bluuebunny/crossref_metadata_2025 huggingface dataset:
Serendipity: Being in the Right Place at the Right Time
Authors: Saidman Lawrence J.
Published: February 2022

Effect of Nitrous Oxide and of Narcotic Premedication on the Alveolar Concentration Required for Anesthesia. By Saidman LJ, Eger EI II. Anesthesiology 1964; 25:302–6.

Hyperthermia during Anesthesia. By Saidman LJ, Havard ES, Eger EI II. JAMA 1964; 190:1029–32.

The minimum alveolar concentration (MAC) of an inhaled anesthetic preventing movement in response to a surgical incision as a measure of equipotency was “invented” in 1964 at the University of California, San Francisco. The principal advantage of MAC is that it allows the pharmacologic effects of inhaled anesthetics to be compared against each other at a similar anesthetic depth. Thus, if the hemodynamic effect (hypotension, decreased cardiac output) of anesthetic “A” is greater than that of anesthetic “B,” the anesthesiologist may elect to use “A” in patients with myocardial dysfunction. A rare side effect of a volatile anesthetic is that in some patients, malignant hyperthermia may occur with or without succinylcholine use. This phenomenon was detected in a patient in whom halothane MAC was being measured. The availability of the Severinghaus blood gas device allowed for the first ever measurement of the metabolic and respiratory acidemia that accompanies malignant hyperthermia.
Novel Cast-saw Alarm System Reduces Blade-to-Skin Contact in a Pediatric Upper Extremity Model
Authors: Cameron Joshuea , Twedt Max , Garvey Jeff , Scherl Susan , Halanski Matthew A.
Published: February 2022

Purpose:

To determine the effectiveness of a novel cast-saw alarm system in minimizing the number and duration of cast-saw blade-to-skin contacts.

Methods:

Twenty orthopaedic residents removed a pair of long-arm casts applied to instrumented pediatric upper extremity models. The model and cast-saw were instrumented to detect blade to “skin” contact at a rate of 600 Hz. Each resident performed cast removal with and without the use of a cast-saw alarm, the order of which was randomized. Eleven additional “new” cast-saw users then removed pairs of casts, without and then with the cast alarm, to evaluate what effect the alarm would have on preventing blade-to-skin contact in users with no previous cast-saw experience. The number and duration of cast-saw touches were then evaluated. Statistical significance was determined paired 1-sided students t tests (number of touches).

Results:

For the residents (n=20), the total number of blade-to-skin contacts was 233. One hundred eighty-one blade-to-skin contacts without the alarm and 52 with the alarm (71% reduction) (t
(19)=−3.42, P=0.001), averaging 6.45 more blade-to-skin contacts per cast without the alarm. The median blade-to-skin contact duration was 0.166 seconds without the alarm and 0.087 seconds with the alarm. This was a 48% reduction in contact time (P=0.073). For the inexperienced users (n=11), the total number of blade-to-skin contacts was 356, 324 blade-to-skin contacts without the alarm and 32 with the alarm (90% reduction) (t
(10)=−2.78, P=0.009), averaging 26.5 more blade-to-skin contacts without the alarm. The median blade-to-skin contact duration for the novice was 0.313 seconds without the alarm and 0.1 seconds with the alarm (68% reduction). Contact time was reduced in both groups but failed to reach statistical significance. However, alarm use significantly reduced the number of touches of >0.5 seconds duration (62 vs. 3) in the novice group, P=0.0176. Blade-to-skin contact of >0.5 seconds were felt to represent touches that were more likely to result in thermal injury to a living patient.

Conclusion:

Blade-to-skin contact can be reduced with the use of a cast-saw alarm. These effects appear most amplified in users with little prior cast-saw experience.

Level of Evidence:

Not applicable.
Acquired von Willebrand Syndrome and Desmopressin Resistance During Venovenous Extracorporeal Membrane Oxygenation in Patients With COVID-19: A Prospective Observational Study
Authors: Kalbhenn Johannes , Glonnegger Hannah , Büchsel Martin , Priebe Hans-Joachim , Zieger Barbara
Published: February 2022

OBJECTIVES:

Although COVID-19 is associated with high von Willebrand factor (vWF) parameters promoting thrombosis, venovenous extracorporeal membrane oxygenation (vvECMO) is associated with the development of acquired von Willebrand syndrome (AVWS) promoting bleeding. This study was designed to assess both the incidence and severity of AVWS in COVID-19 patients undergoing vvECMO, and the benefit of comprehensive vWF analyses.

DESIGN:

Prospective observational study.

SETTING:

ICU at a tertiary-care center.

PATIENTS:

Twenty-seven consecutive COVID-19 patients with acute respiratory distress syndrome (ARDS) requiring vvECMO.

MEASUREMENTS AND MAIN RESULTS:

Comprehensive vWF analyses (including sodium dodecyl-sulfate polyacrylamide gel electrophoresis) were performed before, during, and after vvECMO. In a subgroup of 12 patients with AVWS, effectiveness of treatment with desmopressin was assessed. The patients’ mean age was 53 years (range, 23–73), 70% were male, and all had various comorbidities. Following markedly elevated vwf antigen (vWF: Ag; mean, 546% (sd, 282]), vWF collagen binding capacity (mean, 469% [sd, 271]), vWF activity (vWF:A; mean, 383% [sd, 132]), and factor VIII activity (mean, 302% [sd, 106]), and only borderline decreases in high-molecular-weight (HMW) vWF multimers before vvECMO, all of these variables decreased and HMW vWF multimers became undetectable within hours following initiation of vvECMO. All variables fully recovered within 3–38 hours after discontinuation of vvECMO. During vvECMO, decreases in the vWF:A/vWF:Ag ratio correlated with absent HMW vWF multimers. Desmopressin did not affect vWF parameters.

CONCLUSIONS:

In patients with COVID-19-associated ARDS, AVWS developed soon after initiation of vvECMO. The vWF:A/vWF:Ag ratio was a suitable screening test for AVWS. As desmopressin was ineffective, bleeding during vvECMO-associated AVWS should preferably be treated with concentrates containing vWF.
What Matters to Whom: Patient and Public Involvement in Research
Authors: GIBBINS KAREN J. , LO JAMIE O.
Published: February 2022

We outline a call to action for reproductive health researchers to include patient and public involvement (PPI) in research. PPI prioritizes the patient perspective from study design through dissemination of results which centers the people research intends to serve. PPI highlights the patient as an expert in their own condition. PPI that includes groups harmed by health care disparities can draw attention to these harms and generate novel approaches to address them. Numerous frameworks exist for the use of PPI in research. Because obstetrics and gynecology conditions can be particularly sensitive, PPI is crucial in our field.
The Effect of Care Pathways on Coronary Care Nurses: A Preliminary Study
Authors: Daghash Hanan , Abdullah Khatijah Lim , Ismail Muhammad Dzafir
Published: February 2022

Background and Objectives:

A care pathway is a structured care plan based on best clinical practice for a particular patient group. It reorganizes a complex process by providing structured, standardized care and supportive multidisciplinary teamwork. Although care pathways are used worldwide, the impact and benefit of a care pathway for coronary care practices have been minimally debated. This preliminary study aimed to examine the effect of a care pathway on the autonomy, teamwork, and burnout levels among coronary care nurses in a tertiary hospital.

Methods:

A preliminary study was conducted using a pre/posttest one-group quasi-experimental design. A self-administered questionnaire was provided to 37 registered nurses from the cardiac ward of a tertiary hospital. The care pathway was developed on the basis of the current literature, local guidelines, and expert panel advice. The autonomy, teamwork, and burnout levels at the beginning and 4 months after disseminating the care pathway were measured. Implementing the care pathway included educational sessions, training in using the care pathway, and site visits to monitor nursing practices.

Results:

Most of the respondents were female (94.6%; n = 35), the median age of the respondents was 26.5 years (interquartile range [IQR] = 23-31), and the median length of the clinical experience was 4 years (IQR = 2-8). A statistically significant reduction in the mean burnout score was observed (mean of 58.12 vs 52.69, P < .05). A slight improvement in autonomy level was found, although it was not statistically significant. No statistically significant improvement was found in the teamwork levels.

Conclusion:

The care pathway was associated with reduced nurse burnout. The results showed a slight improvement in autonomy level among coronary care nurses after implementing the care pathway. From a practical viewpoint, the current study can help policy makers and managers reduce burnout. This study highlights the importance of using care pathways as a tool to reorganize the care process and improve the working environment. Managers must support nursing decisions and provide continuous education to enhance nurses' autonomy, which may increase understanding of respective roles, leading to higher levels of teamwork. However, with a small sample size, caution must be applied, as the findings might not be generalizable.
Applying Situational Leadership to Redeployment Duties During COVID-19: Lessons Learned
Authors: Nonaillada Jeannine , Martin Rob Armstrong
Published: February 2022

Background and Objectives:

In March 2020, the coronavirus disease-2019 (COVID-19) pandemic caused many disruptions to usual operations and demands in excess of normal capacity at NYU Langone Hospital Long Island and NYU Long Island School of Medicine. Significant increases in volume of critically ill patients necessitated hospital administrators to redeploy faculty physicians and other staff to support other areas as a way of exercising option value. This commentary describes our experiences as 2 medical school deans and teaching professors where we recently applied the model of situational leadership during our redeployment as unit clerks on newly-created COVID patient care units at the height of the COVID-19 pandemic in our local area. Our experience yielded personal feelings of accomplishment and allowed us to exercise nonlinear thinking, which we believe contributed to greater staff operational efficiency, using principles of situational leadership during these hospital redeployment initiatives.

Key Takeaways:

Situational leadership is an effective management model for hospital academic leaders who are not routinely in clinical operations to initiate in emergency conditions when unprecedented working scenarios and feelings of staff uncertainty are occurring, while option value is being exercised with faculty/staff redeployment. Our experience led to increased self-actualization. We provide recommendations to health care administrators on how to better prepare for future faculty/staff redeployments in the hospital.
Addressing Maternal Depression Through Home Visiting: One State's Experience With a Breakthrough Series Collaborative
Authors: Fifolt Matthew , Johnson Heather H. , Preskitt Julie , Enlow Margaret , Tullier Dianna , Arbour MaryCatherine
Published: February 2022

Background and Objectives:

From 2013 to 2017, a national Breakthrough Series (BTS) collaborative in Maternal, Infant, and Early Childhood Home Visiting programs developed a toolkit that led to improvements in maternal depression outcomes. In 2018, Alabama's home visiting program (First Teacher) aimed to reproduce these impacts with a state-led BTS that enrolled 8 local implementing agencies (LIAs) serving more than 500 families.

Methods:

LIAs tested changes in practices using Plan-Do-Study-Act cycles and tracked data regarding depression screening, referrals, service access, and symptom improvement via run charts. First Teacher administered a post-collaborative survey to assess LIA team members' satisfaction with their BTS experience.

Results:

Alabama's BTS resulted in positive shifts in maternal depression referrals, service access, and symptom improvement. Change ideas that supported these shifts included the use of a screening script, motivational interviewing, “Mothers and Babies,” and a registry. LIAs noted that BTS tools and resources helped build capacity to address the difficult and frequently stigmatized topic of maternal depression.

Conclusion:

Findings from this study indicate that evidence- and experience-based practices regarding maternal depression screening, referrals, and service access can lead to symptom improvement among mothers enrolled in a state-based home visiting program. Results of this investigation corroborate findings from previous studies while also incorporating feedback from LIAs about the BTS experience.
Optimizing Aesthetics in Reconstructive Breast Surgery Using Muscle-Sparing Latissimus Dorsi Flap in Radiated and Nonradiated Patients
Authors: Gal Shaili , Movassaghi Kiya
Published: February 2022

Background

The latissimus dorsi musculocutaneous flap (LDMF) has been a workhorse for breast reconstruction. Its high rate of donor-site morbidity has led to the advent of the muscle-sparing latissimus dorsi flap (MSLDF). However, there are very limited reports using the MSLDF in irradiated patients. Prior studies of MSLDF have either precluded previously radiated patients from receiving MSLDF or have included them as part of their larger MSLSDF cohort without specifically analyzing their outcome as a separate group or comparing them to the traditional LDMF group.

Objective

We describe the technique and outcome of MSLDF in both radiated and nonradiated patients and compare the outcome to our LDMF patients.

Methods

A retrospective chart review of patients undergoing breast reconstruction between 2003 and 2020 using either a pedicled MSLDF or LDMF with a transverse skin paddle was conducted. All patients underwent a 2-stage reconstruction with the flap and tissue expander placement done during the first stage, and replacement with implant and, if needed, fat grafting to enhance soft tissue during the second stage. Complications, subjective functional morbidity, and aesthetic outcomes were reviewed.

Results

A total of 35 MSLDFs and 40 LDMFs were performed: 24 MSLDFs (69%) and 25 LDMFs (63%) were inset into a previously irradiated field. There were 2 cases of infection requiring explantation in both MSLDF (8.3%) and LDMF (8.0%) radiated cohorts. There were no cases of donor-site seroma in the MSLDF cohorts versus 12 (30%) in the LDMF cohorts. Minor distal tip superficial epidermolysis was seen in 5 MSLDFs (14.3%), 3 of which were in the radiated cohort, and in 1 LDMF (2.5%) radiated cohort with no cases of flap loss. Functional and aesthetic outcomes were satisfactory. Four patients who had a unilateral MSLDF had a completion upper back lift.

Conclusions

This is the largest series to date demonstrating the use of the MSLDF in both nonradiated and radiated patients and comparing it to a standard LDMF for breast reconstruction by the same surgeon. The pedicled MSLDF is a versatile option for breast reconstruction in radiated patients, and radiation should not be considered a contraindication for its use.
A Comparison Between Immediate and Babysitter Deep Inferior Epigastric Perforator Flap Breast Reconstruction in Postoperative Outcomes
Authors: Huang Hao , Chadab Tara M. , Wang Marcos Lu , Norman Sofya , Cohen Leslie E. , Otterburn David M.
Published: February 2022

Background

Delayed-immediate, or “babysitter,” deep inferior epigastric perforator (DIEP) flap reconstruction, defined as immediate tissue expander or implant placement at the time of mastectomy followed by eventual exchange for DIEP flap, is becoming increasingly popular in breast cancer patients anticipated to receive adjuvant radiotherapy. In this study, we aim to compare delayed-immediate to immediate DIEP flap patients in postoperative outcomes including major complications and surgical site morbidity.

Methods

A retrospective cohort study between immediate and delayed-immediate DIEP flap patients was performed. Patient demographics, comorbidities, and preoperative cancer treatment were compared between the 2 cohorts. Clinical outcomes of interest included dehiscence, necrosis, and infection of the breast, abdomen, and umbilicus in the 90-day postoperative period as well as breast hematoma, anastomotic failure, flap loss, and venous thromboembolism.

Results

Of the 248 patients (443 breasts) included in this study, 193 women (344 breasts) and 55 women (99 breasts) were in the immediate and delayed-immediate cohorts, respectively. The 2 cohorts were comparable in age, body mass index, and comorbidities (P > 0.05). Despite significantly higher rates of preoperative cancer treatment (P < 0.05), delayed-immediate patients were not at an elevated risk for major complications. The 2 cohorts were also comparable in surgical site outcomes, with the exception of breast skin necrosis, which was significantly higher in incidence in the immediate cohort (16.0% vs 2.0%, P < 0.001).

Conclusions

This study is the first to directly compare delayed-immediate to immediate DIEP flap reconstruction in postoperative outcomes. Our findings show that babysitter DIEP flaps are a safe option for patients, even in those expected to undergo breast irradiation preoperatively.
A Critical Assessment of the Transgender Health Care Workforce in the United States and the Capacity to Deliver Gender-Affirming Bottom Surgery
Authors: Kang Christine O. , Kim Erin , Cuccolo Nicholas , Dagi Alexander , Luther Lauren , Veeramani Anamika , Boskey Elizabeth R. , Lee Bernard , Taghinia Amir H. , Ganor Oren
Published: February 2022

Background

Gender-affirming surgery is a critical component of transgender health care, but access information is limited. The study aim was to assess workforce capacity to perform gender affirming bottom surgeries (GABSs) in the United States.

Methods

A questionnaire was administered via email, phone call, or fax from February to May 2020 to 86 practices identified as performing GABS by searching 10 Web-based databases with standardized keywords. Questions assessed training capacity, surgical capacity, and surgeon experience.

Results

Thirty-two of 86 practices responded, 20 met the inclusion criteria. Practices were identified in 15 states, with an average 2.4 (SD, 1.3) surgeons performing GABS per year. States with the greatest number of total providers offering GABS were Illinois (n = 21), Texas (n = 10), and Massachusetts (n = 13). No significant correlation between number of GABS types offered and geographic population density (r = −0.40, P = 0.08), or between number of providers and geographic population density (r = 0.19, P = 0.44). Vaginoplasty was most frequently performed, with the longest waitlists and highest number of waitlist additions per month. Phalloplasty was the second most common procedure, and waitlist additions per month exceeded provider capacity to perform the procedure. Most surgeons performing GABS were plastic surgeons and urologists, whereas obstetricians/gynecologists performed the majority of hysterectomies.

Conclusions

This study demonstrated a shortage of providers with requisite training and experience to provide GABS. Although more robust studies are needed to better characterize the relationship between the number of patients seeking GABS and available providers, these findings indicate a need for improved training.
Professionalism of Admitting and Consulting Services and Trauma Patient Outcomes
Authors: Cooper William O. , Hickson Gerald B. , Guillamondegui Oscar D. , Cannon Jeremy W , Charles Anthony G. , Hoth J. Jason , Alam Hasan B. , Tillou Areti , Luchette Frederick A. , Skeete Dionne A. , Domenico Henry J. , Meredith J. Wayne , Brennan Theresa M. H. , Smith Brian P , Kelz Rachel R. , Biesterveld Ben E. , Busuttil Ashley , Jopling Jeffrey K. , Hopkins Joseph R. , Emory Cynthia L. , Sullivan Patricia G. , Martin R. Shayn , Howerton Russell M. , Cryer Henry M. , Davidson Heather A. , Gonzalez Richard P. , Spain David A.
Published: February 2022

Objective:

To determine whether trauma patients managed by an admitting or consulting service with a high proportion of physicians exhibiting patterns of unprofessional behaviors are at greater risk of complications or death.

Summary Background Data:

Trauma care requires high-functioning interdisciplinary teams where professionalism, particularly modeling respect and communicating effectively, is essential.

Methods:

This retrospective cohort study used data from 9 level I trauma centers that participated in a national trauma registry linked with data from a national database of unsolicited patient complaints. The cohort included trauma patients admitted January 1, 2012 through December 31, 2017. The exposure of interest was care by 1 or more high-risk services, defined as teams with a greater proportion of physicians with high numbers of patient complaints. The study outcome was death or complications within 30 days.

Results:

Among the 71,046 patients in the cohort, 9553 (13.4%) experienced the primary outcome of complications or death, including 1875 of 16,107 patients (11.6%) with 0 high-risk services, 3788 of 28,085 patients (13.5%) with 1 high-risk service, and 3890 of 26,854 patients (14.5%) with 2+ highrisk services (P < 0.001). In logistic regression models adjusting for relevant patient, injury, and site characteristics, patients who received care from 1 or more high-risk services were at 24.1% (95% confidence interval 17.2% to 31.3%; P < 0.001) greater risk of experiencing the primary study outcome.

Conclusions:

Trauma patients who received care from at least 1 service with a high proportion of physicians modeling unprofessional behavior were at an increased risk of death or complications.
Comparative genomic analysis of Staphylococcus aureus isolates associated with either bovine intramammary infections or human infections demonstrates the importance of restriction-modification systems in host adaptation
Authors: Park Soyoun , Jung Dongyun , O’Brien Bridget , Ruffini Janina , Dussault Forest , Dube-Duquette Alexis , Demontier Élodie , Lucier Jean-François , Malouin François , Dufour Simon , Ronholm Jennifer
Published: February 2022

Staphylococcus aureus

is a major etiological agent of clinical and subclinical bovine mastitis. The versatile and adaptative evolutionary strategies of this bacterium have challenged mastitis control and prevention globally, and the high incidence of

S. aureus

mastitis increases concerns about antimicrobial resistance (AMR) and zoonosis. This study aims to describe the evolutionary relationship between bovine intramammary infection (IMI)-associated

S. aureus

and human pathogenic

S. aureus

and further elucidate the specific genetic composition that leads to the emergence of successful bovine IMI-associated

S. aureus

lineages. We performed a phylogenomic analysis of 187 

S

.

aureus

isolates that originated from either dairy cattle or humans. Our results revealed that bovine IMI-associated

S. aureus

isolates showed distinct clades compared to human-originated

S. aureus

isolates. From a pan-genome analysis, 2070 core genes were identified. Host-specific genes and clonal complex (CC)-specific genes were also identified in bovine

S. aureus

isolates, mostly located in mobile genetic elements (MGEs). Additionally, the genome sequences of three apparent human-adapted isolates (two from CC97 and one from CC8), isolated from bovine mastitis samples, may provide an snapshot of the genomic characteristics in early host spillover events. Virulence and AMR genes were not conserved among bovine IMI-associated

S. aureus

isolates. Restriction-modification (R-M) genes in bovine IMI-associated

S. aureus

demonstrated that the Type I R-M system was lineage-specific and Type II R-M system was sequence type (ST)-specific. The distribution of exclusive, virulence, and AMR genes were closely correlated with the presence of R-M systems in

S. aureus

, suggesting that R-M systems may contribute to shaping clonal diversification by providing a genetic barrier to the horizontal gene transfer (HGT). Our findings indicate that the CC or ST lineage-specific R-M systems may limit genetic exchange between bovine-adapted

S. aureus

isolates from different lineages.
Clinical and Non-clinical Proof of Concept Supporting the Development of RJX As an Adjunct to Standard of Care Against Severe COVID-19
Authors: Uckun Fatih M. , Saeed Muhammad , Awili Mustafa , Ozercan Ibrahim H. , Qazi Sanjive , Lee Cynthia , Shibli Adeel , Skolnick Alan W. , Prusmack Alonso , Varon Joseph , Barrera Cesar I.P. , Orhan Cemal , Volk Michael , Sahin Kazim
Published: February 2022

Background

The identification of effective strategies capable of reducing the case mortality rate of high-risk COVID-19 is an urgent and unmet medical need. We recently reported the clinical safety profile of RJX, a well-defined intravenous GMP-grade pharmaceutical formulation of anti-oxidant and anti-inflammatory vitamins as active ingredients, in a Phase 1 study in healthy volunteers (ClinicalTrials.govIdentifier:NCT03680105) (Uckun et al., Front. Pharmacol. 11, 594321. 10.3389/fphar.2020.594321). Here we report data from a pilot clinical study (RPI-015) which examined the safety, tolerability, and feasibility of using RJX in combination with clinical standard of care (SOC) in hospitalized COVID-19 patients with pneumonia (ClinicalTrials.govIdentifier:NCT04708340). In addition to our early clinical proof of concept (POC) data, we also present non-clinical POC from a mouse model of CRS and ARDS that informed the design of the reported clinical study.

Methods

13 patients, who were hospitalized with COVID-19 pneumonia and abnormally elevated serum inflammatory biomarkers markers ≥3 months prior to the identification of the first confirmed U.S case of the Omicron variant, were treated with IV RJX (daily x 7 days) plus SOC. Non-clinical POC study examined the ability of RJX plus dexamethasone (DEX) to improve the survival outcome in the lipopolysaccharide (LPS)-Galactosamine (GalN) mouse model of fatal cytokine release syndrome (CRS), sepsis and acute respiratory distress syndrome (ARDS).

Findings

In the Phase 1 clinical study, none of the 13 patients developed a treatment-related DLT, SAE, or Grade 3-5 AEs. Nine (9) of the 12 evaluable patients, including 3 patients with hypoxemic respiratory failure, showed rapid clinical recovery. In the non-clinical POC study in LPS-GalN challenged mice, the combination of RJX plus DEX was more effective than RJX alone or DEX alone, reversed the CRS as well as inflammatory tissue damage in the lungs and liver, and improved the survival outcome. Taken together, these findings provide the early clinical and non-clinical POC for the development of RJX as an adjunct to the SOC in the multi-modality management of high-risk COVID-19.
TheAmidellaclade in Europe (AmanitaPers.,Basidiomycota:Amanitaceae): clarification of the contentiousAmanita valensand the importance of taxon-specific PCR primers for identification
Authors: Arraiano-Castilho Ricardo , Silva Ana Cristina , Vila-Viçosa Carlos , Castro Mário Rui , Morgado Luís Neves , Oliveira Paulo
Published: February 2022

The species in genusAmanitasectionAmidellaform a well-defined clade, but some taxa remain difficult to discriminate. In particular, the concept ofAmanita valens(E.-J. Gilbert) Bertault remains controversial. To understand the phylogenetic placement of a set of collections from South Portugal with a novel nrDNA barcode, we have obtained nrDNA sequences for previously unassessed type collections. The taxon formerly described asAmanita curtipesf.pseudovalensNeville & Poumarat is interpreted as a separate species,Amanita pseudovalens(Neville & Poumarat) Arraiano-Castilhoet al. comb. et stat. nov., and is genetically indistinct from the Portuguese collections, thus clarifying their taxonomic context. However, our collections are morphologically and ecologically distinct (respectively, ellipsoid to oblong basidiospores and association withCistuson acidic schist soils), and are proposed as a new variety,Amanita pseudovalensvar.tartessianaArraiano-Castilhoet al.. These developments also enable a better diagnosis ofAmidellataxa in Europe, a progress that is most decisive for the late Winter to Spring season collections, and identification keys are proposed. However, the co-occurrence and morphological similarity of the new variety, in comparison with the prized edibleAmanita ponderosaMalençon & Heim, could leave some collections of either taxa unresolved. Thus, a molecular marker approach was developed, to provide a clear and cost-effective identification aid to complement the keys. The proposed diagnostic tools can be applied toward a review of EuropeanAmidellataxa chorology from existing records, conserved materials, and future collections. Evolutionary convergence may contribute to the determination difficulties in theAmidellaclade.
Rock inhibitors target SRSF2 leukemia by disrupting cell mitosis and nuclear morphology
Authors: Su M , Fleisher T , Grosheva I , Bokstad Horev M , Olszewska M , Barr H , Plotnikov A , Carvalho S , Moskovich Y , Minden MD , Chapal-Ilani N , Papapetrou EP , Dezorella N , Cheng T , Kaushansky N , Geiger B , Shlush LI
Published: February 2022

Spliceosome machinery mutations are common early mutations in myeloid malignancies, however effective targeted therapies against them are still lacking. In the current study, we used an in vitro high-throughput drug screen among four different isogenic cell lines and identified ROCK inhibitors (ROCKi) as selective inhibitors of SRSF2 mutants. ROCKi targeted SRSF2 Mut primary human samples in a xenografts model and were not toxic to mice nor human cells. ROCKi induced mitotic catastrophe through their apparent effects on microtubules and nuclear organization. Transmission electron microscopy revealed that SRSF2 mutations induce deep nuclear indentation and segmentation, driven by microtubule-rich cytoplasmic intrusions, which were exacerbated by ROCKi. The severe nuclear deformation driven by the combination of SRSF2 Mut and ROCKi prevent cells from completing mitosis. These findings shed light on new ways to target SRSF2 and on the role of the microtubule system in SRSF2 Mut cells.
Spatial patterns of biomass change across Finland in 2009–2015
Authors: Haakana Markus , Tuominen Sakari , Heikkinen Juha , Peltoniemi Mikko , Lehtonen Aleksi
Published: February 2022

Forest characteristics vary largely at the regional level and in smaller geographic areas in Finland. The amount of greenhouse gas emissions is related to changes in biomass and the soil type (e.g. upland soils vs. peatlands). Spatially accurate map data of forests and biomass changes could improve the ability to suggest optimal management alternatives for any patch of land, e.g. in terms of climate change mitigation. In our study, estimating and explaining spatial patterns of biomass change across Finland was the main interest. We analysed biomass changes on different soil and site types on forested land using the Finnish Multi-Source National Forest Inventory (MS-NFI) map layers of the 2009 and 2015 datasets. Silvicultural management and treatment units larger than individual pixels were created by automatic segmentation of the thematic maps. The segmented MS-NFI biomass maps of growing stocks, including above and below ground biomass resulted an average estimate of 77.7 tons ha-1 compared to the national forest inventory estimate of 76.5 tons ha-1 in 2015 for Finland. Forest soil type had a similar effect on average biomass in segmented MS-NFI and NFI data. Despite good regional and country-level results, at the segment level the biomass distributions were narrowed and averaging of biomass estimates was observed. Hence, biomass changes on segments can be considered only approximate values; also, those small differences in average biomass may accumulate when map layers from more than one time point are compared. MS-NFI classification results depend on the satellite images and field data used, causing variation in successive inventories. In addition, to avoid false biomass change observations due to the low growth rate of boreal forests, a six-year study period was set. A kappa of 0.44 was achieved for precision when comparing undisturbed and disturbed forest stands in the Global Forest Cover layer and MS-NFI segmented map, indicating the low ability of the global forest map to identify land cover changes for Finland. The segmented biomass maps provide a useful tool for forest owners to analyse carbon stock changes in their forests and how to affect the amount of carbon by forest management.
Global hypo-methylation in a subgroup of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape
Authors: Boot James R , Rosser Gabriel , Kancheva Daliya , Vinel Claire , Lim Yau Mun , Pomella Nicola , Zhang Xinyu , Guglielmi Loredana , Sheer Denise , Barnes Michael R. , Brandner Sebastian , Nelander Sven , Movahedi Kiavash , Marino Silvia
Published: February 2022

We describe a new molecular subgroup of glioblastoma, the most prevalent malignant adult brain tumour, harbouring a bias towards hypomethylation at defined differentially methylated regions. This epigenetic signature correlates with an enrichment for an astrocytic gene signature, which together with the identification of enriched predicted binding sites of transcription factors known to cause demethylation and to be involved in astrocytic/glial lineage specification, point to a shared ontogeny between this glioblastoma subgroup and astroglial progenitors. At functional level, increased invasiveness, at least in part mediated by SRPX2, and macrophage infiltration characterise this glioblastoma subgroup.
Fibrosis resolution in the mouse liver: role of Mmp12 and potential role of Calpain 1/2
Authors: Sato Toshifumi , Head Kimberly Z. , Li Jiang , Dolin Christine E. , Wilkey Daniel , Skirtich Nolan , McCreary Dylan D. , Liu Sylvia , Beier Juliane I , McEnaney Ryan M. , Merchant Michael L , Arteel Gavin E
Published: February 2022

Although most work has focused on resolution of collagen ECM, fibrosis resolution involves changes to several ECM proteins. The purpose of the current study was two-fold: 1) to examine the role of MMP12 and elastin; and 2) to investigate the changes in degraded proteins in plasma (i.e., the “degradome”) in a preclinical model of fibrosis resolution. Fibrosis was induced by 4 weeks carbon tetrachloride (CCl4) exposure, and recovery was monitored for an additional 4 weeks. Some mice were treated with daily MMP12 inhibitor (MMP408) during the resolution phase. Liver injury and fibrosis was monitored by clinical chemistry, histology and gene expression. The release of degraded ECM peptides in the plasma was analyzed using by 1D-LC-MS/MS, coupled with PEAKS Studio (v10) peptide identification. Hepatic fibrosis and liver injury rapidly resolved in this mouse model. However, some collagen fibrils were still present 28d after cessation of CCl4. Despite this persistent collagen presence, expression of canonical markers of fibrosis were also normalized. The inhibition of MMP12 dramatically delayed fibrosis resolution under these conditions. LC-MS/MS analysis identified that several proteins were being degraded even at late stages of fibrosis resolution. Calpains 1/2 were identified as potential new proteases involved in fibrosis resolution. CONCLUSION. The results of this study indicate that remodeling of the liver during recovery from fibrosis is a complex and highly coordinated process that extends well beyond the degradation of the collagenous scar. These results also indicate that analysis of the plasma degradome may yield new insight into the mechanisms of fibrosis recovery, and by extension, new “theragnostic” targets. Lastly, a novel potential role for calpain activation in the degradation and turnover of proteins was identified.
Antisense oligonucleotide-mediated perturbation of long non-coding RNA reveals functional features in stem cells and across cell types
Authors: Yip Chi Wai , Hon Chung-Chau , Yasuzawa Kayoko , Sivaraman Divya M. , Ramilowski Jordan A. , Shibayama Youtaro , Agrawal Saumya , Prabhu Anika V. , Parr Callum , Severin Jessica , Lan Yan Jun , Dostie Josée , Petri Andreas , Nishiyori-Sueki Hiromi , Tagami Michihira , Itoh Masayoshi , López-Redondo Fernando , Kouno Tsukasa , Chang Jen-Chien , Luginbühl Joachim , Kato Masaki , Murata Mitsuyoshi , Yip Wing Hin , Shu Xufeng , Abugessaisa Imad , Hasegawa Akira , Suzuki Harukazu , Kauppinen Sakari , Yagi Ken , Okazaki Yasushi , Kasukawa Takeya , de Hoon Michiel , Carninci Piero , Shin Jay W.
Published: February 2022

Within the scope of FANTOM6 consortium, we perform a large-scale knockdown of 200 long non-coding RNAs (lncRNAs) in human induced pluripotent stem (iPS) cells, and systematically characterize their roles in self-renewal and pluripotency. We find 36 lncRNAs (18%) exhibiting cell growth inhibition From the knockdown of 123 lncRNAs with transcriptome profiling, 36 lncRNAs (29.3%) show molecular phenotypes. Integrating the molecular phenotypes with chromatin-interaction assays further revealscis- andtrans-interacting partners as potential primary targets. Additionally, cell type enrichment analysis identifies lncRNAs associated with pluripotency while the knockdown ofLINC02595,CATG00000090305.1andRP11-148B6.2modulates colony formation of iPS cells. We compare our results with previously published fibroblasts phenotyping data and find that 2.9% of the lncRNAs exhibit consistent cell growth phenotype, whereas we observe 58.3% agreement in molecular phenotypes. This highlights molecular phenotyping is more comprehensive in revealing affected pathways.
Proteomic analysis of the actin cortex in interphase and mitosis
Authors: Vadnjal Neža , Nourreddine Sami , Lavoie Geneviève , Serres Murielle , Roux Philippe P. , Paluch Ewa K.
Published: February 2022

In animal cells, many shape changes are driven by gradients in the contractile tension of the actomyosin cortex, a thin cytoskeletal network that supports the plasma membrane. Elucidating how cortical tension is controlled is thus essential for understanding cell and tissue morphogenesis. Increasing evidence shows that alongside myosin II activity, actin network organisation and composition are key to cortex tension regulation. However, how cortex composition changes when cortical tension changes remains poorly understood. Here, we compared cortices from cells in interphase and in mitosis, as mitosis entry is associated with a strong increase in cortical tension. We purified cortex-enriched cellular fractions and analysed their composition using mass spectrometry, identifying 922 proteins consistently represented in both interphase and mitotic cortices. We curated this dataset by focusing on actin-related proteins, narrowing down to 238 candidate regulators of the cortex during the mitotic cortical tension increase. Among these candidates, our analysis pointed to a role for septins, and in particular septin 9, in the control of mitotic cell rounding. Overall, our study brings insight into the regulation of mitotic rounding, and paves the way for systematic investigations of the regulation of cell surface mechanics.
Contribution of the Wolffian duct mesenchyme to the formation of the female reproductive tract
Authors: Zhao Fei , Grimm Sara A , Jia Shua , Yao Humphrey Hung-Chang
Published: February 2022

The female reproductive tract develops from its embryonic precursor, the Müllerian duct.

In close proximity to the Müllerian duct lies the precursor for the male reproductive tract, the Wolffian duct, which is eliminated in the female embryo during sexual differentiation. We discovered that a component of the Wolffian duct, its mesenchyme, is not eliminated after sexual differentiation. Instead, the Wolffian duct mesenchyme underwent changes in transcriptome and chromatin accessibility from male tract to female tract identity, and became a unique mesenchymal population in the female reproductive tract with localization and transcriptome distinct from the mesenchyme derived from the Müllerian duct. Partial ablation of the Wolffian duct mesenchyme stunted the growth of the fetal female reproductive tract. These findings reveal a new fetal origin of mesenchymal tissues for female reproductive tract formation and reshape our understanding of sexual differentiation of reproductive tracts.

Significance statement

A female embryo initially possesses both the primitive female and male reproductive tracts, also known as the Müllerian and Wolffian duct. During sexual differentiation, the female eliminates the Wolffian duct and maintains the Müllerian duct that eventually differentiates into the female reproductive tract organs. However, in this paper, we show the female embryo retains mesenchymal cells surrounding the Wolffian duct for its reproductive tract formation. When incorporated into the female reproductive tract organs, the Wolffian duct mesenchyme shows unique anatomical localization and transcriptome and plays critical roles in female reproductive tract growth. This discovery provides new insights into female reproductive tract development and advances our understanding of sexual differentiation of reproductive tracts.
Predicted structure of the hepatitis B virus polymerase reveals an ancient conserved protein fold
Authors: Tajwar Razia , Bradley Daniel P. , Ponzar Nathan L. , Tavis John E.
Published: February 2022

Hepatitis B virus (HBV) replicates by protein-primed reverse transcription. It chronically infects >250 million people, and the dominant anti-HBV drugs are nucleos(t)ide analogs targeting the viral polymerase (P). P has four domains, the terminal protein (TP) that primes DNA synthesis, a spacer, the reverse transcriptase (RT), and the ribonuclease H (RNaseH). Despite being a major drug target and catalyzing a reverse transcription pathway very different from the retroviral pathway, HBV P has resisted structural analysis for decades. Here, we exploited advances in protein structure prediction to model the structure of P. The predicted HBV RT and RNaseH domains aligned to the HIV RT-RNaseH at 3.75 Å RMSD, had a nucleic acid binding groove spanning the two active sites, had DNA polymerase active site motifs in their expected positions, and accommodated two Mg++ ions in both active sites. Surprisingly, the TP domain wrapped around the RT domain, with the priming tyrosine poised over the RT active site. This model was validated using published mutational analyses, and by docking RT and RNaseH inhibitors, RNA:DNA heteroduplexes, and the HBV ε RNA stem-loop that templates DNA priming into the model. The HBV P fold, including the orientation of the TP domain, was conserved among hepadnaviruses from rodents to fish and in P from a fish nackednavirus, but not in other non-retroviral RTs. Therefore, this protein fold has persisted since the hepadnaviruses diverged from nackednaviruses >400 million years ago. This model will guide drug development and mechanistic studies into P’s function.

Significance

The hepatitis B virus (HBV) polymerase (P) catalyzes an unusual reverse transcription pathway and is a major drug target. However, P’s insolubility and instability have long prevented its structural analyses. This work predicts the structure of P proteins from human to fish viruses, revealing an unanticipated conserved protein fold that is at least 400 million years old. The HBV P model was validated by mechanistically interpreting mutations with strong phenotypes and by computationally docking nucleic acids to P and inhibitors into both of its active sites. The model will advance mechanistic studies into the function of P and enable drug discovery against targets on P other than the reverse transcriptase and ribonuclease H active sites.
Accessibility and Disability Inclusion Among Top-Funded U.S. Undergraduate Institutions
Authors: Campanile Jessica , Cerilli Caroline , Varadaraj Varshini , Sweeney Fiona , Smith Jared , Zhu Jiafeng , Yenokyan Gayane , Swenor Bonnielin K.
Published: February 2022

Background

There is limited data to assess, track, or quantify accessibility and disability inclusion across universities.

Objective

This study assessed disability inclusion and accessibility at the top 50 National Institutes of Health (NIH)-funded undergraduate programs in the United States. We hypothesized that there is no association between NIH funding and the University Disability Inclusion Score

Methods

A novel tool, the University Disability Inclusion Score assessed disability inclusion and accessibility using 10 indicators spanning 4 categories: (1) accessibility of built and virtual environment, (2) public image of disability inclusion, (3) accommodations processes and procedures, and (4) grievance policy. Based upon the total points (out of a total score of 100), each university was assigned a letter grade (A-F).

Results

Of the top 50 NIH-funded institutions, 6% received an A grade on the Score, while 60% received D or F. The mean scores were 15.2 (SD=5) for accessibility of built and virtual environment (20 points), 10 (SD=3) for public image of disability inclusion (20 points), 30.6 (SD=10) for accommodations processes and procedures (50 points), and 8.1 (SD=3) for grievance policy (10 points).

Conclusions

Our findings suggest room for improvement in disability inclusion and accessibility among top university recipients of NIH funding. To provide an equitable academic experience, universities must prioritize disability inclusion.
COVID-19-related Smell and Taste Impairment with Widespread Diffusion of SARS-CoV-2 Omicron Variant
Authors: Boscolo-Rizzo Paolo , Tirelli Giancarlo , Meloni Pierluigi , Hopkins Claire , Madeddu Giordano , De Vito Andrea , Gardenal Nicoletta , Valentinotti Romina , Tofanelli Margherita , Borsetto Daniele , Lechien Jerome R. , Polesel Jerry , De Riu Giacomo , Vaira Luigi Angelo
Published: February 2022

Background

The aim of this study was to estimate the prevalence of self-reported chemosensory dysfunction in a study cohort of subjects who developed a mild-to-moderate COVID-19 in the period from January 17, 2022 to February 4, 2022 (Omicron proxy period) and compared that with a historical series of patients tested positive for SARS-CoV-2 infection between March and April, 2020 (comparator period).

Methods

Prospective study based on the sinonasal outcome tool 22 (SNOT-22), item “sense of smell or taste” and additional outcomes.

Results

Patients’ characteristics and clinical presentations of COVID-19 were evaluated and compared in 779 patients, 338 of the study cohort and 441 of the historical series. The prevalence of self-reported chemosensory dysfunction during the proxy Omicron period (32.5%; 95% CI, 27.6-37.8) was significantly lower from that during the comparator period (66.9%; 95% CI, 62.3-71.3) (p<.001). 24.6% (95% CI, 20.1-29.5) of patients reported an altered sense of smell during the proxy Omicron period compared to 62.6% (95% CI, 57.9-67.1) during the comparator period (p<.001). Similarly, the prevalence of an altered sense of taste dropped from 57.4% (95% CI, 52.6-62.0) during the comparator period to 26.9% (95% CI, 22.3-32.0) during the proxy Omicron period (p<.001). The severity of chemosensory dysfunction was lower in proxy Omicron period compared to comparator period (p<.001).

Conclusions

The prevalence and the severity of COVID-19 associated smell and taste dysfunction has dropped significantly with the advent of the Omicron variant.