bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated bone mineral density prediction and fracture risk assessment using plain radiographs via deep learning
Authors: Hsieh Chen-I , Zheng Kang , Lin Chihung , Mei Ling , Lu Le , Li Weijian , Chen Fang-Ping , Wang Yirui , Zhou Xiaoyun , Wang Fakai , Xie Guotong , Xiao Jing , Miao Shun , Kuo Chang-Fu
Published: September 2021

Dual-energy X-ray absorptiometry (DXA) is underutilized to measure bone mineral density (BMD) and evaluate fracture risk. We present an automated tool to identify fractures, predict BMD, and evaluate fracture risk using plain radiographs. The tool performance is evaluated on 5164 and 18175 patients with pelvis/lumbar spine radiographs and Hologic DXA. The model is well calibrated with minimal bias in the hip (slope = 0.982, calibration-in-the-large = −0.003) and the lumbar spine BMD (slope = 0.978, calibration-in-the-large = 0.003). The area under the precision-recall curve and accuracy are 0.89 and 91.7% for hip osteoporosis, 0.89 and 86.2% for spine osteoporosis, 0.83 and 95.0% for high 10-year major fracture risk, and 0.96 and 90.0% for high hip fracture risk. The tool classifies 5206 (84.8%) patients with 95% positive or negative predictive value for osteoporosis, compared to 3008 DXA conducted at the same study period. This automated tool may help identify high-risk patients for osteoporosis.
Spatially and optically tailored 3D printing for highly miniaturized and integrated microfluidics
Authors: Sanchez Noriega Jose L. , Chartrand Nicholas A. , Valdoz Jonard Corpuz , Cribbs Collin G. , Jacobs Dallin A. , Poulson Daniel , Viglione Matthew S. , Woolley Adam T. , Van Ry Pam M. , Christensen Kenneth A. , Nordin Gregory P.
Published: September 2021

Traditional 3D printing based on Digital Light Processing Stereolithography (DLP-SL) is unnecessarily limiting as applied to microfluidic device fabrication, especially for high-resolution features. This limitation is due primarily to inherent tradeoffs between layer thickness, exposure time, material strength, and optical penetration that can be impossible to satisfy for microfluidic features. We introduce a generalized 3D printing process that significantly expands the accessible spatially distributed optical dose parameter space to enable the fabrication of much higher resolution 3D components without increasing the resolution of the 3D printer. Here we demonstrate component miniaturization in conjunction with a high degree of integration, including 15 μm × 15 μm valves and a 2.2 mm × 1.1 mm 10-stage 2-fold serial diluter. These results illustrate our approach’s promise to enable highly functional and compact microfluidic devices for a wide variety of biomolecular applications.
ADAR-mediated RNA editing of DNA:RNA hybrids is required for DNA double strand break repair
Authors: Jimeno Sonia , Prados-Carvajal Rosario , Fernández-Ávila María Jesús , Silva Sonia , Silvestris Domenico Alessandro , Endara-Coll Martín , Rodríguez-Real Guillermo , Domingo-Prim Judit , Mejías-Navarro Fernando , Romero-Franco Amador , Jimeno-González Silvia , Barroso Sonia , Cesarini Valeriana , Aguilera Andrés , Gallo Angela , Visa Neus , Huertas Pablo
Published: September 2021

The maintenance of genomic stability requires the coordination of multiple cellular tasks upon the appearance of DNA lesions. RNA editing, the post-transcriptional sequence alteration of RNA, has a profound effect on cell homeostasis, but its implication in the response to DNA damage was not previously explored. Here we show that, in response to DNA breaks, an overall change of the Adenosine-to-Inosine RNA editing is observed, a phenomenon we call the RNA Editing DAmage Response (REDAR). REDAR relies on the checkpoint kinase ATR and the recombination factor CtIP. Moreover, depletion of the RNA editing enzyme ADAR2 renders cells hypersensitive to genotoxic agents, increases genomic instability and hampers homologous recombination by impairing DNA resection. Such a role of ADAR2 in DNA repair goes beyond the recoding of specific transcripts, but depends on ADAR2 editing DNA:RNA hybrids to ease their dissolution.
Transverse barrier formation by electrical triggering of a metal-to-insulator transition
Authors: Salev Pavel , Fratino Lorenzo , Sasaki Dayne , Berkoun Rani , del Valle Javier , Kalcheim Yoav , Takamura Yayoi , Rozenberg Marcelo , Schuller Ivan K.
Published: September 2021

Application of an electric stimulus to a material with a metal-insulator transition can trigger a large resistance change. Resistive switching from an insulating into a metallic phase, which typically occurs by the formation of a conducting filament parallel to the current flow, is a highly active research topic. Using the magneto-optical Kerr imaging, we found that the opposite type of resistive switching, from a metal into an insulator, occurs in a reciprocal characteristic spatial pattern: the formation of an insulating barrier perpendicular to the driving current. This barrier formation leads to an unusual N-type negative differential resistance in the current-voltage characteristics. We further demonstrate that electrically inducing a transverse barrier enables a unique approach to voltage-controlled magnetism. By triggering the metal-to-insulator resistive switching in a magnetic material, local on/off control of ferromagnetism is achieved using a global voltage bias applied to the whole device.
METTL3-mediated m6A RNA methylation promotes the anti-tumour immunity of natural killer cells
Authors: Song Hao , Song Jiaxi , Cheng Ming , Zheng Meijuan , Wang Tian , Tian Sha , Flavell Richard A. , Zhu Shu , Li Hua-Bing , Ding Chen , Wei Haiming , Sun Rui , Peng Hui , Tian Zhigang
Published: September 2021

Natural killer (NK) cells exert critical roles in anti-tumor immunity but how their functions are regulated by epitranscriptional modification (e.g., N6-methyladenosine (m6A) methylation) is unclear. Here we report decreased expression of the m6A “writer” METTL3 in tumor-infiltrating NK cells, and a positive correlation between protein expression levels of METTL3 and effector molecules in NK cells. Deletion of Mettl3 in NK cells alters the homeostasis of NK cells and inhibits NK cell infiltration and function in the tumor microenvironment, leading to accelerated tumor development and shortened survival in mice. The gene encoding SHP-2 is m6A modified, and its protein expression is decreased in METTL3-deficient NK cells. Reduced SHP-2 activity renders NK cells hyporesponsive to IL-15, which is associated with suppressed activation of the AKT and MAPK signaling pathway in METTL3-deficient NK cells. These findings show that m6A methylation safeguards the homeostasis and tumor immunosurveillance function of NK cells.
A method for intuitively extracting macromolecular dynamics from structural disorder
Authors: Pearce Nicholas M. , Gros Piet
Published: September 2021

Macromolecular dynamics manifest as disorder in structure determination, which is subsequently accounted for by displacement parameters (also called temperature factors, or B-factors) or alternate conformations. Though B-factors contain detailed information about structural dynamics, they are the total of multiple sources of disorder, making them difficult to interpret and thus little-used in structural analysis. We report here an analytical approach for decomposing molecular disorder into a parsimonious hierarchical series of contributions, providing an intuitive basis for quantitative structural-dynamics analysis. We demonstrate the decomposition of disorder on example SARS-CoV-2 and STEAP4 structures, from both crystallographic and cryo-electron microscopy data, and reveal how understanding of the macromolecular disorder leads to deeper understanding of molecular motions and flexibility, and suggests hypotheses for molecular mechanisms.
Neural encoding of perceived patch value during competitive and hazardous virtual foraging
Authors: Silston Brian , Wise Toby , Qi Song , Sui Xin , Dayan Peter , Mobbs Dean
Published: September 2021

Natural observations suggest that in safe environments, organisms avoid competition to maximize gain, while in hazardous environments the most effective survival strategy is to congregate with competition to reduce the likelihood of predatory attack. We probed the extent to which survival decisions in humans follow these patterns, and examined the factors that determined individual-level decision-making. In a virtual foraging task containing changing levels of competition in safe and hazardous patches with virtual predators, we demonstrate that human participants inversely select competition avoidant and risk diluting strategies depending on perceived patch value (PPV), a computation dependent on reward, threat, and competition. We formulate a mathematically grounded quantification of PPV in social foraging environments and show using multivariate fMRI analyses that PPV is encoded by mid-cingulate cortex (MCC) and ventromedial prefrontal cortices (vMPFC), regions that integrate action and value signals. Together, these results suggest humans utilize and integrate multidimensional information to adaptively select patches highest in PPV, and that MCC and vMPFC play a role in adapting to both competitive and predatory threats in a virtual foraging setting.
Nanofluidic voidless electrode for electrochemical capacitance enhancement in gel electrolyte
Authors: Xiao Kefeng , Yang Taimin , Liang Jiaxing , Rawal Aditya , Liu Huabo , Fang Ruopian , Amal Rose , Xu Hongyi , Wang Da-Wei
Published: September 2021

Porous electrodes with extraordinary capacitances in liquid electrolytes are oftentimes incompetent when gel electrolyte is applied because of the escalating ion diffusion limitations brought by the difficulties of infilling the pores of electrode with gels. As a result, porous electrodes usually exhibit lower capacitance in gel electrolytes than that in liquid electrolytes. Benefiting from the swift ion transport in intrinsic hydrated nanochannels, the electrochemical capacitance of the nanofluidic voidless electrode (5.56% porosity) is nearly equal in gel and liquid electrolytes with a difference of ~1.8%. In gel electrolyte, the areal capacitance reaches 8.94 F cm−2 with a gravimetric capacitance of 178.8 F g−1 and a volumetric capacitance of 321.8 F cm−3. The findings are valuable to solid-state electrochemical energy storage technologies that require high-efficiency charge transport.
Examining air pollution (PM10), mental health and well-being in a representative German sample
Authors: Petrowski Katja , Bührer Stefan , Strauß Bernhard , Decker Oliver , Brähler Elmar
Published: September 2021

There is a growing debate on the role of the physical environment and what constitute risk and protective factors for mental health. Various forms of air pollution have shown links to physical and mental health concerns and considering that Germany does not meet the WHO air quality standards—poor air quality affects a large proportion of Germans and is more important now than ever. This study investigates the physical environmental factor, air pollution, measured by particulate matter of particles with an aerodynamic diameter smaller than 10 µm (PM10) and effects on determinants of mental health and well-being (life satisfaction, stress resilience, anxiety, depression, and self-esteem). A representative sample of N = 3020 German adults with 54% females (46% males) and an age range between 18 and 92 years (M = 49.04, S.D. ± 17.27) was used. Multivariate linear regression analyses show that higher life satisfaction, more self-esteem and higher stress resilience are predicted by less air pollution (PM10). Individual income, age, and gender were taken into account for each regression model. Gender specific sub-analyses revealed similar predictions for PM10 and stress resilience whereas PM10 and self-esteem were only significantly associated for females. Associations between mental health or well-being determinants and air pollution (PM10) are found in the representative German sample.
Musical components important for the Mozart K448 effect in epilepsy
Authors: Quon Robert J. , Casey Michael A. , Camp Edward J. , Meisenhelter Stephen , Steimel Sarah A. , Song Yinchen , Testorf Markus E. , Leslie Grace A. , Bujarski Krzysztof A. , Ettinger Alan B. , Jobst Barbara C.
Published: September 2021

There is growing evidence for the efficacy of music, specifically Mozart’s Sonata for Two Pianos in D Major (K448), at reducing ictal and interictal epileptiform activity. Nonetheless, little is known about the mechanism underlying this beneficial “Mozart K448 effect” for persons with epilepsy. Here, we measured the influence that K448 had on intracranial interictal epileptiform discharges (IEDs) in sixteen subjects undergoing intracranial monitoring for refractory focal epilepsy. We found reduced IEDs during the original version of K448 after at least 30-s of exposure. Nonsignificant IED rate reductions were witnessed in all brain regions apart from the bilateral frontal cortices, where we observed increased frontal theta power during transitions from prolonged musical segments. All other presented musical stimuli were associated with nonsignificant IED alterations. These results suggest that the “Mozart K448 effect” is dependent on the duration of exposure and may preferentially modulate activity in frontal emotional networks, providing insight into the mechanism underlying this response. Our findings encourage the continued evaluation of Mozart’s K448 as a noninvasive, non-pharmacological intervention for refractory epilepsy.
Alpha activity neuromodulation induced by individual alpha-based neurofeedback learning in ecological context: a double-blind randomized study
Authors: Grosselin Fanny , Breton Audrey , Yahia-Cherif Lydia , Wang Xi , Spinelli Giuseppe , Hugueville Laurent , Fossati Philippe , Attal Yohan , Navarro-Sune Xavier , Chavez Mario , George Nathalie
Published: September 2021

The neuromodulation induced by neurofeedback training (NFT) remains a matter of debate. Investigating the modulation of brain activity specifically associated with NF requires controlling for multiple factors, such as reward, performance, congruency between task and targeted brain activity. This can be achieved using sham feedback (FB) control condition, equating all aspects of the experiment but the link between brain activity and FB. We aimed at investigating the modulation of individual alpha EEG activity induced by NFT in a double-blind, randomized, sham-controlled study. Forty-eight healthy participants were assigned to eitherNF(n = 25) orcontrol(n = 23) group and performed alpha upregulation training (over 12 weeks) with a wearable EEG device. Participants of theNF groupreceived FB based on their individual alpha activity. Thecontrol groupreceived the auditory FB of participants of theNF group. An increase of alpha activity across training sessions was observed in theNF grouponly (p < 0.001). This neuromodulation was selective in that there was no evidence for similar effects in the theta (4–8 Hz) and low beta (13–18 Hz) bands. While alpha upregulation was found in theNF grouponly, psychological outcome variables showed overall increased feeling of control, decreased anxiety level and increased relaxation feeling, without any significant difference between theNFand thecontrolgroups. This is interpreted in terms of learning context and placebo effects. Our results pave the way to self-learnt, NF-based neuromodulation with light-weighted, wearable EEG systems.
Acute carbon monoxide poisoning with low saturation of carboxyhaemoglobin: a forensic retrospective study in Shanghai, China
Authors: Liu Zheng , Meng Hang , Huang Juntian , Kwangwari Pascal , Ma Kaijun , Xiao Bi , Li Liliang
Published: September 2021

Carbon monoxide (CO) poisoning is a common cause of death, leading to morbidity and mortality worldwide. Features of the CO poisoning with low carboxyhemoglobin (COHb) levels remain to be characterized. This study collected a total of 307 CO poisoning cases from Shanghai Public Security Bureau, an official organization that handles the most complicated and life-threatening cases across Shanghai municipality in China, and regrouped these cases into three categories: group 1, 10% < COHb% < 30% (n = 58); group 2, 30% ≤ COHb% < 50% (n = 79); group 3, COHb% ≥ 50% (n = 170). Epidemiological, demographic, and forensic aspects of the CO poisoning cases, particularly those with low COHb levels, were analyzed. Our results showed that group 2 and 3 were mostly observed in younger victims (≤ 30 years), while group 1 equally distributed to all age groups (p = 0.03). All the CO poisoning from group 2 and 3 occurred in enclosed spaces, whereas cases from group 1 died additionally in outdoor spaces (p = 0.01). 81.03% of group 1 cases died in fire circumstances, while only 45.57% from group 2 and 30.59% from group 3 were fire-related (p = 0.00). Accordingly, group 1 was mostly related with fire burns, while group 2 or 3 were largely associated with gas leakage (p = 0.00). A combination with alcohol, but not other psychotropic drugs, associated with significant higher levels of blood COHb% in fire-unrelated (p = 0.021) but not fire-related cases (p = 0.23). Five extremely low COHb% (< 30%)-related poisoning deaths were negative of any cardiopulmonary pathology and psychoactive substances. In conclusion, CO poisoning with low COHb% significantly associates with fire circumstances and outdoor spaces and has no age preference. Further diagnostic markers mandates to be identified in order to avoid disputes in cases of extremely low COHb%-related poisoning.
Micronutritional status after pylorus preserving duodenopancreatectomy: analysis of data from a randomized controlled trial
Authors: Tabriz Navid , Uslar Verena Nicole , Obonyo Dennis , Weyhe Dirk
Published: September 2021

Physical frailty and nutritional malassimilation are often observed after pancreaticoduodenectomy for pancreatic cancer. But long-term data concerning the course of micronutrient status is still missing. Micronutrient status after pylorus preserving pancreaticoduodenectomy with a follow-up of 12 months was evaluated using data of a randomized controlled trial. 47 patients were randomized with respect to the physiotherapy regimen they received (intensified physiotherapy: n = 22; standard physiotherapy: n = 25). Nutritional status was recorded preoperatively and postoperatively after one week, 3, 6 and 12 months. BMI, body fat measurement and albumin, lipid, iron and bone metabolism parameters, vitamins A, B1 B6 and B12, homocysteine, folic acid, and trace elements were measured. Laboratory values were analyzed descriptively. Differences between the groups were analyzed using the t-test in SPSS. For vitamin D, B1, B6 and iron a deficiency over time could be demonstrated with 50% of all patients or more being below normal range. The other laboratory values were in low normal range after 3 months and later. Significant differences between groups were found in cholesterol, HDL and selenium levels (corrected p-values < 0.033 in all cases). Vitamin D and iron should be supplemented postoperatively in the long term, and vitamin B1 and B6 substitution should be considered in symptomatic patients. Levels of malnutrition induced fatigue should be comparable between both groups. However, the role of nutritional status on other health-related aspects such as quality of life should be the focus of further studies.

Trial Registration Number in the German Registry for Clinical Studies: DRKS00006786; Date of Registration: 01.10.2014.
The influence of a lost society, the Sadlermiut, on the environment in the Canadian Arctic
Authors: Viehberg Finn A. , Medeiros Andrew S. , Plessen Birgit , Wang Xiaowa , Muir Derek , Pienitz Reinhard
Published: September 2021

High latitude freshwater ecosystems are sentinels of human activity and environmental change. The lakes and ponds that characterize Arctic landscapes have a low resilience to buffer variability in climate, especially with increasing global anthropogenic stressors in recent decades. Here, we show that a small freshwater pond in proximity of the archaeological site “Native Point” on Southampton Island (Nunavut, Arctic Canada) is a highly sensitive environmental recorder. The sediment analyses allowed for pinpointing the first arrival of Sadlermiut culture at Native Point to ~ 1250 CE, followed by a dietary shift likely in response to the onset of cooling in the region ~ 1400 CE. The influence of the Sadlermiut on the environment persisted long after the last of their population perished in 1903. Presently, the pond remains a distorted ecosystem that has experienced fundamental shifts in the benthic invertebrate assemblages and accumulated anthropogenic metals in the sediment. Our multi-proxy paleolimnological investigation using geochemical and biological indicators emphasizes that direct and indirect anthropogenic impacts have long-term environmental implications on high latitude ecosystems.
An efficient context-aware screening system for Alzheimer's disease based on neuropsychology test
Authors: Tsai Austin Cheng-Yun , Hong Sheng-Yi , Yao Li-Hung , Chang Wei-Der , Fu Li-Chen , Chang Yu-Ling
Published: September 2021

Alzheimer's disease (AD) and other dementias have become the fifth leading cause of death worldwide. Accurate early detection of the disease and its precursor, Mild Cognitive Impairment (MCI), is crucial to alleviate the burden on the healthcare system. While most of the existing work in the literature applied neural networks directly together with several data pre-processing techniques, we proposed in this paper a screening system that is to perform classification based on automatic processing of the transcripts of speeches from the subjects undertaking a neuropsychological test. Our system is also shown applicable to different datasets and languages, suggesting that our system holds a high potential to be deployed widely in hospitals across regions. We conducted comprehensive experiments on two different languages datasets, the Pitt dataset and the NTUHV dataset, to validate our study. The results showed that our proposed system significantly outperformed the previous works on both datasets, with the score of the area under the receiver operating characteristic curve (AUROC) of classifying AD and healthy control (HC) being as high as 0.92 on the Pitt dataset and 0.97 on the NTUHV dataset. The performance on classifying MCI and HC remained promising, with the AUROC being 0.83 on the Pitt dataset and 0.88 on the NTUHV dataset.
A symbiotic aphid selfishly manipulates attending ants via dopamine in honeydew
Authors: Kudo Tatsumi , Aonuma Hitoshi , Hasegawa Eisuke
Published: September 2021

Symbiotic relationships are widespread in nature, but the mechanisms maintaining these relationships remain to be elucidated because symbiosis incurs a maintenance cost to each participant, which lowers its reproductive rate. In host-parasite relationships, parasites are known to manipulate the host's behavior selfishly, and there is an arms race between them. Selfish manipulations also occur in symbiosis, but the effects of selfish manipulations on symbiosis are not fully understood. Here, we show that an ant-associated aphid manipulates attending ants to receive stronger protection. Aphid honeydew regurgitated by ants contains dopamine (DA). The ants showed low aggressiveness before contact with the aphids, but it rose after contact. Administration of DA to the ants increased ant aggressiveness as the concentration increased, while an antagonist of DA inhibited this effect. The other 3 amines showed no effect on aggressiveness. A previous study showed that attending ants selfishly manipulate aphids by increasing the reproductive rate of green morph to obtain high-quality honeydew. These results suggest that mutual selfish manipulation benefits both participants and is likely to strengthen symbiosis. The selfishness of each participant may contribute to sustaining this symbiosis because their selfishness increases their long-term fitness.
Epidemiological risk factors associated with primary infection by Epstein–Barr virus in HIV-1-positive subjects in the Brazilian Amazon region
Authors: Pereira Leonn Mendes Soares , dos Santos França Eliane , Costa Iran Barros , Lima Igor Tenório , Freire Amaury Bentes Cunha , de Paula Ramos Francisco Lúzio , Monteiro Talita Antonia Furtado , Macedo Olinda , Sousa Rita Catarina Medeiros , Freitas Felipe Bonfim , Costa Igor Brasil , Vallinoto Antonio Carlos Rosário
Published: September 2021

To identify the prevalence and risk factors for primary Epstein–Barr virus (EBV) infection in human immunodeficiency virus (HIV)-1-positive adult treatment-naïve patients between January 2018 and December 2019 in a state of the Brazilian Amazon region. A total of 268 HIV-1 positive patients and 65 blood donors participated in the study. Epidemiological data were obtained from medical records and through a designed questionnaire. EBV infection was screened by the semiquantitative detection of anti-viral capsid antigen (VCA) EBV IgM and IgG, followed by molecular detection of the EBNA-3C gene. The plasma viral loads of HIV-1 and EBV were quantified using a commercial kit. The prevalence of primary coinfection was 7.12%. The associated risk factors were education level, family income, history of illicit drug use and sexually transmitted infections, homosexual contact and condom nonuse. Approximately 58.5% had late initiation of highly active antiretroviral therapy, which influenced the risk of HIV-EBV 1/2 multiple infection (odds ratio (OR): 4.76; 95% CI 1.51–15.04) and symptom development (p = 0.004). HIV viral load was associated with patient age (OR: 2.04; 95% CI 2.01–2.07; p = 0.026) and duration of illicit drug use (OR: 1.57; 95% CI 1.12–2.22; p = 0.0548). EBV viral load was associated with younger age (OR: 0.82; 95% CI 0.79–1.03; p = 0.0579). The replication of both viruses was associated with symptom development (HIV = OR: 2.06; 95% CI 1.22–3.50; p = 0.0073; EBV = OR: 8.81; 95% CI 1–10; p = 0.0447). The prevalence of HIV/EBV coinfection was lower than that observed in other studies, and social vulnerability and promiscuous sexual behavior were associated risk factors. A long time of HIV-1 infection, without therapy, influenced the risk of coinfection and disease progression. The viral loads of both viruses may be associated with some epidemiological aspects of the population.
Impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality
Authors: Elenkov Angel , Melander Olle , Nilsson Peter M. , Zhang He , Giwercman Aleksander
Published: September 2021

Childless men are reported to have a higher risk of cardiovascular disease (CVD) and mortality. Information on inherited genetic risk for CVD has improved the predictive models. Presuming that childlessness is a proxy of infertility we aimed to investigate if childless men inherit more often genetic traits for CVD and if combining genetic and parenthood information improves predictive models for CVD morbidity and mortality. Data was sourced from a large prospective population-based cohort where genetic risk score (GRS) was calculated using two sets of either 27 (GRS 27) or 50 (GRS 50) single nucleotide polymorphisms (SNPs) previously found to be associated with CVD. Part of the participants (n = 2572 men) were randomly assigned to a sub-cohort with focus on CVD which served as an exploratory cohort. The obtained statistically significant results were tested in the remaining (confirmatory) part of the cohort (n = 9548 men). GRS distribution did not differ between childless men and fathers (p-values for interaction between 0.29 and 0.76). However, when using fathers with low GRS as reference high GRS was a strong predictor for CVD mortality, the HR (95% CI) increasing from 1.92 (1.10–3.36) for GRS 50 and 1.54 (0.87–2.75) for GRS 27 in fathers to 3.12 (1.39–7.04) for GRS50 and 3.73 (1.75–7.99) for GRS27 in childless men. The confirmatory analysis showed similar trend. Algorithms including paternal information and GRS were more predictive for CVD mortality at 5 and 10 years follow-ups when compared to algorithms including GRS only (AUC 0.88 (95% CI 0.84–0.92) and 0.86 (95% CI 0.84–0.90), and, AUC 0.81 (95% CI 0.75–0.87) and 0.78 (95% CI 0.73–0.82), respectively). Combining information on parental status and GRS for CVD may improve the predictive power of risk algorithms in middle-aged men. Childless men and those with severe infertility problem may be an important target group for prevention of CVD.
Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway
Authors: Mukherjee Indrani , Dhar Ruby , Singh Sunil , Sharma Jai Bhagwan , Nag Tapas Chandra , Mridha Asit Ranjan , Jaiswal Parul , Biswas Subhrajit , Karmakar Subhradip
Published: September 2021

Pre-eclampsia (PE) is a pregnancy-specific disorder, characterized by hypertension and proteinuria. In PE, trophoblasts mediated inadequate remodeling of uterine spiral arteries seem to interrupt uteroplacental blood flow, one of the hallmarks in the early onset of PE (EO-PE). This, in turn, results in placental ischemia–reperfusion injury during hypoxia and reoxygenation episodes, leading to the generation of reactive oxygen species (ROS) and oxidative stress (OS). But still it is debatable if OS is a cause or consequence of PE. In this present study, we have investigated the effects of OS on PE placentae and trophoblast cell functions using BeWo and HTR8/SVneo cell lines. PE placental tissues showed abnormal ultrastructure, high level of reactive oxygen species (ROS) with altered unfolded protein responses (UPR) in compare with term placental tissues. Similar to PE placentae, during OS induction, the trophoblast cells showed altered invasion and migration properties with significantly variable expression of differentiation and invasion markers, e.g., syncytin and MMPs. The effect was rescued by antioxidant, N-acetyl cysteine, thereby implying a ROS-specific effect and in the trophoblast cells, OS triggers UPR pathway through IRE1α-XBP1 axis. Taken together, these findings highlight the harmful effect of unfolded protein response, which was induced due to OS on trophoblast cells and deformed invasion and differentiation programme and can be extended further to clinical settings to identify clinically approved antioxidants during pregnancy as a therapeutic measure to reduce the onset of PE.
An anthropometric study of sexual orientation and gender identity in Thailand
Authors: Skorska Malvina N. , Coome Lindsay A. , Peragine Diana E. , Aitken Madison , VanderLaan Doug P.
Published: September 2021

The biodevelopment of psychological sex differentiation is putatively reflected in several anthropometrics. We examined eight anthropometrics in 1404 Thai participants varying in sex, sexual orientation, and gender identity/expression: heterosexual men and women, gay men, lesbian women, bisexual women, sao praphet song (transgender birth-assigned males), toms (transgender birth-assigned females), and dees (birth-assigned females attracted to toms). Exploratory factor analyses indicated the biomarkers should be analyzed independently. Using regressions, in birth-assigned males, less male-typical second-to-fourth digit ratios in the left hand were associated with sexual orientation towards men regardless of gender identity/expression, whereas shorter height and long-bone growth in the arms and legs were more evident among sao praphet song—who are both sexually oriented towards men and markedly feminine. In birth-assigned females, there were no clear sexual orientation effects, but there were possible gender-related effects. Groups of individuals who tend to be more masculine (i.e., toms, lesbians) showed more male-typical patterns on weight and leg length than some groups of individuals who tend to be less masculine (i.e., heterosexual women, dees). Thus, it appears the various anthropometrics inform separate biodevelopmental processes that differentially relate to sexual orientation and gender identity/expression depending on the measure in question as well as birth-assigned sex.
Abundance of domestic mites in dwellings of children and adolescents with asthma in relation to environmental factors and allergy symptoms
Authors: Solarz Krzysztof , Obuchowicz Anna , Asman Marek , Nowak Wacław , Witecka Joanna , Pietrzak Jolanta , Marek Marta , Łonak Aldona , Stadnicka Izabela , Hajduga-Staśko Bernadeta
Published: September 2021

Exposure to house dust allergens, mainly from domestic mites, is an important cause of allergic reactions in sensitized asthmatic patients. A total of 63 dust samples were collected from 16 flats in Bytom (south Poland); in each flat a person (age 4–17 years) suffering from bronchial asthma lived with his/her family. Mite density was calculated as the number of specimens per g of dust. The results were compared with household features and the data were statistically analyzed. In total 566 mite specimens were isolated, including 526 members of the family Pyroglyphidae (93%). The dominant species were Dermatophagoides pteronyssinus (60% of the total count) and Dermatophagoides farinae (32%). Pyroglyphids were found in all mite positive samples (68%) of which 35% also contained non-pyroglyphids, including glycyphagids, cheyletids and gamasids. The results suggest associations between the density of some mite taxa (per g of dust) and the following indoor environmental factors: presence of pets, number of inhabitants, coal-stoves as a type of heating, cleaning frequency, higher relative humidity, presence of flowers and PVC windows. The severity of asthma seems to be associated with the numbers of D. farinae, total domestic mites and live mites per g of dust.
A novel ATPase gene, Ab-atps, plays an important role in the interaction of rice and white tip nematode, Aphelenchoides besseyi
Authors: Wang Hong-Le , Xu Chun-Ling , Chen Chun , Ding Shan-Wen , Li Jun-Yi , Yang Si-Hua , Xie Hui
Published: September 2021

Plant kinases containing the LysM domain play important roles in pathogen recognition and self-defense reactions. And it could recognize microbe-associated molecules including chitin and other polypeptides. The white tip nematode Aphelenchoides besseyi is a migratory parasitic nematode that infects plant shoots. It is distributed over almost all rice-producing areas and causes up to 50% economic losses. The rice OsRLK3 gene was a defense-related LysM kinase gene of rice. This study showed that the rice LysM kinase OsRLK3 could be induced by flg22, jasmonic acid, salicylic acid, and chitin. An interaction gene, Ab-atps from A. besseyi, was identified by screening the interaction between the rice gene OsRLK3 and an A. besseyi cDNA library using yeast two-hybrid screening. Ab-atps is a novel ATP synthase gene with a full length of 1341 bp, coding for 183 amino acids. The mRNA of Ab-atps was located in the esophagus and reproductive system of A. besseyi. The expression of Ab-atps was assessed at different developmental stages of the nematode and found to be the highest in the juvenile, followed by the egg, female, and male. Reproduction was significantly decreased in nematodes treated with Ab-atps double-stranded RNA (dsRNA) (p < 0.05). Transient expression experiments showed that Ab-ATPS-GFP was distributed in the nucleus, cytoplasm, and cell membrane, and Ab-ATPS-GFP triggered plant cell death. OsRLK3 was expressed significantly higher at 0.5 day and 1 day (p < 0.05) in rice plants inoculated with nematodes treated with Ab-atps dsRNA and gfp dsRNA for 0.5–7 days, respectively. Further, OsRLK3 expression under Ab-atps dsRNA treatment was significantly lower than with gfp dsRNA treatment at 0.5 day (p < 0.05) and significantly higher than with gfp dsRNA treatment at 1 day (p < 0.05). These results suggest that rice OsRLK3 could interact with A. besseyi Ab-atps, which plays an important role in growth, reproduction, and infection of the nematode. Our findings provide a theoretical basis to further understand the parasitic strategy of A. besseyi and its interaction mechanism with host plants, suggesting new ideas and targets for controlling A. besseyi.
Toxicity of amantadine hydrochloride on cultured bovine cornea endothelial cells
Authors: Lee Po-Yen , Lai Yu-Hung , Liu Po-Len , Liu Ching-Chih , Su Chia-Cheng , Chiu Fang-Yen , Cheng Wei-Chung , Hsu Shiuh-Liang , Cheng Kai-Chun , Chiu Li-Yi , Kao Tzu-En , Lin Chia-Ching , Chang Yo-Chen , Wang Shu-Chi , Li Chia-Yang
Published: September 2021

Amantadine hydrochloride (HCl) is commonly prescribed for treating influenza A virus infection and Parkinson’s disease. Recently, several studies have indicated that the use of amantadine HCl is associated with corneal edema; however, the cytotoxic effect of amantadine HCl has not been investigated. In the present study, the effects of amantadine HCl on cell growth, proliferation, and apoptosis in bovine cornea endothelial cells, and in vitro endothelial permeability were examined. Results showed that lower doses of amantadine HCl do not affect cell growth (≤ 20 μΜ), whereas higher doses of amantadine HCl inhibits cell growth (≥ 50 μΜ), induces apoptosis (2000 μΜ), increases sub-G1 phase growth arrest (2000 μΜ), causes DNA damage (≥ 1000 μΜ), and induces endothelial hyperpermeability (≥ 1000 μΜ) in bovine cornea endothelial cells; additionally, we also found that amantadine HCl attenuates the proliferation (≥ 200 μΜ) and arrests cell cycle at G1 phase (≥ 200 μΜ) in bovine cornea endothelial cells. In the present study, we measured the cytotoxic doses of amantadine HCl on cornea endothelial cells, which might be applied in evaluating the association of corneal edema.
Modelling COVID-19 severity in the Republic of Ireland using patient co-morbidities, socioeconomic profile and geographic location, February to November 2020
Authors: Boudou M. , ÓhAiseadha C. , Garvey P. , O’Dwyer J. , Hynds P.
Published: September 2021

Understanding patient progression from symptomatic COVID-19 infection to a severe outcome represents an important tool for improved diagnoses, surveillance, and triage. A series of models have been developed and validated to elucidate hospitalization, admission to an intensive care unit (ICU) and mortality in patients from the Republic of Ireland. This retrospective cohort study of patients with laboratory-confirmed symptomatic COVID-19 infection included data extracted from national COVID-19 surveillance forms (i.e., age, gender, underlying health conditions, occupation) and geographically-referenced potential predictors (i.e., urban/rural classification, socio-economic profile). Generalised linear models and recursive partitioning and regression trees were used to elucidate COVID-19 progression. The incidence of symptomatic infection over the study-period was 0.96% (n = 47,265), of whom 3781 (8%) required hospitalisation, 615 (1.3%) were admitted to ICU and 1326 (2.8%) died. Models demonstrated an increasingly efficacious fit for predicting hospitalization [AUC 0.816 (95% CI 0.809, 0.822)], admission to ICU [AUC 0.885 (95% CI 0.88 0.89)] and death [AUC of 0.955 (95% CI 0.951 0.959)]. Severe obesity (BMI ≥ 40) was identified as a risk factor across all prognostic models; severely obese patients were substantially more likely to receive ICU treatment [OR 19.630] or die [OR 10.802]. Rural living was associated with an increased risk of hospitalization (OR 1.200 (95% CI 1.143–1.261)]. Urban living was associated with ICU admission [OR 1.533 (95% CI 1.606–1.682)]. Models provide approaches for predicting COVID-19 prognoses, allowing for evidence-based decision-making pertaining to targeted non-pharmaceutical interventions, risk-based vaccination priorities and improved patient triage.
Biochar as a low-cost, eco-friendly, and electrically conductive material for terahertz applications
Authors: Park Woongkyu , Kim Hyuntae , Park Hajung , Choi Soobong , Hong Sung Ju , Bahk Young-Mi
Published: September 2021

We investigate conducting characteristics of biochar derived from the pyrolysis of a paper at terahertz frequencies. Paper is annealed under temperatures ranging from 600 to 1000 °C to modify structural and electrical properties. We experimentally observe that the terahertz conductivity increases above 102 S/m as the annealing temperature increases up to 800 °C. From structural characterization using energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy, we confirm that more graphitic biochars are produced in high annealing temperature, in agreement with the improvement of terahertz conductivity. Our results show that biochar can be a highly promising candidate to be used in paper-based devices operating at terahertz frequencies.
Basic locomotor muscle synergies used in land walking are finely tuned during underwater walking
Authors: Yokoyama Hikaru , Kato Tatsuya , Kaneko Naotsugu , Kobayashi Hirofumi , Hoshino Motonori , Kokubun Takanori , Nakazawa Kimitaka
Published: September 2021

Underwater walking is one of the most common hydrotherapeutic exercises. Therefore, understanding muscular control during underwater walking is important for optimizing training regimens. The effects of the water environment on walking are mainly related to the hydrostatic and hydrodynamic theories of buoyancy and drag force. To date, muscular control during underwater walking has been investigated at the individual muscle level. However, it is recognized that the human nervous system modularly controls multiple muscles through muscle synergies, which are sets of muscles that work together. We found that the same set of muscle synergies was shared between the two walking tasks. However, some task-dependent modulation was found in the activation combination across muscles and temporal activation patterns of the muscle synergies. The results suggest that the human nervous system modulates activation of lower-limb muscles during water walking by finely tuning basic locomotor muscle synergies that are used during land walking to meet the biomechanical requirements for walking in the water environment.
Dynamical behavior of coal shearer under the influence of multiple factors in slant-cutting conditions
Authors: Yang Xinwei , Zou Xianfeng , Zhang Shuai , Chen Hongyue , Wei Yajing , Li Pengfei
Published: September 2021

Aiming at the problem of severe vibration and abnormal wear and tear of various components in coal shearer under slant-cutting conditions, a non-linear dynamics model with 13 degrees of freedom for a coal shearer under slant-cutting conditions is developed using vibration mechanics and multi-body dynamics theory, and the characteristics of the slide shoes-middle groove contact, the ranging arm-haulage unit connection with gaps and the guidance sliding boots-pin rail multi-surface contact with gaps are described based on three-dimensional fractal theory and Hertz contact theory. Based on Huco's law, the ranging arm and the hydraulic rod are assumed to be flexible beams, the rigidity characteristics of the ranging arm itself, the connection characteristics of the haulage unit and the fuselage are described, a drum correction load with a traction speed correction factor is proposed as the external excitation of the system, and the model is solved and analyzed. The research results show that the change of traction speed has a greater influence on the vibration swing angle and displacement of the front drum, front ranging arm and front walking unit, and the vibration swing angle and displacement of the three increase with the increase of traction speed, while the change of coalface hardness coefficient has less influence on the vibration displacement of the key components of the coal shearer. Under the working parameters of v = 3 m/min and f = 3, the swing angle and displacement of the front ranging arm and front drum fluctuate in the ranges of − 0.4–0.1 rad and – 15–15 mm respectively; the vibration acceleration is – 300–300 rad/s2 and – 200–200 mm/s2 respectively, the main vibration frequencies are 16.63 Hz and 12.14 Hz respectively, and finally the results are verified by experimental methods.
DNA methylation changes following narrative exposure therapy in a randomized controlled trial with female former child soldiers
Authors: Carleial Samuel , Nätt Daniel , Unternährer Eva , Elbert Thomas , Robjant Katy , Wilker Sarah , Vukojevic Vanja , Kolassa Iris-Tatjana , Zeller Anja C. , Koebach Anke
Published: September 2021

The aftermath of traumatization lives on in the neural and epigenetic traces creating a momentum of affliction in the psychological and social realm. Can psychotherapy reorganise these memories through changes in DNA methylation signatures? Using a randomised controlled parallel group design, we examined methylome-wide changes in saliva samples of 84 female former child soldiers from Eastern DR Congo before and six months after Narrative Exposure Therapy. Treatment predicted differentially methylated positions (DMPs) related toALCAM,RIPOR2,AFAP1andMOCOS. In addition, treatment associations overlapped at gene level with baseline clinical and social outcomes. Treatment related DMPs are involved in memory formation—the key agent in trauma focused treatments—and enriched for molecular pathways commonly affected by trauma related disorders. Results were partially replicated in an independent sample of 53 female former child soldiers from Northern Uganda. Our results suggest a molecular impact of psychological treatment in women with war-related childhood trauma.

Trial registration: Addressing Heightened Levels of Aggression in Traumatized Offenders With Psychotherapeutic Means (ClinicalTrials.gov Identifier: NCT02992561, 14/12/2016).
A deep learning approach for successful big-bubble formation prediction in deep anterior lamellar keratoplasty
Authors: Hayashi Takahiko , Masumoto Hiroki , Tabuchi Hitoshi , Ishitobi Naofumi , Tanabe Mao , Grün Michael , Bachmann Björn , Cursiefen Claus , Siebelmann Sebastian
Published: September 2021

The efficacy of deep learning in predicting successful big-bubble (SBB) formation during deep anterior lamellar keratoplasty (DALK) was evaluated. Medical records of patients undergoing DALK at the University of Cologne, Germany between March 2013 and July 2019 were retrospectively analyzed. Patients were divided into two groups: (1) SBB or (2) failed big-bubble (FBB). Preoperative images of anterior segment optical coherence tomography and corneal biometric values (corneal thickness, corneal curvature, and densitometry) were evaluated. A deep neural network model, Visual Geometry Group-16, was selected to test the validation data, evaluate the model, create a heat map image, and calculate the area under the curve (AUC). This pilot study included 46 patients overall (11 women, 35 men). SBBs were more common in keratoconus eyes (KC eyes) than in corneal opacifications of other etiologies (non KC eyes) (p = 0.006). The AUC was 0.746 (95% confidence interval [CI] 0.603–0.889). The determination success rate was 78.3% (18/23 eyes) (95% CI 56.3–92.5%) for SBB and 69.6% (16/23 eyes) (95% CI 47.1–86.8%) for FBB. This automated system demonstrates the potential of SBB prediction in DALK. Although KC eyes had a higher SBB rate, no other specific findings were found in the corneal biometric data.