bluuebunny/crossref_metadata_2025 huggingface dataset:
Multidimensional analysis of immune responses identified biomarkers of recent Mycobacterium tuberculosis infection
Authors: Lloyd Tessa , Steigler Pia , Mpande Cheleka A. M. , Rozot Virginie , Mosito Boitumelo , Schreuder Constance , Reid Timothy D. , Hatherill Mark , Scriba Thomas J. , Little Francesca , Nemes Elisa ,   the ACS Study Team
Published: July 2021

The risk of tuberculosis (TB) disease is higher in individuals with recentMycobacterium tuberculosis(M.tb) infection compared to individuals with more remote, established infection. We aimed to define blood-based biomarkers to distinguish between recent and remote infection, which would allow targeting of recently infected individuals for preventive TB treatment. We hypothesized that integration of multiple immune measurements would outperform the diagnostic performance of a single biomarker. Analysis was performed on different components of the immune system, including adaptive and innate responses to mycobacteria, measured on recently and remotelyM.tbinfected adolescents. The datasets were standardized using variance stabilizing scaling and missing values were imputed using a multiple factor analysis-based approach. For data integration, we compared the performance of a Multiple Tuning Parameter Elastic Net (MTP-EN) to a standard EN model, which was built to the individual adaptive and innate datasets. Biomarkers with non-zero coefficients from the optimal single data EN models were then isolated to build logistic regression models. A decision tree and random forest model were used for statistical confirmation. We found no difference in the predictive performances of the optimal MTP-EN model and the EN model [average area under the receiver operating curve (AUROC) = 0.93]. EN models built to the integrated dataset and the adaptive dataset yielded identically high AUROC values (average AUROC = 0.91), while the innate data EN model performed poorly (average AUROC = 0.62). Results also indicated that integration of adaptive and innate biomarkers did not outperform the adaptive biomarkers alone (Likelihood Ratio Testχ2= 6.09, p = 0.808). From a total of 193 variables, the level of HLA-DR on ESAT6/CFP10-specific Th1 cytokine-expressing CD4 cells was the strongest biomarker for recentM.tbinfection. The discriminatory ability of this variable was confirmed in both tree-based models.

A single biomarker measuringM.tb-specific T cell activation yielded excellent diagnostic potential to distinguish between recent and remoteM.tbinfection.
Noise suppression in stochastic genetic circuits using PID controllers
Authors: Modi Saurabh , Dey Supravat , Singh Abhyudai
Published: July 2021

Inside individual cells, protein population counts are subject to molecular noise due to low copy numbers and the inherent probabilistic nature of biochemical processes. We investigate the effectiveness of proportional, integral and derivative (PID) based feedback controllers to suppress protein count fluctuations originating from two noise sources: bursty expression of the protein, and external disturbance in protein synthesis. Designs of biochemical reactions that function as PID controllers are discussed, with particular focus on individual controllers separately, and the corresponding closed-loop system is analyzed for stochastic controller realizations. Our results show that proportional controllers are effective in buffering protein copy number fluctuations from both noise sources, but this noise suppression comes at the cost of reduced static sensitivity of the output to the input signal. In contrast, integral feedback has no effect on the protein noise level from stochastic expression, but significantly minimizes the impact of external disturbances, particularly when the disturbance comes at low frequencies. Counter-intuitively, integral feedback is found to amplify external disturbances at intermediate frequencies. Next, we discuss the design of a coupled feedforward-feedback biochemical circuit that approximately functions as a derivate controller. Analysis using both analytical methods and Monte Carlo simulations reveals that this derivative controller effectively buffers output fluctuations from bursty stochastic expression, while maintaining the static input-output sensitivity of the open-loop system. In summary, this study provides a systematic stochastic analysis of biochemical controllers, and paves the way for their synthetic design and implementation to minimize deleterious fluctuations in gene product levels.
The blood flow-klf6a-tagln2 axis drives vessel pruning in zebrafish by regulating endothelial cell rearrangement and actin cytoskeleton dynamics
Authors: Wen Lin , Zhang Tao , Wang Jinxuan , Jin Xuepu , Rouf Muhammad Abdul , Luo Desha , Zhu Yuan , Lei Daoxi , Gregersen Hans , Wang Yeqi , Wang Guixue
Published: July 2021

Recent studies have focused on capillary pruning in various organs and species. However, the way in which large-diameter vessels are pruned remains unclear. Here we show that pruning of the zebrafish caudal vein (CV) from ventral capillaries of the CV plexus in different transgenic embryos is driven by endothelial cell (EC) rearrangement, which involves EC nucleus migration, junction remodeling, and actin cytoskeleton remodeling. Further observation reveals a growing difference in blood flow velocity between the two vessels in CV pruning in zebrafish embryos. With this model, we identify the critical role of Kruppel-like factor 6a (klf6a) in CV pruning. Disruption of klf6a functioning impairs CV pruning in zebrafish. klf6a is required for EC nucleus migration, junction remodeling, and actin cytoskeleton dynamics in zebrafish embryos. Moreover, actin-related protein transgelin 2 (tagln2) is a direct downstream target of klf6a in CV pruning in zebrafish embryos. Together these results demonstrate that the klf6a-tagln2 axis regulates CV pruning by promoting EC rearrangement.
Effect of sanitation improvements on soil-transmitted helminth eggs in courtyard soil from rural Bangladesh: Evidence from a cluster-randomized controlled trial
Authors: Kwong Laura H. , Sen Debashis , Islam Sharmin , Shahriar Sunny , Benjamin-Chung Jade , Arnold Benjamin F. , Hubbard Alan , Parvez Sarker Masud , Islam Mahfuza , Unicomb Leanne , Rahman Md. Mahbubur , Nelson Kara , Colford John M. , Luby Stephen P. , Ercumen Ayse
Published: July 2021

Improved sanitation has been hypothesized to reduce soil-transmitted helminth (STH) infections by reducing the prevalence and concentration of STH eggs/larvae in soil. We evaluated the effect of a randomized sanitation program (providing households with an improved dual-pit latrine, tools for child/animal feces management, and behavioral messaging) on reducing the prevalence and concentration of STH eggs in soil from household courtyards. We collected soil samples from 1405 households enrolled in the sanitation intervention (n = 419) and control (n = 914) groups of a cluster-randomized controlled trial (WASH Benefits) in rural Bangladesh approximately 2 years after the initiation of the interventions. We analyzed samples for Ascaris lumbricoides, Trichuris trichiura, and hookworm eggs by microscopy. We estimated prevalence ratios (PR) and egg count ratio (ECR) to compare the prevalence of STH eggs and arithmetic and geometric mean egg counts for STH eggs per gram of soil in the sanitation and control arms. Among intervention households, latrines achieved high and sustained user uptake by adults while child open defecation remained common and most households did not dispose of child feces hygienically. In courtyard soil from control households, the prevalence of any STH eggs was 75.7% and the prevalence of any larvated STH eggs was 67.3%. A. lumbricoides was detected in 63.0% of control samples and T. trichiura in 55.7% of control samples; hookworm was not detected in any sample. In the control arm, the arithmetic mean egg count for any STH was 3.96 eggs/dry gram, while the geometric mean was 1.58 eggs/dry gram. There was no difference between the intervention and control groups in the prevalence of any STH eggs (PR = 0.98 (95% CI: 0.91, 1.05)) or mean egg counts (ECR = 0.08 (95% CI: -0.10, 0.26) for geometric mean and 0.07 (95% CI: -0.22, 0.37) for arithmetic mean). Adjusted models gave similar results. A compound-level sanitation intervention that provided improved latrines and tools for disposal of child and animal feces did not have an impact on STH eggs in soil. In order to effectively reduce the prevalence and concentration of STH eggs in the environment, sustained, widespread use of sanitation strategies to isolate and hygienically dispose of child and animal feces may need to complement traditional strategies for containment of adult human feces.

Trial Registration: NCT01590095.
Associations between early postoperative pain outcome measures and late functional outcomes in patients after knee arthroplasty
Authors: Dubljanin Raspopović Emilija , Meissner Winfried , Zaslansky Ruth , Kadija Marko , Tomanović Vujadinović Sanja , Tulić Goran
Published: July 2021

Introduction/Aim

Early rehabilitation, return to daily life activities and function are the ultimate goals of perioperative care. It is unclear which pain-related patient-reported outcome measures (PROM) mirror treatment effects or are related with early and late functional outcomes.

Methods

We examined associations between two approaches of pain management (scheduled vs ‘on demand’) and PROMs on post-operative days one and five (POD1, 5) with function on POD5 and 3 months after surgery in patients undergoing Total Knee Arthroplasty (TKA) in a single centre. The scheduled pain management consisted of pain assessment and routine administration of non-opioid drugs, and a weak opioid based on severity of pain reported by patients. The ‘on demand’ group received non-opioids and/or a weak opioid only when asking ‘on demand’ for analgesics.

Results

On POD1, patients in the scheduled treatment group reported reduced severity of worst pain, less interference of pain with activities in-bed and sleep, and a higher proportion got out of bed. On POD5, these patients reported as well significantly less worst pain, spent significantly less time in severe pain, experienced less interference of pain with activities in bed, and felt less helpless. Furthermore, tests of function, extension and flexion ranges, Barthel index and 6 minutes walking test on POD5, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) 3 months later were significantly better in the scheduled treatment group compared to the ‘on demand’ treatment group. Pain related PROMs assessed at POD1 and especially at POD5 are associated with better knee range of motion, better performance in activities of daily living, and faster gait speed, as well as less pain, better performance in activities of daily living, as well as higher knee-related quality of life 3 months postoperatively.

Conclusions

Our study demonstrates that severe postoperative pain after TKA might have long lasting consequences, and even small improvements in treatment, although being far from optimal, are accompanied by improved outcomes.
Basking shark sub-surface behaviour revealed by animal-towed cameras
Authors: Rudd Jessica L. , Bartolomeu Tiago , Dolton Haley R. , Exeter Owen M. , Kerry Christopher , Hawkes Lucy A. , Henderson Suzanne M. , Shirley Marcus , Witt Matthew J.
Published: July 2021

While biologging tags have answered a wealth of ecological questions, the drivers and consequences of movement and activity often remain difficult to ascertain, particularly marine vertebrates which are difficult to observe directly. Basking sharks, the second largest shark species in the world, aggregate in the summer in key foraging sites but despite advances in biologging technologies, little is known about their breeding ecology and sub-surface behaviour. Advances in camera technologies holds potential for filling in these knowledge gaps by providing environmental context and validating behaviours recorded with conventional telemetry. Six basking sharks were tagged at their feeding site in the Sea of Hebrides, Scotland, with towed cameras combined with time-depth recorders and satellite telemetry. Cameras recorded a cumulative 123 hours of video data over an average 64-hour deployment and confirmed the position of the sharks within the water column. Feeding events only occurred within a metre depth and made up ¾ of the time spent swimming near the surface. Sharks maintained similar tail beat frequencies regardless of whether feeding, swimming near the surface or the seabed, where they spent surprisingly up to 88% of daylight hours. This study reported the first complete breaching event and the first sub-surface putative courtship display, with nose-to-tail chasing, parallel swimming as well as the first observation of grouping behaviour near the seabed. Social groups of sharks are thought to be very short term and sporadic, and may play a role in finding breeding partners, particularly in solitary sharks which may use aggregations as an opportunity to breed. In situ observation of basking sharks at their seasonal aggregation site through animal borne cameras revealed unprecedented insight into the social and environmental context of basking shark behaviour which were previously limited to surface observations.
Developing a model for estimating the activity of colonic microbes after intestinal surgeries
Authors: Marcus Andrew , Davis Taylor L. , Rittmann Bruce E. , DiBaise John K. , Carnero Elvis A. , Corbin Karen , Smith Steven R. , Krajmalnik-Brown Rosa
Published: July 2021

Background

The large intestine provides a compensatory role in energy recovery when surgical interventions such as extensive small intestinal resections or bypass operations lower the efficiency of nutrient absorption in the upper gastrointestinal (GI) tract. While microorganisms in the colon are known to play vital roles in recovering energy, their contributions remain to be qualified and quantified in the small intestine resection.

Objective

We develop a mathematical model that links nutrient absorption in the upper and lower GI tract in two steps.

Methods

First, we describe the effects of small intestine resection on the ileocecal output (ICO), which enters the colon and provides food for microbes. Second, we describe energy recovered by the colon’s microorganisms via short-chain fatty acid (SCFA) production. We obtain model parameters by performing a least-squares regression analysis on clinical data for subjects with normal physiology and those who had undergone small intestine resection.

Results

For subjects with their intestines intact, our model provided a metabolizable energy value that aligns well with the traditional Atwater coefficients. With removal of the small intestine, physiological absorption became less efficient, and the metabolizable energy decreased. In parallel, the inefficiencies in physiological absorption by the small intestine are partly compensated by production of short-chain fatty acids (SCFA) from proteins and carbohydrates by microorganisms in the colon. The colon recovered more than half of the gross energy intake when the entire small intestine was removed. Meanwhile, the quality of energy absorbed changed, because microbe-derived SCFAs, not the original components of food, become the dominant form of absorbed energy.

Conclusion

The mathematical model developed here provides an important framework for describing the effect of clinical interventions on the colon’s microorganisms.
Cost-effectiveness of procedure-less intragastric balloon therapy as substitute or complement to bariatric surgery
Authors: Mital Shweta , Nguyen Hai V.
Published: July 2021

Background

Procedure-less intragastric balloon (PIGB) eliminates costs and risks of endoscopic placement/removal and involves lower risk of serious complications compared with bariatric surgery, albeit with lower weight loss. Given the vast unmet need for obesity treatment, an important question is whether PIGB treatment is cost-effective—either stand-alone or as a bridge to bariatric surgery.

Methods

We developed a microsimulation model to compare the costs and effectiveness of six treatment strategies: PIGB, gastric bypass or sleeve gastrectomy as stand-alone treatments, PIGB as a bridge to gastric bypass or sleeve gastrectomy, and no treatment.

Results

PIGB as a bridge to bariatric surgery is less costly and more effective than bariatric surgery alone as it helps to achieve a lower post-operative BMI. Of the six strategies, PIGB as a bridge to sleeve gastrectomy is the most cost-effective with an ICER of $3,781 per QALY gained. While PIGB alone is not cost-effective compared with bariatric surgery, it is cost-effective compared with no treatment with an ICER of $21,711 per QALY.

Conclusions

PIGB can yield cost savings and improve health outcomes if used as a bridge to bariatric surgery and is cost-effective as a stand-alone treatment for patients lacking access or unwilling to undergo surgery.
Soil gas radon and soil permeability assessment: Mapping radon risk areas in Perak State, Malaysia
Authors: Nuhu Habila , Hashim Suhairul , Aziz Saleh Muneer , Syazwan Mohd Sanusi Mohamad , Hussein Alomari Ahmad , Jamal Mohamad Hidayat , Abdullah Rini Asnida , Hassan Sitti Asmah
Published: July 2021

In this study geogenic radon potential (GRP) mapping was carried out on the bases of field radon in soil gas concentration and soil gas permeability measurements by considering the corresponding geological formations. The spatial pattern of soil gas radon concentration, soil permeability, and GRP and the relationship between geological formations and these parameters was studied by performing detailed spatial analysis. The radon activity concentration in soil gas ranged from 0.11 to 434.5 kBq m−3 with a mean of 18.96 kBq m−3, and a standard deviation was 55.38 kBq m−3. The soil gas permeability ranged from 5.2×10−14 to 5.2×10−12 m2, with a mean of 5.65×10−13 m2. The GRP values were computed from the 222Rn activity concentration and soil gas permeability data. The range of GRP values was from 0.04 to 154.08. Locations on igneous granite rock geology were characterized by higher soil radon gas activity and higher GRP, making them radon-prone areas according to international standards. The other study locations fall between the low to medium risk, except for areas with high soil permeability, which are not internationally classified as radon prone. A GRP map was created displaying radon-prone areas for the study location using Kriging/Cokriging, based on in situ and predicted measured values. The GRP map assists in human health risk assessment and risk reduction since it indicates the potential of the source of radon and can serve as a vital tool for radon combat planning.
Neural correlates of error-monitoring and mindset: Back to the drawing board?
Authors: Janssen Tieme W. P. , Nieuwenhuis Smiddy , Hoefakker Jamie , Dreier Gligoor Patricia D. , Bonte Milene , van Atteveldt Nienke
Published: July 2021

The different ways students deal with mistakes is an integral part of mindset theory. While previous error-monitoring studies found supporting neural evidence for mindset-related differences, they may have been confounded by overlapping stimulus processing. We therefore investigated the relationship between mindset and event-related potentials (ERPs) of error-monitoring (response-locked Ne, Pe), with and without overlap correction. In addition, besides behavioral measures of remedial action after errors (post-error slowing and accuracy), we investigated their neural correlates (stimulus-locked N2). Results indicated comparable Ne, but larger Pe amplitudes in fixed-minded students; however, after overlap correction, the Pe results were rendered non-significant. A likely explanation for this overlap was a near-significant effect of mindset on the preceding stimulus P3. Finally, although N2 was larger for trials following errors, mindset was unrelated. The current study shows that the relationship between error-monitoring and mindset is more complex and should be reconsidered. Future studies are advised to explore stimulus processing as well, and if needed, to correct for stimulus overlap. In addition, contextual influences on and individual variation in error-monitoring need more scrutiny, which may contribute to refining mindset theory.
Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19
Authors: Briggs Neima , Gormally Michael V. , Li Fangyong , Browning Sabrina L. , Treggiari Miriam M. , Morrison Alyssa , Laurent-Rolle Maudry , Deng Yanhong , Hendrickson Jeanne E. , Tormey Christopher A. , Desruisseaux Mahalia S.
Published: July 2021

Background

Limited therapeutic options exist for coronavirus disease 2019 (COVID-19). COVID-19 convalescent plasma (CCP) is a potential therapeutic, but there is limited data for patients with moderate-to-severe disease.

Research question

What are outcomes associated with administration of CCP in patients with moderate-to-severe COVID-19 infection?

Study design and methods

We conducted a propensity score-matched analysis of patients with moderate-to-severe COVID-19. The primary endpoints were in-hospital mortality. Secondary endpoints were number of days alive and ventilator-free at 30 days; length of hospital stay; and change in WHO scores from CCP administration (or index date) to discharge. Of 151 patients who received CCP, 132 had complete follow-up data. Patients were transfused after a median of 6 hospital days; thus, we investigated the effect of convalescent plasma before and after this timepoint with 77 early (within 6 days) and 55 late (after 6 days) recipients. Among 3,217 inpatients who did not receive CCP, 2,551 were available for matching.

Results

Early CCP recipients, of whom 31 (40%) were on mechanical ventilation, had lower 14-day (15% vs 23%) and 30-day (38% vs 49%) mortality compared to a matched unexposed cohort, with nearly 50% lower likelihood of in-hospital mortality (HR 0.52, [95% CI 0.28–0.96]; P = 0.036). Early plasma recipients had more days alive and ventilator-free at 30 days (+3.3 days, [95% CI 0.2 to 6.3 days]; P = 0.04) and improved WHO scores at 7 days (-0.8, [95% CI: -1.2 to -0.4]; P = 0.0003) and hospital discharge (-0.9, [95% CI: -1.5 to -0.3]; P = 0.004) compared to the matched unexposed cohort. No clinical differences were observed in late plasma recipients.

Interpretation

Early administration of CCP improves outcomes in patients with moderate-to-severe COVID-19, while improvement was not observed with late CCP administration. The importance of timing of administration should be addressed in specifically designed trials.
Factors associated with school achievement of children aged 8–10 years in rural Bangladesh: Findings from a post hoc analysis of a community-based study
Authors: Hossain Sheikh Jamal , Tofail Fahmida , Sujan Hasan Mahmud , Arifeen Shams El , Hamadani Jena
Published: July 2021

Background

Education is one of the most important human capitals. Investment in education at early age returns best. A lot of factors influence children’s educational achievement. Studies in developed countries well established the relation of school achievement with its associated variables. But information is lack on what factors play important role for school achievement at early age in low resource settings like Bangladesh. We aimed to find factors associated with school achievement in rural Bangladesh.

Method

The data were acquired from a long-term follow up study, conducted in 8–10 years old children (n = 372). We used a locally developed school achievement tool based on Wide Range Achievement Test-4 to measure reading, spelling and math computation, Wechsler abbreviated scale of intelligence to measure intelligence Quotient (IQ), Digit span forward and backward for short term memory, and locally available Strength and Difficulties Questionnaire to measure behaviour. Socioeconomic and anthropometric information of the mothers and children were also collected. Multicollinearity of the data was checked. Unadjusted and adjusted multiple linear regression analysis was performed.

Findings

Years of schooling and short-term memory were positively related to reading, spelling and math computation. For years of schooling it was-reading B = 8.09 (CI 5.84, 10.31), spelling 4.43 (4.33, 8.53) and math computation 5.23 (3.60, 6.87) and for short term memory- reading 3.56 (2.01,5.05), spelling 4.01 (2.56, 5.46) and math computation 2.49 (1.37, 3.62). Older children had lower scores of reading -0.48 (-0.94, -0.02), spelling -0.41 (-0.88, -0.02) and math computation -0.47 (-0.80, -0.14). Children’s IQ predicted reading 0.48 (0.14, 0.81) and spelling 0.50 (0.18, 0.82) skills. Mother and father’s education predicted Spelling 0.82 (0.16, 1.48) and reading 0.68 (0.06, 1.30) capacity respectively. Children enrolled in private schools had higher reading 10.28 (5.05, 15.51) and spelling 6.22 (1.31, 11.13) than those in the government schools. Children with more difficult behaviour tended to have lower scores in reading -0.51 (-0.96, -0.05).

Conclusion

Children’s school achievement is influenced by their IQ, years of schooling, type of school and parents’ education. Therefore, intervention should be made to focus specifically on these variables and establish the effect of this intervention through robust research design.
Computational modelling unveils how epiblast remodelling and positioning rely on trophectoderm morphogenesis during mouse implantation
Authors: Dokmegang Joel , Yap Moi Hoon , Han Liangxiu , Cavaliere Matteo , Doursat René
Published: July 2021

Understanding the processes by which the mammalian embryo implants in the maternal uterus is a long-standing challenge in embryology. New insights into this morphogenetic event could be of great importance in helping, for example, to reduce human infertility. During implantation the blastocyst, composed of epiblast, trophectoderm and primitive endoderm, undergoes significant remodelling from an oval ball to an egg cylinder. A main feature of this transformation is symmetry breaking and reshaping of the epiblast into a “cup”. Based on previous studies, we hypothesise that this event is the result of mechanical constraints originating from the trophectoderm, which is also significantly transformed during this process. In order to investigate this hypothesis we propose MG# (MechanoGenetic Sharp), an original computational model of biomechanics able to reproduce key cell shape changes and tissue level behavioursin silico. With this model, we simulate epiblast and trophectoderm morphogenesis during implantation. First, our results uphold experimental findings that repulsion at the apical surface of the epiblast is essential to drive lumenogenesis. Then, we provide new theoretical evidence that trophectoderm morphogenesis indeed can dictate the cup shape of the epiblast and fosters its movement towards the uterine tissue. Our results offer novel mechanical insights into mouse peri-implantation and highlight the usefulness of agent-based modelling methods in the study of embryogenesis.
Affective states in digital game-based learning: Thematic evolution and social network analysis
Authors: Chen Xieling , Zou Di , Kohnke Lucas , Xie Haoran , Cheng Gary
Published: July 2021

Research has indicated strong relationships between learners’ affect and their learning. Emotions relate closely to students’ well-being, learning quality, productivity, and interaction. Digital game-based learning (DGBL) has been widely recognized to be effective in enhancing learning experiences and increasing student motivation. The field of emotions in DGBL has become an active research field with accumulated literature available, which calls for a comprehensive understanding of the up-to-date literature concerning emotions in virtual DGBL among students at all educational levels. Based on 393 research articles collected from the Web of Science, this study, for the first time, explores the current advances and topics in this field. Specifically, thematic evolution analysis is conducted to explore the evolution of topics that are categorized into four different groups (i.e., games, emotions, applications, and analytical technologies) in the corpus. Social network analysis explores the co-occurrences between topics to identify their relationships. Interesting results are obtained. For example, with the integration of diverse applications (e.g., mobiles) and analytical technologies (e.g., learning analytics and affective computing), increasing types of affective states, socio-emotional factors, and digital games are investigated. Additionally, implications for future research include 1) children’s anxiety/attitude and engagement in collaborative gameplay, 2) individual personalities and characteristics for personalized support, 3) emotion dynamics, 4) multimodal data use, 5) game customization, 6) balance between learners’ skill levels and game challenge as well as rewards and learning anxiety.
A drug comorbidity index to predict mortality in men with castration resistant prostate cancer
Authors: Fallara Giuseppe , Gedeborg Rolf , Bill-Axelson Anna , Garmo Hans , Stattin Pär
Published: July 2021

Background

The Charlson Comorbidity Index is a poor predictor of mortality in men with castration resistant prostate cancer (CRPC). To improve this prediction, we created a comorbidity index based on filled prescriptions intended to be used in registry-based studies.

Materials and methods

In a population-based cohort of men with CPRC a drug comorbidity index (DCI-CRPC) was calculated based on prescriptions filled during a 365-day period before the date of CRPC diagnosis to predict mortality. Five risk categories for men with CRPC were defined based on PSA kinetics. Mortality rates were described by Kaplan-Meier curves. The predictive ability of the DCI-CRPC was compared in univariable models to that of the original DCI, derived from men in the general population, and to that of the Charlson Comorbidity Index.

Results

In 1,885 men with CRPC the median overall survival ranged from 3.0 years (95% confidence interval [CI] 2.8 to 3.4) in the first tertile of the DCI-CRPC, to 1.0 year (95% CI 0.9 to 1.1) in the third tertile of the DCI-CRPC. The index had higher discriminative ability (C-index 0.667) than the Charlson Comorbidity Index (C-index 0.508). The discriminative ability of the DCI-CRPC was highest in the subgroup with least aggressive cancer (C-index 0.651) and lowest in men with most aggressive cancer (C-index 0.618). The performance of the DCI-CRPC was comparable to that of the original DCI.

Conclusion

Our newly created comorbidity index using filled prescriptions predicted death in men with CRPC better than the Charlson Comorbidity Index.
Antiparkinsonian drugs as potent contributors to nocturnal sleep in patients with Parkinson’s disease
Authors: Taguchi Soutarou , Koide Hirofumi , Oiwa Hiroko , Hayashi Miku , Ogawa Kazuhiro , Ito Chihiro , Nakashima Koji , Yuasa Tomoko , Yasumoto Akihiro , Ando Hiroaki , Fujikake Akifumi , Fukuoka Takaaki , Tokui Keisuke , Izumi Masayuki , Tsunoda Yuka , Kawagashira Yuichi , Okada Yohei , Niwa Jun-ichi , Doyu Manabu
Published: July 2021

Objective

To clarify whether antiparkinsonian drugs contribute to nocturnal sleep disturbances in patients with Parkinson’s disease (PD).

Background

Although the major antiparkinsonian drugs L-dopa and dopamine agonists (DAs) have been found to affect sleep, little is known about the effects of specific drugs on sleep in PD patients.

Methods

The study participants consisted of 112 PD patients (median age 72.5 years [inter-quartile range: IQR 65–79]; mean disease duration 8.44 years [standard deviation: 7.33]; median Hoehn and Yahr stage 3 [IQR 2–3.75]) taking one of three types of non-ergot extended-release DAs (rotigotine 32; pramipexole 44; ropinirole 36) with or without L-dopa (median daily total dosage of antiparkinsonian drugs 525.5 mg [IQR 376.25–658] levodopa equivalent dose [LED]). Participants were assessed using the PD Sleep Scale-2 (PDSS-2).

Results

For the whole PD patient cohort, the PDSS-2 sleep disturbance domain score and the scores for item 1 assessing sleep quality and item 8 assessing nocturia were positively correlated with daily total dosage of antiparkinsonian drugs and dosage of L-dopa, but not with the dosage of DAs. Sub-analysis according to DA treatment revealed that DA dosage was not correlated with item 1 or 8 score in any of the subgroups. The LED ratio of rotigotine to the total dosage of antiparkinsonian drugs was inversely correlated with the item 1 score.

Conclusions

These data suggest that antiparkinsonian drugs, in particular L-dopa, adversely affect nocturnal sleep in PD patients, especially in terms of sleep quality and nocturia. Thus, adjusting both the total dosage of antiparkinsonian drugs and the dose-ratio of L-dopa might be key actions for alleviating poor sleep quality in patients with PD. Among DAs, we found a clear positive correlation between the dose-ratio of rotigotine and sleep quality. Thus, partial L-dopa replacement with rotigotine could improve sleep quality in patients with PD.
A mixed methods study to evaluate participatory mapping for rural water safety planning in western Kenya
Authors: Okotto-Okotto Joseph , Yu Weiyu , Kwoba Emmah , Thumbi Samuel M. , Okotto Lorna Grace , Wanza Peggy , Trajano Gomes da Silva Diogo , Wright Jim
Published: July 2021

Water safety planning is an approach to ensure safe drinking-water access through comprehensive risk assessment and water supply management from catchment to consumer. However, its uptake remains low in rural areas. Participatory mapping, the process of map creation for resource management by local communities, has yet to be used for rural water safety planning. In this mixed methods study, to evaluate the validity of participatory mapping outputs for rural water safety planning and assess community understanding of water safety, 140 community members in Siaya County, Kenya, attended ten village-level participatory mapping sessions. They mapped drinking-water sources, ranked their safety and mapped potential contamination hazards. Findings were triangulated against a questionnaire survey of 234 households, conducted in parallel. In contrast to source type ranking for international monitoring, workshop participants ranked rainwater’s safety above piped water and identified source types such as broken pipes not explicitly recorded in water source typologies often used for formal monitoring. Participatory mapping also highlighted the overlap between livestock grazing areas and household water sources. These findings were corroborated by the household survey and subsequent participatory meetings. However, comparison with household survey data suggested participatory mapping outputs omitted some water sources and landscape-scale contamination hazards, such as open defecation areas or flood-prone areas. In follow-up visits, participant groups ranked remediation of rainwater harvesting systems as the most acceptable intervention to address hazards. We conclude that participatory mapping can complement other established approaches to rural water safety planning by capturing informally managed source use and facilitating community engagement.
Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection
Authors: Brügger Melanie , Démoulins Thomas , Barut G. Tuba , Zumkehr Beatrice , Oliveira Esteves Blandina I. , Mehinagic Kemal , Haas Quentin , Schögler Aline , Rameix-Welti Marie-Anne , Eléouët Jean-François , Moehrlen Ueli , Marti Thomas M. , Schmid Ralph A. , Summerfield Artur , Posthaus Horst , Ruggli Nicolas , Hall Sean R. R. , Alves Marco P.
Published: July 2021

Lung-resident (LR) mesenchymal stem and stromal cells (MSCs) are key elements of the alveolar niche and fundamental regulators of homeostasis and regeneration. We interrogated their function during virus-induced lung injury using the highly prevalent respiratory syncytial virus (RSV) which causes severe outcomes in infants. We applied complementary approaches with primary pediatric LR-MSCs and a state-of-the-art model of human RSV infection in lamb. Remarkably, RSV-infection of pediatric LR-MSCs led to a robust activation, characterized by a strong antiviral and pro-inflammatory phenotype combined with mediators related to T cell function. In line with this, following in vivo infection, RSV invades and activates LR-MSCs, resulting in the expansion of the pulmonary MSC pool. Moreover, the global transcriptional response of LR-MSCs appears to follow RSV disease, switching from an early antiviral signature to repair mechanisms including differentiation, tissue remodeling, and angiogenesis. These findings demonstrate the involvement of LR-MSCs during virus-mediated acute lung injury and may have therapeutic implications.
Interview with Beano writer Andy Fanton
Authors: Caro John
Published: July 2021

An interview with Andy Fanton, a current writer for the Beano UK children’s humour comic. Andy got his break writing and drawing for the sadly now-defunct Dandy weekly, and currently writes legacy characters such as Minnie the Minx and The Bash Street Kids. The interview covers Andy’s and DC Thomson’s working practices and methods, considers the role and relevance of Beano in the transmedia age, and defends Beano from accusations that the comic has lost its edge and is no longer as cheeky or rebellious as it once was.
Egiak, munduak eta minak
Authors: Garmendia Ekain
Published: July 2021

"Kripkeren Naming and Necessityk 40 (+1) urte" ale bereziaren aurkezpena
Non-European Immigration, socio-economic benefits and dynamics of inclusion in Spain. Do immigrants consume a disproportionate share of Social Service benefits?
Authors: Jaraíz Arroyo Germán , Caravaca Sánchez Francisco , González Portillo Auxiliadora
Published: July 2021

The problematisation of migration has intensified in Europe over the last decade, as the Financial Crisis of 2008 dealt a major blow to social welfare instruments. This context has reinforced the idea that immigrants would consume a disproportionate share of socio-economic resources available through social services, thus displacing the local population. This article examines the case of Spain, analysing the dynamics of accessing socioeconomic inclusion policies developed by public Social Services among immigrants and non-immigrants at risk of social exclusion, based on different secondary sources. The paper shows that is there no evidence that social services resources are being displaced for the socio-economic inclusion of the immigrant population.
La presencia del factor innovador en el productor agrario en la Comunidad Valenciana. Herramientas para favorecer la innovación en la dialéctica rural-urbana
Authors: Pérez-Ledo Pau , Segovia-Pérez Mónica
Published: July 2021

Este estudio sociológico se centra en la figura del productor agrario valenciano y su comportamiento frente a la innovación. Adoptar una actitud que favorezca la innovación depende de múltiples factores que influyen en la gestión de la empresa agraria. Este estudio utiliza los datos procedentes de una encuesta a productores agrarios valencianos que profundiza en los factores socioeconómicos que pueden decantar al productor agrario hacia una postura favorable a la innovación. Posteriormente, el estudio se centra en obtener un perfil tipo que represente al productor según sus características y las de su explotación, según su actitud innovadora y la orientación hacia factores influyentes, como son la orientación al mercado y la orientación al aprendizaje. Se observa una asociación positiva entre la actitud innovadora y el nivel de formación del agricultor y su proximidad a zonas urbanas, donde existe más acceso a conocimiento y servicios. El artículo concluye con la descripción de unos tipos ideales weberianos sobre agricultores basándose en su orientación hacia la innovación.
Theatre and Performance Studies in English: An Introduction
Authors: Guerrero Llorente Isabel , Rodríguez Verónica
Published: July 2021

Theatre and Performance Studies in English: An Introduction.
Análisis del tratamiento de la familia y de la diversidad familiar en América del Sur. Estudio comparado de casos
Authors: Moreno Parra Leidi Viviana , González-Rodríguez Rubén , Verde-Diego Carmen
Published: July 2021

Esta investigación analiza la consideración de la diversidad familiar en América del Sur. Se ha realizado una revisión sistemática de la literatura (n=41) y se han analizado, por cada país, constituciones (n=10); censos (n=20); el cuerpo normativo (n=93); y políticas sociales (n=67). Los resultados se presentan de forma comparada por países. El principal hallazgo es el escaso reconocimiento a la diversidad familiar.
Fauna associated with Malayan filariasis transmission in Banyuasin, South Sumatra, Indonesia
Authors: Mulyaningsih Budi , Umniyati Sitti Rahmah , Hadisusanto Suwarno , Edyansyah Erwin
Published: July 2021

Background and Aim: Brugia malayi is known to be zoonotically important because it can be transmitted from animals (mammals and primates) to humans or from humans to humans through mosquito vectors. This study was conducted to explore the fauna associated with Malayan filariasis transmission in Sedang village, Suak Tapeh District, Banyuasin Regency, South Sumatra Province, Indonesia.

Materials and Methods: A cross-sectional research design with an observational and analytical approach was applied in this study, and it was conducted in May 2018. Mosquitoes were collected twice using human bait both inside and outside the house from 6:00 p.m. to 6:00 a.m. The presence of competitors, predators, and reservoir hosts in the areas of five breeding habitats of Mansonia spp. was observed. The presence of microfilaria was confirmed under a microscope in night blood samples of inhabitants and cats. The presence of infective larvae (L3) of B. malayi was identified microscopically and based on the polymerase chain reaction method in female Mansonia mosquitoes.

Results: A total of 12 mosquito species were found, among which Mansonia uniformis was the dominant mosquito, and the predominant competitor was Mansonia annulifera. Dragonflies, as predators were found in two breeding habitats and fish were found in one breeding habitat. The L3 of B. malayi were not identified in the mosquitoes, and the microfilariae of B. malayi were not found in the blood samples of inhabitants and cats.

Conclusion: Although Mansonia mosquito population was abundant in Banyuasin Regency, the mosquito was not confirmed as an intermediate host of B. malayi, and the cat was not confirmed as a reservoir of B. malayi in the location.
Synthesis, Characterization and Docking Studies of
Some New Alkyne Containing Thiazole Derivatives
Authors: Mori Navneet P. , Parmar Priti K. , Khedker Vijay M. , Sanghavi Gaurav , Khunt Ranjan C.
Published: July 2021

Thiazole derivatives are potential candidates for drug development. They can be efficiently synthesized
and are extremely active against several diseases, including antimicrobial screening. A series of
2-(2-(3-methoxy-4-(prop-2-yn-1-yloxy)benzylidene)hydrazinyl)-4-(p-tolyl)-4,5-dihydrothiazole (5a-f)
and 2-((2-(4-(4-bromophenyl)-thiazol-2-yl)hydrazono)methyl)-5-(diethylamino)phenol (8g-j). The
synthesized compounds’ have been characterized by spectral analysis, such as mass, FT-IR, 1H & 13C
NMR. All the synthesized compounds were screened for in vitro antibacterial activity against some
Gram-positive (Staphylococcus aureus, Streptococcus pyogenes) and Gram-negative (Escherichia coli,
Klebsila) bacteria. The thiazole derivatives with a pharmacologically potent group provide the valued
therapeutic involvement in the treatment of microbial diseases, especially against bacterial and fungal
infections. Furthermore, to gauze their plausible mechanism of action and thermodynamic interaction
governing these molecules’ binding, a molecular docking study was carried out against crucial target
bacterial DNA, Gyrase.
URGENSI PENALARAN DALAM ARGUMENTASI HUKUM GUNA MENGEMBANGKAN PEMIKIRAN HUKUM YANG KOMPREHENSIF
Authors: Utami Tri Rahayu , Sulistyawan Aditya Yuli
Published: July 2021

Penalaran memiliki peran yang sangat penting dalam pengembangan pengetahuan serta pengkajian-pengkajian pengetahuan tertentu. Sebagai sebuah ilmu pengetahuan ia menjadi dasar yang menentukan pemikiran agar lurus, tepat dan sehat. Sebab fungsi penalaran adalah menyelidiki, merumuskan serta menerapkan hukum-hukum yang ditepati. Penalaran melalui argumentasi hukum merupakan ilmu yang memberikan prinsip-prinsip yang harus diikuti agar dapat berpikir valid menurut aturan yang berlaku. Ini dikarenakan, penalaran ilmiah menghendaki pembuktian kebenaran secara terpadu. Orientasi didalam melakukan penelitian mengindikasikan adanya suatu kaitan yang erat antara pandangan filsafati seorang peneliti dengan metode yang dipilih dan digunakan dalam melakukan penelitian. Tulisan ini ditujukan untuk mengetahui urgensi diperlukannya penalaran hukum bagi para calon maupun ahli dari lulusan hukum untuk diterapkan di masa depan, sehingga dari sini diharapkan dapat melahirkan alur penalaran ilmiah yang baik dan benar.
MENAKAR KEWENANGAN DAN TANGGUNG JAWAB PEJABAT PEMBUAT AKTA TANAH (PPAT) DALAM PERSPEKTIF BESTUURS BEVOEGDHEID
Authors: Wibawa Kadek Cahya Susila
Published: July 2021

Pemerintah (BPN) mempunyai kewajiban yang diperoleh secara atribusi untuk melakukan pendaftaran tanah untuk menjamin kepastian hukum di bidang pertanahan. Kewenangan tersebut kemudian didelegasikan kepada Pejabat Pembuat Akta Tanah (PPAT), selaku pejabat umum yang diberikan kewenangan untuk membuat akta otentik yang berkaitan dengan tanah.Perspektif bestuurs bevoegdheid menjelaskan bahwa sumber wewenang yang diperoleh secara delegasi, maka tanggung jawab dan tanggung gugat sudah berada pada penerima delegasi (delegataris). Berdasarkan hal tersebut, maka PPAT selaku delegataris, memiliki tanggung jawab administrasi apabila terjadi mal administrasi dalam pembuatan akta otentik tersebut. Penerapan sanksi administrasi merupakan bentuk tanggung jawab yang harus diterima oleh PPAT apabila terjadi mal administrasi. Mal administrasi mengakibatkan akta cacat yuridis. Konsekuensi hukum terhadap akta PPAT yang cacat yuridis, dapat berupa terdegradasinya kekuatan bukti sempurna dari akta otentik (pelanggaran syarat formil), dan batal demi hukum atau dapat dibatalkannya suatu akta dalam hal pelanggaran syarat materiil.
MENELISIK TERTIB HUKUM PERATURAN PEMERINTAH PENGGANTI UNDANG-UNDANG MELALUI VALIDITAS SUATU NORMA HUKUM
Authors: Anggraeni Ricca , Sari Indah Mutiara
Published: July 2021

Pergulatan tendensi dalam membentuk suatu peraturan bukanlah hal baru dalam dunia peraturan perundang-undangan. Hukum yang berorientasi pada masyarakat adalah mimpi yang harus segera diwujudkan oleh pemerintah Indonesia. Namun sayangnya, hal ini seperti masih jauh untuk diwujudkan jika melihat pada kebijakan-kebijakan yang dikeluarkan pada saat ini. Seperti Peraturan Pemerintah Pengganti Undang-Undang (Perppu) Nomor 1 Tahun 2020 tentang Kebijakan Keuangan Negara dan Stabilitas Sistem Keuangan Untuk Penanganan Pandemi Corona Virus Disease 2019 (COVID- 19) dan/atau Dalam Rangka Menghadapi Ancaman yang Membahayakan Perekonomian Nasional dan/atau Stabilitas Sistem Keuangan yang sejak ditetapkannya menuai beragam tanggapan negatif yang didominasi oleh kecurigaan masyarakat bahwa melalui instrumen Perppu ini, pemerintah lebih mengakomodasi kepentingan pragmatis dibanding kebutuhan masyarakat. Keberadaan Perppu ini kemudian dipersoalkan validitasnya sebagai sebuah norma hukum yang dikeluarkan dalam waktu singkat dengan alasan keadaan yang memaksa. DPR kemudian dituntut untuk menjadi lembaga pengampu Perppu agar tetap sejalan dengan konsep peraturan perundang-undangan di Indonesia.