bluuebunny/crossref_metadata_2025 huggingface dataset:
LaDIVA: A neurocomputational model providing laryngeal motor control for speech acquisition and production
Authors: Weerathunge Hasini R. , Alzamendi Gabriel A. , Cler Gabriel J. , Guenther Frank H. , Stepp Cara E. , Zañartu Matías
Published: June 2022

Many voice disorders are the result of intricate neural and/or biomechanical impairments that are poorly understood. The limited knowledge of their etiological and pathophysiological mechanisms hampers effective clinical management. Behavioral studies have been used concurrently with computational models to better understand typical and pathological laryngeal motor control. Thus far, however, a unified computational framework that quantitatively integrates physiologically relevant models of phonation with the neural control of speech has not been developed. Here, we introduce LaDIVA, a novel neurocomputational model with physiologically based laryngeal motor control. We combined the DIVA model (an established neural network model of speech motor control) with the extended body-cover model (a physics-based vocal fold model). The resulting integrated model, LaDIVA, was validated by comparing its model simulations with behavioral responses to perturbations of auditory vocal fundamental frequency (fo) feedback in adults with typical speech. LaDIVA demonstrated capability to simulate different modes of laryngeal motor control, ranging from short-term (i.e., reflexive) and long-term (i.e., adaptive) auditory feedback paradigms, to generating prosodic contours in speech. Simulations showed that LaDIVA’s laryngeal motor control displays properties of motor equivalence, i.e., LaDIVA could robustly generate compensatory responses to reflexive vocal fo perturbations with varying initial laryngeal muscle activation levels leading to the same output. The model can also generate prosodic contours for studying laryngeal motor control in running speech. LaDIVA can expand the understanding of the physiology of human phonation to enable, for the first time, the investigation of causal effects of neural motor control in the fine structure of the vocal signal.
Evidence for influenza and RSV interaction from 10 years of enhanced surveillance in Nha Trang, Vietnam, a modelling study
Authors: Waterlow Naomi R. , Toizumi Michiko , van Leeuwen Edwin , Thi Nguyen Hien-Anh , Myint-Yoshida Lay , Eggo Rosalind M. , Flasche Stefan
Published: June 2022

Influenza and Respiratory Syncytial Virus (RSV) interact within their host posing the concern for impacts on heterologous viruses following vaccination. We aimed to estimate the population level impact of their interaction. We developed a dynamic age-stratified two-pathogen mathematical model that includes pathogen interaction through competition for infection and enhanced severity of dual infections. We used parallel tempering to fit its parameters to 11 years of enhanced hospital-based surveillance for acute respiratory illnesses (ARI) in children under 5 years old in Nha Trang, Vietnam. The data supported either a 41% (95%CrI: 36–54) reduction in susceptibility following infection and for 10.0 days (95%CrI 7.1–12.8) thereafter, or no change in susceptibility following infection. We estimate that co-infection increased the probability for an infection in <2y old children to be reported 7.2 fold (95%CrI 5.0–11.4); or 16.6 fold (95%CrI 14.5–18.4) in the moderate or low interaction scenarios. Absence of either pathogen was not to the detriment of the other. We find stronger evidence for severity enhancing than for acquisition limiting interaction. In this setting vaccination against either pathogen is unlikely to have a major detrimental effect on the burden of disease caused by the other.
Assessing the impact of ambient temperature on the risk of hand, foot, and mouth disease in Guangdong, China: New insight from the disease severity and burden
Authors: Du Zhicheng , Zhang Wangjian , Yu Shicheng , Lin Shao , Hao Yuantao
Published: June 2022

Background

The association between the incidence of hand, foot, and mouth disease (HFMD) and ambient temperature has been well documented. Although the severity of symptoms is an important indicator of disease burden and varies significantly across cases, it usually was ignored in previous studies, potentially leading to biased estimates of the health impact of temperature.

Methods

We estimated the disability-adjusted life year (DALY) by considering the severity of symptoms for each HFMD case reported during 2010–2012 in Guangdong and used distributed lag-nonlinear models to estimate the association between the daily average temperature and daily DALY of HFMD cases at the city-level. We investigated the potential effect modifiers on the pathway between temperature and DALY and pooled city-specific estimates to a provincial association using a meta-regression. The overall impact of temperature was further evaluated by estimates of DALYs that could be attributed to HFMD.

Results

The overall cumulative effect of daily mean temperature on the DALY of HFMD showed an inverse-U shape, with the maximum effect estimated to beβ= 0.0331 (95%CI: 0.0199–0.0463) DALY at 23.8°C. Overall, a total of 6.432 (95%CI: 3.942–8.885) DALYs (attributable fraction = 2.721%, 95%CI: 1.660–3.759%) could be attributed to temperature exposure. All the demographic subgroups had a similar trend as the main analysis, while the magnitude of the peak of the temperature impact tended to be higher among the males, those aged ≥3yrs or from the Pear-River Delta region. Additionally, the impact of temperature on DALY elevated significantly with the increasing population density, per capita GDP, and per capita green space in parks.

Conclusions

Temperature exposure was associated with increased burden of HFMD nonlinearly, with certain groups such as boys and those from areas with greater population density being more vulnerable.
Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity
Authors: Park Ji-Hoon , Kim Min-Hee , Sutanto Edwin , Na Seok-Won , Kim Min-Jae , Yeom Joon Sup , Nyunt Myat Htut , Abbas Elfaki Mohammed Mohieldien , Abdel Hamid Muzamil Mahdi , Cha Seok Ho , Alemu Sisay Getachew , Sriprawat Kanlaya , Anstey Nicholas M. , Grigg Matthew J. , Barber Bridget E. , William Timothy , Gao Qi , Liu Yaobao , Pearson Richard D. , Price Ric N. , Nosten Francois , Yoon Sung-Il , No Joo Hwan , Han Eun-Taek , Auburn Sarah , Russell Bruce , Han Jin-Hee
Published: June 2022

Plasmodium vivax is the most widespread cause of human malaria. Recent reports of drug resistant vivax malaria and the challenge of eradicating the dormant liver forms increase the importance of vaccine development against this relapsing disease. P. vivax reticulocyte binding protein 1a (PvRBP1a) is a potential vaccine candidate, which is involved in red cell tropism, a crucial step in the merozoite invasion of host reticulocytes. As part of the initial evaluation of the PvRBP1a vaccine candidate, we investigated its genetic diversity and antigenicity using geographically diverse clinical isolates. We analysed pvrbp1a genetic polymorphisms using 202 vivax clinical isolates from six countries. Pvrbp1a was separated into six regions based on specific domain features, sequence conserved/polymorphic regions, and the reticulocyte binding like (RBL) domains. In the fragmented gene sequence analysis, PvRBP1a region II (RII) and RIII (head and tail structure homolog, 152–625 aa.) showed extensive polymorphism caused by random point mutations. The haplotype network of these polymorphic regions was classified into three clusters that converged to independent populations. Antigenicity screening was performed using recombinant proteins PvRBP1a-N (157–560 aa.) and PvRBP1a-C (606–962 aa.), which contained head and tail structure region and sequence conserved region, respectively. Sensitivity against PvRBP1a-N (46.7%) was higher than PvRBP1a-C (17.8%). PvRBP1a-N was reported as a reticulocyte binding domain and this study identified a linear epitope with moderate antigenicity, thus an attractive domain for merozoite invasion-blocking vaccine development. However, our study highlights that a global PvRBP1a-based vaccine design needs to overcome several difficulties due to three distinct genotypes and low antigenicity levels.
M-CSF-stimulated myeloid cells can convert into epithelial cells to participate in re-epithelialization and hair follicle regeneration during dermal wound healing
Authors: Li Yunyuan , Alnojeidi Hatem , Kilani Ruhangiz T. , Ghahary Aziz
Published: June 2022

Dermal wound healing is a complex process which requires the interaction of many cell types and mediators in a highly sophisticated temporal sequence. Myeloid cells which compose of a significant proportion of the inflammatory cells infiltrate to the to a wound site where they play important roles in clearance of damaged tissue and microorganisms. Myeloid cells have the capacity to be converted into fibroblast-like cells and endothelial cells during wound healing process. However, whether myeloid cells in wounds can convert into epithelial cells where they contribute to healing process is not clear. In this study, we performed double immunofluorescent staining with antibodies for hematopoietic cells and keratinocytes as well as cell tracing technique to investigate hematopoietic cell conversion. The result showed that during the healing process, some of the CD45-positive hematopoietic cells also expressed keratin 14, a marker for keratinocytes. Further, double immunofluorescent staining in dermal wounds, using CD11b and K14 antibodies indicated that CD11b-positive myeloid cells were the origin of newly generated epithelial cells. Through tracing injected labeled splenocyte-derived myeloid cells in skin, we confirmed that myeloid cells were able to convert into keratinocytes in repaired skin. Furthermore, our results fromin vivoexperiments provided new information on contribution of myeloid cells in hair follicle regeneration. In conclusion, this work highlights the myeloid cell contributions in wound repair and hair follicle regeneration through conversion of M-CSF-stimulated CD11b-positive myeloid cells into epithelial cells in a murine model.
Chaperonin containing TCP1 as a marker for identification of circulating tumor cells in blood
Authors: Cox Amanda , Martini Ana , Ghozlan Heba , Moroose Rebecca , Zhu Xiang , Lee Eunkyung , Khaled Amr S. , Barr Louis , Alemany Carlos , Fanaian Na’im , Griffith Elizabeth , Sause Ryan , Litherland S. A. , Khaled Annette R.
Published: June 2022

Herein we report the use of Chaperonin-Containing TCP-1 (CCT or TRiC) as a marker to detect circulating tumor cells (CTCs) that are shed from tumors during oncogenesis. Most detection methods used in liquid biopsy approaches for enumeration of CTCs from blood, employ epithelial markers like cytokeratin (CK). However, such markers provide little information on the potential of these shed tumor cells, which are normally short-lived, to seed metastatic sites. To identify a marker that could go beyond enumeration and provide actionable data on CTCs, we evaluated CCT. CCT is a protein-folding complex composed of eight subunits. Previously, we found that expression of the second subunit (CCT2 or CCTβ) inversely correlated with cancer patient survival and was essential for tumorigenesis in mice, driving tumor-promoting processes like proliferation and anchorage-independent growth. In this study, we examined CCT2 expression in cancer compared to normal tissues and found statistically significant increases in tumors. Because not all blood samples from cancer patients contain detectable CTCs, we used the approach of spiking a known number of cancer cells into blood from healthy donors to test a liquid biopsy approach using CCT2 to distinguish rare cancer cells from the large number of non-cancer cells in blood. Using a clinically validated method for capturing CTCs, we evaluated detection of intracellular CCT2 staining for visualization of breast cancer and small cell lung (SCLC) cancer cells. We demonstrated that CCT2 staining could be incorporated into a CTC capture and staining protocol, providing biologically relevant information to improve detection of cancer cells shed in blood. These results were confirmed with a pilot study of blood from SCLC patients. Our studies demonstrate that detection of CCT2 could identify rare cancer cells in blood and has application in liquid biopsy approaches to enhance the use of minimally invasive methods for cancer diagnosis.
The prevalence of AstraZeneca COVID-19 vaccine side effects among Nigist Eleni Mohammed memorial comprehensive specialized hospital health workers. Cross sectional survey
Authors: Desalegn Mitiku , Garoma Gelana , Tamrat Habtamu , Desta Adane , Prakash Ajay
Published: June 2022

Introduction

The best way to eradicate corona virus disease (COVID-19) viral infection is mass vaccination. Many studies demonstrate vaccination is associated with some local and systemic side effects. This study aimed to provide evidence on AstraZeneca COVID-19 vaccine side effects.

Methodology

Institutional based cross-sectional survey was conducted among 254 health workers at Nigist Eleni Mohammed memorial comprehensive specialized hospital (from July 01/ 2021 to July 30/2021). Data were collected consecutively through self-administered online survey created on Google Forms of platform which had been randomly delivered via (Facebook or telegram pages). Demographic data of participants, side effect after first and second dose of vaccine were covered.

Result

The prevalence of at least one side effect after first dose was 91.3% and after second dose was 67%. Injection site pain (63.8% vs. 50.4%), headache (48.8% vs. 33.5%), fever (38.8% vs. 20.9%), muscle pain (38.8% vs. 21.7%), fatigue (26% vs. 28.7%, tenderness at the site (27.6% vs. 21.7%), and joint pain (27.6% vs. 20.9%) were the most commonly reported side effects after first and second dose vaccine respectively. Most of participants reported that their symptoms emerged after 6hr of vaccination and only less than 5% of participant’s symptoms lasted more than 72hr of post vaccination. The younger age (≤29 year) were more susceptible to at least one side effect (χ 2 = 4.2; p = 0.04) after first dose.

Conclusion

The prevalence of side effect after first and second dose vaccine was higher. Most of the symptoms were short lived and mild. This result might help to solve an emerging public health challenge (vaccine hesitancy) nurtured by misinformation related to vaccines safety.
Developing health and environmental warning messages about red meat: An online experiment
Authors: Taillie Lindsey Smith , Prestemon Carmen E. , Hall Marissa G. , Grummon Anna H. , Vesely Annamaria , Jaacks Lindsay M.
Published: June 2022

Introduction

The United States has among the highest per capita red meat consumption in the world. Reducing red meat consumption is crucial for minimizing the environmental impact of diets and improving health outcomes. Warning messages are effective for reducing purchases of products like sugary beverages but have not been developed for red meat. This study developed health and environmental warning messages about red meat and explored participants’ reactions to these messages.

Methods

A national convenience sample of US red meat consumers (n= 1,199; mean age 45 years) completed an online survey in 2020 for this exploratory study. Participants were randomized to view a series of either health or environmental warning messages (between-subjects factor) about the risks associated with eating red meat. Messages were presented in random order (within-subjects factor; 8 health messages or 10 environmental messages). Participants rated each warning message on a validated 3-item scale measuring perceived message effectiveness (PME), ranging from 1 (low) to 5 (high). Participants then rated their intentions to reduce their red meat consumption in the next 7 days.

Results

Health warning messages elicited higher PME ratings than environmental messages (mean 2.66 vs. 2.26,p<0.001). Health warning messages also led to stronger intentions to reduce red meat consumption compared to environmental messages (mean 2.45 vs. 2.19,p<0.001). Within category (health and environmental), most pairwise comparisons of harms were not statistically significant.

Conclusions

Health warning messages were perceived to be more effective than environmental warning messages. Future studies should measure the impact of these messages on behavioral outcomes.
Characteristics of pigmentary glaucoma in Japanese individuals
Authors: Yamashita Takehiro , Shiihara Hideki , Terasaki Hiroto , Fujiwara Kazuki , Tanaka Minoru , Sakamoto Taiji
Published: June 2022

Purpose

Myopia is a known risk factor of pigmentary glaucoma (PG), and the increased prevalence of myopia in Asian countries indicates that more cases of PG will likely develop soon. However, there are no diagnostic criteria for PG for Asians. Therefore, the purpose of this study is to determine the characteristics of PG in Japanese individuals and establish three diagnostic signs for PG.

Methods

This was a single-center, retrospective, case series study of glaucoma patients who visited the Kagoshima University Hospital between January 2015 and January 2020. The inclusion criteria were age <50 years at time of diagnosis and presence of pigmentation in the anterior chamber (AC) angle including a Sampaolesi line. Eyes with pigmentation of the AC angle caused by other types of glaucoma such as uveitis, trauma, exfoliation, or childhood glaucoma were excluded. We investigated the classic diagnostic triad of signs of PG; posterior corneal pigmentation, mid peripheral iris transillumination defect, and pigmentation of the trabecular meshwork. We also examined the Sampaolesi line, iris concavity, and midperipheral iris depigmentation in eyes with PG.

Results

Ten eyes of 5 Japanese men and 10 eyes of 5 Japanese women were studied. Their age ranged from 13 to 46 years at the time of diagnosis. One eye had posterior corneal pigmentation and 6 eyes had pigmentation of the trabecular meshwork. None had mid peripheral iris transillumination defect. The Sampaolesi line, iris concavity, and midperipheral iris depigmentation were found in all patients except one patient who lacked the mid peripheral depigmentation. Two eyes had the pigment reversal sign, none had lens pigmentation, and 2 eyes had peripheral retinal degeneration.

Conclusion

The presence of the Sampaolesi line, iris concavity, and midperipheral iris depigmentation may be appropriate signs for the diagnosis of PG in Asians.
Differences in the perceived justice of penalties for road traffic offences between Lithuanian offenders and non-offenders
Authors: Auksė Endriulaitienė , Slavinskienė Justina , Šeibokaitė Laura , Markšaitytė Rasa , Sullman Mark
Published: June 2022

Most countries around the world use the penalties’ system in order to increase compliance with road traffic rules. However, it can be argued that the most penalties’ systems are ineffective, as drivers do not change offending behavior due to received penalty and repeatedly violate them. The perceived fairness of these penalties may be related to the level of adherence to these traffic rules. Therefore, this research explored the perceived justice of penalties for road traffic rules in a sample of Lithuanian drivers and investigated the differences between offenders and non-offenders. The sample consisted of 358 participants (63.4 percent females, aged 18–75, mean age 35.2 years) who completed an online survey. Participants were asked to report how fair they believed penalties were for road traffic rule offences in general and using a list of 23 specific penalties, including: drink driving, speeding, dangerous maneuverings, illegal overtaking, handheld phone use while driving, etc. The survey measured demographic data, as well as data regarding driving exposure, traffic offences and crashes during the last 12 months. The results revealed that in general drivers perceived the penalties as fair or adequate. The answer “adequate/fair” was chosen most frequently for almost all penalties (from 41.1 to 71.3 percent), with only the penalty for carrying a child without a car seat (€30–50) being perceived as too mild (55.5%). Gender differences were found in the evaluation of the penalty for driving under the influence of alcohol, while age and driving frequency differences were found in the perceived fairness of the penalties for not using a seatbelt, aberrant driving and using a handheld mobile phone while driving. Drivers who reported no offences during the last year, perceived the penalties for speeding as being too mild, when compared to drivers with at least one penalty over the previous year. Contrarily, offenders reported the penalties for speeding as being too severe. Offenders, who experienced driving license suspension, perceived the penalties as being too severe for drink driving and aberrant driving than offenders who received monetary fines. In summary, both Lithuanian offenders and non-offenders generally perceived the penalties for traffic rule offences as adequate and fair, but individual differences and the experience of traffic sanctions were related to the perceived justice of specific penalties.
Early warning for healthcare acquired infections in neonatal care units in a low-resource setting using routinely collected hospital data: The experience from Haiti, 2014–2018
Authors: Lenglet Annick , Contigiani Omar , Ariti Cono , Evens Estivern , Charles Kessianne , Casimir Carl-Frédéric , Senat Delva Rodnie , Badjo Colette , Roggeveen Harriet , Pawulska Barbara , Clezy Kate , McRae Melissa , Wertheim Heiman , Hopman Joost
Published: June 2022

In low-resource settings, detection of healthcare-acquired outbreaks in neonatal units relies on astute clinical staff to observe unusual morbidity or mortality from sepsis as microbiological diagnostics are often absent. We aimed to generate reliable (and automated) early warnings for potential clusters of neonatal late onset sepsis using retrospective data that could signal the start of an outbreak in an NCU in Port au Prince, Haiti, using routinely collected data on neonatal admissions. We constructed smoothed time series for late onset sepsis cases, late onset sepsis rates, neonatal care unit (NCU) mortality, maternal admissions, neonatal admissions and neonatal antibiotic consumption. An outbreak was defined as a statistical increase in any of these time series indicators. We created three outbreak alarm classes: 1) thresholds: weeks in which the late onset sepsis cases exceeded four, the late onset sepsis rates exceeded 10% of total NCU admissions and the NCU mortality exceeded 15%; 2) differential: late onset sepsis rates and NCU mortality were double the previous week; and 3) aberration: using the improved Farrington model for late onset sepsis rates and NCU mortality. We validated pairs of alarms by calculating the sensitivity and specificity of the weeks in which each alarm was launched and comparing each alarm to the weeks in which a single GNB positive blood culture was reported from a neonate. The threshold and aberration alarms were the strongest predictors for current and future NCU mortality and current LOS rates (p<0.0002). The aberration alarms were also those with the highest sensitivity, specificity, negative predictive value, and positive predictive value. Without microbiological diagnostics in NCUs in low-resource settings, applying these simple algorithms to routinely collected data show great potential to facilitate early warning for possible healthcare-acquired outbreaks of LOS in neonates. The methods used in this study require validation across other low-resource settings.
Comparative study on the performance of different classification algorithms, combined with pre- and post-processing techniques to handle imbalanced data, in the diagnosis of adult patients with familial hypercholesterolemia
Authors: Albuquerque João , Medeiros Ana Margarida , Alves Ana Catarina , Bourbon Mafalda , Antunes Marília
Published: June 2022

Familial Hypercholesterolemia (FH) is an inherited disorder of cholesterol metabolism. Current criteria for FH diagnosis, like Simon Broome (SB) criteria, lead to high false positive rates. The aim of this work was to explore alternative classification procedures for FH diagnosis, based on different biological and biochemical indicators. For this purpose, logistic regression (LR), naive Bayes classifier (NB), random forest (RF) and extreme gradient boosting (XGB) algorithms were combined with Synthetic Minority Oversampling Technique (SMOTE), or threshold adjustment by maximizing Youden index (YI), and compared. Data was tested through a 10 × 10 repeated k-fold cross validation design. The LR model presented an overall better performance, as assessed by the areas under the receiver operating characteristics (AUROC) and precision-recall (AUPRC) curves, and several operating characteristics (OC), regardless of the strategy to cope with class imbalance. When adopting either data processing technique, significantly higher accuracy (Acc), G-mean and F1 score values were found for all classification algorithms, compared to SB criteria (p < 0.01), revealing a more balanced predictive ability for both classes, and higher effectiveness in classifying FH patients. Adjustment of the cut-off values through pre or post-processing methods revealed a considerable gain in sensitivity (Sens) values (p < 0.01). Although the performance of pre and post-processing strategies was similar, SMOTE does not cause model’s parameters to loose interpretability. These results suggest a LR model combined with SMOTE can be an optimal approach to be used as a widespread screening tool.
Effect of an antenatal diet and lifestyle intervention and maternal BMI on cord blood DNA methylation in infants of overweight and obese women: The LIMIT Randomised Controlled Trial
Authors: Louise Jennie , Deussen Andrea R. , Koletzko Berthold , Owens Julie , Saffery Richard , Dodd Jodie M.
Published: June 2022

Background

To investigate the effect of an antenatal diet and lifestyle intervention, and maternal pre-pregnancy overweight or obesity, on infant cord blood DNA methylation.

Methods

We measured DNA methylation in 645 cord blood samples from participants in the LIMIT study (an antenatal diet and lifestyle intervention for women with early pregnancy BMI ≥25.0 kg/m2) using the Illumina 450K BeadChip array, and tested for any differential methylation related to the intervention, and to maternal early pregnancy BMI. We also analysed differential methylation in relation to selected candidate genes.

Results

No CpG sites were significantly differentially methylated in relation to either the diet and lifestyle intervention, or with maternal early pregnancy BMI. There was no significant differential methylation in any of the selected genes related to the intervention, or to maternal BMI.

Conclusion

We found no evidence of an effect of either antenatal diet and lifestyle, or of maternal early pregnancy BMI, on cord blood DNA methylation.

Clinical trials registration

ACTRN12607000161426
Data-informed deep optimization
Authors: Zhang Lulu , Xu Zhi-Qin John , Zhang Yaoyu
Published: June 2022

Motivated by the impressive success of deep learning in a wide range of scientific and industrial applications, we explore in this work the application of deep learning into a specific class of optimization problems lacking explicit formulas for both objective function and constraints. Such optimization problems exist in many design problems, e.g., rotor profile design, in which objective and constraint values are available only through experiment or simulation. They are especially challenging when design parameters are high-dimensional due to the curse of dimensionality. In this work, we propose a data-informed deep optimization (DiDo) approach emphasizing on the adaptive fitting of the the feasible region as follows. First, we propose a deep neural network (DNN) based adaptive fitting approach to learn an accurate DNN classifier of the feasible region. Second, we use the DNN classifier to efficiently sample feasible points and train a DNN surrogate of the objective function. Finally, we find optimal points of the DNN surrogate optimization problem by gradient descent. To demonstrate the effectiveness of our DiDo approach, we consider a practical design case in industry, in which our approach yields good solutions using limited size of training data. We further use a 100-dimension toy example to show the effectiveness of our approach for higher dimensional problems. Our results indicate that, by properly dealing with the difficulty in fitting the feasible region, a DNN-based method like our DiDo approach is flexible and promising for solving high-dimensional design problems with implicit objective and constraints.
Long term outcomes of patients with tuberculous meningitis: The impact of drug resistance
Authors: Evans Emily E. , Avaliani Teona , Gujabidze Mariam , Bakuradze Tinatin , Kipiani Maia , Sabanadze Shorena , Smith Alison G. C. , Avaliani Zaza , Collins Jeffrey M. , Kempker Russell R.
Published: June 2022

Background

Little is known about the impact of drug-resistance on clinical outcomes among patients with tuberculosis meningitis (TBM).

Methods

A retrospective cohort study among patients treated for TBM in Tbilisi, Georgia. We performed medical chart abstraction to collect patient data. Long-term vital status was assessed using the Georgia National Death Registry. We utilized a Cox proportional-hazards model to evaluate the association of drug-resistance and mortality.

Results

Among 343 TBM suspects, 237 had a presentation consistent with TBM. Drug resistance was suspected (n = 5) or confirmed (n = 31) in 36 patients including 30 with multidrug- or rifampin-resistance and 6 with isoniazid-resistance. Thirty-four patients had HIV. The median follow-up time was 1331 days (IQR, 852–1767). Overall, 73 of 237 (30%) people died with 50 deaths occurring during and 23 after treatment. The proportion of death was higher among patients with drug-resistant vs. drug-susceptible disease (67% vs. 24%, p<0.001) and with HIV versus no HIV (59% vs 27%, p<0.001). Mortality was significantly higher in patients with drug-resistant TBM after 90 days of treatment (aHR = 7.2, CI95% [3.6–14.3], p < 0.001).

Conclusions

Mortality was high among patients with drug-resistant TBM with many deaths occurring post treatment. More effective treatment options are urgently needed for drug-resistant TBM.
Travel pattern-based bus trip origin-destination estimation using smart card data
Authors: Lee Inmook , Cho Shin-Hyung , Kim Kyoungtae , Kho Seung-Young , Kim Dong-Kyu
Published: June 2022

Smart card data are widely used in generating the origin and destination (O–D) matrix for public transit, which contains important information for transportation planning and operation. However, the generation of the O–D matrix is limited by the smart card data information that includes the boarding (origin) information without the alighting (destination) information. To solve this problem, trip chain methods have been proposed, thereby greatly contributing in estimating the destination using the smart card data. Nevertheless, unlinked trips, that is, trips with unknown destinations, are a persisting issue. The purpose of this study is to develop a method for estimating the destination of unlinked trips, in which trip chain methods cannot be applied, using temporal travel patterns and historical boarding records of the passengers based on long-term smart card data. The passengers were clustered by k-means clustering, and the time-of-day travel patterns were estimated for each cluster using a Gaussian mixture model. The travel patterns were formulated to estimate the destination of the passengers from the smart card data. The proposed method was verified using the 2018 smart card data collected in Sejong City, South Korea. The existing trip chain method matched the destinations of 60.0% of the total trips, whereas the proposed method improved the matching to 74.9% by additionally matching the destinations of 37.2% of the unlinked trips.
Potential of Aspergillus oryzae as a biosynthetic platform for indigoidine, a non-ribosomal peptide pigment with antioxidant activity
Authors: Panchanawaporn Sarocha , Chutrakul Chanikul , Jeennor Sukanya , Anantayanon Jutamas , Rattanaphan Nakul , Laoteng Kobkul
Published: June 2022

The growing demand for natural pigments in the industrial sector is a significant driving force in the development of production processes. The production of natural blue pigments, which have wide industrial applications, using microbial systems has been gaining significant attention. In this study, we used Aspergillus oryzae as a platform cell factory to produce the blue pigment indigoidine (InK), by genetic manipulation of its non-ribosomal peptide synthetase system to overexpress the indigoidine synthetase gene (AoinK). Phenotypic analysis showed that InK production from the engineered strain was growth associated, owing to the constitutive control of gene expression. Furthermore, the initial pH, temperature, and glutamine and MgSO4 concentrations were key factors affecting InK production by the engineered strain. The pigment secretion was enhanced by addition of 1% Tween 80 solution to the culture medium. The maximum titer of total InK was 1409.22 ± 95.33 mg/L, and the maximum productivity was 265.09 ± 14.74 mg/L·d. Moreover, the recombinant InK produced by the engineered strain exhibited antioxidant activity. These results indicate that A. oryzae has the potential to be used as a fungal platform for overproduction of extracellular non-ribosomal peptide pigments.
Predictability of combined cataract surgery and trabeculectomy using Barrett Universal Ⅱ formula
Authors: Iijima Kei , Kamiya Kazutaka , Iida Yoshihiko , Kasahara Masayuki , Shoji Nobuyuki
Published: June 2022

Purpose

To compare the predictability of intraocular lens (IOL) power calculation using the Barrett Universal II and the SRK/T formulas in eyes undergoing combined cataract surgery and trabeculectomy.

Methods

We retrospectively reviewed the clinical charts of 56 consecutive eyes undergoing cataract surgery and trabeculectomy. IOL power calculations were performed using the Barrett Universal II and SRK/T formulas. We compared the prediction error, the absolute error, and the percentages within ± 0.5 D and ±1.0 D of the targeted refraction, 3 months postoperatively, and also investigated the relationship of the prediction error with the keratometric readings and axial length, using the two formulas.

Results

The prediction error using the SRK/T formula was significantly more myopic than that using the Barrett Universal II formula (paired t-test, p<0.001). The absolute error using the Barrett Universal II formula was significantly smaller than that using the SRK/T formula (p = 0.039). We found significant correlations of the prediction error with the axial length (Pearson correlation coefficient, r = 0.273, p = 0.042), and the keratometric readings (r = -0.317, p = 0.017), using SRK/T formula, but no significant correlations between them (r = 0.219, p = 0.167, and r = -0.023, p = 0.870), using the Barrett Universal II formula.

Conclusions

The Barrett Universal II formula provides a better predictability of IOL power calculation and is less susceptible to the effect of the axial length and the corneal shape, than the SRK/T formula. The Barrett Universal formula, rather than the SRK/T formula, may be clinically helpful for improving the refractive accuracy in such eyes.
Healthcare provider perspectives on delivering next generation rotavirus vaccines in five low-to-middle-income countries
Authors: Mooney Jessica , Price Jessica , Bain Carolyn , Bawa John Tanko , Gurley Nikki , Kumar Amresh , Liyanage Guwani , Mkisi Rouden Esau , Odero Chris , Seck Karim , Simpson Evan , Hausdorff William P.
Published: June 2022

Background

Live oral rotavirus vaccines (LORVs) have significantly reduced rotavirus hospitalizations and deaths worldwide. However, LORVs are less effective in low- and middle-income countries (LMICs). Next-generation rotavirus vaccines (NGRVs) may be more effective but require administration by injection or a neonatal oral dose, adding operational complexity. Healthcare providers (HPs) were interviewed to assess rotavirus vaccine preferences and identify delivery issues as part of an NGRV value proposition.

Objective

Determine HP vaccine preferences about delivering LORVs compared to injectable (iNGRV) and neonatal oral (oNGRV) NGRVs.

Methods

64 HPs from Ghana, Kenya, Malawi, Peru, and Senegal were interviewed following a mixed-method guide centered on three vaccine comparisons: LORV vs. iNGRV; LORV vs. oNGRV; oNGRV vs. iNGRV. HPs reviewed attributes for each vaccine in the comparisons, then indicated and explained their preference. Additional questions elicited views about co-administering iNGRV+LORV for greater public health impact, a possible iNGRV-DTP-containing combination vaccine, and delivering neonatal doses.

Results

Almost all HPs preferred oral vaccine options over iNGRV, with many emphasizing an aversion to additional injections. Despite this strong preference, HPs described challenges delivering oral doses. Preferences for LORV vs. oNGRV were split, marked by disparate views on rotavirus disease epidemiology and the safety, need, and feasibility of delivering neonatal vaccines. Although overwhelmingly enthusiastic about an iNGRV-DTP-containing combination option, several HPs had concerns. HP views were divided on the feasibility of co-administering iNGRV+LORV, citing challenges around logistics and caregiver sensitization.

Conclusion

Our findings provide valuable insights on delivering NGRVs in routine immunization. Despite opposition to injectables, openness to co-administering LORV+iNGRV to improve efficacy suggests future HP support of iNGRV if adequately informed of its advantages. Rationales for LORV vs. oNGRV underscore needs for training on rotavirus epidemiology and stronger service integration. Expressed challenges delivering existing LORVs merit further examination and indicate need for improved delivery.
Critical factors associated with postpartum maternal death in Ethiopia
Authors: Tesfay Neamin , Tariku Rozina , Zenebe Alemu , Woldeyohannes Fitsum
Published: June 2022

Background

Globally most maternal deaths occur during the postpartum period; however, the burden is disproportionately higher in some Sub-Saharan African countries including Ethiopia. According to Ethiopian Ministry of Health’s annual report, in 2019 alone, nearly 70% of maternal deaths happen during the postpartum period. Although several studies have been conducted on postpartum maternal deaths in Ethiopia, most of the studies were focused either on individual-level or district-level determinants with limited emphasis on the timing of death and in relatively small and localized areas. Therefore, this study aimed at identifying the determinants of postpartum death both at an individual and districts level, which could shed light on designing pragmatic policies to reduce postpartum maternal death.

Methods

The study utilized secondary data obtained from the Ethiopian maternal death surveillance system. A total of 4316 reviewed maternal death from 645 districts of Ethiopia were included in the analysis. A multilevel multinomial logistic regression model was applied to examine factors significantly associated with postpartum maternal death in Ethiopia.

Result

The findings revealed that 65.1% of maternal deaths occurred during the postpartum period. The factors associated with postpartum death included previous medical history (history of ANC follow up and party), medical causes (obstetrics haemorrhage, hypertensive disorder of pregnancy, pregnancy-related infection, and non-obstetrics complication), personal factors (poor knowledge of obstetrics complication), and facility-level barriers (shortage of life-saving maternal commodities and delay in receiving treatment).

Conclusion

Almost seven in ten maternal deaths happen during the postpartum period. The rate was even higher for some women based on their previous medical history, level of awareness about obstetrics complication, medical conditions, as well as the readiness of the health facility at which the women was served. Since the postpartum period is identified as a critical time for reducing maternal death, policies and actions must be directed towards improving health education, ANC service utilization, and facility-level readiness.
Doing well-being: Self-reported activities are related to subjective well-being
Authors: Nilsson August Håkan , Hellryd Erik , Kjell Oscar
Published: June 2022

Activities and Subjective Well-Being (SWB) have been shown to be intricately related to each other. However, no research to date has shown whether individuals understand how their everyday activities relate to their SWB. Furthermore, the assessment of activities has been limited to predefined types of activities and/or closed-ended questions. In two studies, we examine the relationship between self-reported everyday activities and SWB, while allowing individuals to express their activities freely by allowing open-ended responses that were then analyzed with state-of-the-art (transformers-based) Natural Language Processing. In study 1 (N = 284), self-reports of Yesterday’s Activities did not significantly relate to SWB, whereas activities reported as having the most impact on SWB in the past four weeks had small but significant correlations to most of the SWB scales (r = .14 –.23, p < .05). In Study 2 (N = 295), individuals showed strong agreement with each other about activities that they considered to increase or decrease SWB (AUC = .995). Words describing activities that increased SWB related to physically and cognitively active activities and social activities (“football”, “meditation”, “friends”), whereas words describing activities that decreased SWB were mainly activity features related to imbalance (“too”, “much”, “enough”). Individuals reported both activities and descriptive words that reflect their SWB, where the activity words had generally small but significant correlations to SWB (r =. 17 –.33, p < .05) and the descriptive words had generally strong correlations to SWB (r = .39–63, p < .001). We call this correlational gap the well-being/activity description gap and discuss possible explanations for the phenomenon.
The effect of aging on the fracture resistance of different types of screw-cement-retained implant-supported zirconia-based restorations
Authors: Sahebi Safoora , Giti Rashin , Sherafati Arian
Published: June 2022

Structural durability of screw-cement-retained implant-supported zirconia-based restorations is an important factor in choosing the best type of restoration for clinical use. This study aimed to evaluate the effects of thermocycling on the fracture resistance of different types of screw-cement-retained implant-supported zirconia-based restoration. Two experimental groups (monolithic zirconia and porcelain-veneered zirconia) and a control group of porcelain-fused-to-metal restorations were fabricated via CAD-CAM (n = 14 per group). Half of the specimens of each group (n = 7) were subjected to 10000 thermal cycles. The compressive force was applied and the force leading to fracture was measured by using a Universal Testing Machine. The fractured modes were classified under a scanning electron microscope. The data were analyzed through two-way ANOVA, one-way ANOVA, and independent samples t-test (α = 0.05). Among the non-thermocycled subgroups, the monolithic zirconia specimens were significantly more fracture-resistant than the porcelain-veneered zirconia and porcelain-fused-to-metal groups (P<0.05); but it was not the same with aging (P>0.05). Thermocycling decreased the fracture resistance of all groups; however, the difference was not statistically significant (P<0.05). The monolithic zirconia presented higher fracture resistance than the bilayered restorations for screw-cement retained implant-supported restorations. Thermocycling decreased the fracture resistance of all types of restorations insignificantly which can be clinically important.
The structural brain network topology of episodic memory
Authors: Matyi Melanie A. , Spielberg Jeffrey M.
Published: June 2022

Episodic memory is supported by a distributed network of brain regions, and this complex network of regions does not operate in isolation. To date, neuroscience research in this area has typically focused on the activation levels in specific regions or pairwise connectivity between such regions. However, research has yet to investigate how the complex interactions of structural brain networks influence episodic memory abilities. We applied graph theory methods to diffusion-based anatomical networks in order to examine the structural architecture of the medial temporal lobe needed to support effective episodic memory functioning. We examined the relationship between performance on tests of verbal and non-verbal episodic memory with node strength, which indexes how well connected a brain region is in the network. Findings mapped onto the Posterior Medial memory system, subserved by the parahippocampal cortex and overlapped with findings of previous studies of episodic memory employing different methodologies. This expands our current understanding by providing independent evidence for the importance of identified regions and suggesting the particular manner in which these regions support episodic memory.
Interactions between copper homeostasis and the fungal cell wall affect copper stress resistance
Authors: Probst Corinna , Garcia-Santamarina Sarela , Brooks Jacob T. , Van Der Kloet Inge , Baars Oliver , Ralle Martina , Thiele Dennis J. , Alspaugh J. Andrew
Published: June 2022

Copper homeostasis mechanisms are essential for microbial adaption to changing copper levels within the host during infection. In the opportunistic fungal pathogen Cryptococcus neoformans (Cn), the Cn Cbi1/Bim1 protein is a newly identified copper binding and release protein that is highly induced during copper limitation. Recent studies demonstrated that Cbi1 functions in copper uptake through the Ctr1 copper transporter during copper limitation. However, the mechanism of Cbi1 action is unknown. The fungal cell wall is a dynamic structure primarily composed of carbohydrate polymers, such as chitin and chitosan, polymers known to strongly bind copper ions. We demonstrated that Cbi1 depletion affects cell wall integrity and architecture, connecting copper homeostasis with adaptive changes within the fungal cell wall. The cbi1Δ mutant strain possesses an aberrant cell wall gene transcriptional signature as well as defects in chitin / chitosan deposition and exposure. Furthermore, using Cn strains defective in chitosan biosynthesis, we demonstrated that cell wall chitosan modulates the ability of the fungal cell to withstand copper stress. Given the previously described role for Cbi1 in copper uptake, we propose that this copper-binding protein could be involved in shuttling copper from the cell wall to the copper transporter Ctr1 for regulated microbial copper uptake.