bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Occupational Stressors in Restaurant Work Prior to and During the COVID-19 Pandemic
Authors: Lippert Julia F. , Hofman Nila Ginger , Reyes Teofilo
Published: November 2021

Objective:

This exploratory study investigated occupational stress in restaurant work prior to and during the COVID-19 pandemic.

Methods:

The study was a mixed methods design conducted in two phases with biomarker data for stress, questionnaire data, and semi-structured interviews.

Results:

Results indicated elevated stressors elevated stress during normal shift conditions (P < 0.05), low job satisfaction, an effort to reward imbalance (P < 0.05), and the majority (72%, n = 28) of participants reporting discrimination at least a “few times a year.” Interview data revealed four interrelated occupational stressors including: (1) financial hardships; (2) increased exposure to occupational health risks during the reopening phases; (3) increased workloads due to inadequate staffing and fewer hours; and (4) social and psychological pressures and ill treatment.

Conclusion:

These elements were reported prior to the COVID-19 pandemic and have persisted throughout with heightened impacts.
Inadvertent Arterial Peripherally Inserted Central Catheter Insertion With Corresponding Electrocardiographic Tracings: A Case Report
Authors: DiLoreto Emily , Bahl Amit
Published: November 2021

Electrocardiographic (ECG) tip confirmation is a validated technique to place the distal tip of a peripherally inserted central catheter (PICC) in the distal superior vena cava at or near the cavoatrial junction during point-of-care insertions. This case report discusses an inadvertent arterial PICC placement despite navigation technology demonstrating similar confirmatory ECG changes seen in standard venous insertions. The findings demonstrate that ECG navigation technology should not be used to rule out arterial PICC placement.
The Impact of COVID-19
Authors: Abuatiq Alham , Borchardt Carla
Published: November 2021

OBJECTIVE

The aim of this study was to explore the occupational stress perception of nurses and how they manage it during the COVID-19 pandemic.

BACKGROUND

The management of occupational stress is a key factor in promoting nurses' well-being.

METHODS

A descriptive cross-sectional study was conducted.

RESULTS

The top occupational stressors from the nurses' perspectives (N = 236) as measured by using an updated version of the Nursing Stress Scale (NSS) included wearing a face mask at all times in the hospital, unpredictable staffing and scheduling, not enough staff to adequately cover the unit, feeling helpless in the case a patient fails to improve, and being assigned to a COVID-19 patient. The mean stress score was 31.87. The updated NSS Cronbach's α was 0.92, and the interclass interclass correlation coefficient was 0.914.

CONCLUSION

Nurse administrators are in a strategic position to develop interventions (eg, open door policy, meetings, and employee assistance programs) to assist nurses in effectively managing stress.
Treatment of Vestibular Disorders (Inner Ear Balance Problems): How Does Your Physical Therapist Treat Dizziness Related to Inner Ear Balance Problems?
Authors: Hall Courtney D. , Herdman Susan J. , Whitney Susan L. , Anson Eric R. , Carender Wendy J. , Hoppes Carrie W.
Published: November 2021

Dizziness is very common, but it is never normal. Dizziness can make performing daily activities, work, and walking difficult. Inner ear balance problems can make people dizzy when they turn their head, which can cause problems during walking and make people more likely to fall. Most of the time dizziness is not from a life-threatening disease. Often, dizziness is related to a problem of the vestibular (or inner ear balance) system. Vestibular disorders can be caused by infections in the ear, problems with the immune system, medications that harm the inner ear, and rarely from diabetes or stroke because of a lack of blood flow to the inner ear. Stress, poor sleep, migraine headaches, overdoing some activities, and feeling anxious or sad can increase symptoms of dizziness. Updated guidelines for the treatment of inner ear disorders are published in this issue of the Journal of Neurologic Physical Therapy. The guideline recommends which exercises are best to treat the dizziness and balance problems commonly seen with an inner ear problem.
Outcomes and Their State-level Variation in Patients Undergoing Surgery With Perioperative SARS-CoV-2 Infection in the USA
Authors:   COVIDSurg Collaborative
Published: November 2021

Objective:

To report the 30-day outcomes of patients with perioperative SARS-CoV-2 infection undergoing surgery in the USA.

Background:

Uncertainty regarding the postoperative risks of patients with SARS-CoV-2 exists.

Methods:

As part of the COVIDSurg multicenter study, all patients aged ≥17 years undergoing surgery between January 1 and June 30, 2020 with perioperative SARS-CoV-2 infection in 70 hospitals across 27 states were included. The primary outcomes were 30-day mortality and pulmonary complications. Multivariable analyses (adjusting for demographics, comorbidities, and procedure characteristics) were performed to identify predictors of mortality.

Results:

A total of 1581 patients were included; more than half of them were males (n = 822, 52.0%) and older than 50 years (n = 835, 52.8%). Most procedures (n = 1261, 79.8%) were emergent, and laparotomies (n = 538, 34.1%). The mortality and pulmonary complication rates were 11.0 and 39.5%, respectively. Independent predictors of mortality included age ≥70 years (odds ratio 2.46, 95% confidence interval [1.65–3.69]), male sex (2.26 [1.53–3.35]), ASA grades 3–5 (3.08 [1.60–5.95]), emergent surgery (2.44 [1.31–4.54]), malignancy (2.97 [1.58–5.57]), respiratory comorbidities (2.08 [1.30–3.32]), and higher Revised Cardiac Risk Index (1.20 [1.02–1.41]). While statewide elective cancelation orders were not associated with a lower mortality, a sub-analysis showed it to be associated with lower mortality in those who underwent elective surgery (0.14 [0.03–0.61]).

Conclusions:

Patients with perioperative SARS-CoV-2 infection have a significantly high risk for postoperative complications, especially elderly males. Postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the USA during the pandemic peaks.
Assessment of Duration of Smoking Cessation Prior to Surgical Treatment of Non-small Cell Lung Cancer
Authors: Heiden Brendan T. , Eaton Daniel B. , Chang Su-Hsin , Yan Yan , Schoen Martin W. , Chen Li-Shiun , Smock Nina , Patel Mayank R. , Kreisel Daniel , Nava Ruben G. , Meyers Bryan F. , Kozower Benjamin D. , Puri Varun
Published: November 2021

Objective:

To define the relationship between the duration of smoking cessation and postoperative complications for patients with lung cancer undergoing surgical treatment.

Background:

Smoking increases the risk of postoperative morbidity and mortality in patients with lung cancer undergoing surgical treatment. Although smoking cessation before surgery can mitigate these risks, the ideal duration of preoperative smoking cessation remains unclear.

Methods:

Using a uniquely compiled Veterans Health Administration dataset, we performed a retrospective cohort study of patients with clinical stage I non-small cell lung cancer undergoing surgical treatment between 2006 and 2016. We characterized the relationship between duration of preoperative smoking cessation and risk of postoperative complications or mortality within 30-days using multivariable restricted cubic spline functions.

Results:

The study included a total of 9509 patients, of whom 6168 (64.9%) were smoking at the time of lung cancer diagnosis. Among them, only 662 (10.7%) patients stopped smoking prior to surgery. Longer duration between smoking cessation and surgery was associated with lower odds of major complication or mortality (adjusted odds ratio [aOR] for every additional week, 0.919; 95% confidence interval [CI], 0.850-0.993; P = 0.03). Compared to nonsmokers, patients who quit at least 3 weeks before surgery had similar odds of death or major complication (aOR, 1.005; 95% CI, 0.702–1.437; P = 0.98) whereas those who quit within 3 weeks of surgery had significantly higher odds of death or major complication (aOR, 1.698; 95% CI, 1.203–2.396; P = 0.003).

Conclusion:

Smoking cessation at least 3 weeks prior to the surgical treatment of lung cancer is associated with reduced morbidity and mortality. Providers should aggressively encourage smoking cessation in the preoperative period, since it can disproportionately impact outcomes in early-stage lung cancer.
Life over limb: Arterial access-related limb ischemic complications in 48-hour REBOA survivors
Authors: Laverty Robert B. , Treffalls Rebecca N. , McEntire Shane E. , DuBose Joseph J. , Morrison Jonathon J. , Scalea Thomas M. , Moore Laura J. , Podbielski Jeanette M. , Inaba Kenji , Piccinini Alice , Kauvar David S.
Published: November 2021

BACKGROUND

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is increasingly used in some trauma settings. Arterial access-related limb ischemic complications (ARLICs) resulting from the femoral arterial access required for REBOA are largely under reported. We sought to describe the incidence of these complications and the clinical, technical, and device factors associated with their development.

METHODS

This was a retrospective cohort study of records of adult trauma patients from the American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute care surgery registry between October 2013 and September 2020 who had REBOA and survived at least 48 hours. The primary outcome was ARLIC, defined as clinically relevant extremity ischemia or distal embolization. Relevant factors associated with ARLIC were also analyzed.

RESULTS

Of 418 identified patients, 36 (8.6%) sustained at least one ARLIC; 22 with extremity ischemia, 25 with distal embolism, 11 with both. Patient demographics and injury characteristics were similar between ARLIC and no ARLIC groups. Access-related limb ischemic complication was associated with larger profile devices (p = 0.009), cutdown access technique (p = 0.02), and the presence of a pelvic external fixator/binder (p = 0.01). Patients with ARLIC had higher base deficit (p = 0.03) and lactate (p = 0.006). One hundred fifty-six patients received tranexamic acid (TXA), with 22 (14%) ARLICs. The rate of TXA use among ARLIC patients was 61% (vs. 35% TXA for non-ARLIC patients, p = 0.002). Access-related limb ischemic complication did not result in additional in-hospital mortality, however, ARLIC had prolonged hospital LOS (31 vs. 24 days, p = 0.02). Five ARLIC required surgical intervention, three patch angioplasty (and two with associated bypass), and four ARLIC limbs were amputated.

CONCLUSION

Femoral artery REBOA access carries a risk of ARLIC, which is associated with unstable pelvis fractures, severe shock, and strongly with the administration of TXA. Use of lower-profile devices and close surveillance for these complications is warranted in these settings and caution should be exercised when using TXA in conjunction with REBOA.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic, Level III
Developing a National Trauma Research Action Plan: Results from the prehospital and mass casualty research Delphi survey
Authors: Newgard Craig D. , Braverman Maxwell A. , Phuong Jimmy , Shipper Edward S. , Price Michelle A. , Bixby Pamela J. , Goralnick Eric , Daya Mohamud R. , Lerner E. Brooke , Guyette Francis X. , Rowell Susan , Doucet Jay , Jenkins Peter , Mann N. Clay , Staudenmayer Kristan , Blake David P. , Bulger Eileen
Published: November 2021

BACKGROUND

The National Academies of Sciences, Engineering, and Medicine 2016 trauma system report recommended a National Trauma Research Action Plan to strengthen and guide future trauma research. To address this recommendation, 11 expert panels completed a Delphi survey process to create a comprehensive research agenda, spanning the continuum of trauma care. We describe the gap analysis and high-priority research questions generated from the National Trauma Research Action Plan panel on prehospital and mass casualty trauma care.

METHODS

We recruited interdisciplinary national experts to identify gaps in the prehospital and mass casualty trauma evidence base and generate prioritized research questions using a consensus-driven Delphi survey approach. We included military and civilian representatives. Panelists were encouraged to use the Patient/Population, Intervention, Compare/Control, and Outcome format to generate research questions. We conducted four Delphi rounds in which participants generated key research questions and then prioritized the questions on a 9-point Likert scale to low-, medium-, and high-priority items. We defined consensus as ≥60% agreement on the priority category and coded research questions using a taxonomy of 118 research concepts in 9 categories.

RESULTS

Thirty-one interdisciplinary subject matter experts generated 490 research questions, of which 433 (88%) reached consensus on priority. The rankings of the 433 questions were as follows: 81 (19%) high priority, 339 (78%) medium priority, and 13 (3%) low priority. Among the 81 high-priority questions, there were 46 taxonomy concepts, including health systems of care (36 questions), interventional clinical trials and comparative effectiveness (32 questions), mortality as an outcome (30 questions), prehospital time/transport mode/level of responder (24 questions), system benchmarks (17 questions), and fluid/blood product resuscitation (17 questions).

CONCLUSION

This Delphi gap analysis of prehospital and mass casualty care identified 81 high-priority research questions to guide investigators and funding agencies for future trauma research.
Case Series of Thrombosis with Thrombocytopenia Syndrome following COVID-19 vaccination—United States, December 2020–August 2021
Authors: See Isaac , Lale Allison , Marquez Paige , Streiff Michael B. , Wheeler Allison P. , Tepper Naomi K. , Woo Emily Jane , Broder Karen R. , Edwards Kathryn M. , Gallego Ruth , Geller Andrew I. , Jackson Kelly A. , Sharma Shashi , Talaat Kawsar R. , Walter Emmanuel B. , Akpan Imo J. , Ortel Thomas L. , Walker Shannon C. , Yui Jennifer C. , Shimabukuro Tom T. , Mba-Jonas Adamma , Su John R. , Shay David K.
Published: November 2021

Background

Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. TTS presents similarly to autoimmune heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis following Janssen/Johnson & Johnson (Ad26.COV2.S) COVID-19 vaccination have been described.

Objective

Describe surveillance data and reporting rates of TTS cases following COVID-19 vaccination.

Design

Case series.

Setting

United States

Patients

Case-patients reported to the Vaccine Adverse Event Reporting System (VAERS) receiving COVID-19 vaccine from December 14, 2020 through August 31, 2021, with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction). If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for anti-platelet factor 4 antibody was required.

Measurements

Reporting rates (cases/million vaccine doses) and descriptive epidemiology.

Results

52 TTS cases were confirmed following Ad26.COV2.S (n=50) or mRNA-based COVID-19 (n=2) vaccination. TTS reporting rates were 3.55 per million (Ad26.COV2.S) and 0.0057 per million (mRNA-based COVID-19 vaccines). Median age of patients with TTS following Ad26.COV2.S vaccination was 43.5 years (range: 18–70); 70% were female. Both TTS cases following mRNA-based COVID-19 vaccination occurred in males aged >50 years. All cases following Ad26.COV2.S vaccination involved hospitalization including 32 (64%) with intensive care unit admission. Outcomes of hospitalizations following Ad26.COV2.S vaccination included death (12%), discharge to post-acute care (16%), and discharge home (72%).

Limitations

Under-reporting and incomplete case follow-up.

Conclusion

TTS is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the two cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate.

Funding Source

CDC
Novel protein markers of androgen activity in humans: proteomic study of plasma from young chemically castrated men
Authors: Giwercman Aleksander , Sahlin K Barbara , Pla Indira , Pawłowski Krzysztof , Fehniger Carl , Lundberg Giwercman Yvonne , Leijonhufvud Irene , Appelqvist Roger , Marko-Varga György , Sanchez Aniel , Malm Johan
Published: November 2021

Background

Reliable biomarkers ofv androgen activity in humans are lacking. The aim of this study was, therefore, to identify new protein markers of biological androgen activity and test their predictive value in relation to low vs. normal testosterone values and some androgen deficiency linked pathologies.

Methods

Blood samples from 30 healthy GnRH-antagonist treated males were collected at three time points: a) before GnRH antagonist administration; b) 3 weeks later, just before testosterone undecanoate injection, and c) after additional 2 weeks. Subsequently they were analysed by mass spectrometry to identify potential protein biomarkers of testosterone activity. Levels of proteins most significantly associated with testosterone fluctuations were further tested in a cohort of 75 hypo- and eugonadal males suffering from infertility. Associations between levels of those markers and cardio-metabolic parameters, bone mineral density as well as androgen receptor CAG repeat lengths, were explored.

Results

Using ROC analysis, 4-hydroxyphenylpyruvate dioxygenase (4HPPD), insulin-like growth factor-binding protein 6 (IGFBP6) and fructose-bisphosphate aldolase (ALDOB), as well as a Multi Marker Algorithm, based on levels of 4HPPD and IGFBP6, were shown to be best predictors of low (< 8 nmol/L) vs. normal (> 12 nmol/L) testosterone. They were also more strongly associated with metabolic syndrome and diabetes than testosterone levels. Levels of ALDOB and 4HPPD levels also showed association with AR CAG-repeat lengths.

Conclusions

We identified potential new protein biomarkers of testosterone action. Further investigations to eluciadate their clinical potential are warranted.
Identification of a minimal biomarker profile in head-and-neck squamous cell carcinoma tumors
Authors: Sanchez-Diaz Laura , Navas Lola E. , Suarez-Martinez Elisa , Felipe-Abrio Blanca , Fernández-Rozadilla Ceres , Verdugo-Sivianes Eva M , Celis-Romero Manuel A. , Chaves-Conde Manuel , Chiara Maria-Dolores , Garcia-Mayea Yoelsis , LLeonart Matilde E. , Garcia-Heredia Jose Manuel , Muñoz-Galvan Sandra , Carracedo Angel , Rodrigo Juan P. , Carnero Amancio
Published: November 2021

Although important advances have been made in the knowledge of the molecular mechanisms leading to the development, of head and neck squamous cell carcinoma (HNSCC), only PDL1 is used for the immunotherapy (pemborlizumab) treatment in the first line of metastatic or recurrent disease. There are no other molecular biomarkers currently used in clinical practice. The objective of the study was to identify transcriptional alterations in patients with oral cavity cancer that identify gene networks responsible for resistance to treatment and prognosis. To identify possible targets for the treatment or prevention of these tumors, we screened for changes in transcription of genes that were recurrently altered in patients and that successfully stratify tumoral and non-tumoral samples, as well as patient survival, based on expression levels. The gene panels are primarily related to the cell cycle, DNA damage response, cytokine signaling and the immune system but also to the embryonic stem cell core. Validation of these panels in an independent cohort led to the identification of three non-interconnected genes, WDR66, SERPINH1 and ZNF622, that can predict patient survival and are differentially expressed in 3D cultures from HNSCC primary cell lines. These genes are related to stemness phenotype are transcriptional targets of the pluripotency transcription factors Sox2 and c-Myc. Our results suggest that WDR66, SERPINH1 and ZNF622 con-stitute a minimal signature of stemness transcriptional targets able to predict the prognosis of HNSCC tumors.

Simple Summary

The objective of the study was to identify transcriptional alterations in patients with oral cavity cancer to possibly identify gene networks responsible for resistance to treatment and prognosis. We identify bioinformatically gene panels are primarily related to the cell cycle, DNA damage response, cytokine signaling and the immune system but also to the embryonic stem cell core. Validation of these panels in patients independent cohorts led to the identification of three non-interconnected genes, WDR66, SERPINHl and ZNF622, that can predict patient survival and are differentially expressed in cancer stem cells cultures from HNSCC. These genes are related to stemness phenotype and epithelial-to-mesenchymal transition and are transcriptional targets of the pluripotency transcription factors Sox2 and c-Myc.
Age-linked suppression of lipoxin A4 mediates cognitive deficits in mice and humans
Authors: Pamplona Fabrício A. , Vitória Gabriela , Ribeiro Felipe C. , Moraes Carolina A. , Ledur Pitia F. , Karmirian Karina , Ornelas Isis M. , Leo Luciana M. , Paulsen Bruna , Sudo Felipe K. , Coutinho Gabriel , Drummond Claudia , Assunção Naima , Vanderborght Bart , Canetti Claudio , Castro-Faria-Neto Hugo C. , Mattos Paulo , Ferreira Sergio T. , Rehen Stevens K. , Bozza Fernando A. , Lourenco Mychael V. , Tovar-Moll Fernanda
Published: November 2021

Age increases the risk for cognitive impairment and is the single major risk factor for Alzheimer's disease (AD), the most prevalent form of dementia in the elderly. The pathophysiological processes triggered by aging that render the brain vulnerable to dementia involve, at least in part, changes in inflammatory mediators. Here we show that lipoxin A4 (LXA4), a lipid mediator of inflammation resolution known to stimulate endocannabinoid signaling in the brain, is reduced in the aging central nervous system. We demonstrate that genetic suppression of 5-lipoxygenase (5-LOX), the enzyme mediating LXA4 synthesis, promotes learning impairment in mice. Conversely, administration of exogenous LXA4 attenuated cytokine production and memory loss induced by inflammation in mice. We further show that cerebrospinal fluid LXA4 is reduced in patients with dementia and positively associates with memory performance, brain-derived neurotrophic factor (BDNF), and AD-linked amyloid-β. Our findings suggest that reduced LXA4 levels may lead to vulnerability to age-related cognitive disorders and that promoting LXA4 signaling may comprise an effective strategy to prevent early cognitive decline in AD.
Maternal diet disrupts the placenta-brain axis in a sex-specific manner
Authors: Ceasrine Alexis M , Devlin Benjamin A , Bolton Jessica L. , Green Lauren A. , Jo Young Chan , Huynh Carolyn , Patrick Bailey , Washington Kamryn , Sanchez Cristina L. , Joo Faith , Brayan Campos-Salazar A. , Lockshin Elana R. , Kuhn Cynthia , Murphy Susan K. , Simmons Leigh Ann , Bilbo Staci D.
Published: November 2021

High maternal weight is associated with a number of detrimental outcomes in offspring, including increased susceptibility to neurological disorders such as anxiety, depression, and communicative disorders (e.g. autism spectrum disorders)1–8. Despite widespread acknowledgement of sex-biases in the prevalence, incidence, and age of onset of these disorders, few studies have investigated potential sex-biased mechanisms underlying disorder susceptibility. Here, we use a mouse model to demonstrate how maternal high-fat diet, one contributor to overweight, causes endotoxin accumulation in fetal tissue, and subsequent perinatal inflammation influences sex-specific behavioral outcomes in offspring. In male high-fat diet offspring, increased macrophage toll like receptor 4 signaling results in excess phagocytosis of serotonin neurons in the developing dorsal raphe nucleus, decreasing serotonin bioavailability in the fetal and adult brain. Bulk sequencing from a large cohort of matched first trimester human fetal brain, placenta, and maternal decidua samples reveals sex-specific transcriptome-wide changes in placenta and brain tissue in response to maternal triglyceride accumulation (a proxy for dietary fat content). Further, we find that fetal brain serotonin levels decrease as maternal dietary fat intake increases in males only. These findings uncover a microglia-dependent mechanism through which maternal diet may impact offspring susceptibility for neuropsychiatric disorder development in a sex-specific manner.
A novel mechanism of bulk cytoplasmic transport by cortical dynein in Drosophila ovary
Authors: Lu Wen , Lakonishok Margot , Serpinskaya Anna S. , Gelfand Vladimir I.
Published: November 2021

Cytoplasmic dynein, a major minus-end directed microtubule motor, plays essential roles in eukaryotic cells. Drosophila oocyte growth is mainly dependent on the contribution of cytoplasmic contents from the interconnected sister cells, nurse cells. We have previously shown that cytoplasmic dynein is required for Drosophila oocyte growth, and assumed that it transports cargoes along microtubule tracks from nurse cells to the oocyte. Here we report that instead transporting cargoes along microtubules into the oocyte, cortical dynein actively moves microtubules in nurse cells and from nurse cells to the oocyte via the cytoplasmic bridges, the ring canals. We demonstrate this microtubule movement is sufficient to drag even inert cytoplasmic particles through the ring canals to the oocyte. Furthermore, replacing dynein with a minus-end directed plant kinesin linked to the actin cortex is sufficient for transporting organelles and cytoplasm to the oocyte and driving its growth. These experiments show that cortical dynein can perform bulk cytoplasmic transport by gliding microtubules along the cell cortex and through the ring canals to the oocyte. We propose that the dynein-driven microtubule flow could serve as a novel mode of cargo transport for fast cytoplasmic transfer to support rapid oocyte growth.
After the Haiti 2021 Earthquake: Triage and treatment data for a cohort of patients transported for higher level of care
Authors: Edwards Kelly , Ellis David , Oaks Cory , Mann SGM Clayton W. , DeGennaro Vincent
Published: November 2021

Intro

On August 14, a magnitude 7.2 earthquake occurred in the South of Haiti, killing over 2,200 people and leaving at least 12,000 injured. On August 17th, a joint task force coordinated the triage, treatment, and transport for patients arriving at the Port-au-Prince airport from the South.

Methods

From August 17th-27th, approximately 243 patients were encountered at the Port-au-Prince airport. For the first three days of operations, written notes, reports, and various chat logs from WhatsApp were used to compile this data.

Results

243 patents were encountered at the airport Triage and Treatment from August 17 to August 27. Orthopedic injuries were the most common presenting injury with 20% of patients having a pelvis fracture (the most prevalent injury). Of the 174 with known transfer destinations, 118 (68%) were transported to one of three tertiary care hospitals, with 99 going via ground ambulance to the two in Port au Prince, and 19 going via HAA helicopter to Mirebalais. Once treatment operations were initiated, 106 patients received some form of treatment at the airport while awaiting transport.

Discussion

Interagency coordination was the key to rapid scale up. To address the most prevalent patient issues, a treatment bundle was conceptualized a few days into operations that consisted of IV fluids, analgesia, IV antibiotics, wound debridement and cleaning, and tetanus prophylaxis.
Three-dimensional structure of kinetochore-fibers in human mitotic spindles
Authors: Kiewisz Robert , Fabig Gunar , Conway William , Baum Daniel , Needleman Daniel , Müller-Reichert Thomas
Published: November 2021

During cell division, kinetochore microtubules (KMTs) provide a physical linkage between the chromosomes and the rest of the spindle. KMTs in mammalian cells are organized into bundles, so-called kinetochore-fibers (k-fibers), but the ultrastructure of these fibers is currently not well characterized. Here we show by large-scale electron tomography that each k-fiber in HeLa cells in metaphase is composed of approximately nine KMTs, only half of which reach the spindle pole. Our comprehensive reconstructions allowed us to analyze the three-dimensional (3D) morphology of k-fibers and their surrounding MTs in detail. We found that k-fibers exhibit remarkable variation in circumference and KMT density along their length, with the pole-proximal side showing a broadening. Extending our structural analysis then to other MTs in the spindle, we further observed that the association of KMTs with non-KMTs predominantly occurs in the spindle pole regions. Our 3D reconstructions have implications for KMT growth and k-fiber self-organization models as covered in a parallel publication applying complementary live-cell imaging in combination with biophysical modeling (Conway et al., 2022). Finally, we also introduce a new visualization tool allowing an interactive display of our 3D spindle data that will serve as a resource for further structural studies on mitosis in human cells.
Modeling Macroscopic Currents of Ion Channels
Authors: Wu Di
Published: November 2021

Ion-channel functions are often studied by the current-voltage relation, which is commonly fitted by the Boltzmann equation, a powerful model widely used nowadays. However, the Boltzmann model is restricted to a two-state ion-permeation process. Here we present an improved model that comprises a flexible number of states and incorporates both the single-channel conductance and the open-channel probability. Employing the channel properties derived from the single-channel recording experiments, the proposed model is able to describe various current-voltage relations, especially the reversal ion-permeation curves showing the inward- and outward-rectifications. We demonstrate the applicability of the proposed model using the published patch-clamp data of BK and MthK potassium channels, and discuss the similarity of the two channels based on the model studies.
Susceptibility of sheep to experimental co-infection with the ancestral lineage of SARS-CoV-2 and its alpha variant
Authors: Gaudreault Natasha N. , Cool Konner , Trujillo Jessie D. , Morozov Igor , Meekins David A. , McDowell Chester , Bold Dashzeveg , Carossino Mariano , Balaraman Velmurugan , Mitzel Dana , Kwon Taeyong , Madden Daniel W. , Artiaga Bianca Libanori , Pogranichniy Roman M. , Roman-Sosa Gleyder , Wilson William C. , Balasuriya Udeni B. R. , García-Sastre Adolfo , Richt Juergen A.
Published: November 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that has had significant impacts on human health and economies worldwide. SARS-CoV-2 is highly transmissible and the cause of coronavirus disease 2019 (COVID-19) in humans. A wide range of animal species have also been shown to be susceptible to SARS-CoV-2 infection by experimental and/or natural infections. Domestic and large cats, mink, ferrets, hamsters, deer mice, white-tailed deer, and non-human primates have been shown to be highly susceptible, whereas other species such as mice, dogs, pigs, and cattle appear to be refractory to infection or have very limited susceptibility. Sheep (Ovis aries) are a commonly farmed domestic ruminant that have not previously been thoroughly investigated for their susceptibility to SARS-CoV-2. Therefore, we performed in vitro and in vivo studies which consisted of infection of ruminant-derived cell cultures and experimental challenge of sheep to investigate their susceptibility to SARS-CoV-2. Our results showed that sheep-derived cell cultures support SARS-CoV-2 replication. Furthermore, experimental challenge of sheep demonstrated limited infection with viral RNA shed in nasal and oral swabs primarily at 1-day post challenge (DPC), and also detected in the respiratory tract and lymphoid tissues at 4 and 8 DPC. Sero-reactivity was also observed in some of the principal infected sheep but not the contact sentinels, indicating that transmission to co-mingled naïve sheep was not highly efficient; however, viral RNA was detected in some of the respiratory tract tissues of sentinel animals at 21 DPC. Furthermore, we used challenge inoculum consisting of a mixture of two SARS-CoV-2 isolates, representatives of the ancestral lineage A and the B.1.1.7-like alpha variant of concern (VOC), to study competition of the two virus strains. Our results indicate that sheep show low susceptibility to SARS-CoV-2 infection, and that the alpha VOC outcompeted the ancestral lineage A strain.
Orthogonal control of gene expression in plants using synthetic promoters and CRISPR-based transcription factors
Authors: Kar Shaunak , Bordiya Yogendra , Rodriguez Nestor , Kim Junghyun , Gardner Elizabeth C. , Gollihar Jimmy , Sung Sibum , Ellington Andrew D.
Published: November 2021

Background

The construction and application of synthetic genetic circuits is frequently improved if gene expression can be orthogonally controlled, relative to the host. In plants, orthogonality can be achieved via the use of CRISPR-based transcription factors that are programmed to act on natural or synthetic promoters. The construction of complex gene circuits can require multiple, orthogonal regulatory interactions, and this in turn requires that the full programmability of CRISPR elements be adapted to non-natural and non-standard promoters that have few constraints on their design. Therefore, we have developed synthetic promoter elements in which regions upstream of the minimal 35S CaMV promoter are designed from scratch to interact via programmed gRNAs with dCas9 fusions that allow activation of gene expression.

Results

A panel of three, mutually orthogonal promoters that can be acted on by artificial gRNAs bound by CRISPR regulators were designed. Guide RNA expression targeting these promoters was in turn controlled by either Pol III (U6) or ethylene-inducible Pol II promoters, implementing for the first time a fully artificial Orthogonal Control System (OCS). Following demonstration of the complete orthogonality of the designs, the OCS was tied to cellular metabolism by putting gRNA expression under the control of an endogenous plant signaling molecule, ethylene. The ability to form complex circuitry was demonstrated via the ethylene-driven, ratiometric expression of fluorescent proteins in single plants.

Conclusions

The design of synthetic promoters is highly generalizable to large tracts of sequence space, allowing Orthogonal Control Systems of increasing complexity to potentially be generated at will. The ability to tie in several different basal features of plant molecular biology (Pol II and Pol III promoters, ethylene regulation) to the OCS demonstrates multiple opportunities for engineering at the system level. Moreover, given the fungibility of the core 35S CaMV promoter elements, the derived synthetic promoters can potentially be utilized across a variety of plant species.
Resistance profiling of Aspergillus fumigatus to olorofim indicates absence of intrinsic resistance and unveils the molecular mechanisms of acquired olorofim resistance
Authors: Buil Jochem B. , Oliver Jason D. , Law Derek , Baltussen Tim , Zoll Jan , Hokken Margriet W.J. , Tehupeiory-Kooreman Marlou , Melchers Willem J.G. , Birch Mike , Verweij Paul E.
Published: November 2021

Olorofim (F901318) is a new antifungal currently under clinical development that shows both in vitro and in vivo activity against a number of filamentous fungi including Aspergillus fumigatus. In this study we screened A. fumigatus isolates for intrinsic olorofim-resistant A. fumigatus and evaluated the ability of A. fumigatus to acquire an olorofim-resistant phenotype. No intrinsic resistance was found in 975 clinical A. fumigatus isolates. However, we found that isolates with increased olorofim MICs (> 8 mg/L) could be selected using a high number of conidia and olorofim exposure under laboratory conditions. Assessment of the frequency of acquired olorofim resistance development of A. fumigatus was shown to be higher than for voriconazole but lower than for itraconazole. Sequencing the PyrE gene of isogenic isolates with olorofim MICs of >8 mg/L identified various amino acid substitutions with a hotspot at locus G119. Olorofim was shown to have reduced affinity to mutated target protein dihydroorotate dehydrogenase (DHODH) and the effect of these mutations were proven by introducing the mutations directly in A. fumigatus. We then investigated whether G119 mutations were associated with a fitness cost in A. fumigatus. These experiments showed a small but significant reduction in growth rate for strains with a G119V substitution, while strains with a G119C substitution did not exhibit a reduction in growth rate. These in vitro findings were confirmed in an in vivo pathogenicity model.

Importance

Olorofim represents an important new treatment option for patients with difficult to treat invasive fungal infections, including triazole-resistant A. fumigatus infection. Our study provides insights into one resistance mechanism and the potential dynamics of olorofim resistance, which will help to prevent and manage resistance selection. Such insights are critical to antifungal stewardship and to safeguard its prolonged use in clinical practice.
NMR metabolomics of symbioses between bacterial vaginosis associated bacteria
Authors: Horrocks Victoria , Hind Charlotte K. , Wand Matthew E. , Chan Joel , Hopkins Jade C. , Houston Georgina L. , Tribe Rachel M. , Sutton J. Mark , Mason A. James
Published: November 2021

Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome, characterised by low levels of lacto-bacilli and overgrowth of a diverse group of bacteria, and associated with higher risk of a variety of infections, surgical complications, cancer and spontaneous preterm birth (PTB). Despite the lack of a consistently applicable aetiology, Prevotella spp. are often associated with both BV and PTB and P. bivia has known symbiotic relationships with both Peptostreptococcus anaerobius and Gardnerella vaginalis. Higher risk of PTB can also be predicted by a composite of metabolites linked to bacterial metabolism but their specific bacterial source remains poorly understood. Here we characterise diversity of metabolic strategies among BV associated bacteria and lactobacilli and the symbiotic metabolic relationships between P. bivia and its partners and show how these influence the availability of metabolites associated with BV/PTB and/or pro- or anti-inflammatory immune responses. We confirm a commensal relationship between Pe. anaerobius and P. bivia, refining its mechanism; P. bivia supplies tyrosine, phenylalanine, methionine, uracil and proline, the last of which leads to a substantial increase in overall acetate production. In contrast, our data indicate the relationship between P. bivia and G. vaginalis strains, with sequence variant G2, is mutualistic with outcome dependent on the metabolic strategy of the G. vaginalis strain. Seven G. vaginalis strains could be separated according to whether they performed mixed acid fermentation (MAF) or bifid shunt (BS). In co-culture, P. bivia supplies all G. vaginalis strains with uracil and received substantial amounts of asparagine in return. Acetate production, which is lower in BS strains, then matched that of MAF strains while production of aspartate increased for the latter. Taken together, our data show how knowledge of inter- and intra-species metabolic diversity and the effects of symbiosis may refine our understanding of the mechanism and approach to risk prediction in BV and/or PTB.
Predicting SARS-CoV-2 epitope-specific TCR recognition using pre-trained protein embeddings
Authors: Han Youngmahn , Lee Aeri
Published: November 2021

The COVID-19 pandemic is ongoing because of the high transmission rate and the emergence of SARS-CoV-2 variants. The P272L mutation in SARS-Cov-2 S-protein is known to be highly relevant to the viral escape associated with the second pandemic wave in Europe. Epitope-specific T-cell receptor (TCR) recognition is a key factor in determining the T-cell immunogenicity of a SARS-CoV-2 epitope. Although several data-driven methods for predicting epitope-specific TCR recognition have been proposed, they remain challenging owing to the enormous diversity of TCRs and the lack of available training data. Self-supervised transfer learning has recently been demonstrated to be powerful for extracting useful information from unlabeled protein sequences and increasing the predictive performance of the fine-tuned models in downstream tasks.

Here, we present a predictive model based on Bidirectional Encoder Representations from Transformers (BERT), employing self-supervised transfer learning, to predict SARS-CoV-2 T-cell epitope-specific TCR recognition. The fine-tuned model showed notably high predictive performance for independent evaluation using the SARS-CoV-2 epitope-specific TCR CDR3β sequence datasets. In particular, we found the proline at position 4 corresponding to the P272L mutation in the SARS-CoV-2 S-protein269-277 epitope (YLQPRTFLL) may contribute substantially to TCR recognition of the epitope through interpreting the output attention weights of our model.

We anticipate that our findings will provide new directions for constructing a reliable data-driven model to predict the immunogenic T-cell epitopes using limited training data and help accelerate the development of an effective vaccine in response to SARS-CoV-2 variants.
An assessment of the evidence for antibacterial activity of stinging nettle (Urtica dioica) extracts
Authors: Harrison Freya , Furner-Pardoe Jessica , Connelly Erin
Published: November 2021

Stinging nettles (Urtica spp.) have been used in a diverse range of traditional and historical medicines from around the world for the treatment of skin diseases, wounds, urinary disorders, respiratory diseases, bone and joint pain, anaemia and other circulatory problems, as well as in cosmetic preparations for skin and haircare. As part of an interdisciplinary exploration of nettle-based remedies, we performed a systematic review of published evidence for the antimicrobial activity of Urtica spp. extracts against bacteria and fungi that commonly cause skin, soft tissue and respiratory infections. We focussed on studies in which minimum inhibitory concentration (MIC) assays of U. dioica were conducted on the common bacterial opportunistic pathogens Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus. No studies used fresh leaves (all were dried prior to use), and no studies prepared nettles in weak acid (corresponding to vinegar) or in fats/oils, which are common combinations in historical and traditional preparations. We addressed this gap by conducting new antibacterial tests of extracts of fresh U. dioica leaves prepared in vinegar, butter or olive oil against P. aeruginosa and S. aureus. Our systematic review and additional experimental data leads us to conclude that there is no strong evidence for nettles containing molecules with clinically useful antimicrobial activity. It seems most likely that the utility of nettles in traditional topical preparations for wounds may simply be as a “safe” absorbent medium for keeping antibacterial (vinegar) or emollient (oils) ingredients at the treatment site.

Data Summary

All data relating to the systematic review are supplied in the Datasets and Supplementary tables contained in the Supporting Data file.
Periodic ethanol supply as a path towards unlimited lifespan ofC.elegansdauer larvae
Authors: Zhang Xingyu , Penkov Sider , Kurzchalia Teymuras V. , Zaburdeav Vasily
Published: November 2021

The dauer larva is a specialized stage of development optimized for survival under harsh conditions that has been used as a model for stress resistance, metabolic adaptations, and longevity. Recent findings suggest that the dauer larva ofC.elegansmay utilize external ethanol as an energy source to extend their lifespan. It was shown that while ethanol may serve as an effectively infinite source of energy, some toxic compounds accumulating as byproducts of its metabolism may lead to the damage of mitochondria and thus limit the lifespan of larvae. A minimal mathematical model was proposed to explain the connection between the lifespan of dauer larva and its ethanol metabolism. To explore theoretically if it is possible to extend even further the lifespan of dauer larvae, we incorporated two natural mechanisms describing the recovery of damaged mitochondria and elimination of toxic compounds, which were previously omitted in the model. Numerical simulations of the revised model suggest that while the ethanol concentration is constant, the lifespan still stays limited. However, if ethanol is supplied periodically, with a suitable frequency and amplitude, the dauer could survive as long as we observe the system. Analytical methods further help to explain how the feeding frequency and amplitude affect the lifespan extension. Based on comparison of the model with experimental data for fixed ethanol concentration, we propose the range of feeding protocols that could lead to even longer dauer survival and can be tested experimentally.
FBXO47 is essential for preventing the synaptonemal complex from premature disassembly in mouse male meiosis
Authors: Tanno Nobuhiro , Takemoto Kazumasa , Takada-Horisawa Yuki , Shimada Ryuki , Fujimura Sayoko , Tani Naoki , Takeda Naoki , Araki Kimi , Ishiguro Kei-ichiro
Published: November 2021

Meiotic prophase is a prolonged G2 phase that ensures the completion of numerous meiosis-specific chromosome events. During meiotic prophase, homologous chromosomes undergo synapsis to facilitate meiotic recombination yielding crossovers. It remains largely elusive how homolog synapsis is temporally maintained and destabilized during meiotic prophase. Here we show that FBXO47 is the stabilizer of synaptonemal complex during male meiotic prophase. Disruption of FBXO47 shows severe impact on homologous chromosome synapsis and DSB repair processes, leading to male infertility. Notably, in the absence of FBXO47, although once homologous chromosomes are synapsed, the synaptonemal complex is precociously disassembled before progressing beyond pachytene. Remarkably, Fbxo47 KO spermatocytes remain in earlier stage of meiotic prophase and lack crossovers, despite apparently exhibiting diplotene-like chromosome morphology. We propose that FBXO47 functions independently of SCF E3 ligase, and plays a crucial role in preventing synaptonemal complex from premature disassembly during cell cycle progression of meiotic prophase.