bluuebunny/crossref_metadata_2025 huggingface dataset:
Lessons Learned in the Care of the Professional Athlete
Authors: Graham Thomas J.
Published: December 2022

The role of an experienced Hand Surgery Consultant within the complete care matrix for a professional sports organization has evolved in my 3-decade career. Granted, hand injuries may have been demoted in this population where ACL tears, shoulder dislocations, and Lisfranc injuries seem to have much greater visibility, but our experience has told us that Hand injuries often contribute to the most surgeries per team/per season and can result in significant man-game loss of service. In my 30 years as a Consultant, Team Physician and/or Medical Director in all 4 major North American-based Leagues (as well as for “itinerant” independent contractor sports of golf, tennis, and motorsports), we have cared for well over 2000 athletes. This privilege has provided us with unparalleled exposure to the locker rooms, training rooms, and clubhouses for almost every team in professional-level competition and many elite-level collegiate programs. My goal in assembling this volume was to highlight the skilled and experienced colleagues who have contributed so much to the surgical science of caring for the hand and wrist in the professional athlete and furthering the logic of having a Hand Surgeon on “speed dial” for our fellow Team Physicians who want to provide optimal care for their athletes. Regrettably, until recently, the limited number of us who had significant involvement in this cohort probably fell short of engaging in scientific inquiry and publishing our observations or series. I will accept more than my share of that shortcoming, but as these practices have expanded in number and the exposure went from anecdotal to voluminous, our community started to communicate within Hand Surgery ranks, but now we want to share our knowledge with all professional involved in elite athlete care. This collection is not meant to be an exhaustive review of individual pathologies. Fortunately, valued colleagues have done a laudable job of chronicling the common-to-complex pathologies that we see in sports coverage This publication is styled less from the “what” and “how” standpoint, aimed instead at providing Team Physicians with the “when” and “why” of optimizing their player’s outcomes through collaboration with their Hand Specialist.
The Role of the Hand Surgery Consultant in the Care of the Football Athlete
Authors: Rettig Lance A. , Rettig Arthur C.
Published: December 2022

Purpose:

Return–to–play safely focusing on care for professional athletes. Variability on when return-to-play is possible due to differences in dexterity requirements of player's position and upper extremity injuries. This study covers the importance of trust between players and healthcare providers in the incident of upper extremity injury and aspects of when return-to-play is favorable.

Material and Methods:

The methods and materials used in this study were a collection of case reviews and documentation of injuries reported by national leagues. A retrospective review from 2000 to 2012 reviewing case series reported by the NFL Injury Surveillance System (NFL ISS). The case reviews included player activity, external bracing, and clinical notes. The review extracted from the National football league surveyed injuries over a 10-year period from 1996 – 2005. The National Football league's surveillance database was used focusing on the type of injury, the athlete's position, and the type of activity that was occurring at the time of injury.

Results:

The 7 included articles reported most injuries occurred in defensive players. The majority of injuries were sustained while tackling. Additionally, the 7 articles included a discussion of injury types including those of the hand, wrist, forearm, and elbow. Treatment plans were also reviewed catering to the type of injury. Players who were treated non-operatively missed a mean of 25 days and players who were treated operatively missed a mean of 46 days.

Conclusion:

The importance of communication between surgeons, coaches, players, and general managers of teams is vital in caring for injured players. All parties need to be aware of how much time players will miss and the best management techniques to take to get them back on the playing field.
Pneumoperitoneum and Acute Kidney Injury—An Integrative Clinical Concept Review
Authors: Kopitkó Csaba , Rosivall László , Medve László , Gondos Tibor , Soliman Karim M. , Szabó Zsuzsanna , Pettendi Éva , Fülöp Tibor
Published: December 2022

An increased intraabdominal pressure, particularly when occurring during periods of hemodynamic instability or fluid overload, is regarded as a major contributor to acute kidney injury (AKI) in intensive care units. During abdominal laparoscopic procedures, intraoperative insufflation pressures up to 15 mmHg are applied, to enable visualization and surgical manipulation but with the potential to compromise net renal perfusion. Despite the widely acknowledged renal arterial autoregulation, net arterial perfusion pressure is known to be narrow, and the effective renal medullary perfusion is disproportionately impacted by venous and lymphatic congestion. At present, the potential risk factors, mitigators and risk-stratification of AKI during surgical pneumoperitoneum formation received relatively limited attention among nephrologists and represent an opportunity to look beyond mere blood pressure and intake-output balances. Careful charting and reporting duration and extent of surgical pneumoperitoneum represents an opportunity for anesthesia teams to better communicate intraoperative factors affecting renal outcomes for the postoperative clinical teams. In this current article, the authors are integrating preclinical data and clinical experience to provide a better understanding to optimize renal perfusion during surgeries. Future studies should carefully consider intrabdominal insufflation pressure as a key variable when assessing outcomes and blood pressure goals in these settings.
Development of a Long-Term Cross-Sectoral Case and Care Management Manual for Patients With Severe Multiple Sclerosis and Their Caregivers
Authors: Müller Anne , Dillen Kim , Dojan Thomas , Ungeheuer Solveig , Goereci Yasemin , Dunkl Veronika , Voltz Raymond , Löcherbach Peter , Warnke Clemens , Golla Heidrun
Published: December 2022

Purpose/Objectives:

Care and case management (CCM) aims to provide optimal care for patients and their caregivers on an individual and superordinate level of health care providers and authorities. To facilitate a clear and systematic CCM process as part of a clinical study intervention, a semistructured manual is the prerequisite.

Primary Practice Setting(s):

The ongoing COCOS-MS (Communication, Coordination and Security for People with Multiple Sclerosis) study is a randomized controlled Phase II clinical intervention study. The CCM manual is being tested on the intervention group consisting of severely affected individuals with multiple sclerosis (MS; Expanded Disability Status Scale [EDSS] >5) and their caregivers receiving CCM for 12 months in addition to standard care. The intervention comprises monthly personal visits and weekly telephone calls during which the CCM manual is applied.

Findings/Conclusions:

The CCM manual has been developed on the basis of previous literature and well-established questionnaires following theoretical aspects and prior scientific work covering individual domains of life of people with MS. Within the COCOS-MS study, its feasibility is being tested meticulously. It allows for a standardized assessment while being tailored to the individual. At the end of the intervention period, it will be analyzed statistically and qualitatively. Consequently, conclusions can be drawn as to whether the CCM manual is feasible or has to be adapted for use in standard care after analyzation.

Implications for Case Management Practice:

The CCM manual serves as a tool for the continuous, long-term, cross-sectoral care for patients suffering from severe MS and their caregivers. The manual provides guidance in adequately addressing patients' complex symptoms, problems, and needs, as well as assessing existing resources both at the individual patient level and at a superordinate level.
Structured Outpatient Diabetes Education and Telehealth Follow-up to Improve HbA1c
Authors: Harris-Hardaway Marina B. , Novotny Nancy L. , Sawyer Jennifer Dana , Schmitt Erin
Published: December 2022

Background:

More than 10% of Americans have diabetes, with higher rates in Hispanics and African Americans. National Healthy People 2030 goals for expected decrease in HbA1c levels have not been met.

Local Problem:

No standardized diabetes education or follow-up existed at a free clinic. Patients exhibited diabetic self-management inadequacies and elevated HbA1c levels.

Methods:

A pre/postimplementation study design was used to evaluate changes in HbA1c levels, medication adherence, missed appointments, and emergency department visits.

Interventions:

Structured diabetes education and follow-up text/phone messages for patients with HbA1c levels 8% or higher were implemented over 3 months.

Results:

Outcome data were available for 27 of the 34 participants. Postimplementation, there was a significant 1.7% decrease in mean HbA1c levels (P < .001). No significant differences were found for the other outcome measures.

Conclusions:

Structured diabetes education and follow-up text/phone messages in a free clinic improved patients' HbA1c levels.
Medication discharge teaching in pediatric hematopoietic stem cell transplantation: teaching characteristics, caregiver perceptions, and postdischarge adherence
Authors: Szulczewski Lauren , Carmody Julia K. , Tillery Rachel , Nelson Adam S. , Pai Ahna L. H.
Published: December 2022

Background:

Hematopoietic stem cell transplantation (HCT) is an arduous but necessary treatment for many otherwise incurable diseases. It involves a complex medication regimen that is linked to significant clinical outcomes and must be learned by families before discharge. The purpose of this study was to qualitatively explore medication discharge teaching factors and to examine associations between those factors and caregiver self-perceived knowledge and efficacy.

Methods:

Nineteen video-recorded medication discharge teachings, conducted by hematopoietic stem cell transplantation pharmacists, were coded to identify elements of discharge teaching, including information presented, communication, and environmental factors. Caregivers also completed a semistructured interview and a short measure to assess caregiver efficacy regarding their child's medication regimen.

Results:

Pharmacists were consistent in their review of the names, dosages, and frequency of the medications being prescribed. However, there was variability regarding information provided about adherence, specific learnings (ie, how to read/fill syringe), and behavioral strategies to promote adherence (ie, adjust timing to fit family's schedule). Immediately and 1 week after the teaching, caregivers reported high levels of confidence regarding their ability to understand and manage their child's medication regimen.

Conclusion:

Teaching families about the prescribed medication regimen is a critical component of the discharge process. The current findings suggest that increasing the consistency with which information is provided to families regarding the effective management of the medication regimen could potentially be a method to facilitate adherence.
Adverse Events in Pediatric Critical Care Nonsurvivors With a Low Predicted Mortality Risk: A Multicenter Case Control Study*
Authors: Verlaat Carin W. , Zegers Marieke , Klein Richard , van Waardenburg Dick , Kuiper Jan Willem , Riedijk Maaike , Kneyber Martin , Timmers Brigitte , van Heerde Marc , Hazelzet Jan A. , van der Hoeven Johannes , Lemson Joris ,   for the PICE registry (Pediatric Intensive Care Evaluation)/SKIC (Dutch Collaborative PICU Research Network)
Published: December 2022

OBJECTIVES:

Some patients with a low predicted mortality risk in the PICU die. The contribution of adverse events to mortality in this group is unknown. The aim of this study was to estimate the occurrence of adverse events in low-risk nonsurvivors (LN), compared with low-risk survivors (LS) and high-risk PICU survivors and nonsurvivors, and the contribution of adverse events to mortality.

DESIGN:

Case control study. Admissions were selected from the national Dutch PICU registry, containing 53,789 PICU admissions between 2006 and 2017, in seven PICUs. PICU admissions were stratified into four groups, based on mortality risk (low/high) and outcome (death/survival). Random samples were selected from the four groups. Cases were “LN.” Control groups were as follows: “LS,” “high-risk nonsurvivors” (HN), and “high-risk survivors” (HS). Adverse events were identified using the validated trigger tool method.

SETTING:

Patient chart review study.

PATIENTS:

Children admitted to the PICU with either a low predicted mortality risk (< 1%) or high predicted mortality risk (≥ 30%).

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

In total, 419 patients were included (102 LN, 107 LS, 104 HN, and 106 HS). LN had more complex chronic conditions (93.1%) than LS (72.9%; p < 0.01), HN (49.0%; p < 0.001), and HS (48.1%; p < 0.001). The occurrence of adverse events in LN (76.5%) was higher than in LS (13.1%) and HN (47.1%) (p < 0.001). The most frequent adverse events in LN were hospital-acquired infections and drug/fluid-related adverse events. LN suffered from more severe adverse events compared with LS and HS (p < 0.001). In 30.4% of LN, an adverse event contributed to death. In 8.8%, this adverse event was considered preventable.

CONCLUSIONS:

Significant and preventable adverse events were found in low-risk PICU nonsurvivors. 76.5% of LN had one or more adverse events. In 30.4% of LN, an adverse event contributed to mortality.
The Use and Impact of Diaries in PICUs and Neonatal ICUs: A Scoping Review
Authors: Low Sherry Zhi Qing , Kirk Angela , Mok Yee Hui , Lee Jan Hau
Published: December 2022

OBJECTIVE:

Several studies have investigated the impact of diaries in adult ICUs, which have been used as a tool to support recall and reduce post-traumatic stress disorder in patients and their families. We conducted a scoping review to determine the definition of ICU diaries, and the extent, range, and nature of research conducted on NICU and PICU diaries, describe their use and impact, as well as identify gaps in knowledge and areas for future research.

DATA SOURCES:

The following databases were searched from inception to March 2022: Cumulated Index to Nursing and Allied Health Literature, Cochrane Library, Embase, PubMed, and American Psychological Association PsycINFO. Searches were also conducted in the following gray literature databases: Google Scholar, University of South Australia, and WorldCat.

STUDY SELECTION:

All studies that discussed the use and impact of diaries or journals involving patients (<18 yr old) in PICUs and NICUs and/or their family members were included.

DATA SYNTHESIS:

Sixteen studies were identified. Most studies defined diaries as daily entries written by nurses and/or family members regarding the patient’s condition during their ICU admission. The majority reported that diaries were beneficial to children and their families as they helped to fill in memory gaps, provided a means to express their feelings, and served as effective health communication tools. Several gaps were identified: extent of the use of diaries as a means of communication, the significance of diaries as a coping mechanism for bereaved parents, and the impact of PICU diaries on the children, their families, and healthcare professionals.

CONCLUSIONS:

There is a paucity of data on the use of NICU and PICU diaries. Nonetheless, the limited data revealed that NICU and PICU diaries were beneficial to children and their families. Our review demonstrated a heterogeneity in the terminology, content, use of photos, and the author/s of the NICU and PICU diaries. Further research is needed to investigate the impact of the use of NICU and PICU diaries on patient-reported outcomes.
Intraoperative Use of Albumin in Major Noncardiac Surgery: Incidence, Variability, and Association With Outcomes
Authors: Lazzareschi Daniel V. , Fong Nicholas , Mavrothalassitis Orestes , Whitlock Elizabeth L. , Chen Catherine L. , Chiu Catherine , Adelmann Dieter , Bokoch Michael P. , Chen Lee-Lynn , Liu Kathleen D. , Pirracchio Romain , Mathis Michael R. , Legrand Matthieu ,   for the MPOG Collaborators
Published: December 2022

Background:

The impact of albumin use during major surgery is unknown, and a dearth of evidence governing its use in major noncardiac surgery has long precluded its standardization in clinical guidelines.

Objective:

In this study, we investigate institutional variation in albumin use among medical centers in the United States during major noncardiac surgery and explore the association of intraoperative albumin administration with important postoperative outcomes.

Methods:

The study is an observational retrospective cohort analysis performed among 54 U.S. hospitals in the Multicenter Perioperative Outcomes Group and includes adult patients who underwent major noncardiac surgery under general anesthesia between January 2014 and June 2020. The primary endpoint was the incidence of albumin administration. Secondary endpoints are acute kidney injury (AKI), net-positive fluid balance, pulmonary complications, and 30-day mortality. Albumin-exposed and albumin-unexposed cases were compared within a propensity score-matched cohort to evaluate associations of albumin use with outcomes.

Results:

Among 614,215 major surgeries, predominantly iso-oncotic albumin was administered in 15.3% of cases and featured significant inter-institutional variability in use patterns. Cases receiving intraoperative albumin involved patients of higher American Society of Anesthesiologists physical status and featured larger infused crystalloid volumes, greater blood loss, and vasopressor use. Overall, albumin was most often administered at high-volume surgery centers with academic affiliation, and within a propensity score-matched cohort (n=153,218), the use of albumin was associated with AKI (aOR 1.24, 95% CI 1.20–1.28, P<0.001), severe AKI (aOR 1.45, 95% CI 1.34–1.56, P<0.001), net-positive fluid balance (aOR 1.18, 95% CI 1.16–1.20, P<0.001), pulmonary complications (aOR 1.56, 95% CI 1.30–1.86, P<0.001), and 30-day all-cause mortality (aOR 1.37, 95% CI 1.26–1.49, P<0.001).

Conclusions:

Intravenous albumin is commonly administered among noncardiac surgeries with significant inter-institutional variability in use in the United States. Albumin administration was associated with an increased risk of postoperative complications.
Racial Disparity in Placement of Intracranial Pressure Monitoring: A TQIP Analysis
Authors: Zebley James A , Estroff Jordan M , Forssten Maximilian Peter , Leighton Nicolas , Bass Gary Alan , Sarani Babak , Mohseni Shahin
Published: December 2022

BACKGROUND:

The Brain Trauma Foundation recommends intracranial pressure (ICP) monitoring in patients with severe traumatic brain injury (TBI). Race is associated with worse outcomes after TBI. The reasons for racial disparities in clinical decision-making around ICP monitor placement remain unclear.

STUDY DESIGN:

We queried the TQIP database from 2017 to 2019 and included patients 16 years or older, with blunt severe TBI, defined as a head abbreviated injury score 3 or greater. Exclusion criteria were missing race, those without signs of life on admission, length of stay 1 day or less, and AIS of 6 in any body region. The primary outcome was ICP monitor placement, which was calculated using a Poisson regression model with robust SEs while adjusting for confounders.

RESULTS:

A total of 260,814 patients were included: 218,939 White, 29,873 Black, 8,322 Asian, 2,884 American Indian, and 796 Native Hawaiian or Other Pacific Islander. Asian and American Indian patients had the highest rates of midline shift (16.5% and 16.9%). Native Hawaiian or Other Pacific Islanders had the highest rates of neurosurgical intervention (19.3%) and ICP monitor placement (6.5%). Asian patients were found to be 19% more likely to receive ICP monitoring (adjusted incident rate ratio 1.19; 95% CI 1.06 to 1.33; p = 0.003], and American Indian patients were 38% less likely (adjusted incident rate ratio 0.62; 95% CI 0.49 to 0.79; p < 0.001), compared with White patients, respectively. No differences were detected between White and Black patients.

CONCLUSIONS:

ICP monitoring use differs by race. Further work is needed to elucidate modifiable causes of this difference in the management of severe TBI.
Usefulness of quantitative Loop-Mediated Isothermal Amplification Assay in comparison with real time PCR for the diagnosis of invasive pneumococcal disease
Authors: Peela Sreeram Chandra Murthy , Sistla Sujatha
Published: December 2022

Background

Quantitative LAMP (qLAMP) assay is one of the recent and emerging diagnostic tests for infectious diseases. Only a few studies exist comparing this assay with quantitative real-time PCR (qPCR) for the diagnosis of invasive pneumococcal disease (IPD). The present study was performed to compare the diagnostic performance of qLAMP assay with qPCR targeting autolysin gene for the diagnosis of invasive pneumococcal disease.

Methodology/Principal Findings

Ninety six blood samples and 73 CSF samples from patients clinically suspected with community acquired pneumonia and acute meningitis were tested by qPCR and qLAMP assays using previously published primers and protocols. The qPCR was considered as the gold standard test and the diagnostic performance was assessed by calculating sensitivity, specificity, positive and negative predictive values, and kappa coefficient for the level of agreement between the tests. Chi-squared/Fisher exact test was used to compare categorical variables (positive/negative). Thirty two blood samples and 22 CSF samples were positive by qPCR while 24 and 20 samples were positive by qLAMP assay respectively. The sensitivity of qLAMP assay was only 86.4% and 75% when tested on CSF and blood samples respectively. However, the qLAMP assay was in substantial to almost perfect agreement when compared with qPCR. The results were statistically significant in both sample types (P<0.001).

Conclusions

The performance of qLAMP assay can vary based on the specimen type. It has very high specificity and had substantial to almost perfect agreement, and thus may be an alternative to qPCR for the diagnosis of IPD.
Transcriptomic profiling reveals distinct subsets of immune checkpoint inhibitor-induced myositis
Authors: Pinal-Fernandez Iago , Quintana Angela , Milisenda Jose C. , Casal-Dominguez Maria , Muñoz-Braceras Sandra , Derfoul Assia , Torres-Ruiz Jiram , Pak Katherine , Del Orso Stefania , Naz Faiza , Gutierrez-Cruz Gustavo , Milone Margherita , Shelly Shahar , Duque-Jaimez Yaiza , Tobias-Baraja Ester , Matas-Garcia Ana , Garrabou Gloria , Padrosa Joan , Ros Javier , Trallero-Araguás Ernesto , Walitt Brian , Christopher-Stine Lisa , Lloyd Thomas E. , Zhao Chen , Swift Shannon , Rajan Arun , Grau Josep Maria , Selva-O’Callaghan Albert , Liewluck Teerin , Mammen Andrew L.
Published: December 2022

Objectives

Inflammatory myopathy or myositis is a heterogeneous family of immune-mediated diseases including dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Immune checkpoint inhibitors (ICI) can also cause myositis (ICI-myositis). This study was designed to define gene expression patterns in muscle biopsies from patients with ICI-myositis.

Methods

Bulk RNA sequencing was performed on 200 muscle biopsies (35 ICI-myositis, 44 DM, 18 AS, 54 IMNM, 16 IBM, and 33 normal muscle biopsies) and single nuclei RNA sequencing was performed on 22 muscle biopsies (7 ICI-myositis, 4 DM, 3 AS, 6 IMNM, and 2 IBM).

Results

Unsupervised clustering defined three distinct transcriptomic subsets of ICI-myositis: ICI-DM, ICI-MYO1, and ICI-MYO2. ICI-DM included patients with DM and anti-TIF1γ autoantibodies who, like DM patients, overexpressed type 1 interferon-inducible genes. ICI-MYO1 patients had highly inflammatory muscle biopsies and included all patients that developed co-existing myocarditis. ICI-MYO2 was composed of patients with predominant necrotizing pathology and low levels of muscle inflammation. The type 2 interferon pathway was activated both in ICI-DM and ICI-MYO1. Unlike the other types of myositis, all three subsets of ICI-myositis patients overexpressed genes involved in the IL6 pathway.

Conclusions

We identified three distinct types of ICI-myositis based on transcriptomic analyses. The IL6 pathway was overexpressed in all groups, the type I interferon pathway activation was specific for ICI-DM, the type 2 IFN pathway was overexpressed in both ICIDM and ICI-MYO1, and only ICI-MYO1 patients developed myocarditis.
T7 DNA polymerase treatment improves quantitative sequencing of both double-stranded and single-stranded DNA viruses
Authors: Billaud Maud , Theodorou Ilias , Lamy-Besnier Quentin , Shah Shiraz A. , Lecointe François , De Sordi Luisa , De Paepe Marianne , Petit Marie-Agnès
Published: December 2022

Background:Bulk microbiome, as well as virome-enriched shotgun sequencing only reveals the double-stranded DNA (dsDNA) content of a given sample, unless specific treatments are applied. However, genomes of viruses often consist of a circular single-stranded DNA (ssDNA) molecule. Pre- treatment and amplification of DNA using the multiple displacement amplification (MDA) method enables conversion of ssDNA to dsDNA, but this process can lead to over-representation of these circular ssDNA genomes. A more recent alternative permits to bypass the amplification step, as library adapters are ligated to sheared and denatured DNA, after an end-modification step (xGen kit). However, the sonication step might shear ssDNA more efficiently than dsDNA, therefore introducing another bias in virome sequencing. These limitations prompted us to explore an alternative method of DNA preparation for sequencing mixed ssDNA and dsDNA viromes.

Results:Using a synthetic mix of viral particles, we made use of the T7 DNA polymerase (T7pol) to convert viral circular ssDNA molecules to dsDNA, while preventing over-replication of such molecules, as is the case with the Phi29 DNA polymerase. Our findings indicate that using T7pol and a mix of degenerated primers to convert ssDNA to dsDNA prior library preparation is a good alternative to the currently used methods. It better represents the original synthetic mixtures compared to MDA or direct application of the xGen kit. Furthermore, when applied to two complex virome samples, the T7pol treatment improved both the richness and abundance in theMicroviridaefraction.

Conclusion:We conclude that T7pol pretreatment is preferable to MDA for the shotgun sequencing of viromes, which is easy to implement and inexpensive.
The phased diploid genome assembly ofVitis vinifera cv. Shiraz
Authors: Onetto Cristobal A. , Ward Christopher M. , Borneman Anthony R.
Published: December 2022

Shiraz (Syrah) is a dark-skinned cultivar of the wine grapeVitis viniferathat forms the basis of some of the world’s most iconic wines. Worldwide, Shiraz is the fourth most planted grapevine cultivar, however it represents the most planted cultivar in Australia. Given the importance of Shiraz to worldwide wine production, a long-read based reference genome assembly for this cultivar was produced and used to investigate the unique genetic diversity and ancestral origins of this iconic variety. Phylogenetic reconstruction using high-quality genome assemblies for wine grape cultivars provided further support of a kinship between Shiraz and Pinot Noir. Harnessing long-read data, transposable element insertions potentially affecting gene function were characterized in Shiraz and assessed relative to other cultivars. This revealed a heterogenous landscape of transposon insertion points across cultivars and uncovered a specific combination of allelic variants at theTPS24terpene synthase locus, which when combined with appropriate environmental triggers, may allow Shiraz to produce high levels of rotundone, the aroma compound responsible for the distinctive peppery characteristics of this cultivar.
A comparison of survey method efficiency for estimating densities of Zebra Mussels (Dreissena polymorpha)
Authors: Ferguson Jake M. , Jiménez Laura , Keyes Aislyn A. , Hilding Austen , McCartney Michael A. , Clair Katie St. , Johnson Douglas H. , Fieberg John
Published: December 2022

Abundance surveys are a common and practical technique to estimate plant or animal densities. Methods used to conduct these surveys often require jointly estimating uncertainty in both counts and detection probability. The estimation of detection probability requires additional measurements that take time, potentially reducing the efficiency of the survey for high-density populations. We conducted quadrat, removal, and distance surveys of zebra mussels (Dreissena polymorpha) in three central Minnesota lakes and used an efficiency measure to help compare survey designs. Survey efficiency depended on both the survey design and the population density. The efficiency of survey designs that required estimates of detection probabilities (relative to designs that did not) decreased with density, leading to a change in the most efficient survey design at high densities. These results demonstrate that the best survey design may be context-specific, requiring some prior knowledge of the underlying population density and the cost/time needed to collect additional information for estimating detection probabilities.
Single-nucleus co-expression networks of dopaminergic neurons support iron accumulation as a plausible explanation to their vulnerability in Parkinson’s disease
Authors: Gómez-Pascual A. , Martirosyan A. , Hebestreit K. , Mameffe C. , Poovathingal S. , Belgard T. G. , Altar C. A. , Kottick A. , Holt M. , Hanson-Smith V. , Cisterna A. , Mighdoll M. , Scannevin R. , Guelfi S. , Botía J. A.
Published: December 2022

Motivation

gene co-expression networks have been widely applied to identify critical genes and pathways for neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. Now, with the advent of single-cell RNA-sequencing, we have the opportunity to create cell-type specific gene co-expression networks. However, single-cell RNA-sequencing data is characterized by its sparsity, amongst some other issues raised by this new type of data.

Results

We present scCoExpNets, a framework for the discovery and analysis of cell-type specific gene coexpression networks (GCNs) from single-cell RNA-seq data. We propose a new strategy to address the problem of sparsity, named iterative pseudo-cell identification. It consists of adding the gene expression of pairs of cells that belong to the same individual and the same cell-type while the number of cells is over 200, thus creating multiple matrices and multiple scGCNs for the same cell-type, all of them seen as alternative and complementary views of the same phenomena. We applied this new tool on a snRNA-seq dataset human post-mortem substantia nigra pars compacta tissue of 13 controls and 14 Parkinson’s disease (PD) cases (18 males and 9 females) with 30-99 years. We show that one of the hypotheses that support the selective vulnerability of dopaminergic neurons in PD, the iron accumulation, is sustained in our dopaminergic neurons network models. Moreover, after successive pseudo-celluling iterations, the gene groups sustaining this hypothesis remain intact. At the same time, this pseudo-celulling strategy also allows us to discover genes whose grouping changes considerably throughout the iterations and provides new insights. Finally, since some of our models were correlated with diagnosis and age at the same time, we also developed our own framework to create covariate-specific GCNs, called CovCoExpNets. We applied this new software to our snRNA-seq dataset and we identified 11 age-specific genes and 5 diagnosis-specific genes which do not overlap.

Availability and implementation

The CoExpNets implementations are available as R packages: scCoExpNets for creating single-cell GCNs and CovCoExpNets for creating covariate-specific GCNs. Users can either download the development version via githubhttps://github.com/aliciagp/scCoExpNetsandhttps://github.com/aliciagp/CovCoExpNets

Contact

alicia.gomez1@um.es

Supplementary information

supplementary data is available online.
Massonia grandiflora -also known as Massonia depressa- (Hyacinthaceae) is not only pollinated by rodents, but by Elephantulus edwardii as well
Authors: Niedzwetzki-Taubert Tim
Published: December 2022

The authors have withdrawn their manuscript owing to the fact that it will be part of another publication named “Non-flying mammal pollination in Massonia grandiflora”. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Next-generation plasmids for transgenesis in zebrafish and beyond
Authors: Kemmler Cassie L. , Moran Hannah R. , Murray Brooke F. , Scoresby Aaron , Klem John R. , Eckert Rachel L. , Lepovsky Elizabeth , Bertho Sylvain , Nieuwenhuize Susan , Burger Sibylle , D’Agati Gianluca , Betz Charles , Puller Ann-Christin , Felker Anastasia , Ditrychová Karolína , Bötschi Seraina , Affolter Markus , Rohner Nicolas , Lovely C. Ben , Kwan Kristen M. , Burger Alexa , Mosimann Christian
Published: December 2022

Transgenesis is an essential technique for any genetic model. Tol2-based transgenesis paired with Gateway-compatible vector collections has transformed zebrafish transgenesis with an accessible, modular system. Here, we established several next-generation transgenesis tools for zebrafish and other species to expand and enhance transgenic applications. To facilitate gene-regulatory element testing, we generated Gateway middle entry vectors harboring the small mousebeta-globinminimal promoter coupled to several fluorophores, CreERT2, and Gal4. To extend the color spectrum for transgenic applications, we established middle entry vectors encoding the bright, blue-fluorescent protein mCerulean and mApple as an alternative red fluorophore. We present a series of p2A peptide-based 3’ vectors with different fluorophores and subcellular localizations to co-label cells expressing proteins of interest. Lastly, we established Tol2 destination vectors carrying the zebrafishexorhpromoter driving different fluorophores as a pineal gland-specific transgenesis marker active prior to hatching and through adulthood. exorh-based reporters and transgenesis markers also drive specific pineal gland expression in the eye-less cavefish (Astyanax). Together, our vectors provide versatile reagents for transgenesis applications in zebrafish, cavefish, and other models.
Cell-type-specific co-expression inference from single cell RNA-sequencing data
Authors: Su Chang , Xu Zichun , Shan Xinning , Cai Biao , Zhao Hongyu , Zhang Jingfei
Published: December 2022

The inference of gene co-expressions from microarray and RNA-sequencing data has led to rich insights on biological processes and disease mechanisms. However, the bulk samples analyzed in most studies are a mixture of different cell types. As a result, the inferred co-expressions are confounded by varying cell type compositions across samples and only offer an aggregated view of gene regulations that may be distinct across different cell types. The advancement of single cell RNA-sequencing (scRNA-seq) technology has enabled the direct inference of co-expressions in specific cell types, facilitating our understanding of cell-type-specific biological functions. However, the high sequencing depth variations and measurement errors in scRNA-seq data present significant challenges in inferring cell-type-specific gene co-expressions, and these issues have not been adequately addressed in the existing methods. We propose a statistical approach, CS-CORE, for estimating and testing cell-type-specific co-expressions, built on a general expression-measurement model that explicitly accounts for sequencing depth variations and measurement errors in the observed single cell data. Systematic evaluations show that most existing methods suffer from inflated false positives and biased co-expression estimates and clustering analysis, whereas CS-CORE has appropriate false positive control, unbiased co-expression estimates, good statistical power and satisfactory performance in downstream co-expression analysis. When applied to analyze scRNA-seq data from postmortem brain samples from Alzheimer’s disease patients and controls and blood samples from COVID-19 patients and controls, CS-CORE identified cell-type-specific co-expressions and differential co-expressions that were more reproducible and/or more enriched for relevant biological pathways than those inferred from other methods.
What are the criteria for morphological cell death inDunaliella salina?
Authors: Barmshuri Mahnaz , Kholdebarin Bahman , Sadeghi Saber , Faghih Zahra
Published: December 2022

By finding morphological criteria for death in photosynthetic algal cells, one finds that the death of different populations of algae cells is manifested by various morphological changes. Present study, was undertaken to determine morphological criteria to be used in identifying cell death in unicellular green algae in their natural habitats. By applying the principles of formazan crystal formation due to MTT reduction in the presence of cells oxidoreductase enzymes, and the staining of saccharide complexes produced in photosynthesis by iodine reagent, morphological criteria were determined for cell death inDunaliella salinacollected from Maharloo lake and three different types of deaths were identified. Further studies have shown that these criteria can also be applied for fresh water algae and other taxon. Different ways of cell death in unicellular aquatic organisms can be used as monitoring tools for early warning of environmental hazards. We invite scientists, editors and reviewers to embark on establishing a much needed cell death classification committee for identifying different types of cell death and investigate mechanisms involved in unicellular aquatic algal cells.

Significance Statement

Staining with MTT and iodine reagents, are the best tools for distinguishing damages done to photosynthetic system in aquatic unicellular green algae following which cell death classification will be determined.
Striated muscle-specific base editing enables correction of mutations causing dilated cardiomyopathy
Authors: Grosch Markus , Schraft Laura , Chan Adrian , Küchenhoff Leonie , Rapti Kleopatra , Ferreira Anne-Maud , Kornienko Julia , Li Shengdi , Radke Michael H , Krämer Chiara , Clauder-Münster Sandra , Perlas Emerald , Gotthardt Michael , Dieterich Christoph , van den Hoogenhof Maarten MG , Grimm Dirk , Steinmetz Lars M
Published: December 2022

Dilated cardiomyopathy (DCM) is the second most common cause for heart failure with no cure except a high-risk heart transplantation. Approximately 30% of DCM patients harbor heritable mutations which are amenable to CRISPR-based gene therapy1. However, challenges related to delivery of the editing complex and off-target concerns hamper the broad applicability of CRISPR agents in the heart2. We employed a combination of the viral gene transfer vector AAVMYO with superior targeting specificity of heart muscle tissue3and CRISPR base editors to repair patient mutations in the cardiac splice factorRbm20, which cause aggressive and arrhythmogenic DCM4. Using optimized conditions, we could improve splice defects in human iPSC-derived cardiomyocytes (iPSC-CMs) and repair >70% of cardiomyocytes in twoRbm20knock-in mouse models that we generated to serve as anin vivoplatform of our editing strategy. Treatment of juvenile mice restored the localization defect of RBM20 in 75% of cells and splicing of RBM20 targets including TTN. Three months after injection, cardiac dilation and ejection fraction reached wildtype levels. Single-nuclei RNA sequencing (snRNA-seq) uncovered restoration of the transcriptional profile across all major cardiac cell types and whole-genome sequencing (WGS) revealed no evidence for aberrant off-target editing. Our study highlights the potential of base editors combined with AAVMYO to achieve gene repair for treatment of hereditary cardiac diseases.
Vaporous essential oils and isolates restore pyrethroid-treated netting efficacy toAedes aegypti(Diptera: Culicidae)
Authors: Rault Leslie C. , O’Neal Scott T. , Johnson Ellis J. , Anderson Troy D.
Published: December 2022

Decreasing opportunities for mosquitoes to bite is critical in the reduction of mosquito-borne pathogen transmission, such asPlasmodium spp. or dengue, yellow fever, and West Nile viruses. Field-evolved resistance to a large selection of synthetic insecticides is crippling efforts to reduce mosquito populations and new strategies are necessary to sustain the efficacy of commercially available tools.Aedes aegypti(L.), among other species, have evolved pyrethroid resistance in the field and the pyrethroid-resistant Puerto Rico (PR) strain is a valuable tool for understanding resistance mechanisms. A previous study showed that pyrethroid efficacy can be enhanced by pre-exposing the PR strain to essential oil vapors before topical application of deltamethrin. Insecticide-treated nets (ITNs) and long-lasting insecticidal nets (LLINs) are current products commercialized for mosquito bite protection, but nets using pyrethroids are losing efficacy in the field due to field-evolved pyrethroid resistance. This study tested essential oils previously identified to affect pyrethroid efficacy, as well as their main isolates, to assess if they can restore the efficacy of pyrethroid-treated LLIN against the PR strain. We show that although amyris (Amyris balsamifera) expectedly decreases net efficacy, increased mortality can be obtained after exposure to tagetes (Tagetes bipinnata) and cajeput (Melaleuca cajuputi)oils, but also after exposure to their isolates, such as dihydro tagetone and ocimene, from 1 h after exposure to the net. This study provides a selection of promising synergists used as vaporous emanations to restore pyrethroid efficacy and counteract field-evolved resistance in mosquitoes.
Genetic diversity landscapes in outcrossing and selfingCaenorhabditisnematodes
Authors: Teterina Anastasia A. , Willis John H. , Lukac Matt , Jovelin Richard , Cutter Asher D. , Phillips Patrick C.
Published: December 2022

Caenorhabditisnematodes form an excellent model for studying how the mode of reproduction affects genetic diversity, as some species reproduce via outcrossing whereas others can self-fertilize. Currently, chromosome-level patterns of diversity and recombination are only available for self-reproducingCaenorhabditis, making the generality of genomic patterns across the genus unclear given the profound potential influence of reproductive mode. Here we present a whole-genome diversity landscape, coupled with a new genetic map, for the outcrossing nematodeC. remanei. We demonstrate that the genomic distribution of recombination inC. remanei, like the model nematodeC. elegans, shows high recombination rates on chromosome arms and low rates toward the central regions. Patterns of genetic variation across the genome are also similar between these species, but differ dramatically in scale, being 10-fold greater for C. remanei. Historical reconstructions of variation in effective population size over the past million generations echo this difference in polymorphism. Evolutionary simulations demonstrate how selection, recombination, mutation, and selfing shape variation along the genome, and that multiple drivers can produce patterns similar to those observed in natural populations. Convolutional neural networks demonstrate the potential for classifying distinct evolutionary scenarios in simulated populations. Distinguishing these forces confidently with the empirical data, however, will benefit from larger population genomic samples from multiple populations and consideration of an even more extensive training set of simulations.
Multimodal measures of spontaneous brain activity reveals both common and divergent patterns of cortical functional organization
Authors: Vafaii Hadi , Mandino Francesca , Desrosiers-Grégoire Gabriel , O’Connor David , Shen Xilin , Ge Xinxin , Herman Peter , Hyder Fahmeed , Papademetris Xenophon , Chakravarty Mallar , Crair Michael C. , Constable R. Todd , Lake Evelyn MR. , Pessoa Luiz
Published: December 2022

Work in humans and animals shows that the brain can be decomposed into large-scale functional networks. Whereas most studies, especially in humans, use the blood-oxygenation-level-dependent (BOLD) signal, the relationship between BOLD and neuronal activity is complex and incompletely understood. This limits our ability to interpret and apply measures derived from fMRI-BOLD. Here, we employ wide-field Ca2+imaging simultaneously recorded with fMRI-BOLD in highly-sampled mice expressing GCaMP6f in excitatory neurons. These unique data enabled us to characterize the similarities and differences between networks discoverable by each modality. Importantly, we applied a network partitioning approach that uses a mixed-membership algorithm, which allows brain regions to participate in multiple networks with varying strengths. This contrasts with assuming regions belong to only one network. Our findings demonstrate that (1) most BOLD networks are detected via Ca2+signals. (2) There is considerable overlapping—as opposed to disjoint—network organization that is evident from both modalities. (3) Large-scale networks determined by Ca2+signals at low temporal frequencies (0.01 – 0.5Hz)—as opposed to higher frequencies (0.5 – 5Hz)—are more similar to those determined by BOLD. (4) Despite many similarities, differences emerge across modes including the spatial distribution of membership diversity (the extent to which regions affiliate with multiple networks). In sum, Ca2+imaging of excitatory neurons confirms that the mouse cortex is functionally organized into overlapping large-scale networks in a manner that reflects many, but not all, properties observable with simultaneous fMRI-BOLD; affirming the neural origins of patterns of brain organization that are evident in a clinically accessible neuroimaging modality.