak , Gociman Barbu , Momeni Arash
Published: March 2021

Background:

The accepted “one-size-fits-all” dose strategy for prophylactic enoxaparin may not optimize the medication’s risks and benefits after surgical procedures. The authors hypothesized that weight-based administration might improve the pharmacokinetics of prophylactic enoxaparin when compared to fixed-dose administration.

Methods:

The FIxed or Variable Enoxaparin (FIVE) trial was a randomized, double-blind trial that compared the pharmacokinetic and clinical outcomes of patients assigned randomly to postoperative venous thromboembolism prophylaxis using enoxaparin 40 mg twice daily or enoxaparin 0.5 mg/kg twice daily. Patients were randomized after surgery and received the first enoxaparin dose at 8 hours after surgery. Primary hypotheses were (1) weight-based administration is noninferior to a fixed dose for avoiding underanticoagulation (anti–factor Xa <0.2 IU/ml) and (2) weight-based administration is superior to fixed-dose administration for avoiding overanticoagulation (anti–factor Xa >0.4 IU/ml). Secondary endpoints were 90-day venous thromboembolism and bleeding.

Results:

In total, 295 patients were randomized, with 151 assigned to fixed-dose and 144 to weight-based administration of enoxaparin. For avoidance of under anticoagulation, weight-based administration had a greater effectiveness (79.9 percent versus 76.6 percent); the 3.3 percent (95 percent CI, –7.5 to 12.5 percent) greater effectiveness achieved statistically significant noninferiority relative to the a priori specified −12 percent noninferiority margin (p = 0.004). For avoidance of overanticoagulation, weight-based enoxaparin administration was superior to fixed-dose administration (90.6 percent versus 82.2 percent); the 8.4 percent (95 percent CI, 0.1 to 16.6 percent) greater effectiveness showed significant safety superiority (p = 0.046). Ninety-day venous thromboembolism and major bleeding were not different between fixed-dose and weight-based cohorts (0.66 percent versus 0.69 percent, p = 0.98; 3.3 percent versus 4.2 percent, p = 0.72, respectively).

Conclusion:

Weight-based administration showed superior pharmacokinetics for avoidance of underanticoagulation and overanticoagulation in postoperative patients receiving prophylactic enoxaparin.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, I.
Opioid Overprescribing and Procedure-Specific Opioid Consumption Patterns for Plastic and Reconstructive Surgery Patients
Authors: Chu Jacqueline J. , Janis Jeffrey E. , Skoracki Roman , Barker Jenny C.
Published: March 2021

Background:

Opioid prescribing practices contribute to opioid misuse, dependency, and diversion. There are currently no comprehensive and quantitative evidence-based guidelines that give procedure-specific recommendations regarding opioid prescribing in plastic surgery.

Methods:

A retrospective review of 479 plastic surgery patients encompassing 23 different plastic surgery procedure categories was performed. Opioid prescribing patterns and patient-reported opioid use at 1 and 3 months postoperatively are reported.

Results:

Opioid overprescribing was common, averaging an excess of 13 pills per patient across all procedure categories (prescribed versus consumed, 25.4 ± 23.1 versus 12.1 ± 19.7; p = 3.0 × 10−19), with a total excess of 5895 pills (30,967 oral morphine equivalents) for the study’s sample. Fifty-two percent of all opioid pills prescribed went unused. Opioid consumption ranged between four and 37 pills across procedure categories. A greater proportion of patients who reported a history of preoperative opioid use were still using opioids at the time of their 1-month and 3-month follow-up appointments (62 percent versus 9 percent at 1 month, and 31 percent versus 1 percent at 3 months). Most patients (83 percent) did not store opioids in a locked location, and 64 percent did not dispose of opioids at 1 month.

Conclusions:

Opioids are commonly overprescribed by plastic surgery providers. This study determined procedure-specific opioid consumption patterns, which can help providers reduce opioid waste. In addition, patients do not properly store or dispose of opioids, demonstrating the need for better patient education.
Surgical Treatment of Lymphedema: A Systematic Review and Meta-Analysis of Controlled Trials. Results of a Consensus Conference
Authors: Chang David W. , Dayan Joseph , Greene Arin K. , MacDonald John K. , Masia Jaume , Mehrara Babak , Neligan Peter C. , Nguyen Dung
Published: March 2021

Background:

The goal of this consensus conference, sponsored by the American Association of Plastic Surgeons, was to perform a systematic review and meta-analysis of controlled trials to examine both the benefits and risks of surgical treatment and surgical prevention of upper and lower extremity lymphedema.

Methods:

The panel met in Boston for a 3-day, face-to-face meeting in July of 2017. After an exhaustive review of the existing literature, the authors created consensus recommendations using the Grading of Recommendations, Assessment, Development and Evaluation criteria. Important directions for future research were also identified.

Results:

There is evidence to support that lymphovenous anastomosis can be effective in reducing severity of lymphedema (grade 1C). There is evidence to support that vascular lymph node transplantation can be effective in reducing severity of lymphedema (grade 1B). Currently, there is no consensus on which procedure (lymphovenous bypass versus vascular lymph node transplantation) is more effective (grade 2C). A few studies show that prophylactic lymphovenous bypass in patients undergoing extremity lymphadenectomy may reduce the incidence of lymphedema (grade 1B). More studies with longer follow-up are required to confirm this benefit. Debulking procedures such as liposuction are effective in addressing a nonfluid component such as fat involving lymphedema (grade 1C). There is a role for liposuction combined with physiologic procedures although the timing of each procedure is currently unresolved (grade 1C).

Conclusions:

Many studies seem to support some efficacy of lymphovenous bypass and vascular lymph node transplantation. Many studies show the important role of lymphedema therapy and other procedures such as liposuction and debulking. The management of lymphedema is a challenging field with many promising advances. However, many questions remain unanswered.
SARS-CoV-2 transmission and control in a hospital setting: an individual-based modelling study
Authors: Huang Qimin , Mondal Anirban , Jiang Xiaobing , Horn Mary Ann , Fan Fei , Fu Peng , Wang Xuan , Zhao Hongyang , Ndeffo-Mbah Martial , Gurarie David
Published: March 2021

Development of strategies for mitigating the severity of COVID-19 is now a top public health priority. We sought to assess strategies for mitigating the COVID-19 outbreak in a hospital setting via the use of non-pharmaceutical interventions. We developed an individual-based model for COVID-19 transmission in a hospital setting. We calibrated the model using data of a COVID-19 outbreak in a hospital unit in Wuhan. The calibrated model was used to simulate different intervention scenarios and estimate the impact of different interventions on outbreak size and workday loss. The use of high-efficacy facial masks was shown to be able to reduce infection cases and workday loss by 80% (90% credible interval (CrI): 73.1–85.7%) and 87% (CrI: 80.0–92.5%), respectively. The use of social distancing alone, through reduced contacts between healthcare workers, had a marginal impact on the outbreak. Our results also indicated that a quarantine policy should be coupled with other interventions to achieve its effect. The effectiveness of all these interventions was shown to increase with their early implementation. Our analysis shows that a COVID-19 outbreak in a hospital's non-COVID-19 unit can be controlled or mitigated by the use of existing non-pharmaceutical measures.
The vocal tract as a time machine: inferences about past speech and language from the anatomy of the speech organs
Authors: Dediu Dan , Moisik Scott R. , Baetsen W. A. , Bosman Abel Marinus , Waters-Rist Andrea L.
Published: March 2021

While speech and language do not fossilize, they still leave traces that can be extracted and interpreted. Here, we suggest that the shape of the hard structures of the vocal tract may also allow inferences about the speech of long-gone humans. These build on recent experimental and modelling studies, showing that there is extensive variation between individuals in the precise shape of the vocal tract, and that this variation affects speech and language. In particular, we show that detailed anatomical information concerning two components of the vocal tract (the lower jaw and the hard palate) can be extracted and digitized from the osteological remains of three historical populations from The Netherlands, and can be used to conduct three-dimensional biomechanical simulations of vowel production. We could recover the signatures of inter-individual variation between these vowels, in acoustics and articulation. While ‘proof-of-concept’, this study suggests that older and less well-preserved remains could be used to draw inferences about historic and prehistoric languages. Moreover, it forces us to clarify the meaning and use of the uniformitarian principle in linguistics, and to consider the wider context of language use, including the anatomy, physiology and cognition of the speakers.

This article is part of the theme issue ‘Reconstructing prehistoric languages’.
Metaphors: the evolutionary journey from bidirectionality to unidirectionality
Authors: Gil David , Shen Yeshayahu
Published: March 2021

Metaphors, a ubiquitous feature of human language, reflect mappings from one conceptual domain onto another. Although founded on bidirectional relations of similarity, their linguistic expression is typically unidirectional, governed by conceptual hierarchies pertaining to abstractness, animacy and prototypicality. The unidirectional nature of metaphors is a product of various asymmetries characteristic of grammatical structure, in particular, those related to thematic role assignment. This paper argues that contemporary metaphor unidirectionality is the outcome of an evolutionary journey whose origin lies in an earlier bidirectionality. Invoking the Complexity Covariance Hypothesis governing the correlation of linguistic and socio-political complexity, the Evolutionary Inference Principle suggests that simpler linguistic structures are evolutionarily prior to more complex ones, and accordingly that bidirectional metaphors evolved at an earlier stage than unidirectional ones. This paper presents the results of an experiment comparing the degree of metaphor unidirectionality in two languages: Hebrew and Abui (spoken by some 16 000 people on the island of Alor in Indonesia). The results of the experiment show that metaphor unidirectionality is significantly higher in Hebrew than in Abui. Whereas Hebrew is a national language, Abui is a regional language of relatively low socio-political complexity. In accordance with the Evolutionary Inference Principle, the lower degree of metaphor unidirectionality of Abui may accordingly be reconstructed to an earlier stage in the evolution of language. The evolutionary journey from bidirectionality to unidirectionality in metaphors argued for here may be viewed as part of a larger package, whereby the development of grammatical complexity in various domains is driven by the incremental increases in socio-political complexity that characterize the course of human prehistory.

This article is part of the theme issue ‘Reconstructing prehistoric languages’.
Persuasive conversation as a new form of communication inHomo sapiens
Authors: Ferretti Francesco , Adornetti Ines
Published: March 2021

The aim of this paper is twofold: to propose that conversation is the distinctive feature ofHomo sapiens' communication; and to show that the emergence of modern language is tied to the transition from pantomime to verbal and grammatically complex forms of narrative. It is suggested that (animal and human) communication is a form of persuasion and that storytelling was the best tool developed by humans to convince others. In the early stage of communication, archaic hominins used forms of pantomimic storytelling to persuade others. Although pantomime is a powerful tool for persuasivecommunication, it is proposed that it is not an effective tool for persuasiveconversation: conversation is characterized by a form of reciprocal persuasion among peers; instead, pantomime has a mainly asymmetrical character. The selective pressure towards persuasive reciprocity of the conversational level is the evolutionary reason that allowed the transition from pantomime to grammatically complex codes inH. sapiens, which favoured the evolution of speech.

This article is part of the theme issue ‘Reconstructing prehistoric languages’.
Pantomimic fossils in modern human communication
Authors: Żywiczyński Przemysław , Wacewicz Sławomir , Lister Casey
Published: March 2021

Bodily mimesis, the capacity to use the body representationally, was one of the key innovations that allowed early humans to go beyond the ‘baseline’ of generalized ape communication and cognition. We argue that the original human-specific communication afforded by bodily mimesis was based on signs that involve three entities: an
expression
that represents an
object
(i.e. communicated content) for an
interpreter
. We further propose that the core component of this communication, pantomime, was able to transmit referential information that was not limited to select semantic domains or the ‘here-and-now’, by means of motivated—most importantly iconic—signs. Pressures for expressivity and economy then led to conventionalization of signs and a growth of linguistic characteristics: semiotic systematicity and combinatorial expression. Despite these developments, both naturalistic and experimental data suggest that the system of pantomime did not disappear and is actively used by modern humans. Its contemporary manifestations, or
pantomimic fossils
, emerge when language cannot be used, for instance when people do not share a common language, or in situations where the use of (spoken) language is difficult, impossible or forbidden. Under such circumstances, people bootstrap communication by means of pantomime and, when these circumstances persist, newly emergent pantomimic communication becomes increasingly language-like.

This article is part of the theme issue ‘Reconstructing prehistoric languages’.
Haem toxicity provides a competitive advantage to the clinically relevant Staphylococcus aureus small colony variant phenotype
Authors: Herrin Brittany E. , Islam Shariful , Rentschler Kaitlin N. , Pert Lauren H. , Kopanski Stephanie P. , Wakeman Catherine A.
Published: March 2021

Microorganisms encounter toxicities inside the host. Many pathogens exist as subpopulations to maximize survivability. Subpopulations of

Staphylococcus aureus

include antibiotic-tolerant small colony variants (SCVs). These mutants often emerge following antibiotic treatment but can be present in infections prior to antibiotic exposure. We hypothesize that haem toxicity in the host selects for respiration-deficient

S. aureus

SCVs in the absence of antibiotics. We demonstrate that some but not all respiration-deficient SCV phenotypes are more protective than the haem detoxification system against transient haem exposure, indicating that haem toxicity in the host may contribute to the dominance of menaquinone-deficient and haem-deficient SCVs prior to antibiotic treatment.
Anticoagulation trends in adults aged 65 and over with atrial fibrillation; a cohort study
Authors: Lund J , Saunders CL , Edwards D , Mant J
Published: March 2021

Objective

To describe patterns of anticogulation prescribing and persistence for those aged ≥65 years with atrial fibrillation (AF).

Methods

Descriptive cohort study using electronic general practice records of patients in England who attended a flu vaccination aged ≥65, and were diagnosed with AF between 2008-2018. Patients were stratified by 10 year age group and year of diagnosis. Proportion anticoagulated, type of anticoagulation (direct oral anticoagulant (DOAC) or Warfarin) initiated at diagnosis, and persistence with anticoagulation over time are reported.

Results

42,290 patients (49% female), aged 65-74 (n=11,722), 75-84 (n=19,055) and 85+ (n=11,513) at AF diagnosis are included. Prescription of anticoagulation at diagnosis increased over the time period from 55% to 86% in people aged 65-74, from 54% to 86% in people aged 75-84 and from 27% to 75% in people aged 85 and over. No patients were prescribed DOACs as a first anticoagulation agent in 2008, by 201892% of new AF patients were started on DOACs. Survivor function for 5 year persistence for patients taking only a single type of anticoagulant was 0.80 (0.77:0.82) for DOACs and0.71(0.70:0.72) for warfarin, Survivor function for any anticoagulation at 5 years was0.79(0.78:0.81), 0.73(0.72:0.75), 0.58(0.59:0.64) for people aged 65-74, 75-84 and 85+ respectively.

Conclusions

Rates of anticoagulation for new AF in those aged ≥65 have increased from 2008 to 2018, over which time there has been a shift from initiating anticoaguation with warfarin to DOACs. Persistence with anticoagulation is higher in people on DOACs than on warfarin, and in people under the aged of 85.

Key Messages

What is already known?

Anticoagulation is a highly effective way of reducing the risk of stroke associated with AF, but is underused, particularly in older people. The introduction of DOACs has been associated with increasing use of anticoagulation in AF.

What does this study add?

Our study provides up to date information on anticoagulation for AF in older people who are most at risk of AF related stroke and highlights particular increases in use of anticoagulation in people aged 85 and over.

DOACs are now the major class of anticoagulant prescribed to patients with new AF in UK general practice.

Long term persistence with anticoagulation is higher with DOACs than warfarin, but drops in all age groups over 5 years.

How might this impact on clinical practice?

Improved uptake of anticoagulation at all ages removes one of the potential barriers to screening for atrial fibrillation, but new strategies may be needed to enhance longer term persistence with treatment.
Limit of detection in different matrices of nineteen commercially available rapid antigen tests for the detection of SARS-CoV-2
Authors: Cubas-Atienzar Ana I. , Kontogianni Konstantina , Edwards Thomas , Wooding Dominic , Buist Kate , Thompson Caitlin R. , Williams Christopher T. , Patterson Edward I , Hughes Grant , Baldwin Lisa , Escadafal Camille , Sacks Jilian A. , Adams Emily R.
Published: March 2021

In the context of the coronavirus disease 2019 (COVID-19) pandemic there has been an increase of the use of antigen-detection rapid diagnostic tests (Ag-RDT). The performance of Ag-RDT vary greatly between manufacturers and evaluating their analytical limit of detection (LOD) has become high priority. Here we describe a manufacturer-independent evaluation of the LOD of 19 marketed Ag-RDT using live SARS-CoV-2 spiked in different matrices: direct culture supernatant, a dry swab, and a swab in Amies. Additionally, the LOD using dry swab was investigated after 7 days’ storage at −80°C of the SARS-CoV-2 serial dilutions. An LOD of ≈ 5.0 × 102pfu/ml (1.0 × 106genome copies/ml) in culture media is defined as acceptable by the World Health Organization. Fourteen of nineteen Ag-RDTs (ActiveXpress, Espline, Excalibur, Innova, Joysbio, Mologic, NowCheck, Orient, PanBio, RespiStrip, Roche, Standard-F, Standard-Q and Sure-Status) exceeded this performance criteria using direct culture supernatant applied to the Ag-RDT. Six Ag-RDT were not compatible with Amies media and a decreased sensitivity of 2 to 20-fold was observed for eleven tests on the stored dilutions at −80°C for 7 days. Here, we provide analytical sensitivity data to guide appropriate test and sample type selection for use and for future Ag-RDT evaluations.
Temporal Window based Feature Extraction Technique for Motor-Imagery EEG Signal Classification
Authors: Chatterjee Rajdeep , Datta Ankita , Sanyal Debarshi Kumar , Banerjee Swati
Published: March 2021

Electroencephalogram (EEG) based motor-imagery classification is one of the most popular Brain Computer Interface (BCI) research areas due to its portability and low cost. In this paper, we have compared Wavelet Energy-entropy based different prediction models and empirically proven that temporal window based approach in motor-imagery classification provides more consistent and better results than popular filter-bank approach. In order to examine the robustness and stability of the proposed method, we have also employed multiple types of classifiers at the end and found that mix-bagging (bagging ensemble learning with multiple types of learners) technique out-smarts other frequently used classifiers. In our study, BCI Competition II Data-set III has been used with four experimental setup: (a) The whole signal (for each trial) as one segment, (b) The whole signal (for each trial) is divided into non-overlapping segments, (c) The whole signal (for each trial) is divided into overlapping segments, and (d) The filter-bank approach where the whole signal (each trial) is segmented based on different frequency bands. The result obtained from the experiment (c) i.e. 91.43% classification accuracy which outperforms the other approaches not only in this paper but to best of our knowledge it is the highest performance for this dataset so far.
Lack of Cdk5 activity is involved on Dopamine Transporter expression and function: Evidences from an animal model of Attention-Deficit Hyperactivity Disorder
Authors: Guillermo Fernández , Favio Krapacher , Soledad Ferreras , Gonzalo Quassollo , Mariel Mari Macarena , María Victoria Pisano , Antonella Montemerlo , María Dolores Rubianes , Claudia Bregonzio , Arias Carlos , María Gabriela Paglini
Published: March 2021

Attention deficit/Hyperactivity disorder (ADHD) is one of the most diagnosed psychiatric disorders nowadays. The core symptoms of the condition include hyperactivity, impulsiveness and inattention. The main pharmacological treatment consists of psychostimulant drugs affecting Dopamine Transporter (DAT) function. We have previously shown that genetically modified mice lacking p35 protein (p35KO), which have reduced Cdk5 activity, present key hallmarks resembling those described in animal models useful for studying ADHD. The p35KO mouse displays spontaneous hyperactivity and shows a calming effect of methylphenidate or amphetamine treatment. Interestingly, dopaminergic neurotransmission is altered in these mice as they have an increased Dopamine (DA) content together with a low DA turnover. This led us to hypothesize that the lack of Cdk5 activity affects DAT expression and/or function in this animal model. In this study, we performed biochemical assays, cell-based approaches, quantitative fluorescence analysis and functional studies that allowed us to demonstrate that p35KO mice exhibit decreased DA uptake and reduced cell surface DAT expression levels in the striatum (STR). These findings are supported byin vitroobservations in which the inhibition of Cdk5 activity in N2a cells induced a significant increase in constitutive DAT endocytosis with a concomitant increase in DAT localization to recycling endosomes. Taken together, these data provide evidences regarding the role of Cdk5/p35 in DAT expression and function, thus contributing to the knowledge of DA neurotransmission physiology and also providing therapeutic options for the treatment of DA pathologies such as ADHD.
Song complexity in relation to repertoire size and phonological syntax in the breeding song of Purple Sunbird
Authors: Chorol Sonam , Jain Manjari
Published: March 2021

There are multiple measures for bird song complexity such as repertoire size, phonological or compositional syntax and complex vocal mechanism (CVM). We examined these in an old-world passerine, Purple Sunbird. First, we identified and acoustically characterised the repertoire size (of notes and phrases). We then assessed positional fidelity and ordering of notes within phrases. We found 23 distinct notes by aural-visual inspection of spectrograms which was validated using a Classification and Regression Tree based on 5 acoustic parameters. These notes combined in different iterations to form 30 different phrases. Phrases comprised of an overall structure with an introductory note (prefix) at the onset, followed by notes occurring at specific positions within the phrase body, and terminated with a trill (suffix syllable(s)). Prefix was present in 93% of phrases whereas suffix syllable(s) occurred in 27% of phrases only. We found that notes exhibited positional fidelity and combined in specific order to form a phrase. This is indicative of underlying phonological syntax that limits the ways in which notes combine to form phrase and offers insights to song complexity. Finally, we found that suffix syllables exhibit the presence of mini-breath (very short inter-note interval) which are known to be produced by CVM.
Convergence of clinically relevant manipulations on dopamine-regulated prefrontal activity underlying stress-coping responses
Authors: Wilke Scott A. , Lavi Karen , Byeon Sujin , Sohal Vikaas S.
Published: March 2021

Background

Depression is a pleiotropic condition that can be produced or ameliorated by diverse genetic, environmental, and pharmacological manipulations. In this context, identifying patterns of circuit activity on which many of these manipulations converge would be important, because studying these patterns could reveal underlying biological processes related to depression and/or new therapies. In particular, the prefrontal cortex and dopaminergic signaling have both been implicated in depression. Nevertheless, how dopamine influences disease-relevant patterns of prefrontal circuit activity remains unknown.

Methods

We used calcium imaging in brain slices to identify depression-relevant patterns of activity in prefrontal microcircuits, and measure how these are modulated by dopamine D2 receptors (D2Rs). Then, we used optogenetic and genetic manipulations to test how dopamine and D2Rs contribute to stress-coping behavior in a paradigm commonly used to assay how manipulations promote or ameliorate depression-like states.

Results

Patterns of correlated activity in prefrontal microcircuits are enhanced by D2R stimulation as well as by two mechanistically distinct antidepressants: ketamine and fluoxetine. Conversely, this D2R-driven effect was disrupted in two etiologically distinct models of depression: a genetic susceptibility model and chronic social defeat. Phasic stimulation of dopamine afferents to prefrontal cortex increased effortful responses to tail suspension stress. Conversely, deleting prefrontal D2R receptors reduced the duration of individual struggling episodes.

Conclusions

Correlated prefrontal microcircuit activity represents a point of convergence for multiple depression-related manipulations. Prefrontal D2Rs enhance this activity. Through this mechanism, prefrontal dopamine signaling may promote network states associated with antidepressant actions that manifest as effortful responses to stress.
piRNA pathway is essential for generating functional oocytes in golden hamster
Authors: Zhang Hongdao , Zhang Fengjuan , Chen Jinghua , Li Mingzhi , Lv Xiaolong , Xiao Yali , Zhang Zhaozhen , Hou Li , Lai Yana , Xiao Wen , Zhang Aihua , Fu Heling , Zhou Jianli , Diao Feiyang , Shi Aimin , Su Youqiang , Zeng Wentao , Wu Ligang , Li Jianmin
Published: March 2021

Piwi-interacting RNAs (piRNAs) are small RNAs predominantly expressed in germ cells that are critical for gametogenesis in various species. However, PIWI-deficient female mice are fertile and mouse oocytes express a panel of small RNAs that do not appear widely representative of mammals, and piRNA function in the oogenesis of other mammals has therefore remained elusive. Recent studies revealed the small RNA andPIWItranscriptional profiles in golden hamster oocytes more closely resemble that of humans than mice. Herein, we generatedPIWIL1-,PLD6-andMOV10L1-deficient golden hamsters and found that all female mutants were sterile, with embryos arrested at the two-cell stage. InPIWIL1mutant oocytes, we observed transposon accumulation and broad transcriptomic dysregulation, while zygotic gene activation was impaired in early embryos. Intriguingly, PIWIL1-piRNAs exhibited a unique, preferential silencing of endogenous retroviruses (ERVs), whereas silencing LINE1s depended on both PIWIL1- and PIWIL3-piRNAs. Moreover, we showed that piRNAs participate in the degradation of maternal mRNAs in MII oocytes and embryos via partially complementary targets. Together, our findings demonstrate that piRNAs are indispensable for generating functional oocytes in golden hamster, and show the informative value of this model for functional and mechanistic investigations of piRNAs, especially those related to female infertility.
Information-Efficient, Off-Center Sampling Results in Improved Precision in 3D Single Particle Tracking Microscopy
Authors: Zhang Chen , Welsher Kevin
Published: March 2021

In this work, we present a 3D single-particle tracking system that can apply tailored sampling patterns to selectively extract photons that yield the most information for particle localization. We demonstrate that off-center sampling at locations predicted by Fisher information utilizes photons most efficiently. When performing localization in a single dimension, optimized off-center sampling patterns gave doubled precision compared to uniform sampling. A ~20% increase in precision compared to uniform sampling can be achieved when a similar off-center pattern is used in 3D localization. Here we systematically investigated the photon efficiency of different emission patterns in a diffraction-limited system and achieved higher precision than uniform sampling. The ability to maximize information from the limited number of photons demonstrated here is critical for particle tracking applications in biological samples, where photons may be limited.
Thiamin-Diphosphate Enzymes Are an Ancient Family of Repeat Proteins
Authors: Merski Matthew , Górna Maria
Published: March 2021

A repeating sequence and structure pattern that is highly similar to the canonical cofactor binding motif has been identified in the thiamin-diphosphate dependent (ThDP) enzyme family. We have identified more than a thousand of these repeats in a non-redundant set (N = 58) of ThDP enzyme structures. The repeating element has a helix-turn-strand secondary structure which typically begins with an [G/A]{X(1,2)}[G/A] sequence motif with a typical length of 29 residues. The catalytically important diphosphate and aminopyrimidine interacting domains are comprised of a set of six of these repeats in a conserved architecture with a flavodoxin-like 213465 strand order. The canonical ThDP binding motif is the fourth repeat in the ThDP binding domain, while the conserved aminopyrimidine interacting glutamate is part of the second repeat in its domain. The third and fourth repeats form a contact between the functional domains, while the fifth repeat in the N-terminal domain forms an inter-chain contact. The conservation of these functional properties highlights the role of these repeats in the function and structure of this well-studied enzyme family and agrees with the principle of modular assembly in protein ancestry.
An epigenome atlas of neural progenitors within the embryonic mouse forebrain
Authors: Rhodes Christopher T. , Thompson Joyce J. , Mitra Apratim , Asokumar Dhanya , Lee Dongjin R. , Lee Daniel J. , Zhang Yajun , Jason Eva , Dale Ryan K. , Rocha Pedro P. , Petros Timothy J.
Published: March 2021

A comprehensive characterization of epigemonic organization in the embryonic mouse forebrain will enhance our understanding of neurodevelopment and provide insight into mechanisms of neurological disease. We collected single-cell chromatin accessibility profiles from four distinct neurogenic regions of the embryonic mouse forebrain using single nuclei ATAC-Seq (snATAC-Seq). We identified thousands of differentially accessible peaks, many restricted to distinct progenitor cell types or brain regions. We integrated snATAC-Seq and single cell transcriptome data to characterize changes of chromatin accessibility at enhancers and promoters with associated transcript abundance. Multi-modal integration of histone modifications (CUT&Tag and CUT&RUN), promoter-enhancer interactions (Capture-C) and high-order chromatin structure (Hi-C) extended these initial observations. This dataset reveals a diverse chromatin landscape with region-specific regulatory mechanisms and genomic interactions in distinct neurogenic regions of the embryonic mouse brain and represents an extensive public resource of a ‘ground truth’ epigenomic landscape at this critical stage of neurogenesis.
SPART, a versatile and standardized data exchange format for species partition information
Authors: Miralles Aurélien , Ducasse Jacques , Brouillet Sophie , Flouri Tomas , Fujisawa Tomochika , Kapli Paschalia , Knowles L. Lacey , Kumari Sangeeta , Stamatakis Alexandros , Sukumaran Jeet , Lutteropp Sarah , Vences Miguel , Puillandre Nicolas
Published: March 2021

A wide range of data types can be used to delimit species and various computer-based tools dedicated to this task are now available. Although these formalized approaches have significantly contributed to increase the objectivity of SD under different assumptions, they are not routinely used by alpha-taxonomists. One obvious shortcoming is the lack of interoperability among the various independently developed SD programs. Given the frequent incongruences between species partitions inferred by different SD approaches, researchers applying these methods often seek to compare these alternative species partitions to evaluate the robustness of the species boundaries. This procedure is excessively time consuming at present, and the lack of a standard format for species partitions is a major obstacle. Here we propose a standardized format, SPART, to enable compatibility between different SD tools exporting or importing partitions. This format reports the partitions and describes, for each of them, the assignment of individuals to the “inferred species”. The syntax also allows to optionally report support values, as well as original trees and the full command lines used in the respective SD analyses. Two variants of this format are proposed, overall using the same terminology but presenting the data either optimized for human readability (matricial SPART) or in a format in which each partition forms a separate block (SPART.XML). ABGD, DELINEATE, GMYC, PTP and TR2 have already been adapted to output SPART files and a new version of LIMES has been developed to import, export, merge and split them.
Evolution of MEG: a first MEG-feasible fluxgate magnetometer
Authors: Koshev N. , Butorina A. , Skidchenko E. , Kuzmichev A. , Ossadtchi A. , Ostras M. , Fedorov M. , Vetoshko P.
Published: March 2021

In the current article we present a first solid-state sensor feasible for magnetoencephalography (MEG), and working at room temperature. The sensor is a fluxgate magnetometer based on yttrium-iron garnet films (YIGM). In this feasibility study we prove the concept of usage the YIGM in terms of MEG by registering a simple brain induced field: the human alpha rhythm1. All the experiments and results are validated with usage of another kind of high-sensitive magnetometers - optically pumped magnetometer (OPM), which currently appears to be well-established in terms of MEG.
Replicative senescence dictates the emergence of disease-associated microglia and contributes to Aβ pathology
Authors: Hu Yanling , Fryatt Gemma L. , Ghorbani Mohammadmersad , Obst Juliane , Menassa David A. , Martin-Estebane Maria , Muntslag Tim A. O. , Olmos-Alonso Adrian , Guerrero-Carrasco Monica , Thomas Daniel , Cragg Mark S. , Gomez-Nicola Diego
Published: March 2021

The sustained proliferation of microglia is a key hallmark of Alzheimer’s disease (AD), accelerating its progression. Here, we sought to understand the long-term impact of the early and prolonged microglial proliferation observed in AD, hypothesising that extensive and repeated cycling would engender a distinct transcriptional and phenotypic trajectory. We found that the early and sustained microglial proliferation seen in an AD-like model promotes replicative senescence, characterised by increased βgal activity, a senescence-associated transcriptional signature and telomere shortening, correlating with the appearance of disease-associated microglia (DAM) and senescent microglial profiles in human post-mortem AD cases. Prevention of early microglial proliferation hindered the development of senescence and DAM, impairing the accumulation of Aβ and associated neuritic damage. Overall, our results support that excessive microglial proliferation leads to the generation of senescent DAM, which contribute to early Aβ pathology in AD.
Functional variants in hematopoietic transcription factor footprints and their roles in the risk of immune system diseases
Authors: Kubota Naoto , Suyama Mikita
Published: March 2021

Genome-wide association studies (GWAS) have been performed to identify thousands of variants in the human genome as disease risk markers, but functional variants that actually affect gene regulation and their genomic features remain largely unknown. Here we performed a comprehensive survey of functional variants in the regulatory elements of the human genome. We integrated hematopoietic transcription factor (TF) footprints datasets generated by ENCODE project with multiple quantitative trait locus (QTL) datasets (eQTL, caQTL, bQTL, and hQTL) and investigated the associations of functional variants and immune system disease risk. We identified candidate regulatory variants highly linked with GWAS lead variants and found that they were strongly enriched in active enhancers in hematopoietic cells, emphasizing the clinical relevance of enhancers in disease risk. Moreover, we found some strong relationships between traits and hematopoietic cell types or TFs. We highlighted some credible regulatory variants and found that a variant, rs2291668, which potentially functions in the molecular pathogenesis of multiple sclerosis, is located within a TF footprint present in a protein-coding exon of theTNFSF14gene, indicating that protein-coding exons as well as noncoding regions can possess clinically relevant regulatory elements. Collectively, our results shed light on the molecular pathogenesis of immune system diseases. The methods described in this study can readily be applied to the study of the risk factors of other diseases.