bluuebunny/crossref_metadata_2025 huggingface dataset:
On The Vibrations of Pyramidal Beams With Rectangular Cross-Section and Application to Unswept Wings
Authors: Campos L M B C , Marta A C
Published: November 2020

The bending frequencies of an unswept wing are calculated based on the model of a beam clamped at the root and free at the tip. For a tapered wing with straight leading- and trailing-edges, the chord is a linear function of the span; the same linear function of the span applies to thickness, in the case of constant thickness-to-chord ratio. The latter is usually small, so that the beam differs from the more frequent cases of a conical beam with a circular cross-section or a prismatic beam with a square cross-section. Thus, the bending modes of a non-uniform beam are considered, with mass and area moment of inertia which are respectively quadratic and quartic functions of the span. There is no exact solution expressible in finite terms using elementary functions, and thus power series expansions are used. The bending frequencies are calculated for a delta wing and compared with a rectangular wing, with the same span, mean chord and thickness, mass density and Young’s modulus. It is shown that the fundamental frequency is higher by a factor 4.96 for the delta wing; it is also shown that the general case of the tapered wing is intermediate between the delta and the rectangular wing. Lastly, the analytical results obtained for the bending modes are compared with numerical modal analyses of general tapered wing beams using high-fidelity finite-element model software.
Interpersonal brain synchronization under bluffing in strategic games
Authors: Wang Zhihao , Wang Yiwen , Zhou Xiaolin , Yu Rongjun
Published: November 2020

People commonly use bluffing as a strategy to manipulate other people’s beliefs about them for gain. Although bluffing is an important part of successful strategic thinking, the inter-brain mechanisms underlying bluffing remain unclear. Here, we employed a functional near-infrared spectroscopy hyperscanning technique to simultaneously record the brain activity in the right temporal-parietal junction in 32 pairs of participants when they played a bluffing game against each other or with computer opponents separately. We also manipulated the penalty for bluffing (high vs low). Under the condition of high relative to low penalty, results showed a higher bluffing rate and a higher calling rate in human-to-human as compared to human-to-computer pairing. At the neural level, high relative to low penalty condition increased the interpersonal brain synchronization (IBS) in the right angular gyrus (rAG) during human-to-human as compared to human-to-computer interaction. Importantly, bluffing relative to non-bluffing, under the high penalty and human-to-human condition, resulted in an increase in response time and enhanced IBS in the rAG. Participants who bluffed more frequently also elicited stronger IBS. Our findings support the view that regions associated with mentalizing become synchronized during bluffing games, especially under the high penalty and human-to-human condition.
Molecular epidemiology in the HIV and SARS-CoV-2 pandemics
Authors: Lorenzo-Redondo Ramon , Ozer Egon A. , Achenbach Chad J. , D’Aquila Richard T. , Hultquist Judd F.
Published: November 2020

Purpose of review

The aim of this review was to compare and contrast the application of molecular epidemiology approaches for the improved management and understanding of the HIV versus SARS-CoV-2 epidemics.

Recent findings

Molecular biology approaches, including PCR and whole genome sequencing (WGS), have become powerful tools for epidemiological investigation. PCR approaches form the basis for many high-sensitivity diagnostic tests and can supplement traditional contact tracing and surveillance strategies to define risk networks and transmission patterns. WGS approaches can further define the causative agents of disease, trace the origins of the pathogen, and clarify routes of transmission. When coupled with clinical datasets, such as electronic medical record data, these approaches can investigate co-correlates of disease and pathogenesis. In the ongoing HIV epidemic, these approaches have been effectively deployed to identify treatment gaps, transmission clusters and risk factors, though significant barriers to rapid or real-time implementation remain critical to overcome. Likewise, these approaches have been successful in addressing some questions of SARS-CoV-2 transmission and pathogenesis, but the nature and rapid spread of the virus have posed additional challenges.

Overall, molecular epidemiology approaches offer unique advantages and challenges that complement traditional epidemiological tools for the improved understanding and management of epidemics.
Response to a Skin Puncture Contaminated with 238Pu at Los Alamos National Laboratory
Authors: Klumpp John , Bertelli Luiz , Dumit Sara , Gadd Milan , Poudel Deepesh , Waters Tom L.
Published: November 2020

The three principal pathways for intakes of plutonium are ingestion, inhalation, and contaminated wounds. In August 2018, a glovebox worker at Los Alamos National Laboratory (LANL) sustained a puncture from a thread of a braided steel cable contaminated with 238Pu. The puncture produced no pain, no blood, and little or no visible mark. As a result, the potential for a contaminated wound was not immediately recognized, and a wound count was not conducted until elevated urine bioassay results were received 12 d after the incident. This paper discusses the circumstances of the incident, along with the medical response and dose assessment, and a discussion of the risks and benefits of the medical interventions.
Cutaneous Manifestations of Celiac Disease
Authors: Zheng Xin , Shaha Sneha , Khawar Talha
Published: November 2020

Celiac disease is a systemic immune-mediated enteropathy that is primarily characterized by its gastrointestinal symptoms with significant extraintestinal manifestations. A multidisciplinary approach is often required to appropriately recognize and manage the disease. Dermatology providers play an important role in the early recognition and diagnosis of this disease especially in those individuals who initially present with prominent cutaneous manifestations. This review article focuses on the cutaneous manifestations of celiac disease with the aim to increase awareness of this disease among dermatology providers to facilitate an early diagnosis and referral to appropriate specialty providers.
Associations Between Cyberbullying Perpetration, Sleep Quality, and Emotional Distress Among Adolescents
Authors: Liu Caimeng , Liu Zhen , Yuan Guangzhe
Published: November 2020

Previous studies demonstrate that cyberbullying perpetration and sleep quality likely have vital linkages to each other and to emotional distress. In this article, we examine the bidirectional association between cyberbullying perpetration, sleep quality, and emotional distress in a longitudinal data set with two waves of data collection (T1 and T2, 8 months apart). The participants included 661 Chinese junior high school students (n = 661; mean age, 14.02; 61.4% male) who filled out the Revised Cyber Bullying Inventory–Cyberbullying Subscale, Pittsburgh Sleep Quality Index, and Depression Anxiety Stress Scales. Results revealed that cyberbullying and sleep quality would predict each other over time, and significant bidirectional relationships were found between sleep quality and emotional distress across T1 and T2. Cyberbullying at T1 would not predict the emotional distress at T2, whereas emotional distress at T1 was associated with cyberbullying at T2.
Pulmonary Embolism Versus Mimics on Dual-energy Spectral Computed Tomography: An Algorithmic Approach
Authors: Kikano Elias George , Laukamp Kai Roman , Azeze Samuel , Smith Daniel , Rahnemai-Azar Amir-Ata , Gupta Aekta , Gupta Amit
Published: November 2020

Pulmonary embolism is a commonly encountered diagnosis that is traditionally identified on conventional computed tomography angiography. Dual-energy computed tomography (DECT) is a new technology that may aid the initial identification and differential diagnosis of pulmonary embolism. In this review, we present an algorithmic approach for assessing pulmonary embolism on DECT, including acute versus chronic pulmonary embolism, relationship to conventional computed tomography angiography, surrogate for likelihood of hemodynamic significance, and alternative diagnoses for DECT perfusion defects.
Subclassification of BI-RADS 4 Magnetic Resonance Lesions: A Systematic Review and Meta-Analysis
Authors: Li Jianyu , Zheng Hui , Cai Weiguo , Wang Yanfang , Zhang Hanfei , Liao Meiyan
Published: November 2020

Objective

This research aims to investigate and evaluate the diagnostic efficacy of magnetic resonance imaging (MRI) in classifying Breast Imaging Reporting and Data System (BI-RADS) 4 lesions into subcategories: 4a, 4b, and 4c, so as to limit biopsies of suspected lesions in the breast.

Methods

The PubMed, Web of Science, Embase, and Cochrane Library foreign language databases were searched for literature published between January 2000 and July 2018. After analyzing the selection, data extraction, and quality assessment, a meta-analysis was performed, including data pooling, heterogeneity testing, and meta-regression.

Results

Fourteen articles, including 18 studies, met the inclusion criteria. The diagnostic efficacy of MRI for BI-RADS 4–weighted summary assay sensitivity and specificity were estimated at 0.95 [95% confidence interval (CI), 0.89–0.98] and 0.87 (95% CI, 0.81–0.91), respectively. The positive and negative likelihood ratios were 7.1 (95% CI, 4.7–10.7) and 0.06 (95% CI, 0.02–0.14), respectively. The diagnostic odds ratio was 126 (95% CI, 37–426), and the area under the receiver operating characteristic curve was 0.95 (95% CI, 0.93–0.97). The malignancy ratio of BI-RADS 4a, 4b, and 4c and malignancy range were 2.5% to 18.3%, 23.5% to 57.1%, and 58.0% to 95.2%, respectively.

Conclusion

Risk stratification of suspected lesions (BI-RADS categories 4a, 4b, and 4c) can be achieved by MRI. The MRI is an effective auxiliary tool to further subclassify BI-RADS 4 lesions and prevent unnecessary biopsy of BI-RADS 4a lesions.
What Are COVID Toes? A Case Study
Authors: Beuscher Tara L. , Andrews Sarah E.
Published: November 2020

BACKGROUND:

COVID-19 symptoms mimic many other common conditions, making it difficult to identify patients infected with COVID-19. Adult patients may exhibit what is called “COVID toes” later in their course of illness. Noteworthy is that COVID toes may be the only symptom in otherwise asymptomatic young adults and children.

CASE:

We present experience with an adult female patient residing in the United States with presumed COVID-19 infection who was self-isolating with illness not severe enough to require hospitalization. COVID toes were one symptom experienced as a part of her illness. Because COVID toes are usually seen in the recovery phase of COVID-19, and often in patients with less severe cases, many providers are unfamiliar with this new symptom.

CONCLUSION:

Familiarity with COVID toes will help foot care providers to identify patients who may not have been diagnosed with COVID-19 but could still be infectious and need to be isolated. COVID toe signs may be subtle and often mimic other conditions such as chilblains/pernio, thus a thorough history and physical examination are required.
Public Health response to an outbreak of SARS-CoV2 infection in a Barcelona prison
Authors: Marco A , Gallego C , Pérez-Cáceres V , Guerrero RA , Sánchez-Roig M , Sala-Farré RM , Fernández-Náger J , Turu E
Published: November 2020

An outbreak of SARS-CoV2 infection in a Barcelona prison was studied after seven cases appeared in nine days. One hundred and eighty-four people (148 inmates and 36 prison staff) were evaluated by rt-PCR. Thirty-nine (24.1%) were positive: 33 inmates and six staff members. The inmates were isolated in prison module 4, which was converted into an emergency COVID unit. Two people (one inmate and one health worker) were admitted to hospital for clinical deterioration. There were no deaths. Outbreaks pose a huge risk, must be detected early, are difficult to manage, and require optimal coordination between health and prison authorities.
Risk of acute arterial and venous thromboembolic events in Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss syndrome)
Authors: Bettiol Alessandra , Sinico Renato Alberto , Schiavon Franco , Monti Sara , Bozzolo Enrica Paola , Franceschini Franco , Govoni Marcello , Lunardi Claudio , Guida Giuseppe , Lopalco Giuseppe , Paolazzi Giuseppe , Vacca Angelo , Gregorini Gina , Leccese Pietro , Piga Matteo , Conti Fabrizio , Fraticelli Paolo , Quartuccio Luca , Alberici Federico , Salvarani Carlo , Bettio Silvano , Negrini Simone , Selmi Carlo , Sciascia Savino , Moroni Gabriella , Colla Loredana , Manno Carlo , Urban Maria Letizia , Vannacci Alfredo , Pozzi Maria Rosa , Fabbrini Paolo , Polti Stefano , Felicetti Mara , Marchi Maria Rita , Padoan Roberto , Delvino Paolo , Caporali Roberto , Montecucco Carlomaurizio , Dagna Lorenzo , Cariddi Adriana , Toniati Paola , Tamanini Silvia , Furini Federica , Bortoluzzi Alessandra , Tinazzi Elisa , Delfino Lorenzo , Badiu Iuliana , Rolla Giovanni , Venerito Vincenzo , Iannone Florenzo , Berti Alvise , Bortolotti Roberto , Racanelli Vito , Jeannin Guido , Padula Angela , Cauli Alberto , Priori Roberta , Gabrielli Armando , Bond Milena , Tedesco Martina , Pazzola Giulia , Tomietto Paola , Pellecchio Marco , Marvisi Chiara , Maritati Federica , Palmisano Alessandra , Dejaco Christian , Willeit Johann , Kiechl Stefan , Olivotto Iacopo , Willeit Peter , Prisco Domenico , Vaglio Augusto , Emmi Giacomo
Published: November 2020

Background and objective

Systemic small vessel vasculitides carry an increased risk of acute arterial and venous thromboembolic events (AVTE); however, this risk has not been systematically explored in Eosinophilic Granulomatosis with Polyangiitis (EGPA). This study assessed the occurrence and main risk factors of AVTE among EGPA patients as compared to the general community from the population-based Bruneck cohort.

Methods

We conducted a retrospective multicenter cohort study on 573 EGPA patients. Clinical and serological data were collected at diagnosis. Occurrence of AVTE and time to the first AVTE after EGPA diagnosis were recorded. Age-standardized event rate (SER) of AVTE as compared to the reference cohort was assessed. Cox regression was applied to identify AVTE predictors.

Results

129 EGPA patients (22.5%) had AVTE, considered as potentially life-threatening in 55.8%. Seventy patients experienced an AVTE prior to diagnosis (of whom 58.6% in the two years before diagnosis) and 75 following EGPA diagnosis, of whom 56% in the two subsequent years. The SER of AVTE as compared to the reference cohort was 2.10 (95% CI 1.67-2.63). This risk was particularly increased in patients with history of AVTE and with a Birmingham Vasculitis Activity Score ≥20 at diagnosis. Patients receiving immunosuppression within 2 months of diagnosis were at lower risk, while antiplatelet or anticoagulant treatment did not confer measurable benefit.

Conclusion

EGPA is associated with AVTE in approximately one quarter of patients, particularly around diagnosis. Immunosuppressants seemed to exert a protective effect, while anticoagulant and antiplatelet agents did not.
Characterising COVID-19 as a Viral Clotting Fever: A Mixed Methods Scoping Review
Authors: Marley Justin , Marley Nisha
Published: November 2020

Background

The COVID-19 pandemic has claimed over 1 million lives globally and results from the SARS-COV2 virus. COVID-19 is associated with a coagulopathy. In this mixed-methods PRISMA-compliant scoping review, we set out to determine if ARDS, sepsis and DIC could account for the coagulopathy and if there were any other features of the coagulopathy we could determine so as to inform future research. Methods: We used a search strategy to identify papers with clinically relevant thromboembolic events in COVID-19. We then developed a technique referred to as an Abridged Thematic Analysis (ATA) to quickly identify themes in the papers so as to increase the yield of clinically relevant information. We further developed Validated Abridged Thematic Analysis (VATA) to validate the resulting taxonomy of themes. Finally we developed a number of methods that can be used by other researchers to take forwards this work. Results: We identified 56 studies with 10,523 patients, 456 patients with COVID-19 and thromboembolic events (TBE’s) and 586 thrombembolic events. There were an average of 1.3 TBE’s per patient. There were five main arterial territories with corresponding clinical sequelae: Acute limb ischaemia, myocardial infarcts, strokes, mesenteric ischaemia and pulmonary embolism. We also identified DVT’s. There were two further groups: medical-device-related coagulopathy and dermal lesions. In a subgroup of 119 patients we found mortality ranged from 26% in DVT to 79% in acute limb ischaemia although there was evidence of selection bias in the latter group. All patients were hospitalised and the average age of survivors was 63 versus 73 for those who died. 91/150 patients with TE’s had fever. From the ATA, we identified 16 characteristics of the clotting pathology in COVID-19. From the VATA, we identified 34 mechanisms leading to coagulopathy and grouped them according to Virchow’s triad of vascular damage, stasis and hypercoagulability. Coagulopathy occurred with and without each of ARDS, Sepsis and DIC. We conclude that COVID-19 leads to the syndrome of a viral clotting fever in a subgroup of patients and that the presentation of coagulopathy and fever should raise the possibility of COVID-19 as a differential. We make recommendations for future research studies.
Anti-SARS-CoV-2 IgG responses are powerful predicting signatures for the outcome of COVID-19 patients
Authors: Lei Qing , Yu Cai-zheng , Li Yang , Hou Hong-yan , Xu Zhao-wei , Yao Zong-jie , Zhang Yan-di , Lai Dan-yun , Ndzouboukou Jo-Lewis Banga , Zhang Bo , Chen Hong , Ouyang Zhu-qing , Xue Jun-biao , Lin Xiao-song , Zheng Yun-xiao , Wang Xue-ning , Jiang He-wei , Zhang Hai-nan , Qi Huan , Guo Shu-juan , He Mei-an , Sun Zi-yong , Wang Feng , Tao Sheng-ce , Fan Xiong-lin
Published: November 2020

The COVID-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for early predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies evolved with disease progression and severity in COIVD-19 patients. We assumed that antibodies may serve as biomarkers for predicting disease outcome. By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgG responses against 20 proteins of SARS-CoV-2 in 1,034 hospitalized COVID-19 patients on admission and followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality. We found that nonsurvivors induced higher levels of IgG responses against most of non-structural proteins than survivors on admission. In particular, the magnitude of IgG antibodies against 8 non-structural proteins (NSP1, NSP4, NSP7, NSP8, NSP9, NSP10, RdRp, and NSP14) and 2 accessory proteins (ORF3b and ORF9b) possessed significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory biomarkers for disease severity (all with p trend < 0.05). Additionally, IgG responses to all of these 10 non-structural/accessory proteins were also associated with the severity of disease, and differential kinetics and serum positive rate of these IgG responses were confirmed in COVID-19 patients of varying severities within 20 days after symptoms onset. The AUCs for these IgG responses, determined by computational cross-validations, were between 0.62 and 0.71. Our findings have important implications for improving clinical management, and especially for developing medical interventions and vaccines.
Non-occupational and occupational factors associated with specific SARS-CoV-2 antibodies among Hospital Workers – a multicentre cross-sectional study
Authors: Kahlert Christian R. , Persi Raphael , Güsewell Sabine , Egger Thomas , Leal-Neto Onicio B. , Sumer Johannes , Flury Domenica , Brucher Angela , Lemmenmeier Eva , Möller J. Carsten , Rieder Philip , Stocker Reto , Vuichard-Gysin Danielle , Wiggli Benedikt , Albrich Werner C. , Flury Baharak Babouee , Besold Ulrike , Fehr Jan , Kuster Stefan P. , McGeer Allison , Risch Lorenz , Schlegel Matthias , Friedl Andrée , Vernazza Pietro , Kohler Philipp
Published: November 2020

Objectives

Protecting healthcare workers (HCW) from Coronavirus Disease-19 (COVID-19) is critical to preserve the functioning of healthcare systems. We therefore assessed seroprevalence and identified risk factors for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) seropositivity in this population.

Methods

Between June 22nd and August 15th 2020, HCW from institutions in Northern/Eastern Switzerland were screened for SARS-CoV-2 antibodies. We recorded baseline characteristics, non-occupational and occupational risk factors. We used pairwise tests of associations and multivariable logistic regression to identify factors associated with seropositivity.

Results

Among 4’664 HCW from 23 healthcare facilities, 139 (3%) were seropositive. Non-occupational exposures independently associated with seropositivity were contact with a COVID-19-positive household (adjusted OR=54, 95%-CI: 31-97) and stay in a COVID-19 hotspot (aOR=2.2, 95%-CI: 1.1-3.9). Blood group 0 vs. non-0 (aOR=0.4, 95%-CI: 0.3-0.7), active smoking (aOR=0.5, 95%-CI: 0.3-0.9) and living with children <12 years (aOR=0.3, 95%-CI: 0.2-0.6) were associated with decreased risk. Occupational risk factors were close contact to COVID-19 patients (aOR=2.8, 95%-CI: 1.5-5.5), exposure to COVID-19-positive co-workers (aOR=2.0, 95%-CI: 1.2-3.1), poor knowledge of standard hygiene precautions (aOR=2.0, 95%-CI: 1.3-3.2), and frequent visits to the hospital canteen (aOR=1.9, 95%-CI: 1.2-3.1).

Conclusions

Living with COVID-19-positive households showed by far the strongest association with SARS-CoV-2 seropositivity. We identified several potentially modifiable risk factors, which might allow mitigation of the COVID-19 risk among HCW. The lower risk among those living with children, even after correction for multiple confounders, is remarkable and merits further study.
Awareness, knowledge and trust in the Greek authorities towards COVID-19 pandemic: results from the Epirus Health Study cohort
Authors: Kanellopoulou Afroditi , Koskeridis Fotios , Markozannes Georgios , Bouras Emmanouil , Soutziou Chrysa , Chaliasos Konstantinos , Doumas Michail T , Sigounas Dimitrios E , Tzovaras Vasilios T , Panos Agapios , Stergiou Yiolanda , Mellou Kassiani , Papamichail Dimitrios , Aretouli Eleni , Chatzidimitriou Dimitrios , Chatzopoulou Fani , Bairaktari Eleni , Tzoulaki Ioanna , Evangelou Evangelos , Rizos Evangelos C , Ntzani Evangelia , Vakalis Konstantinos , Tsilidis Konstantinos K
Published: November 2020

Background

To assess the level of knowledge and trust in the policy decisions taken regarding the coronavirus disease (COVID-19) pandemic among Epirus Health Study (EHS) participants.

Methods

The EHS is an ongoing and deeply-phenotyped prospective cohort study that has recruited 667 participants in northwest Greece until August 31st, 2020. Level of knowledge on coronavirus (SARS-CoV-2) transmission and COVID-19 severity was labeled as poor, moderate or good. Variables assessing knowledge and beliefs towards the pandemic were summarized overall and by gender, age group (25-39, 40-49, 50-59, ≥60 years) and period of report (before the lifting of lockdown measures in Greece: March 30thto May 3rd, and two post-lockdown time periods: May 4thto June 31st, July 1stto August 31st). An exposure-wide association analysis was conducted to evaluate the associations between 153 explanatory variables and participants’ knowledge. Correction for multiple comparisons was applied using a false discovery rate (FDR) threshold of 5%.

Results

A total of 563 participants (49 years mean age; 60% women) had available information on the standard EHS questionnaire, the clinical and biochemical measurements, and the COVID-19-related questionnaire. Percentages of poor, moderate and good knowledge status regarding COVID-19 were 4.5%, 10.0% and 85.6%, respectively. The majority of participants showed absolute or moderate trust in the Greek health authorities for the management of the epidemic (90.1%), as well as in the Greek Government (84.7%) and the official national sources of information (87.4%). Trust in the authorities was weaker in younger participants and those who joined the study after the lifting of lockdown measures (p-value≤0.001). None of the factors examined was associated with participants’ level of knowledge after correction for multiple testing.

Conclusions

High level of knowledge about the COVID-19 pandemic and trust in the Greek authorities was observed, possibly due to the plethora of good quality publicly available information and the timely management of the pandemic at its early stages in Greece. Information campaigns for the COVID-19 pandemic should be encouraged even after the lifting of lockdown measures to increase public awareness.
Parkinson’s Disease, Smoking, and Lower Endoscopy
Authors: Davis Susan M.
Published: November 2020

Parkinson’s disease (PD) is inversely associated with smoking. Whether this association is due to a causal relationship or to confounding by a covariate of smoking is still debated.

The Institute for Health Metrics and Evaluation (IHME) released refreshed data on October 15, 2020. This study included that recently released data. The study included populations of the United States and ten U.S. states from 2004 to 2018. The ten U.S. states included the five states with the highest PD incidence rates in 2019 (Maine, Vermont, Kansas, Alaska, Missouri) and the five states with the lowest PD incidence rates in 2019 (Arkansas, Mississippi, South Dakota, Nebraska, Delaware). The study used scatter plots to explore the association between PD incidence and smoking and the association between PD incidence and a covariate of smoking, lower endoscopy utilization.

For PD verses smoking, the results indicate that there is an inverse correlation for the United States, but there is no association for the ten states. The coefficient of determination (R2) for the United States was 0.714 and ranged from a low of 0.004 for South Dakota to 0.613 for Mississippi. The average R 2 for the ten states was 0.357.

For PD verses lower endoscopy, the results indicate that the best model fit to the data is a polynomial. When the fitting curve examined in the regression analysis was a 3rd order (cubic) polynomial, there was a positive correlation between PD and lower endoscopy for the United States and for all ten states. The R2 for the US was 0.971 and ranged from a low of 0.709 for Alaska to 0.970 for Kansas. The average R2 for the ten states was 0.878.

The results suggest that the inverse association between PD incidence and smoking is confounded by a positive association between PD and lower endoscopy utilization. Further investigation of a possible relationship between PD incidence and lower endoscopy utilization is warranted and may provide a means for reducing PD incidence.
Heavy load carrying and musculoskeletal health: An exploratory study of sand miners in Pokhara, Kaski District, Nepal
Authors: Koyuncu Aybüke , Bates Michael N. , Petrin Ziva , Cope Myles , McCoy Sandra I. , Prata Ndola , Sijali Tula Ram , Harris-Adamson Carisa
Published: November 2020

Background

Trends in urbanization contribute to the growing global demand for raw construction materials. The health effects of load carrying among occupational groups that mine and carry sand and stone used for construction of roads and buildings remains poorly understood.

Methods

We conducted an exploratory cross-sectional study among a convenience sample of sand miners working at an excavation site on the Seti River in Pokhara, Nepal. Load carrying weight, duration, and frequency were used to categorize miners as having “low” or “high” load-carrying exposures. Probable musculoskeletal disorders (MSDs) were identified using self-reported symptoms of moderate to severe musculoskeletal pain, as well as physical examinations.

Results

The average loads carried by female and male sand miners weighed 66.3 kg and 87.3 kg, respectively. Among all participants (N=42), 45.2% reported moderate to severe musculoskeletal pain in at least one body region and 16 (38.1%) had probable MSDs identified using specified case criteria. The prevalence of MSDs was lower among miners carrying, on average, heavier loads compared to those carrying lighter loads (ORa=0.29; 95% CI: 0.05, 1.8), possibly indicative of the healthy worker survival effect. Miners carrying loads for longer durations and frequencies had higher odds of MSDs compared with those carrying for shorter durations and frequencies.

Conclusion

Despite the pervasiveness of load carrying as an income generating activity throughout the developing world, these populations remain largely excluded from global occupational health agendas. Larger epidemiologic studies are needed to justify action to protect the health and safety of these unrecognized and understudied groups.
Full activation of an α7-α3β4 nicotinic receptor complex avoids receptor desensitization in human chromaffin cells
Authors: Jiménez-Pompa Amanda , Sanz-Lázaro Sara , Medina-Polo José , González-Enguita Carmen , Blázquez Jesús , McIntosh J. Michael , Albillos Almudena
Published: November 2020

α7 nicotinic receptors have been involved in numerous pathologies. A hallmark of these receptors is their extremely fast desensitization, a process not fully understood yet. Here we show that human native α7 and α3β4 nicotinic receptors physically interact in human chromaffin cells of adrenal glands. The full activation of this α7-α3β4 receptor complex avoids subtypes receptor desensitization, leading to gradual increase of currents with successive acetylcholine pulses. Instead, full and partial activation with choline of α7 and α3β4 subtypes, respectively, of this linked receptor leads to α7 receptor desensitization. Therefore choline, a product of the acetylcholine hydrolysis, acts as a brake by limiting the increase of currents by acetylcholine. Very importantly, the efficiency of the α7-α3β4 interaction diminishes in subjets older than 50 years, accordingly increasing receptor desensitization and decreasing nicotinic currents. These results open a new line of research to achieve improved therapeutic treatments for nicotinic receptors related diseases.
Multilevel Twin Models: Geographical Region as a Third Level Variable
Authors: Tamimy Zenab , Kevenaar Sofieke T. , Hottenga Jouke Jan , Hunter Michael D. , de Zeeuw Eveline L. , Neale Michael C. , van Beijsterveldt Catharina E.M. , Dolan Conor V. , van Bergen Elsje , Boomsma Dorret I.
Published: November 2020

The classical twin model can be reparametrized as an equivalent multilevel model. The multilevel parameterization has underexplored advantages, such as the possibility to include higher-level clustering variables in which lower levels are nested. When this higher-level clustering is not modeled, its variance is captured by the common environmental variance component. In this paper we illustrate the application of a 3-level multilevel model to twin data by analyzing the regional clustering of 7-year-old children’s height in the Netherlands. Our findings show that 1.8%, of the phenotypic variance in children’s height is attributable to regional clustering, which is 7% of the variance explained by between-family or common environmental components. Since regional clustering may represent ancestry, we also investigate the effect of region after correcting for genetic principal components, in a subsample of participants with genome-wide SNP data. After correction, region did no longer explain variation in height. Our results suggest that the phenotypic variance explained by region actually represent ancestry effects on height.
Recovering genomes and phenotypes using allele-specific gene expression
Authors: Gürsoy Gamze , Lu Nancy , Wagner Sarah , Gerstein Mark
Published: November 2020

With the recent increase in RNA sequencing efforts using large cohorts of individuals, studying allele-specific gene expression is becoming increasingly important. Here, we report that, despite not containing explicit variant information, a list of allele-specific gene names of an individual is enough to recover key variants and link the individual back to their genome or phenotype. This creates a privacy conundrum.
Dissociable effects of subliminal incentives on initiation and velocity control of goal-directed eye movements
Authors: Hinze Vasko Kilian , Uslu Ozge , Antono Jessica Emily , Wilke Melanie , Pooresmaeili Arezoo
Published: November 2020

Over the last decades, several studies have demonstrated that conscious and unconscious reward incentives both affect performance in physical and cognitive tasks, suggesting that goal-pursuit can arise from an unconscious will. Whether the planning of goal-directed saccadic eye movements during an effortful task can also be affected by subliminal reward cues has not been systematically investigated. We employed a novel task where participants had to make several eye movements back and forth between a fixation point and a number of peripheral targets. The total number of targets visited by the eyes in a fixed amount of time determined participants’ monetary gain. The magnitude of the reward at stake was briefly shown at the beginning of each trial and was masked by pattern images superimposed in time. We found that when reward cues were fully visible and thus consciously perceived, higher reward enhanced all saccade parameters. However, a dissociation was observed between the effects of subliminal rewards on saccade initiation and peak velocities. While truly subliminal reward cues did increase the number of saccades, they did not enhance saccades’ peak velocity. Additionally, participants who had reached a truly subliminal level of reward perception showed a decrement in accuracy as a function of reward across all visibility levels, as saccade endpoint error was larger when higher reward incentives were expected. This suboptimal speed-accuracy trade-off did not occur in the supraliminal group. These results suggest that although saccades’ initiation can be triggered by subconscious mechanisms, conscious awareness is required to optimally adjust the velocity and accuracy of eye movements based on the expected rewards.
Distinct population code for movement kinematics and changes of ongoing movements in human subthalamic nucleus
Authors: London Dennis , Fazl Arash , Katlowitz Kalman , Soula Marisol , Pourfar Michael H , Mogilner Alon Y , Kiani Roozbeh
Published: November 2020

The subthalamic nucleus (STN) is theorized to globally suppress movement through connections with downstream basal ganglia structures. Current theories are supported by increased STN activity when subjects withhold an uninitiated action plan, but a critical test of these theories requires studying STN responses when an ongoing action is replaced with an alternative. Here, we perform this test using an extended reaching task with instructions to switch movement trajectory mid-action. We show that STN activity decreases during action switches, contrary to prevalent theories. Further, beta oscillations in the local field potential in STN, which are associated with movement inhibition do not show increased power or entraining of neuronal firing during switches. We report an inhomogeneous population neural code in STN, with one sub-population encoding movement kinematics and direction and another encoding unexpected action switches. We suggest an elaborate neural code in STN that contributes to planning actions and changing the plans.
Local topology, bifurcations and mutation hot-spots in proteins with SARS-CoV-2 spike protein as an example
Authors: Peng Xubiao , Niemi Antti J
Published: November 2020

Novel topological methods are introduced to protein research. The aim is to identify hot-spot sites where a bifurcation can change the local topology of the protein backbone. Since the shape of a protein is intimately related to its biological function, a mutation that takes place at such a bifurcation hot-spot has an enhanced capacity to change the protein’s biological function. The methodology applies to any protein but it is developed with the SARS-CoV-2 spike protein as a timely example. First, topological criteria are introduced to identify and classify potential mutation hot-spot sites along the protein backbone. Then, the expected outcome of a substitution mutation is estimated for a general class of hot-spots, by a comparative analysis of the backbone segments that surround the hot-spot sites. This analysis employs the statistics of commensurable amino acid fragments in the Protein Data Bank, in combination with general stereochemical considerations. It is observed that the notorious D614G substitution of the spike protein is a good example of such a mutation hot-spot. Several topologically similar examples are then analyzed in detail, some of them are even better candidates for a mutation hot-spot than D614G. The local topology of the recently observed N501Y mutation is also inspected, and it is found that this site is prone to a different kind of local topology changing bifurcation.
Synaptic integration of subquantal neurotransmission by co-localized G protein coupled receptors in presynaptic terminals
Authors: Church Emily , Hamid Edaeni , Zurawski Zack , Potcoava Mariana , Flores-Barrera Eden , Caballero Adriana , Tseng Kuei Y. , Alford Simon
Published: November 2020

In presynaptic terminals, membrane-delimited Gi/o-mediated presynaptic inhibition is ubiquitous and acts through Gβγ to inhibit Ca2+ entry, or directly at SNARE complexes to inhibit Ca2+-dependent synaptotagmin-SNARE complex interactions. At CA1-subicular presynaptic terminals 5-HT1B and GABAB receptors colocalize. GABAB receptors inhibit Ca2+ entry, whereas 5-HT1B receptors target SNARE complexes. We demonstrate in male and female rats that GABAB receptors receptors alter Pr, whereas 5-HT1B receptors reduce evoked cleft glutamate concentrations allowing differential inhibition of AMPA and NMDA receptor EPSCs. This reduction in cleft glutamate concentration was confirmed by imaging glutamate release using a genetic sensor (iGluSnFR).Simulations of glutamate release and postsynaptic glutamate receptor currents were made. We tested effects of changes in vesicle numbers undergoing fusion at single synapses, relative placement of fusing vesicles and postsynaptic receptors, and the rate of release of glutamate from a fusion pore. Experimental effects of Pr changes, consistent with GABAB receptor effects, were straightforwardly represented by changes in numbers of synapses. The effects of 5-HT1B receptor-mediated inhibition are well-fit by simulated modulation of the release rate of glutamate into the cleft. Colocalization of different actions of GPCRs provide synaptic integration within presynaptic terminals. Train-dependent presynaptic Ca2+ accumulation forces frequency-dependent recovery of neurotransmission during 5-HT1B receptor activation. This is consistent with competition between Ca2+-synaptotagmin and Gβγ at SNARE complexes. Thus, stimulus trains in 5-HT1B receptor agonist unveil dynamic synaptic modulation and a sophisticated hippocampal output filter that itself is modulated by colocalized GABAB receptors which alter presynaptic Ca2+. In combination these pathways allow complex presynaptic integration.

Significance Statement

Two G protein coupled receptors colocalize at presynaptic sites, to mediate presynaptic modulation by Gβγ, but one – a GABAB receptor inhibits Ca2+ entry while another – a 5-HT1B receptor competes with Ca2+-synaptotagmin binding to the synaptic vesicle machinery. We have investigated downstream effects of signaling and integrative properties of these receptors. Their effects are profoundly different. GABAB receptors alter Pr leaving synaptic properties unchanged, while 5-HT1B receptors fundamentally change properties of synaptic transmission, modifying AMPA receptor but sparing NMDA receptor responses. Co-activation of these receptors allows synaptic integration because of convergence of GABAB receptor alteration on Ca2+ and the effect of this altered Ca2+ signal on 5-HT1B receptor signaling. This presynaptic convergence provides a novel form of synaptic integration.
Extracellular signal-regulated kinase mediates chromatin rewiring and lineage transformation in lung cancer
Authors: Inoue Yusuke , Nikolic Ana , Farnsworth Dylan , Liu Alvin , Ladanyi Marc , Somwar Romel , Gallo Marco , Lockwood William W.
Published: November 2020

Lineage transformation between lung cancer subtypes is a poorly understood phenomenon associated with resistance to treatment and poor patient outcomes. Here, we aimed to model this transition to define underlying biological mechanisms and identify potential avenues for therapeutic intervention. Small cell lung cancer (SCLC) is neuroendocrine in origin and, in contrast to non-SCLC (NSCLC), rarely contains mutations that drive the MAPK pathway. Likewise, NSCLCs that transform to SCLC concomitantly with development of therapy resistance downregulate MAPK signaling, suggesting an inverse relationship between pathway activation and lineage state. To test this, we activated MAPK in SCLC through conditional expression of mutant KRAS or EGFR, which revealed suppression of the neuroendocrine differentiation program via ERK. We found that ERK induces the expression of ETS factors that mediate transformation into a NSCLC-like state. ATAC-seq demonstrated ERK-driven changes in chromatin accessibility at putative regulatory regions and global chromatin rewiring at neuroendocrine and ETS transcriptional targets. Further, ERK-mediated induction of ETS factors as well as suppression of neuroendocrine differentiation were dependent on histone acetyltransferase activities of CBP/p300. Overall, we describe how the ERK-CBP/p300-ETS axis promotes a lineage shift between neuroendocrine and non-neuroendocrine lung cancer phenotypes and provide rationale for the disruption of this program during transformation-driven resistance to targeted therapy.
A Multiplexed Bacterial Two-Hybrid for Rapid Characterization of Protein-Protein Interactions and Iterative Protein Design
Authors: Boldridge W. Clifford , Ljubetič Ajasja , Kim Hwangbeom , Lubock Nathan , Szilágyi Dániel , Lee Jonathan , Brodnik Andrej , Jerala Roman , Kosuri Sriram
Published: November 2020

Myriad biological functions require protein-protein interactions (PPIs), and engineered PPIs are crucial for applications ranging from drug design to synthetic cell circuits. Understanding and engineering specificity in PPIs is particularly challenging as subtle sequence changes can drastically alter specificity. Coiled-coils are small protein domains that have long served as a simple model for studying the sequence-determinants of specificity and have been used as modular building blocks to build large protein nanostructures and synthetic circuits. Despite their simple rules and long-time use, building large sets of well-behaved orthogonal pairs that can be used together is still challenging because predictions are often inaccurate, and, as the library size increases, it becomes difficult to test predictions at scale. To address these problems, we first developed a method called the Next-Generation Bacterial Two-Hybrid (NGB2H), which combines gene synthesis, a bacterial two-hybrid assay, and a high-throughput next-generation sequencing readout, allowing rapid exploration of interactions of programmed protein libraries in a quantitative and scalable way. After validating the NGB2H system on previously characterized libraries, we designed, built, and tested large sets of orthogonal synthetic coiled-coils. In an iterative set of experiments, we assayed more than 8,000 PPIs, used the dataset to train a novel linear model-based coiled-coil scoring algorithm, and then characterized nearly 18,000 interactions to identify the largest set of orthogonal PPIs to date with twenty-two on-target interactions.
Nanodroplet-Benzalkonium Chloride Formulation DemonstratesIn VitroandEx-VivoBroad-Spectrum Antiviral Activity Against SARS-CoV-2 and other Enveloped Viruses
Authors: Pannu Jessie , Ciotti Susan , Ganesan Shyamala , Arida George , Costley Chad , Fattom Ali
Published: November 2020

The Covid-19 pandemic has highlighted the importance of aerosolized droplets inhaled into the nose in the transmission of respiratory viral disease. Inactivating pathogenic viruses at the nasal portal of entry may reduce viral loads, thereby reducing transmission and contagion. We have developed an oil-in-water nanoemulsion (nanodroplet)formulationcontaining the potent antiseptic 0.13% Benzalkonium Chloride (NE-BZK) which demonstrates safe and broad anti-viral activity. While The Centers for Disease Control and Prevention (CDC) have reported that BZK may have less reliable activity than ethyl alcohol against certain viruses, including coronaviruses, we have demonstrated that NE-BZK exhibits broad-spectrum, long-lasting antiviral activity with >99.99%in vitrokilling of enveloped viruses including SARS-CoV-2, human coronavirus, RSV and influenza B. Furthermore,in vitrostudies demonstrated that NE-BZK continues to kill >99.99% of human coronavirus even when diluted 20-fold, while 0.13% aqueous BZK solution (AQ-BZK) did not.Ex vivostudies of NE-BZK on human cadaver skin demonstrated persistent >99.99% killing of human coronavirus for at least 8 hours after application. AQ-BZK failed to demonstrate durable antimicrobial activity on skin over time. The repeated application of NE-BZK, twice daily for 2 weeks on to rabbit nostrils indicated safety with no irritation. These findings demonstrate that formulating BZK on the surface of proprietary nanodroplets offers a safe and effective antiviral as a significant addition to strategies to combat the spread of respiratory viral infectious diseases.
Extended spectrum β-lactamase and carbapenemase genes are substantially and sequentially reduced during conveyance and treatment of urban sewage
Authors: Li Liguan , Nesme Joseph , Quintela-Baluja Marcos , Balboa Sabela , Hashsham Syed , Williams Maggie R. , Yu Zhuofeng , Sørensen Søren J. , Graham David W. , Romalde Jesús L. , Dechesne Arnaud , Smets Barth F.
Published: November 2020

Integrated and quantitative observations of antibiotic resistance genes (ARGs) in urban water systems (UWSs) are lacking. We sampled three UWSs for clinically important extended spectrum β-lactamase (ESBL) and carbapenemase (CP) genes, mobile genetic elements and microbial communities. Sewage – especially from hospitals – carried substantial loads of ESBL and CP genes (106– 107per person equivalent), but those loads progressively declined along the UWS, resulting in minimal emissions (101– 104copies per person equivalent). Removal was primarily during sewage conveyance (65% ± 36%) rather than within sewage treatment (34% ± 23%). The ARGs clustered in groups based on their persistence; less persistent groups were associated to putative host taxa (especiallyEnterobacteriaceaeandMoraxellaceae), while more persistent groups appear horizontally transferred as they correlated with mobile genetic elements. This first documentation of a substantial ARG reduction during sewage conveyance provides opportunities for antibiotic resistance management and a caution for sewage-based ARG surveillance.