bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain white matter microstructure abnormalities in children with optimal outcome from autism: a four-year follow-up study
Authors: Zhang Manxue , Hu Xiao , Jiao Jian , Yuan Danfeng , Li Sixun , Luo Tingting , Wang Meiwen , Situ Mingjing , Sun Xueli , Huang Yi
Published: November 2022

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder, with only a small proportion of people obtaining optimal outcomes. We do not know if children with ASD exhibit abnormalities in the white matter (WM) microstructure or if this pattern would predict ASD prognosis in a longitudinal study. 182 children with ASD were recruited for MRI and clinical assessment; 111 completed a four-year follow-up visit (30 with optimal outcomes, ASD−; 81 with persistent diagnosis, ASD+). Additionally, 72 typically developing controls (TDC) were recruited. The microstructural integrity of WM fiber tracts was revealed using tract-based spatial statistics (TBSS) and probabilistic tractography analyses. We examined the neuroimaging abnormality associated with ASD and its relationship to ASD with optimal outcome. The ASD+ and TDC groups were propensity score matched to the ASD− group in terms of age, gender, and IQ. TBSS indicated that children with ASD exhibited abnormalities in the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), and extending to the anterior thalamic radiation (ATR) and cingulum; whereas the ASD+ group showed more severe abnormalities than the ASD- group. Probabilistic tractography analysis revealed that ASD+ group exhibited lower Fractional Anisotropy (FA) of the left superior thalamic radiation (STR L) than ASD− group, and that FA value of the STR L was a significant predictor of optimal outcome (EX(B), 6.25; 95% CI 2.50—15.63; p < 0.001). Children with ASD showed significant variations in SLF_L and STR_L, and STR_L was a predictor of ‘ASD with optimal outcome’. Our findings may aid in comprehension of the mechanisms of ‘ASD with optimal outcome’.
Fertilization treatments affect soil CO2 emission through regulating soil bacterial community composition in the semiarid Loess Plateau
Authors: Wang Jinbin , Xie Junhong , Li Lingling , Effah Zechariah , Xie Lihua , Luo Zhuzhu , Zhou Yongjie , Jiang Yuji
Published: November 2022

A growing body of literature have emphasized the effects of fertilization regimes on soil respiration and microbial community in the semiarid region, however, fertilization treatment effects on the soil CO2emission, soil bacterial community, and their relationships from long-term experiments is lacking. In the present study, we investigated the effects of long-term fertilization regimes on soil bacterial community and thereafter on soil CO2emission. A 9-year field experiment was conducted with five treatments, including no fertilizer (NA) and four fertilization treatments (inorganic fertilizer (CF), inorganic plus organic fertilizer (SC), organic fertilizer (SM), and maize straw (MS)) with equal N input as N 200 kg hm–2. The results indicated that CO2emission was significantly increased under fertilization treatments compared to NA treatment. The bacterial abundance was higher under MS treatment than under NA treatment, while the Chao1 richness showed opposite trend. MS treatment significantly change soil bacterial community composition compared to NA treatment, the phyla (Alphaproteobacteria and Gammaproteobacteria) and potential keystone taxa (NitrosomonadaceaeandBeijerinckiaceae) were higher, while the Acidobacteriota was lower under MS treatment than under NA treatment. CO2emission was positively correlated with the abundance of Alphaproteobacteria, Gammaproteobacteria, and keystone taxa, negatively correlated with these of Acidobacteriota. Random forest modeling and structural equation modeling determined soil organic carbon, total nitrogen, and the composition and network module III of the bacterial community are the main factors contribute to CO2emission. In conclusion, our results suggest that the increased CO2emission was affected by the varied of soil bacterial community composition derived from fertilization treatments, which was related to Alphaproteobacteria, Gammaproteobacteria, Acidobacteriota, and potential keystone taxa (Nitrosomonadaceae and Beijerinckiaceae), and highlight that the ecological importance of the bacterial community in mediating carbon cycling in the semiarid Loess Plateau.
Multisensory-driven facilitation within the peripersonal space is modulated by the expectations about stimulus location on the body
Authors: Rossi Sebastiano Alice , Ronga Irene , Fossataro Carlotta , Galigani Mattia , Poles Karol , Garbarini Francesca
Published: November 2022

Compelling evidence from human and non-human studies suggests that responses to multisensory events are fastened when stimuli occur within the space surrounding the bodily self (i.e., peripersonal space; PPS). However, some human studies did not find such effect. We propose that these dissonant voices might actually uncover a specific mechanism, modulating PPS boundaries according to sensory regularities. We exploited a visuo-tactile paradigm, wherein participants provided speeded responses to tactile stimuli and rated their perceived intensity while ignoring simultaneous visual stimuli, appearing near the stimulated hand (VTNear) or far from it (VTFar; near the non-stimulated hand). Tactile stimuli could be delivered only to one hand (unilateral task) or to both hands randomly (bilateral task). Results revealed that a space-dependent multisensory enhancement (i.e., faster responses and higher perceived intensity in VTNear than VTFar) was present when highly predictable tactile stimulation induced PPS to be circumscribed around the stimulated hand (unilateral task). Conversely, when stimulus location was unpredictable (bilateral task), participants showed a comparable multisensory enhancement in both bimodal conditions, suggesting a PPS widening to include both hands. We propose that the detection of environmental regularities actively shapes PPS boundaries, thus optimizing the detection and reaction to incoming sensory stimuli.
Effects of yam varieties on flour physicochemical characteristics and resultant instant fufu pasting and sensory attributes
Authors: Ufondu Helen E. , Maziya‐Dixon Busie , Okoyeuzu Chigozie F. , Okonkwo Thomas M. , Okpala Charles Odilichukwu R.
Published: November 2022

Challenges and constraints deter the effective gathering of adequate information specific to the characteristics of yam (Dioscorea rotundata) landraces capable of producing a promising instant pounded fufu product. This current work, therefore, investigated the effects of yam varieties on flour physicochemical characteristics and resultant instant fufu pasting and sensory attributes. The D. rotundata varieties, obtained from the International Institute of Tropical Agriculture (IITA) (yam-breeding programme) experimental plots, included commercially available Fekatsa (control), alongside ten (N = 10) improved (varieties) namely: TDr 08/00068, TDr 10/00912, TDr 89/02665, TDr 95/01932, TDr 95/18544, TDr 97/00632, TDr 97/00917, TDr Agwekachi, TDr Ebute, and TDr Meccakusa). Compared to control, the improved yam varieties produced promising characteristic range values, for instance, amylose (15.77–33.89%), bulk density (0.77–0.86 g/cm3), setback (99.5–503.46 RVU), peak time (4.93–7.00 min) along with peak temperature (83.99 °C). From the correlation coefficient and principal component analysis, it was possible to deduce how flour physicochemical characteristics were associated with the resultant instant fufu pasting and sensory attributes. Considering the totality of results of this current study, both TDr 10/00912, and TDr Meccakusa yam varieties demonstrate a high potential on instant pounded flour towards producing an acceptable quality and promising fufu product.
IL-37 alleviates Coxsackievirus B3-induced viral myocarditis via inhibiting NLRP3 inflammasome-mediated pyroptosis
Authors: Sun Lin , Yuan Haitao , Zhao Gang
Published: November 2022

Our study aims to verify the potential effects and underlying mechanisms of IL-37 in Coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC). VMC model was established by intraperitoneal injection of CVB3 into 6-week-old male balb-c mice on day 0. Each mouse of the IL-37-control group and IL-37-VMC CVB3 groups was intraperitoneally injected with IL-37 on day 4 and day 7. The cardiac function was evaluated by transthoracic echocardiography including LVEF, LVFE, IVSs and IVSd. Myocardial injury was measured by Elisa for serum cTnI. The inflammation infiltration and fibrosis were evaluated by hematoxylin and eosin (HE) staining and Masson staining. The expression levels of NLRP3 inflammasome components in pyroptosis were determined by western blot, Elisa, and immunofluorescent analysis. We also detected the expression of IL-37-IL-1R8 in PBMCs by immunofluorescence after injection with CVB3 and IL-37. Compared with the VMC group, mice received CVB3 and IL-37 have improved cardiac function, reduced inflammation infiltration and fibrosis, and with lower expression of cTnI, IL-1β, IL-18 and NLRP3 inflammasome component. IL-37 weakened the upregulation of GSDMD and phosphorylation of NF-κB p65 induced by CVB3. Exogenous addition of IL-37 with CVB3 further increases the production of IL-37-IL-1R8 -IL-18RA complex in vitro. Our findings indicate that IL-37 alleviates CVB3-induced VMC, which may be produced by inhibiting NLRP3 inflammasome-mediated pyroptosis, NF-κB signaling pathway, and IL-37-IL-1R8 -IL-18RA complex.
Northeast Yucatan hurricane activity during the Maya Classic and Postclassic periods
Authors: Sullivan Richard M. , van Hengstum Peter J. , Donnelly Jeffrey P. , Tamalavage Anne E. , Winkler Tyler S. , Little Shawna N. , Mejia-Ortiz Luis , Reinhardt Eduard G. , Meacham Sam , Schumacher Courtney , Korty Robert
Published: November 2022

The collapse of the Maya civilization in the late 1st/early 2nd millennium CE has been attributed to multiple internal and external causes including overpopulation, increased warfare, and environmental deterioration. Yet the role hurricanes may have played in the fracturing of Maya socio-political networks, site abandonment, and cultural reconfiguration remains unexplored. Here we present a 2200 yearlong hurricane record developed from sediment recovered from a flooded cenote on the northeastern Yucatan peninsula. The sediment archive contains fine grain autogenic carbonate interspersed with anomalous deposits of coarse carbonate material that we interpret as evidence of local hurricane activity. This interpretation is supported by the correlation between the multi-decadal distribution of recent coarse beds and the temporal distribution of modern regional landfalling storms. In total, this record allows us to reconstruct the variable hurricane conditions impacting the northern lowland Maya during the Late Preclassic, Classic, and Postclassic Periods. Strikingly, persistent above-average hurricane frequency between ~ 700 and 1450 CE encompasses the Maya Terminal Classic Phase, the declines of Chichén Itza, Cobá, and subsequent rise and fall of the Mayapán Confederacy. This suggests that hurricanes may have posed an additional environmental stressor necessary of consideration when examining the Postclassic transformation of northern Maya polities.
Qualitative analysis and phase of chaos control of the predator-prey model with Holling type-III
Authors: AL-Kaff Mohammed O. , El-Metwally Hamdy A. , Elabbasy El-Metwally M.
Published: November 2022

In this study, we investigate the dynamics of a discrete-time with predator-prey system with a Holling-III type functional response model. The center manifold theorem and bifurcation theory are used to create existence conditions for flip bifurcations and Neimark-Sacker bifurcations. Bifurcation diagrams, maximum Lyapunov exponents, and phase portraits are examples of numerical simulations that not only show the soundness of theoretical analysis but also show complicated dynamical behaviors and biological processes. From the point of view of biology, this implies that the tiny integral step size can steady the system into locally stable coexistence. Yet, the large integral step size may lead to instability in the system, producing more intricate and richer dynamics. This also means that when the intrinsic death rate of the predator is high, this leads to a chaotic growth rate of the prey. The model has bifurcation features that are similar to those seen in logistic models. In addition, there is a bidirectional Neimark-Sacker bifurcation for both prey and predator, and therefore we obtain a direct correlation in symbiosis. This means that the higher the growth rate of the prey, the greater the growth rate of the predator. Therefore, the operation of predation has increased. The opposite is also true. Finally, the OGY approach is used to control chaos in the predator and prey model. which led to a new concept which we call bifurcation phase of control chaos.
Individualized anemia management enhanced by ferric pyrophosphate citrate protocol
Authors: Chait Yossi , Nathanson Brian H. , Germain Michael J.
Published: November 2022

The optimal use of erythropoiesis-stimulating agents (ESAs) and parenteral iron in managing anemia in end-stage renal disease (ESRD) remains controversial. One-size-fits-all rule-based algorithms dominate dosing protocols for ESA and parenteral iron. However, the Food & Drug Administration (FDA) guidelines for using ESAs in chronic kidney disease recommend individualized therapy for the patient. This prospective quality assurance project was at a single hemodialysis (HD) center comprising three 6-month phases (A, B, C) separated by 3-month washout periods. Standard bi-weekly ESA dose titration and intravenous (IV) iron sucrose protocols were used in baseline Phase A, and ferric pyrophosphate citrate (FPC) augmented iron in Phase B. In Phase C, an FPC protocol and weekly, individualized ESA management were used. We examined clinic-level mean differences in hemoglobin (Hb) and ESRD-related outcomes by phase with repeated ANOVA. To examine the Hb at the patient level, we used multi-level mixed-effect regression adjusting for phase, month, and other relevant confounders at each month over time to derive the mean marginal effects of phase. There were 54, 78, and 66 patients in phases A, B, and C, respectively, with raw mean Hb values of 9.9, 10.2, and 10.3 g/dL. The percentage of Hb values < 9 g/dL declined from 14.3% in Phase A to 7.6% in Phase C (p = 0.007). The multivariable mixed-effect regression results showed mean marginal Hb was higher by 0.3 mg/dL and 0.4 mg/dL in Phases B and C, respectively, compared to Phase A. We also observed reduced ferritin (p = 0.003) and transferrin saturation (TSAT) (p = 0.008) levels from Phase A to Phase C with the repeated ANOVA analysis. Ferric pyrophosphate citrate (FPC) appears to support more efficient ESA-stimulated erythropoiesis. Moreover, individualized ESA management combined with FPC (Phase C) was associated with further improvement in efficiency as we observed the fewest patients with Hb values < 9 g/dL concurrent with greater decreases in ferritin levels and reduced ESA doses. However, future prospective studies to confirm these findings on a larger, more diverse cohort of ESRD patients are warranted.
A portable analog front-end system for label-free sensing of proteins using nanowell array impedance sensors
Authors: Tayyab Muhammad , Xie Pengfei , Sami Muhammad Ahsan , Raji Hassan , Lin Zhongtian , Meng Zhuolun , Mahmoodi Seyed Reza , Javanmard Mehdi
Published: November 2022

Proteins are useful biomarkers for a wide range of applications such as cancer detection, discovery of vaccines, and determining exposure to viruses and pathogens. Here, we present a low-noise front-end analog circuit interface towards development of a portable readout system for the label-free sensing of proteins using Nanowell array impedance sensing with a form factor of approximately 35cm2. The electronic interface consists of a low-noise lock-in amplifier enabling reliable detection of changes in impedance as low as 0.1% and thus detection of proteins down to the picoMolar level. The sensitivity of our system is comparable to that of a commercial bench-top impedance spectroscope when using the same sensors. The aim of this work is to demonstrate the potential of using impedance sensing as a portable, low-cost, and reliable method of detecting proteins, thus inching us closer to a Point-of-Care (POC) personalized health monitoring system. We have demonstrated the utility of our system to detect antibodies at various concentrations and protein (45 pM IL-6) in PBS, however, our system has the capability to be used for assaying various biomarkers including proteins, cytokines, virus molecules and antibodies in a portable setting.
Insulin-like growth factor-1 levels are associated with high comorbidity of metabolic disorders in obese subjects; a Japanese single-center, retrospective-study
Authors: Kubo Haremaru , Sawada Shojiro , Satoh Michihiro , Asai Yoichiro , Kodama Shinjiro , Sato Toshihiro , Tomiyama Seitaro , Seike Junro , Takahashi Kei , Kaneko Keizo , Imai Junta , Katagiri Hideki
Published: November 2022

Insulin like growth factor-1 (IGF-1) plays important roles in metabolic functions, especially in adulthood. Additionally, obese subjects are reportedly predisposed to having low absolute IGF-1 levels. However, the prevalence and clinical characteristics of obese subjects with low IGF-1 levels are unknown. We examined 64 obese subjects with a body mass index (BMI) ≥ 35 kg/m2, with no history of endocrinological disorders, receiving inpatient care. IGF-1 levels were interpreted based on the IGF-1 standard deviation score (SDS) clinically used and standardized by age and sex (low IGF-1 group; ≤ − 2.0 SDS and standard IGF-1 group; − 2.0 < and <  + 2.0 SDS). Notably, 26.6% of the subjects had low IGF-1. Body fat mass and percentage, but not BMI, were significantly higher in the low than in the standard IGF-1 group. Furthermore, natural log-transformed high-sensitivity C-reactive protein, and the frequencies of dyslipidemia and hyperuricemia were higher in the low IGF-1 group. Moreover, among the subjects without diabetes, fasting glucose levels were significantly higher in the low IGF-1 group. Stepwise variable selection procedure revealed body fat percentage to be a parameter most strongly associated with low IGF-1. Thus, low IGF-1 levels may be an important marker of adiposity-associated metabolic disorders in obese patients.
A rapid multiplex cell-free assay on biochip to evaluate functional aspects of double-strand break repair
Authors: Tatin Xavier , Muggiolu Giovanna , Libert Sarah , Béal David , Maillet Thierry , Breton Jean , Sauvaigo Sylvie
Published: November 2022

The repair of DNA double-strand breaks (DSBs) involves interdependent molecular pathways, of which the choice is crucial for a cell’s fate when facing a damage. Growing evidence points toward the fact that DSB repair capacities correlate with disease aggressiveness, treatment response and treatment-related toxicities in cancer. Scientific and medical communities need more easy-to-use and efficient tools to rapidly estimate DSB repair capacities from a tissue, enable routine-accessible treatment personalization, and hopefully, improve survival. Here, we propose a new functional biochip assay (NEXT-SPOT) that characterizes DSB repair-engaged cellular pathways and provides qualitative and quantitative information on the contribution of several pathways in less than 2 h, from 10 mg of cell lysates. We introduce the NEXT-SPOT technology, detail the molecular characterizations of different repair steps occurring on the biochip, and show examples of DSB repair profiling using three cancer cell lines treated or not with a DSB-inducer (doxorubicin) and/or a DNA repair inhibitor (RAD51 inhibitor; DNA-PK inhibitor; PARP inhibitor). Among others, we demonstrate that NEXT-SPOT can accurately detect decreased activities in strand invasion and end-joining mechanisms following DNA-PK or RAD51 inhibition in DNA-PK-proficient cell lines. This approach offers an all-in-one reliable strategy to consider DSB repair capacities as predictive biomarkers easily translatable to the clinic.
High daily energy expenditure of Tuvan nomadic pastoralists living in an extreme cold environment
Authors: Sellers Adam J. , Khovalyg Dolaana , Plasqui Guy , van Marken Lichtenbelt Wouter
Published: November 2022

Research investigating thermoregulatory energy costs in free-living humans is limited. We determined the total energy expenditure (TEE) of Tuvan pastoralists living in an extreme cold environment and explored the contribution of physical activity and cold-induced thermogenesis. Twelve semi-nomadic pastoralists (47 ± 8 years, 64 ± 8 kg) living under traditional circumstances, in Tuva, south-central Siberia, Russia, were observed during two consecutive 6-day periods in winter. TEE was measured via the doubly labelled water technique. Skin and ambient temperatures, and physical activity were continuously monitored. The outdoor temperature during the observation period was − 27.4 ± 5.4 °C. During the daytime, the participants were exposed to ambient temperatures below 0 °C for 297 ± 131 min/day. The Tuvan pastoralists were more physically active compared to western populations (609 ± 90 min/day of light, moderate, and vigorous physical activity). In addition, TEE was 13.49 ± 1.33 MJ/day (3224 ± 318 kcal/day), which was significantly larger by 17% and 31% than predicted by body mass, and fat-free mass, respectively. Our research suggests the daily cold exposure combined with high levels of physical activity contributed to the elevated TEE. Future research should reconsider the assumption that energy costs due to thermoregulation are negligible in free-living humans.
Movie editing influences spectators’ time perception
Authors: Kovarski Klara , Dos Reis Joanna , Chevais Claire , Hamel Anaïs , Makowski Dominique , Sperduti Marco
Published: November 2022

Filmmakers use different techniques (e.g., camera movements, editing) to shape viewers' experience. In particular, editing can be used to handle the temporal unfolding of events represented in a movie. Nevertheless, little is known about how different editing types impact viewers’ time perception. In an exploratory on-line study (90 participants) and a pre-registered conceptual replication study (60 participants), we asked participants to judge (Study 1) or reproduce (Study 2) the duration of 45 excerpts of the movie “Le Ballon Rouge” containing either continuous editing, action discontinuity editing or no editing. Each excerpt was formatted in three durations (2000, 2500 or 3000 ms). In both studies, we reported that scenes containing continuous editing were perceived as longer than the other two scene types. Moreover, scenes containing action discontinuity editing were perceived as longer than scenes with no editing. This study contributes to the emerging field of psycho-cinematics which could ultimately develop the dialog between arts and science.
Prevalence and associated factors of stunting, wasting and underweight of children below five using quintile regression analysis (PDHS 2017–2018)
Authors: Siddiqa Maryam , Zubair Amber , Kamal Asifa , Ijaz Muhammad , Abushal Tahani
Published: November 2022

The objective of the current study is to identify the risk factors for malnutrition among the age of under-five children’s in Pakistan. This is secondary data analysis for the data taken from Pakistan Demographic and Health Survey (PDHS 2017–18) and was analyzed by implementing quantile regression analysis. The sample size included 12,708 alive children in the study, for which the data collection period was from November 22, 2017, to April 30, 2018. The prevalence of malnutrition among boys is high (51.2%). Older age mother’s children have more prevalence of malnutrition (20.7%). A child born with small body size (underweight: Q0.25: − 0.625; Q0.50: − 0.623; Q0.75: − 0.426 and wasting: Q0.50: − 0.513); having uneducated mother (underweight: Q0.25: − 0.387; Q0.50: − 0.247; Q0.75: − 0.328), belonged to a poor household (underweight: Q0.50: − 0.251),residing in rural areas (underweight: Q0.25: − 0.443), not following properly breastfeeding practices (underweight: Q0.50: − 0.439; Q0.75: − 0.438) have negative effect on different measures of malnutrition and this effect is significantly raises across different quantiles of stunting , wasting and underweight (atp value < 0.01 and < 0.05). Older age mother (stunting: Q0.50: 0.777; Q0.75: 1.078; underweight Q0.20: 0.568; Q0.50: 0.429; Q0.75: 0.524) and higher birth order number (stunting: Q0.50: 0.415; Q0.75: 0.535), have a positive effect on three measures of under-nutrition and this effect is gradual raises at different quantile of stunting, wasting and underweight. Elder and smoker mothers were proved associated risk factors of both stunting and being underweight in Pakistan. Moreover, Proper breastfeeding practices, better economic status, average or above the average birth weight of the child, and milk consumption are found protective factors against stunting, wasting, and underweight children in Pakistan.
The clinical experience of the prognosis in opposite CEA and image change after therapy in stage IV colorectal cancer
Authors: Su Yi-Tien , Chen Jia-Wan , Chang Shih-Ching , Jiang Jeng-Kai , Huang Sheng-Chieh
Published: November 2022

Carcinoembryonic antigen (CEA) levels and imaging are used to guide treatment for metastatic colorectal cancer (mCRC). This study evaluated changes in CEA and imaging findings in mCRC patients following systemic therapy and their clinical significance, especially the ones with inconsistent results of CEA and image findings. We enrolled 330 stage IV CRC patients who systemic therapy. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) and a modification for CEA, patients were stratified into consistent and inconsistent response groups. Clinicopathological features and prognoses were compared between each groups. Different CEA/IMG groups showed no significant differences in terms of tumor location, initial CEA level, mucinous component, tumor differentiation and further surgical treatment rate. Inconsistent responses were observed in half of the patients (n = 165, 50%). The prognosis in the inconsistent groups with either CEA-SD or IMG-SD was dependent on the result of the other evaluation method (PR or PD). Cases with conflicting results between CEA and image groups (CEA-RD/IMG-PD, CEA-PD/IMG-PR) had an OS close to that of CEA-SD/IMG-SD (18.2 m, 16.2 m vs. 18.8 m, P = 0.620). The overall survival (OS) in the consistent (PR/PR ro PD/PD) groups were significantly different (P < 0.001). Combining CEA and imaging provides more information about mCRC patients who have undergone systemic therapy. Approximately half the patients have inconsistent responses, which is still valuable in predicting the prognosis.
Protein biomarkers of cardiac remodeling and inflammation associated with HFpEF and incident events
Authors: Regan Jessica A. , Truby Lauren K. , Tahir Usman A. , Katz Daniel H. , Nguyen Maggie , Kwee Lydia Coulter , Deng Shuliang , Wilson James G. , Mentz Robert J. , Kraus William E. , Hernandez Adrian F. , Gerszten Robert E. , Peterson Eric D. , Holman Rury R. , Shah Svati H.
Published: November 2022

There is increasing evidence that HFpEF is a heterogeneous clinical entity and distinct molecular pathways may contribute to pathophysiology. Leveraging unbiased proteomics to identify novel biomarkers, this study seeks to understand the underlying molecular mechanisms of HFpEF. The discovery cohort consisted of HFpEF cases and non-HF controls from the CATHGEN study (N = 176); the validation cohort consisted of participants from the TECOS trial of patients with diabetes (N = 109). Proteins associated with HFpEF were included in a LASSO model to create a discriminative multi-protein model and assessed in the validation cohort. Survival models and meta-analysis were used to test the association of proteins with incident clinical outcomes, including HF hospitalization, mortality and HFpEF hospitalization in CATHGEN, TECOS and the Jackson Heart Study. In the derivation set, 190 proteins were associated with HFpEF in univariate analysis, of which 65 remained significant in the multivariate model. Twenty (30.8%) of these proteins validated in TECOS, including LCN2, U-PAR, IL-1ra, KIM1, CSTB and Gal-9 (OR 1.93–2.77, p < 0.01). LASSO regression yielded a 13-protein model which, when added to a clinical model inclusive of NT-proBNP, improved the AUC from 0.82 to 0.92 (p = 1.5 × 10–4). Five proteins were associated with incident HF hospitalization, four with HFpEF hospitalization and eleven with mortality (p < 0.05). We identified and validated multiple circulating biomarkers associated with HFpEF as well as HF outcomes. These biomarkers added incremental discriminative capabilities beyond clinical factors and NT-proBNP.
Lactate causes downregulation of Helicobacter pylori adhesin genes sabA and labA while dampening the production of proinflammatory cytokines
Authors: Somiah Tanvi , Gebremariam Hanna G. , Zuo Fanglei , Smirnova Ksenija , Jonsson Ann-Beth
Published: November 2022

Chronic inflammation induced by Helicobacter pylori is strongly associated with gastric cancer development, which is influenced by both bacterial virulence and host genetics. The sialic acid-binding adhesin SabA and the MUC5AC-binding adhesin LabA are important H. pylori virulence factors that facilitate adhesion of the bacterium, which is a crucial step in colonization. Lactate utilization has been reported to play a key role in the pathogenicity of different bacterial species. However, this is poorly understood in H. pylori. In this study, we investigated the effect of lactate on H. pylori adhesin gene expression and the regulation of host inflammatory cytokines. We show that the bacterial adhesins SabA and LabA were downregulated at the transcriptional level during incubation of H. pylori with lactate. Downregulation of sabA required the involvement of the two-component system ArsRS, while labA was regulated via the CheA/CheY system, indicating differences in the regulation of these genes in response to lactate. The levels of the proinflammatory cytokines TNF and IL-6 in H. pylori-stimulated macrophages were reduced when lactate was present. Interestingly, glucose did not prevent the secretion of these cytokines. Taken together, our data suggest that lactate affects H. pylori adhesin gene expression and the host response upon infection.
Development and validation of a predictive model for the risk of developing trichomonas vaginitis in women
Authors: Li Qi , Li Yaqin , Bai Ying , Zhang Honglei , Zhao Weihong
Published: November 2022

Trichomonas vaginitis (TV) is the most common non-viral sexually transmitted infection (STI) worldwide. The high prevalence of TV combined with mild or asymptomatic early symptoms leads to clinical vulnerability from delayed diagnosis. Latent infection can increase the incidence of pelvic infections, infertility, and adverse pregnancy complications. Data from 898 women who underwent vaginal flora testing from June 2014 to December 2014 were used to create a nomogram to assess the risk of TV in women in order to guide TV prevention and clinical intervention. The prediction model was evaluated in terms of identification, calibration, and clinical utility using the C-index, calibration plots, decision curve analysis, and internal validation. Predictors in the TV nomogram included age, occupation, yearly income, tea drinking, bathing frequency, menopause, spontaneous abortion, use of contraceptives, history of gynecological surgery, and HPV infection. The C-index of the TV risk prediction model was 0.732 (95% confidence interval: 0.695–0.768). It showed good discriminatory and predictive power. Decision curve analysis indicated that the nomogram had a good net benefit when the threshold probability of TV in women was 2–80%. The established TV prediction model easily, accurately, and quickly predicts the risk of TV onset.
Cone-beam CT delta-radiomics to predict genitourinary toxicities and international prostate symptom of prostate cancer patients: a pilot study
Authors: Delgadillo Rodrigo , Spieler Benjamin O. , Deana Anthony M. , Ford John C. , Kwon Deukwoo , Yang Fei , Studenski Matthew T. , Padgett Kyle R. , Abramowitz Matthew C. , Dal Pra Alan , Stoyanova Radka , Dogan Nesrin
Published: November 2022

For prostate cancer (PCa) patients treated with definitive radiotherapy (RT), acute and late RT-related genitourinary (GU) toxicities adversely impact disease-specific quality of life. Early warning of potential RT toxicities can prompt interventions that may prevent or mitigate future adverse events. During intensity modulated RT (IMRT) of PCa, daily cone-beam computed tomography (CBCT) images are used to improve treatment accuracy through image guidance. This work investigated the performance of CBCT-based delta-radiomic features (DRF) models to predict acute and sub-acute International Prostate Symptom Scores (IPSS) and Common Terminology Criteria for Adverse Events (CTCAE) version 5 GU toxicity grades for 50 PCa patients treated with definitive RT. Delta-radiomics models were built using logistic regression, random forest for feature selection, and a 1000 iteration bootstrapping leave one analysis for cross validation. To our knowledge, no prior studies of PCa have used DRF models based on daily CBCT images. AUC of 0.83 for IPSS and greater than 0.7 for CTCAE grades were achieved as early as week 1 of treatment. DRF extracted from CBCT images showed promise for the development of models predictive of RT outcomes. Future studies will include using artificial intelligence and machine learning to expand CBCT sample sizes available for radiomics analysis.
Effects of virtual target size, position, and parallax on vergence-accommodation conflict as estimated by actual gaze
Authors: Lin Chiuhsiang Joe , Canny Susmitha
Published: November 2022

Due to the increased utilization of stereoscopic displays, the scope of the vergence–accommodation conflict has been studied extensively to reveal how the human visual system operates. The purpose of this work was to study the phenomenon of vergence–accommodation conflict by comparing the theoretical eye vergence angle (vergence response) and gaze-based eye vergence angle (vergence stimulus) based on eye tracker gaze data. The results indicated that the gaze-based eye vergence angle was largest at the greatest parallax. The result also revealed that the eye vergence angle accuracy was significantly highest at the nearest parallax. Generally, accuracy improves when virtual objects are put in the middle and close to participants' positions. Moreover, the signed error decreases significantly when the virtual object is in the middle. Based on the results of this study, we can gain a greater understanding of the vergence–accommodation conflict in the stereoscopic environment.
Quantifying fluorescent nanoparticle uptake in mammalian cells using a plate reader
Authors: Shin Hye Ji , Kwak Minjeong , Joo Sihwa , Lee Ji Youn
Published: November 2022

In keeping with the rapid expansion of nanoparticle applications, various tools are required to investigate how nanoparticles interact with biological entities. Many assays have been developed to measure the cellular uptake of nanoparticles, but so far most of the methods are laborious and often non-quantitative. Here we developed an easily accessible and robust quantitative measurement method of the level of cellular uptake of fluorescently labeled nanoparticles using a plate reader. In the experimental design, potential issues that could lead to measurement variation were identified and addressed. For example, the variation in fluorescence intensity of samples due to differences in cell number was normalized to optical density, which is a physical value corresponding to the cell number. Number of washings and sample handling temperature were optimized to minimize the interference by residual nanoparticles and possible efflux of nanoparticles from cells, respectively. The developed assay was demonstrated with the lymphocyte cell line Jurkat to measure the cellular uptake of fluorescently labeled 50 nm polystyrene beads, and its applicability was further confirmed with the lung carcinoma cell line A549 and another lymphocyte cell line RPMI8226.
Feasibility and clinical implications of 3-day bladder diary derived classification of female storage lower urinary tract symptoms
Authors: Hsiao Sheng-Mou , Lin Ho-Hsiung
Published: November 2022

Our aim was to assess the feasibility of a bladder diary (BD) classification as a surrogate for urodynamic studies in women with storage lower urinary tract symptoms. A total of 3823 women who underwent urodynamic studies were reviewed. Nearly the scores of Patient Perception of Bladder Condition, Indevus Urgency Severity Scale and Overactive Bladder Symptom Score decreased gradually from the overactive bladder (OAB) wet-BD, OAB dry-BD, hypersensitive bladder (HSB) -BD, nocturia-BD to normal-BD groups (all p < 0.001). In addition, there is a trend that the rates of bladder oversensitivity decreased gradually from the OAB wet-BD, OAB dry-BD, HSB-BD, nocturia-BD to normal-BD groups (chi-square test, p < 0.001). Moreover, almost the volumes of first desire to void, normal desire to void, strong desire to void, and urgency increased gradually from the OAB wet-BD, OAB dry-BD, HSB-BD, nocturia-BD to normal-BD groups (all p < 0.001). Thus, this BD classification is correlated significantly with symptom severity, the rate of bladder oversensitivity, and bladder capacity. Nonetheless, a combination of urodynamics, clinical history, and BD is still needed for a thorough diagnosis, but that BD provides an efficient diagnosis in a proportion of patients.
Quantifying deep neural network uncertainty for atrial fibrillation detection with limited labels
Authors: Chen Brian , Javadi Golara , Hamilton Alexander , Sibley Stephanie , Laird Philip , Abolmaesumi Purang , Maslove David , Mousavi Parvin
Published: November 2022

Atrial fibrillation (AF) is the most common arrhythmia found in the intensive care unit (ICU), and is associated with many adverse outcomes. Effective handling of AF and similar arrhythmias is a vital part of modern critical care, but obtaining knowledge about both disease burden and effective interventions often requires costly clinical trials. A wealth of continuous, high frequency physiological data such as the waveforms derived from electrocardiogram telemetry are promising sources for enriching clinical research. Automated detection using machine learning and in particular deep learning has been explored as a solution for processing these data. However, a lack of labels, increased presence of noise, and inability to assess the quality and trustworthiness of many machine learning model predictions pose challenges to interpretation. In this work, we propose an approach for training deep AF models on limited, noisy data and report uncertainty in their predictions. Using techniques from the fields of weakly supervised learning, we leverage a surrogate model trained on non-ICU data to create imperfect labels for a large ICU telemetry dataset. We combine these weak labels with techniques to estimate model uncertainty without the need for extensive human data annotation. AF detection models trained using this process demonstrated higher classification performance (0.64–0.67 F1 score) and improved calibration (0.05–0.07 expected calibration error).
Universal logic-in-memory cell enabling all basic Boolean algebra logic
Authors: Baek Eunwoo , Cho Kyoungah , Kim Sangsig
Published: November 2022

Among the promising approaches for implementing high-performance computing, reconfigurable logic gates and logic-in-memory (LIM) approaches have been drawing increased research attention. These allow for improved functional scaling of a chip, owing to the improved functionality per unit area. Although numerous studies have been conducted independently for either reconfigurable logic or LIM units, attempts to construct a hybrid structure based on reconfigurable logic and LIM units remain relatively rare. In this study, we merge reconfigurable logic gates and LIM units to achieve a universal logic-in-memory (ULIM) cell for enabling all basic Boolean logic operations and data storage in a single cell. A ULIM cell consisting of silicon memory devices with reconfigurable n- and p-program modes can reconfigure logic operations within the complete set of Boolean logic operations. Moreover, the ULIM cell exhibits memory behaviors for storing output logic values without supply voltages for a certain period, resulting in zero static power consumption. Hence, this study provides a way to realize high-performance electronics by utilizing the silicon devices with a hybrid function of reconfigurable logic and LIM.
Drivers and potential distribution of anthrax occurrence and incidence at national and sub-county levels across Kenya from 2006 to 2020 using INLA
Authors: Ndolo Valentina A. , Redding David William , Lekolool Isaac , Mwangangi David Mumo , Odhiambo David Onyango , Deka Mark A. , Conlan Andrew J. K. , Wood James L. N.
Published: November 2022

Anthrax is caused by,Bacillus anthracis, a soil-borne bacterium that infects grazing animals. Kenya reported a sharp increase in livestock anthrax cases from 2005, with only 12% of the sub-counties (decentralised administrative units used by Kenyan county governments to facilitate service provision) accounting for almost a third of the livestock cases. Recent studies of the spatial extent ofB. anthracissuitability across Kenya have used approaches that cannot capture the underlying spatial and temporal dependencies in the surveillance data. To address these limitations, we apply the first Bayesian approach using R-INLA to analyse a long-term dataset of livestock anthrax case data, collected from 2006 to 2020 in Kenya. We develop a spatial and a spatiotemporal model to investigate the distribution and socio-economic drivers of anthrax occurrence and incidence at the national and sub-county level. The spatial model was robust to geographically based cross validation and had a sensitivity of 75% (95% CI 65–75) against withheld data. Alarmingly, the spatial model predicted high intensity of anthrax across the Northern counties (Turkana, Samburu, and Marsabit) comprising pastoralists who are often economically and politically marginalized, and highly predisposed to a greater risk of anthrax. The spatiotemporal model showed a positive link between livestock anthrax risk and the total human population and the number of exotic dairy cattle, and a negative association with the human population density, livestock producing households, and agricultural land area. Public health programs aimed at reducing human-animal contact, improving access to healthcare, and increasing anthrax awareness, should prioritize these endemic regions.
Improper weapons are a neglected category of harmful objects
Authors: Frugarello Paolo , Rusconi Elena , Job Remo
Published: November 2022

According to legislation, objects are typically classified as weapons if they are offensive per se (referred to here as proper) and if they are adapted for use as weapons or carried with the intent of causing injury (referred to here as improper), with specific regulations on their usage and possession in public spaces. However, little evidence exists on the validity of this distinction in psychology, despite a widespread recognition of the importance of psychological states and subjective perceptions in risk assessment. We conducted an online survey to evaluate hazard perceptions in relation to three dimensions (dangerousness, frequency of events, controllability) of three object categories: proper weapons, improper weapons, and everyday objects. The data from our 300 respondents reveal that the three categories of objects differ from one another on the three dimensions. Moreover, hazard perceptions differ between males and females for improper weapons but less so for proper weapons. These findings suggest that proper and improper weapons are two psychologically distinct categories, albeit with fuzzy boundaries. Investigations into their differential properties may thus help improve risk assessment in security contexts.
Augmented screwdrivers can increase the performance of orthopaedic surgeons compared with use of normal screwdrivers
Authors: Fletcher James W. A. , Neumann Verena , Silva Juan , Burdon Abigail , Mys Karen , Panagiotopoulou Vasiliki C. , Gueorguiev Boyko , Richards R. Geoff , Whitehouse Michael R. , Preatoni Ezio , Gill Harinderjit S.
Published: November 2022

Orthopaedic screws insertion can be trivialised as a simple procedure, however it is frequently performed poorly. Limited work exists defining how well surgeons insert screws or whether augmented screwdrivers can aid surgeons to reduce stripping rates and optimise tightness. We aimed to establish the performance of surgeons inserting screws and whether this be improved with screwdriver augmentation. 302 orthopaedic surgeons tightened 10 non-locking screws to what they determined to be optimum tightness into artificial bone sheets. The confidence in the screw purchase was given (1–10). A further 10 screws were tightened, using an augmented screwdriver that indicated when a predetermined optimum tightness was reached. The tightness for unstripped insertions under normal conditions and with the augmented screwdriver were 81% (95% CI 79–82%)(n = 1275) and 70% (95% CI 69–72%)(n = 2577) (p < 0.001). The stripping rates were 58% (95% CI 54–61%) and 15% (95% CI 12–17%) respectively (p < 0.001). The confidences when using the normal and augmented screwdrivers respectively were 7.2 and 7.1 in unstripped insertions and 6.2 and 6.5 in stripped insertions. Performance improved with an augmented screwdriver, both in reduced stripping rates and greater accuracy in detecting stripping. Augmenting screwdrivers to indicate optimum tightness offer potentially enormous clinical benefits by improving screw fixation.
Development of airflow limitation, dyspnoea, and both in the general population: the Nagahama study
Authors: Kogo Mariko , Sato Susumu , Muro Shigeo , Matsumoto Hisako , Nomura Natsuko , Tashima Noriyuki , Oguma Tsuyoshi , Sunadome Hironobu , Nagasaki Tadao , Murase Kimihiko , Kawaguchi Takahisa , Tabara Yasuharu , Matsuda Fumihiko , Chin Kazuo , Hirai Toyohiro
Published: November 2022

Subjects with subclinical respiratory dysfunction who do not meet the chronic obstructive pulmonary disease (COPD) criteria have attracted attention with regard to early COPD intervention. Our aim was to longitudinally investigate the risks for the development of airflow limitation (AFL) and dyspnoea, the main characteristics of COPD, in a large-scale community-based general population study. The Nagahama study included 9789 inhabitants, and a follow-up evaluation was conducted after 5 years. AFL was diagnosed using a fixed ratio (forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) < 0.7). We enrolled normal subjects aged 40–75 years with no AFL, dyspnoea or prior diagnosis of asthma or COPD at baseline. In total, 5865 subjects were analysed, 310 subjects had subclinical respiratory dysfunction (FEV1/FVC < the lower limit of normal; n = 57, and FEV1 < 80% of the predicted value (preserved ratio impaired spirometry); n = 256). A total of 5086 subjects attended the follow-up assessment, and 449 and 1021 subjects developed AFL and dyspnoea, respectively. Of these, 100 subjects developed AFL with dyspnoea. Baseline subclinical respiratory dysfunction was independently and significantly associated with AFL with dyspnoea development within 5 years. Subjects with subclinical respiratory dysfunction are at risk of developing COPD-like features and require careful monitoring.