bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmentally enriched housing conditions affect pig welfare, immune system and gut microbiota in early life
Authors: Wen Caifang , van Dixhoorn Ingrid , Schokker Dirkjan , Woelders Henri , Stockhofe-Zurwieden Norbert , Rebel Johanna M. J. , Smidt Hauke
Published: July 2021

Background

Conventional pig housing and management conditions are associated with gastrointestinal pathophysiology and disease susceptibility in early life. Developing new strategies to reduce both therapeutic and prophylactic antibiotic use is urgent for the sustainable swine production globally. To this end, housing methodology providing effective environmental enrichment could be a promising alternative approach to reduce antibiotic usage, as it has been proven to positively influence pig welfare and immune status and reduce susceptibility to infections. It is, however, poorly understood how this enriched housing affects systemic and local pulmonary immune status and gut microbiota colonization during early life. In the present study, we compared the effects of two housing conditions, i.e., conventional housing: (CH) versus enriched housing (EH), on immune status and gut microbiota from birth until 61 days of age.

Results

The expected benefits of enrichment on pig welfare were confirmed as EH pigs showed more positive behaviour, less aggression behaviour during the weaning transition and better human animal relation during the post weaning phase. Regarding the pigs’ immune status, EH pigs had higher values of haemoglobin and mean corpuscular volume in haematological profiles and higher percentages of T cells and cytotoxic T cells in peripheral blood. Furthermore, EH pigs showed higher ex vivo secretion of IL1ß and TNF-α after lipopolysaccharide stimulation of whole blood than CH pigs. The structure of the developing faecal microbiota of CH and EH pigs significantly differed as early as day 12 with an increase in the relative abundance of several bacterial groups known to be involved in the production of short chain fatty acids, such asPrevotella_2,Christensenellaceae_R_7_group andRuminococcus gauvreauiigroup. Furthermore, the main difference between both housing conditions post weaning was that on day 61, CH pigs had significantly larger inter-individual variation of ileal and colonic microbiota than EH pigs. In addition to housing, other intrinsic factors (e.g., sex) were associated with gut microbiota development and immune competence.

Conclusions

In addition to the known welfare benefits for pigs, environmentally enriched housing also positively drives important aspects of the development of the immune system and the establishment of gut microbiota in early life. Consequently, EH may contribute to increasing productivity of pigs and reducing antibiotic use.
Simulation and measurement of air quality in the traffic congestion area
Authors: Yu Shin , Chang Chang Tang , Ma Chih Ming
Published: July 2021

The traffic congestion in the Hsuehshan tunnel and at the Toucheng interchange has led to traffic-related air pollution with increasing concern. To ensure the authenticity of our simulation, the concentration of the last 150 m in Hsuehshan tunnel was simulated using the computational fluid dynamics fluid model. The air quality at the Toucheng interchange along a 2 km length highway was simulated using the California Line Source Dispersion Model. The differences in air quality between rush hours and normal traffic conditions were also investigated. An unmanned aerial vehicle (UAV) with installed PM2.5 sensors was developed to obtain the three-dimensional distribution of pollutants. On different roads, during the weekend, the concentrations of pollutants such as SOx, CO, NO, and PM2.5 were observed to be in the range of 0.003–0.008, 7.5–15, 1.5–2.5 ppm, and 40–80 μg m− 3, respectively. On weekdays, the vehicle speed and the natural wind were 60 km h− 1 and 2.0 m s− 1, respectively. On weekdays, the SOx, CO, NO, and PM2.5 concentrations were found to be in the range of 0.002–0.003, 3–9, 0.7–1.8 ppm, and 35–50 μg m− 3, respectively. The UAV was used to verify that the PM2.5 concentrations of vertical changes at heights of 9.0, 7.0, 5.0, and 3.0 m were 45–48, 30–35, 25–30, and 50–52 μg m− 3, respectively. In addition, the predicted PM2.5 concentrations were 40–45, 25–30, 45–48, and 45–50 μg m− 3 on weekdays. These results provide a reference model for environmental impact assessments of long tunnels and traffic jam-prone areas. These models and data are useful for transportation planners in the context of creating traffic management plans.
The association between bone mineral density and postoperative drainage volume following cruciate-substituting primary total knee arthroplasty: a cross-sectional study
Authors: Peerakul Yuthasak , Leeyaphan Jirapong , Rojjananukulpong Karn
Published: July 2021

Background

The prevalence of osteoporosis in patients who undergo a primary total knee arthroplasty (TKA) is increasing. Low bone mineral density (BMD) is related to unfavorable outcomes following TKA such as migration of uncemented tibial components. Postoperative blood loss in TKA is an important complication. Non-modifying predicting factors for postoperative blood loss in patients undergoing primary TKA need further elucidation. Studies on the association between BMD and blood loss after TKA are limited. We aimed to demonstrate the relationship between BMD and postoperative drainage volume following primary TKA.

Methods

A cross-sectional study was conducted between January 2014 and August 2020. A total of 119 primary varus osteoarthritis knees with BMD results were included in the study. Patients with secondary causes of osteoporosis were excluded.

Results

The median postoperative drainage volume of participants in the normal total hip BMD group and the normal trochanter BMD group was higher than that of patients in the low total hip BMD group and the low trochanter BMD group (285.0 ml vs 230.0 ml, P = 0.003; 282.5 ml vs 240.0 ml, P = 0.013, respectively). Multivariate regression analyses showed that operative time, spinal anesthesia, and normal total hip BMD status were significant predictive factors associated with increased postoperative drainage volume (P = 0.014, 0.022, and 0.013, respectively). No association was identified between the lumbar spine BMD status and postoperative drainage volume.

Conclusions

The relationship between BMD and postoperative blood loss in primary TKA was identified in this study. Normal total hip BMD was found to be associated with an increased postoperative drainage volume after primary TKA compared with low BMD.
Development and validation of RP HPLC method for the estimation of Sofosbuvir and related impurity in bulk and pharmaceutical dosage form
Authors: Ganji Shiny , Dhulipala Satyavati , Nemala Appala Raju
Published: July 2021

Background

The present work is aimed at development and validation of RP HPLC method which is simple, specific, precise, and accurate for estimation of Sofosbuvir and its process-related impurity in bulk and pharmaceutical dosage forms. Extensive literature survey revealed no method for estimation of the above said. The chromatographic separation was achieved on Agilent Eclipse XDB-C18, 4.6 × 250 mm, 5 μm with mobile phase composed of 0.1% trifluoroacetic acid in 1000 ml of water:acetonitrile (50:50) using an isocratic mode of elution. Detection was made using UV detector at 260.0 nm and LC solution software for analysis of data. The developed method was validated according to ICH guidelines.

Results

The linearity of calibration curve for Sofosbuvir in concentration range of 160-480 μg/ml was good. The curve was linear for its process related impurity (Phosphoryl) in concentration range of 10-30 μg/ml. There exists a good correlation between peak area and analyte concentration. Retention time for Sofosbuvir was found to be 3.674 min and its impurity was 5.704 min. Relative standard deviation values for Sofosbuvir is 1.741 and its process related impurity is 0.043. LOD for Sofosbuvir and its impurity was found to be 0.01% (0.04 μg) and 0.03% (0.12 μg) respectively. LOQ for Sofosbuvir and its impurity was found to be 0.50% (0.125 μg) and 1.50% (0.375 μg) respectively.

Conclusion

All the results reveal that the proposed method was found to be highly sensitive, simple, precise, accurate, robust, and fast. Large number of samples can be analyzed in shorter time due to shorter retention times, so it can be successfully applied for routine analysis of Sofosbuvir and related phosphoryl impurity in bulk and pharmaceutical dosage forms.
A Blood-based Polyamine Signature Associated With MEN1 Duodenopancreatic Neuroendocrine Tumor Progression
Authors: Fahrmann Johannes F , Wasylishen Amanda R , Pieterman Carolina R C , Irajizad Ehsan , Vykoukal Jody , Murage Eunice , Wu Ranran , Dennison Jennifer B , Krishna Hansini , Peterson Christine B , Lozano Guillermina , Zhao Hua , Do Kim-Anh , Halperin Daniel M , Agarwal Sunita K , Blau Jenny E , Del Rivero Jaydira , Nilubol Naris , Walter Mary F , Welch James M , Weinstein Lee S , Vriens Menno R , van Leeuwaarde Rachel S , van Treijen Mark J C , Valk Gerlof D , Perrier Nancy D , Hanash Samir M
Published: July 2021

Context

Duodenopancreatic neuroendocrine tumors (dpNETs) frequently occur in patients with multiple endocrine neoplasia type 1 (MEN1), and metastatic dpNET is the primary cause of disease-related mortality. There is a need for biomarkers that can identify patients with MEN1-related dpNETs that are at high risk of developing distant metastasis. Polyamines have tumor-promoting roles in several cancer types.

Objective

We hypothesized that MEN1-dpNET–related disease progression is associated with elevated levels of circulating polyamines.

Methods

Through an international collaboration between The University of Texas MD Anderson Cancer Center, the National Institutes of Health, and the University Medical Center Utrecht, plasma polyamine levels were assessed using mass spectrometry in 84 patients with MEN1 (20 with distant metastatic dpNETs [patients] and 64 with either indolent dpNETs or no dpNETs [controls]). A mouse model of MEN1-pNET, Men1fl/flPdx1-CreTg, was used to test time-dependent changes in plasma polyamines associated with disease progression.

Results

A 3-marker plasma polyamine signature (3MP: N-acetylputrescine, acetylspermidine, and diacetylspermidine) distinguished patients with metastatic dpNETs from controls in an initial set of plasmas from the 3 participating centers. The fixed 3MP yielded an area under the curve of 0.84 (95% CI, 0.62-1.00) with 66.7% sensitivity at 95% specificity for distinguishing patients from controls in an independent test set from MDACC. In Men1fl/flPdx1-CreTg mice, the 3MP was elevated early and remained high during disease progression.

Conclusion

Our findings provide a basis for prospective testing of blood-based polyamines as a potential means for monitoring patients with MEN1 for harboring or developing aggressive disease.
Dexmedetomidine Ameliorates Perioperative Neurocognitive Disorders by Suppressing Monocyte-Derived Macrophages in Mice With Preexisting Traumatic Brain Injury
Authors: Kii Natsumi , Sawada Atsushi , Yoshikawa Yusuke , Tachibana Shunsuke , Yamakage Michiaki
Published: July 2021

BACKGROUND:

Traumatic brain injury (TBI) initiates immune responses involving infiltration of monocyte-derived macrophages (MDMs) in the injured brain tissue. These MDMs play a key role in perioperative neurocognitive disorders (PNDs). We tested the hypothesis that preanesthetic treatment with dexmedetomidine (DEX) could suppress infiltration of MDMs into the hippocampus of TBI model mice, ameliorating PND.

METHODS:

We first performed bone marrow transplantation from green fluorescent protein-transgenic mice to C57BL/6 mice to identify MDMs. We used only male mice for homogeneity. Four weeks after transplantation, a controlled cortical impact model of TBI was created using recipient mice. Four weeks after TBI, mice received pretreatment with DEX before general anesthesia (GA). Mice performed the Barnes maze test (8–12 mice/group) 2 weeks after GA and were euthanized for immunohistochemistry (4–5 mice/group) or immunoblotting (7 mice/group) 4 weeks after GA.

RESULTS:

In Barnes maze tests, TBI model mice showed longer primary latency (mean difference, 76.5 [95% confidence interval, 41.4–111.6], P < .0001 versus Naïve), primary path length (431.2 [98.5–763.9], P = .001 versus Naïve), and more primary errors (5.7 [0.62–10.7], P = .017 versus Naïve) than Naïve mice on experimental day 3. Expression of MDMs in the hippocampus was significantly increased in TBI mice compared to Naïve mice (2.1 [0.6–3.7], P = .003 versus Naïve). Expression of monocyte chemotactic protein-1 (MCP1)-positive areas in the hippocampus was significantly increased in TBI mice compared to Naïve mice (0.38 [0.09–0.68], P = .007 versus Naïve). Immunoblotting indicated significantly increased expression of interleukin-1β in the hippocampus in TBI mice compared to Naïve mice (1.59 [0.08–3.1], P = .035 versus Naïve). In contrast, TBI mice pretreated with DEX were rescued from these changes and showed no significant difference from Naïve mice. Yohimbine, an α2 receptor antagonist, mitigated the effects of DEX (primary latency: 68.3 [36.5–100.1], P < .0001 versus TBI-DEX; primary path length: 414.9 [120.0–709.9], P = .0002 versus DEX; primary errors: 6.6 [2.1–11.2], P = .0005 versus TBI-DEX; expression of MDMs: 2.9 [1.4–4.4], P = .0001 versus TBI-DEX; expression of MCP1: 0.4 [0.05–0.67], P = .017 versus TBI-DEX; expression of interleukin-1β: 1.8 [0.34–3.35], P = .01 versus TBI-DEX).

CONCLUSIONS:

Preanesthetic treatment with DEX suppressed infiltration of MDMs in the hippocampus and ameliorated PND in TBI model mice. Preanesthetic treatment with DEX appears to suppress infiltration of MDMs in the hippocampus and may lead to new treatments for PND in patients with a history of TBI.
Napalm Colonization: Native Peoples in Brazil's Aeronautical Frontiers
Authors: Cruz Felipe Fernandes
Published: July 2021

This article investigates how aviation shaped Brazilian frontier colonization beginning in the 1940s and how Indigenous peoples came to use aviation for their own purposes. Backed by a technocratic ideology, the Getúlio Vargas regime saw aeronautics as a fix for the state's lack of control over the frontiers. Beginning with its March to the West program, the government used aviation to quickly explore and colonize vast territories previously out of its reach. The military radically transformed this method in the 1960s, using napalm and paratroopers to quickly create outposts and settlements. This article introduces the term aeronautical frontier to define unique regions where flying was the primary mode of transportation. While much of the discourse on Indigenous peoples and aviation has focused on defensive reactions to the incoming airplanes, this article shows how Native Brazilians appropriated the technology for their own means, mastering it for their own use in aeronautical frontiers.
The snake heart pacemaker is localized near the sinoatrial valve
Authors: Abramochkin Denis V. , Kuzmin Vladislav S. , Matchkov Vladimir , Kamensky Andrey A. , Wang Tobias
Published: July 2021

To provide the first description of the exact location of primary pacemaker of the squamate heart, we used sharp microelectrode impalements and optical mapping of isolated sinus venosus preparations from Burmese pythons. We located the dominant pacemaker site at the base of the right leaflet of the sinoatrial valve (SAV), but latent pacemakers were also identified in a circular region around the SAV. Acetylcholine (10−5 mol l−1) or noradrenaline (10−6 mol l−1) induced shifts of the leading pacemaker site to other points near the SAV. The ionic currents of most of the cardiomyocytes isolated enzymatically from the SAV region resembled those of typical working myocytes from the sinus venosus. However, seven cells lacked the background inward rectifier current (IK1) and had a time-dependent hyperpolarization-induced inward current identified as the ‘funny’ pacemaker current (If). Therefore, the region proximal to SAV demonstrates pacemaking activity and contains cells that resemble the electrophysiological properties of mammalian pacemaker myocytes.
The Long-Run Effects of Childhood Insurance Coverage: Medicaid Implementation, Adult Health, and Labor Market Outcomes
Authors: Goodman-Bacon Andrew
Published: July 2021

This paper estimates the long-run effects of childhood Medicaid eligibility on adult health and economic outcomes using the program’s original introduction ( 1966–1970) and its mandated coverage of welfare recipients. The design compares cohorts born in different years relative to Medicaid implementation, in states with different preexisting welfare-based eligibility. Early childhood Medicaid eligibility reduces mortality and disability, increases employment, and reduces receipt of disability transfer programs up to 50 years later. Medicaid has saved the government more than its original cost and saved more than 10 million quality adjusted life years. (JEL H51, I12, I18, I32, I38, J13)
What to Expect from the Lower Bound on Interest Rates: Evidence from Derivatives Prices
Authors: Mertens Thomas M. , Williams John C.
Published: July 2021

This paper analyzes the effects of the lower bound for interest rates on the distributions of inflation and interest rates. In a New Keynesian model with a lower bound, two equilibria emerge: policy is mostly unconstrained in the “target equilibrium,” whereas policy is mostly constrained in the “liquidity trap equilibrium.” Using options data on interest rates and inflation, we find forecast densities consistent with the target equilibrium and find no evidence in favor of the liquidity trap equilibrium. The lower bound has a sizable effect on the distribution of interest rates, but its impact on inflation is relatively modest. (JEL E12, E23, E31, E43, E52, G13)
Place-Based Drivers of Mortality: Evidence from Migration
Authors: Finkelstein Amy , Gentzkow Matthew , Williams Heidi
Published: July 2021

We estimate the effect of current location on elderly mortality by analyzing outcomes of movers in the Medicare population. We control for movers’ origin locations as well as a rich vector of pre-move health measures. We also develop a novel strategy to adjust for remaining unobservables, using the correlation of residual mortality with movers’ origins to gauge the importance of omitted variables. We estimate substantial effects of current location. Moving from a tenth to a ninetieth percentile location would increase life expectancy at age 65 by 1.1 years, and equalizing location effects would reduce cross-sectional variation in life expectancy by 15 percent. Places with favorable life expectancy effects tend to have higher quality and quantity of health care, less extreme climates, lower crime rates, and higher socioeconomic status. (JEL H51, I1, I11)
Predictive value of contrast-enhanced ultrasound combined with conventional ultrasound in solid renal parenchymal lesions
Authors: Cai Yingyu , Li Fan , Li Zhaojun , Li Xin , Li Chunxiao , Xia Zhen , Du Lianfang , Wu Rong
Published: July 2021

Objective:

This study aimed to develop a model to predict the risk of malignancy in solid renal parenchymal lesions based on the imaging features of combined conventional and contrast-enhanced ultrasound (CEUS).

Methods:

A retrospective review was performed among patients with focal solid renal parenchymal lesions on ultrasound images. Ultrasound features were characterized by two experienced radiologists independently. A multiple logistic regression analysis was performed to determine the most relevant features and to estimate the risk of malignancy. Scoring and counting methods were developed based on the most relevant features. The diagnostic performance was evaluated by the sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver operating characteristic curve (AUC).

Results:

A total of 519 renal lesions were included in this study. The conventional ultrasound features of diameter, echogenicity, hypoechoic rim and the CEUS feature of heterogeneity were identified as the most relevant features for prediction of malignancy. The sensitivity and specificity for the logistic regression model, the scoring method and the counting method were 95.3 and 93.4%, 93.8 and 87.8%, 88.8 and 93.9%, respectively. The logistic model had the best performance for diagnosing malignant renal lesions with AUC of 0.978, compared with the scoring method and the counting method with AUCs of 0.958 and 0.965.

Conclusion:

The combination of contrast-enhanced ultrasound with conventional ultrasound improved the diagnostic performance of solid renal lesions based on the logistic regression model.

Advances in knowledge:

In this study, we revealed that the combination of CEUS and conventional ultrasound provided higher accuracy for diagnosing malignant renal tumors.
The diagnostic performance of chest radiographs for lung malignancy in symptomatic primary-care populations: A systematic review and meta-analysis
Authors: Dwyer-Hemmings Louis , Fairhead Cassandra
Published: July 2021

Objectives:

To synthesise existing evidence for the diagnostic accuracy of chest radiographs to detect lung malignancy in symptomatic patients presenting to primary care.

Methods:

A systematic review was performed and reported in accordance with the PRISMA framework, using a protocol prospectively registered with the PROSPERO database (CRD42020212450). Nine databases were searched for relevant studies. Data were extracted and chest radiograph sensitivity and specificity calculated where possible. Risk of bias was assessed using a validated tool. Random effects meta-analysis was performed.

Results:

Ten studies were included. Sensitivity meta-analysis was performed in five studies which were not the high risk of bias, with summary sensitivity of 81% (95% CI: 74–87%). Specificity could be calculated in five studies, with summary specificity of 68% (95% CI: 49–87%).

Conclusions:

The sensitivity of chest radiographs for detecting lung malignancy in primary care is relatively low. Physicians and policymakers must consider strategies to attenuate the possibility of false reassurance with a negative chest radiograph for this significant pathology. Options include widening access to cross-sectional imaging in primary care; however, any intervention would need to take into account the medical and financial costs of possible over-investigation. Prospective trials with long-term follow-up are required to further evaluate the risks and benefits of this strategy.

Advances in knowledge:

The chest radiograph has a sensitivity of 81% and specificity of 68% for lung malignancy in a symptomatic primary-care population. A negative chest radiograph does not exclude lung cancer, and physicians should maintain a low threshold to consider specialist referral or cross-sectional imaging.
Functional and non-functional types of adrenal tumors: a case series
Authors: Indrawan Dwiki Haryo , Prapiska Fauriski Febrian , Warli Syah Mirsya , Sihombing Bungaran , Siregar Ginanda Putra
Published: July 2021

Adrenal gland masses could be classified into functional, malignant, or benign. An adrenal cortical adenoma is one of the most common incidentalomas found with either functional or non-functional type. Pheochromocytoma is a neural crest cell origin tumor associated with catecholamine production. A classic triad of headache, sudden episodic perspiration, and tachycardia marked a pheochromocytoma. We report three patients with adrenal tumors. First, a 52-year-old woman with complaints of pain in the left flank suggests a left kidney tumor. The patient has an increased blood pressure intraoperatively. Adrenal cortical adenoma was found postoperatively. The second case is an Indonesian male 27-year-old with pain in the upper right abdomen. Intraoperative, the patient also has an escalation in blood pressure. Antihypertensive drugs are also used in this patient. Postoperatively, a pathology result of pheochromocytoma was revealed from this patient. The third case, adrenal myelolipoma, was suspected in a 48-year-old male and underwent surgery because of tumor growth. Later, a histopathological examination revealed myelolipoma of the adrenal. Management of adrenal tumor should be done individually based on each patient. In the first and second cases, blood pressure was unstable intraoperatively and was managed using several drugs, and was stable at follow-up. In the third case was no hemodynamic problem. In the case of an adrenal tumor, management tailoring should be based on the individual patient.
Conceptualizing an inquiry-based lingua-cultural learning through telecollaborative exchanges
Authors: Ismailov Murod
Published: July 2021

In recent years, telecollaboration has been gaining popularity among scholars, teachers, and students engaged in foreign language education because it facilitates the use of Internet-mediated communication tools to connect language and culture learners in geographically distant locations. Telecollaboration, as currently viewed in academic and classroom settings, places greater emphasis on the development of learners’ intercultural communicative competence. The problem with this approach is that this process may not consider the possibility that learners engaged in online intercultural exchanges could have limited or no knowledge about certain aspects of their own lingua-culture. We argue that, for learners to effectively share lingua-cultural knowledge with their online peers abroad, there must be a framework that supports the construction of learners’ own intra-cultural knowledge to provide a solid foundation for intercultural learning and communication. In this paper, we develop an inquiry-based model of telecollaboration incorporating both inquiry and online exchange based on the inquiry cycle, which includes engagement, exploration, explanation, elaboration, and evaluation. This paper builds a case for the application of inquiry-based telecollaboration in a real classroom environment, which could not only help learners obtain and eventually share more authentic, deeper knowledge about their lingua-culture, but also promote informed intercultural exchange.
No one left behind: has the pursuit of FP2020’s 120 million additional users goal left some women behind?
Authors: Farid Shiza , Bremner Jason , Anderson Emma
Published: July 2021

Background: An important question is whether the FP2020’s “120 million additional users” goal exacerbated inequities and led to a prioritization of populations within countries where substantial gains towards the goal could be made. We examine FP2020 country data and policies for signs of inequity in gains in modern contraceptive prevalence (MCP) and in the focus of family planning programs and policies.

Methods: We selected 11 countries (Bangladesh, Burundi, Ethiopia, Haiti, Malawi, Mali, Nepal, Pakistan, Senegal, Sierra Leone, Uganda, and Zimbabwe) to conduct a bivariate analysis. We evaluated if MCP growth had been equitable by assessing MCP between two surveys stratified by residence, levels of education, age groups, marital status, and wealth.

Results: In most countries, MCP increased among rural women and in seven African countries these gains were significant. In six countries, MCP gains were significant both among women with no education and in the lowest wealth group. MCP gains among young women aged 15-19 and 20-24 were seen in four African countries: Malawi, Senegal, Sierra Leone, and Uganda.

Conclusions: Our findings suggest that between two surveys since 2010 many countries saw MCP gains across different dimensions of equity and do not suggest a focus on expanded coverage at the expense of equity. As the family planning community begins to look ahead to the next partnership, this analysis can help inform the emerging FP2030 framework, which includes equity as a guiding principle.
Ethics review of multicenter neuro-psychiatric & neurodevelopmental genetics research protocols: a case study of the NeuroDev & NeuroGap-Psychosis studies
Authors: Wolde Telahun Teka , Musesengwa Rosemary , Palk Andrea , Mwaka Erisa, S , Naanyu Violet , Addissie Adamu , Tadele Getnet
Published: July 2021

Complex research such as neuropsychiatric genetics presents unique challenges for research ethics committees (REC), particularly in Africa where genetics research on mental & neurological disorders is still in its infancy. To reflect on these experiences of reviewing Neuropsychiatric Genetic studies we use two multicenter studies, the NeuroDev and NeuroGap-Psychosis studies.

We explored the content of the national guidelines and regulatory frameworks and the processes for ethics review in the participating African countries, to identify regulatory challenges, and to recommend areas for improvement. We also held reflective discussions with REC members involved in the review of the two studies were interviewed discussing their experiences of reviewing the two studies from the point of view of an African REC/REC member who reviewed the studies.

Across all sites, a distinct theme was that the RECs did not have adequate knowledge and expertise for reviewing genetics and genomics studies in general. The review of guidelines showed the need to proactively update guidelines to meet the increasing complexity of research, ensure awareness creation, and continual capacity building of REC members.
Dealing with flexible working requests
Authors: Chander Tina
Published: July 2021

With flexible working requests predicted to rise as the country returns to normal working practices after the pandemic lockdowns, managers should take the time to consider each request on its own merits, says Tina Chander
Refractive-index guiding single crystal optical fiber with air–solid cladding
Authors: Ding Jinmin , Meng Fanchao , Zhao Xiaoting , Yang Lvyun , Wang Xin , Lou Shuqin , Sheng Xinzhi , Buczyński Ryszard , Tao Guangming , Liang Sheng
Published: July 2021

In this study, a refractive-index guiding single-crystal fiber (SCF) with air–solid cladding was proposed and numerical simulation investigation was carried out. In general, refractive-index guided cladding was constructed through air-holes in the solid material. It resulted in the effective reduction in the number of guided-modes, and the single-mode and few-mode transmission could be realized. The influences of different materials with different refractive indices, cladding structure, and fabrication errors on the confinement loss and effective guided-mode number with the variation in wavelength from 2.5 to 3.2 µm were numerically investigated by the finite element method. Thus, the optimal design of the SCF was successfully obtained. This study may open a new avenue for the design of SCFs and their applications in the fiber lasers and sensors.
Long wavelength infrared imaging under ambient thermal radiation via an all-silicon metalens
Authors: Huang Luocheng , Coppens Zachary , Hallman Kent , Han Zheyi , Böhringer Karl F. , Akozbek Neset , Raman Ashok , Majumdar Arka
Published: July 2021

Further miniaturization of imaging systems is prevented by the prevalent, traditional bulky refractive optics today. Meta-optics have recently generated great interest in the visible wavelength as a replacement for refractive optics thanks to their low weight, small size, and amenability to high-throughput semiconductor manufacturing. Here, we extend these meta-optics to the long-wave infrared (LWIR) regime and demonstrate imaging with a 2 cm aperture f/1 all-silicon metalens under ambient thermal emission. We showed that even with the strongly chromatic nature of the metalenses, we can perform ambient light imaging, primarily due to the lack of wavelength discrimination in the sensor, as is the norm for an RGB-camera in the visible.
Evolution to alternative levels of stable diversity leaves areas of niche space unexplored
Authors: Rubin Ilan N. , Ispolatov Iaroslav , Doebeli Michael
Published: July 2021

One of the oldest and most persistent questions in ecology and evolution is whether natural communities tend to evolve toward saturation and maximal diversity. Robert MacArthur’s classical theory of niche packing and the theory of adaptive radiations both imply that populations will diversify and fully partition any available niche space. However, the saturation of natural populations is still very much an open area of debate and investigation. Additionally, recent evolutionary theory suggests the existence of alternative evolutionary stable states (ESSs), which implies that some stable communities may not be fully saturated. Using models with classical Lotka-Volterra ecological dynamics and three formulations of evolutionary dynamics (a model using adaptive dynamics, an individual-based model, and a partial differential equation model), we show that following an adaptive radiation, communities can often get stuck in low diversity states when limited by mutations of small phenotypic effect. These low diversity metastable states can also be maintained by limited resources and finite population sizes. When small mutations and finite populations are considered together, it is clear that despite the presence of higher-diversity stable states, natural populations are likely not fully saturating their environment and leaving potential niche space unfilled. Additionally, within-species variation can further reduce community diversity from levels predicted by models that assume species-level homogeneity.
Modelling the visual world of a velvet worm
Authors: Ljungholm Mikael , Nilsson Dan-E.
Published: July 2021

In many animal phyla, eyes are small and provide only low-resolution vision for general orientation in the environment. Because these primitive eyes rarely have a defined image plane, traditional visual-optics principles cannot be applied. To assess the functional capacity of such eyes we have developed modelling principles based on ray tracing in 3D reconstructions of eye morphology, where refraction on the way to the photoreceptors and absorption in the photopigment are calculated incrementally for ray bundles from all angles within the visual field. From the ray tracing, we calculate the complete angular acceptance function of each photoreceptor in the eye, revealing the visual acuity for all parts of the visual field. We then use this information to generate visual filters that can be applied to high resolution images or videos to convert them to accurate representations of the spatial information seen by the animal. The method is here applied to the 0.1 mm eyes of the velvet worm Euperipatoides rowelli (Onychophora). These eyes of these terrestrial invertebrates consist of a curved cornea covering an irregular but optically homogeneous lens directly joining a retina packed with photoreceptive rhabdoms. 3D reconstruction from histological sections revealed an asymmetric eye, where the retina is deeper in the forward-pointing direction. The calculated visual acuity also reveals performance differences across the visual field, with a maximum acuity of about 0.11 cycles/deg in the forward direction despite laterally pointing eyes. The results agree with previous behavioural measurements of visual acuity, and suggest that velvet worm vision is adequate for orientation and positioning within the habitat.
Negative linkage disequilibrium between amino acid changing variants reveals interference among deleterious mutations in the human genome
Authors: Garcia Jesse A. , Lohmueller Kirk E.
Published: July 2021

Evolutionary forces like Hill-Robertson interference and negative epistasis can lead to deleterious mutations being found on distinct haplotypes. However, the extent to which these forces depend on the selection and dominance coefficients of deleterious mutations and shape genome-wide patterns of linkage disequilibrium (LD) in natural populations with complex demographic histories has not been tested. In this study, we first used forward-in-time simulations to predict how negative selection impacts LD. Under models where deleterious mutations have additive effects on fitness, deleterious variants less than 10 kb apart tend to be carried on different haplotypes relative to pairs of synonymous SNPs. In contrast, for recessive mutations, there is no consistent ordering of how selection coefficients affect LD decay, due to the complex interplay of different evolutionary effects. We then examined empirical data of modern humans from the 1000 Genomes Project. LD between derived alleles at nonsynonymous SNPs is lower compared to pairs of derived synonymous variants, suggesting that nonsynonymous derived alleles tend to occur on different haplotypes more than synonymous variants. This result holds when controlling for potential confounding factors by matching SNPs for frequency in the sample (allele count), physical distance, magnitude of background selection, and genetic distance between pairs of variants. Lastly, we introduce a new statistic HR(j) which allows us to detect interference using unphased genotypes. Application of this approach to high-coverage human genome sequences confirms our finding that nonsynonymous derived alleles tend to be located on different haplotypes more often than are synonymous derived alleles. Our findings suggest that interference may play a pervasive role in shaping patterns of LD between deleterious variants in the human genome, and consequently influences genome-wide patterns of LD.
Oligopaint DNA FISH reveals telomere-based meiotic pairing dynamics in the silkworm, Bombyx mori
Authors: Rosin Leah F. , Gil Jose , Drinnenberg Ines A. , Lei Elissa P.
Published: July 2021

Accurate chromosome segregation during meiosis is essential for reproductive success. Yet, many fundamental aspects of meiosis remain unclear, including the mechanisms regulating homolog pairing across species. This gap is partially due to our inability to visualize individual chromosomes during meiosis. Here, we employ Oligopaint FISH to investigate homolog pairing and compaction of meiotic chromosomes and resurrect a classical model system, the silkworm Bombyx mori. Our Oligopaint design combines multiplexed barcoding with secondary oligo labeling for high flexibility and low cost. These studies illustrate that Oligopaints are highly specific in whole-mount gonads and on meiotic squashes. We show that meiotic pairing is robust in both males and females and that pairing can occur through numerous partially paired intermediate structures. We also show that pairing in male meiosis occurs asynchronously and seemingly in a transcription-biased manner. Further, we reveal that meiotic bivalent formation in B. mori males is highly similar to bivalent formation in C. elegans, with both of these pathways ultimately resulting in the pairing of chromosome ends with non-paired ends facing the spindle pole. Additionally, microtubule recruitment in both C. elegans and B. mori is likely dependent on kinetochore proteins but independent of the centromere-specifying histone CENP-A. Finally, using super-resolution microscopy in the female germline, we show that homologous chromosomes remain associated at telomere domains in the absence of chiasma and after breakdown and modification to the synaptonemal complex in pachytene. These studies reveal novel insights into mechanisms of meiotic homolog pairing both with or without recombination.
The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study
Authors: Cerqueira Selma Regina Penha Silva , Deps Patrícia Duarte , Cunha Débora Vilela , Bezerra Natanael Victor Furtunato , Barroso Daniel Holanda , Pinheiro Ana Bárbara Sapienza , Pillegi Gecilmara Salviato , Repsold Taynah Alves Rocha , Kurizky Patrícia Shu , Collin Simon M. , Gomes Ciro Martins
Published: July 2021

Background

Protective effects of Bacillus Calmette–Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19.

Methodology/Principal findings

We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93–13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04–4.06) were significant risk factors for COVID-19.

Conclusions/Significance

Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.
The suppression effect of emotional contagion in the COVID-19 pandemic: A multi-layer hybrid modelling and simulation approach
Authors: Guo Xudong , Tong Junbo , Chen Peiyu , Fan Wenhui
Published: July 2021

The entire world has suffered a lot since the outbreak of the novel coronavirus (COVID-19) in 2019, so simulation models of COVID-19 dynamics are urgently needed to understand and control the pandemic better. Meanwhile, emotional contagion, the spread of vigilance or panic, serves as a negative feedback to the epidemic, but few existing models take it into consideration. In this study, we proposed an innovative multi-layer hybrid modelling and simulation approach to simulate disease transmission and emotional contagion together. In each layer, we used a hybrid simulation method combining agent-based modelling (ABM) with system dynamics modelling (SDM), keeping spatial heterogeneity while reducing computation costs. We designed a new emotion dynamics model IWAN (indifferent, worried, afraid and numb) to simulate emotional contagion inside a community during an epidemic. Our model was well fit to the data of China, the UK and the US during the COVID-19 pandemic. If there weren’t emotional contagion, our experiments showed that the confirmed cases would increase rapidly, for instance, the total confirmed cases during simulation in Guangzhou, China would grow from 334 to 2096, which increased by 528%. We compared the calibrated emotional contagion parameters of different countries and found that the suppression effect of emotional contagion in China is relatively more visible than that in the US and the UK. Due to the experiment results, the proposed multi-layer network model with hybrid simulation is valid and can be applied to the quantitative analysis of the epidemic trends and the suppression effect of emotional contagion in different countries. Our model can be modified for further research to study other social factors and intervention policies in the COVID-19 pandemic or future epidemics.
Machine learning predicts treatment sensitivity in multiple myeloma based on molecular and clinical information coupled with drug response
Authors: Venezian Povoa Lucas , Ribeiro Carlos Henrique Costa , Silva Israel Tojal da
Published: July 2021

Providing treatment sensitivity stratification at the time of cancer diagnosis allows better allocation of patients to alternative treatment options. Despite many clinical and biological risk markers having been associated with variable survival in cancer, assessing the interplay of these markers through Machine Learning (ML) algorithms still remains to be fully explored. Here, we present a Multi Learning Training approach (MuLT) combining supervised, unsupervised and self-supervised learning algorithms, to examine the predictive value of heterogeneous treatment outcomes for Multiple Myeloma (MM). We show that gene expression values improve the treatment sensitivity prediction and recapitulates genetic abnormalities detected by Fluorescence in situ hybridization (FISH) testing. MuLT performance was assessed by cross-validation experiments, in which it predicted treatment sensitivity with 68.70% of AUC. Finally, simulations showed numerical evidences that in average 17.07% of patients could get better response to a different treatment at the first line.
Mechanical energy and propulsion mechanics in roller-skiing double-poling at increasing speeds
Authors: Danielsen Jørgen , Sandbakk Øyvind , McGhie David , Ettema Gertjan
Published: July 2021

Objectives

The aim of this study was to examine the effect of speed on mechanical energy fluctuations and propulsion mechanics in the double-poling (DP) technique of cross-country skiing.

Methods

Kinematics and dynamics were acquired while fourteen male skiers performed roller-skiing DP on a treadmill at increasing speeds (15, 21 and 27 km∙h-1). Kinetic (Ekin), potential (Epot), and total (Ebody) body mechanical energy and pole power (Ppole) were calculated. Inverse dynamics was used to calculate arm power (Parm). Trunk+leg power (PT+L) was estimated, as was the power associated with body movements perpendicular to goal-direction (E.body⊥).

Results

Ekin and Epot fluctuated out-of-phase throughout the cycle, at first sight indicating that pendulum-like behaviour occurs partly in DP. However, during the swing phase, the increase in Epot (body heightening) was mainly driven by positive PT+L, while the decrease in Ekin was lost to rolling friction, and during the poling phase, considerable positive Parm generation occurs. Thus, possible exchange between Ekin and Epot seem not to occur as directly and passively as in classic pendulum locomotion (walking). During the poling phase, E.body⊥fluctuated out-of-phase with Ppole, indicating a transfer of body energy to Ppole. In this way, power generated by trunk+leg mainly during the swing phase (body heightening) can be used in the poling phase as pole power. At all speeds, negative PT+L occurred during the poling phase, suggesting energy absorption of body energy not transferred to pole power. Thus, DP seem to resemble bouncing ball-like behaviour more than pendulum at faster speeds. Over the cycle, Parm contribution to Ppole (external power) was 63% at 15 km∙h-1 and 66% at 21 and 27 km∙h-1, with the remainder being PT+L contribution.

Conclusions

When speed increases in level DP, both power production and absorption by trunk+leg actions increase considerably. This enhanced involvement of the legs at faster speeds is likely a prerequisite for effective generation of pole power at high speeds with very short poling times. However, the relative trunk+leg power contribution did not increase at the speeds studied here.