bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emulating complex simulations by machine learning methods
Authors: Stolfi Paola , Castiglione Filippo 
Published: November 2021

Abstract
Background
The aim of the present paper is to construct an emulator of a complex biological system simulator using a machine learning approach. More specifically, the simulator is a patient-specific model that integrates metabolic, nutritional, and lifestyle data to predict the metabolic and inflammatory processes underlying the development of type-2 diabetes in absence of familiarity. Given the very high incidence of type-2 diabetes, the implementation of this predictive model on mobile devices could provide a useful instrument to assess the risk of the disease for aware individuals. The high computational cost of the developed model, being a mixture of agent-based and ordinary differential equations and providing a dynamic multivariate output, makes the simulator executable only on powerful workstations but not on mobile devices. Hence the need to implement an emulator with a reduced computational cost that can be executed on mobile devices to provide real-time self-monitoring.

Results
Similarly to our previous work, we propose an emulator based on a machine learning algorithm but here we consider a different approach which turn out to have better performances, indeed in terms of root mean square error we have an improvement of two order magnitude. We tested the proposed emulator on samples containing different number of simulated trajectories, and it turned out that the fitted trajectories are able to predict with high accuracy the entire dynamics of the simulator output variables. We apply the emulator to control the level of inflammation while leveraging on the nutritional input.

Conclusion
The proposed emulator can be implemented and executed on mobile health devices to perform quick-and-easy self-monitoring assessments.
Long-read sequencing settings for efficient structural variation detection based on comprehensive evaluation
Authors: Jiang Tao , Liu Shiqi , Cao Shuqi , Liu Yadong , Cui Zhe , Wang Yadong , Guo Hongzhe 
Published: November 2021

AbstractBackgroundWith the rapid development of long-read sequencing technologies, it is possible to reveal the full spectrum of genetic structural variation (SV). However, the expensive cost, finite read length and high sequencing error for long-read data greatly limit the widespread adoption of SV calling. Therefore, it is urgent to establish guidance concerning sequencing coverage, read length, and error rate to maintain high SV yields and to achieve the lowest cost simultaneously.ResultsIn this study, we generated a full range of simulated error-prone long-read datasets containing various sequencing settings and comprehensively evaluated the performance of SV calling with state-of-the-art long-read SV detection methods. The benchmark results demonstrate that almost all SV callers perform better when the long-read data reach 20× coverage, 20 kbp average read length, and approximately 10–7.5% or below 1% error rates. Furthermore, high sequencing coverage is the most influential factor in promoting SV calling, while it also directly determines the expensive costs.ConclusionsBased on the comprehensive evaluation results, we provide important guidelines for selecting long-read sequencing settings for efficient SV calling. We believe these recommended settings of long-read sequencing will have extraordinary guiding significance in cutting-edge genomic studies and clinical practices.
In silico analysis and expression profiling of S-domain receptor-like kinases (SD-RLKs) under different abiotic stresses in Arabidopsis thaliana
Authors: Mondal Raju , Biswas Subhankar , Srivastava Akanksha , Basu Suvajit , Trivedi Maitri , Singh Sunil Kumar , Mishra Yogesh 
Published: November 2021

Abstract
Background
S-domain receptor-like kinases (SD-RLKs) are an important and multi-gene subfamily of plant receptor-like/pelle kinases (RLKs), which are known to play a significant role in the development and immune responses of Arabidopsis thaliana. The conserved cysteine residues in the extracellular domain of SD-RLKs make them interesting candidates for sensing reactive oxygen species (ROS), assisting oxidative stress mitigation and associated signaling pathways during abiotic stresses. However, how closely SD-RLKs are interrelated to abiotic stress mitigation and signaling remains unknown in A. thaliana.

Results
This study was initiated by examining the chromosomal localization, phylogeny, sequence and differential expression analyses of 37 SD-RLK genes using publicly accessible microarray datasets under cold, osmotic stress, genotoxic stress, drought, salt, UV-B, heat and wounding. Out of 37 SD-RLKs, 12 genes displayed differential expression patterns in both the root and the shoot tissues. Promoter structure analysis suggested that these 12 SD-RLK genes harbour several potential cis-regulatory elements (CREs), which are involved in regulating multiple abiotic stress responses. Based on these observations, we investigated the expression patterns of 12 selected SD-RLKs under ozone, wounding, oxidative (methyl viologen), UV-B, cold, and light stress at different time points using semi-qRT-PCR. Of these 12 SD-SRKs, the genes At1g61360, At1g61460, At1g61380, and At4g27300 emerged as potential candidates that maintain their expression in most of the stress treatments till exposure for 12 h. Expression patterns of these four genes were further verified under similar stress treatments using qRT-PCR. The expression analysis indicated that the gene At1g61360, At1g61380, and At1g61460 were mostly up-regulated, whereas the expression of At4g27300 either up- or down-regulated in these conditions.

Conclusions
To summarize, the computational analysis and differential transcript accumulation of SD-RLKs under various abiotic stresses suggested their association with abiotic stress tolerance and related signaling in A. thaliana. We believe that a further detailed study will decipher the specific role of these representative SD-RLKs in abiotic stress mitigation vis-a-vis signaling pathways in A. thaliana.
Imaging features of intrahepatic cholangiocarcinoma mimicking a liver abscess: an analysis of 8 cases
Authors: Liu Manrong , Chen Jiong , Huang Ruisui , Huang Jianning , Li Lin , Li Yunqian , Qin Mi , Qin Wenqi , Nong Haiyang , Ding Ke 
Published: November 2021

Abstract
Background
In rare cases, intrahepatic cholangiocarcinoma can present as a pyogenic liver abscess and are often misdiagnosed. This study aimed to analyze the imaging features of intrahepatic cholangiocarcinoma mimicking a pyogenic liver abscess.

Methods
The clinical data and imaging results of eight patients with pathologically confirmed intrahepatic cholangiocarcinoma mimicking a liver abscess were retrospectively collected.

Results
The mean age was 58 years with a range of 46–68 years. Fever and leukocytosis were present in six patients. All the eight lesions were a single mass. Air–liquid levels were present in two patients. Only one patient showed hepatic lobar atrophy and hepatic capsule retraction. The double target sign of liver abscess was not noticed in the CT/MRI images of all eight patients. The inner wall of the lesion was rough and irregular, with multiple dot/patchy and wall nodule enhancements. The abscess wall and the marginal parenchyma were supplied by the hepatic artery in four patients, and the intralesional arteries were rough and disrupted. Bile duct dilatation was seen adjacent to the lesion. In seven patients, diffusion-weighted images showed irregular patchy restricted diffusion in the marginal parenchyma of the necrotic area in addition to the prominent restricted diffusion in the necrotic area. Two patients with cholangiolithiasis showed patchy slight CT hypodensity, slight T1 hypointensity, slight T2 hyperintensity, and patchy delayed enhancement. Multiple lymph nodes enlargement in the hepatic hilar area and the retroperitoneal space were seen in five patients.

Conclusion
Intrahepatic cholangiocarcinoma mimicking a pyogenic liver abscess have unique imaging features and require careful image examination to avoid misdiagnosis.
Functional decline in hospitalized older patients with coronavirus disease 2019: a retrospective cohort study
Authors: Hosoda Tomohiro , Hamada Shota 
Published: November 2021

Abstract
Background
This study aimed to determine the frequency of functional decline and to identify the factors related to a greater risk of functional decline among hospitalized older patients with coronavirus disease 2019 (COVID-19).

Methods
We reviewed the medical records of patients aged over 65 years who were admitted to a tertiary care hospital for COVID-19 over 1 year from February 2020. We evaluated the proportion of functional decline, which was defined as a decrease in the Barthel Index score from before the onset of COVID-19 to discharge. Multivariable logistic regression analyses were performed to evaluate the associations between the demographic and clinical characteristics of patients at admission and a greater risk of functional decline. Two sensitivity analyses with different inclusion criteria were performed: one in patients without very severe functional decline before the onset of COVID-19 (i.e., limited to those with Barthel Index score ≥ 25), and the other with a composite outcome of functional decline and death at discharge.

Results
The study included 132 patients with COVID-19; of these, 72 (54.5%) developed functional decline. The severity of COVID-19 did not differ between patients with functional decline and those without (P = 0.698). Factors associated with a greater risk of functional decline included female sex (adjusted odds ratio [aOR], 3.14; 95% confidence interval [CI], 1.25 to 7.94), Barthel Index score < 100 before the onset of COVID-19 (aOR, 13.73; 95% CI, 3.29 to 57.25), and elevation of plasma D-dimer level on admission (aOR, 3.19; 95% CI, 1.12 to 9.07). The sensitivity analyses yielded similar results to those of the main analysis.

Conclusions
Over half of the older patients who recovered from COVID-19 developed functional decline at discharge from a tertiary care hospital in Japan. Baseline activities of daily living impairment, female sex, and elevated plasma D-dimer levels at admission were associated with a greater risk of functional decline.
Prolonged rectal shedding of SARS-CoV-2 in a 22-day-old-neonate: a case report
Authors: Holm-Jacobsen Julie Niemann , Vonasek Julia Helena , Hagstrøm Søren , Donneborg Mette Line , Sørensen Suzette 
Published: November 2021

Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the novel coronavirus disease 2019 (COVID-19), which is characterized by a diverse clinical picture. Children are often asymptomatic or experience mild symptoms and have a milder disease course compared to adults. Rectal shedding of SARS-CoV-2 has been observed in both adults and children, suggesting the fecal-oral route as a potential route of transmission. However, only a few studies have investigated this in neonates. We present a neonate with a mild disease course and prolonged rectal SARS-CoV-2 shedding.

Case presentation
A 22-day old neonate was admitted to the hospital with tachycardia and a family history of COVID-19. The boy later tested positive for COVID-19. His heart rate normalized overnight without intervention , but a grade 1/6 heart murmur on the left side of the sternum was found. After excluding signs of heart failure, the boy was discharged in a habitual state after three days of admission. During his admission, he was enrolled in a clinical study examining the rectal shedding of SARS-CoV-2. He was positive for SARS-CoV-2 in his pharyngeal swabs for 11 days after initial diagnosis and remained positive in his rectal swabs for 45 days. Thereby, the boy remained positive in his rectal swabs for 29 days after his first negative pharyngeal swab.

Conclusions
The presented case shows that neonates with a mild disease course can shed SARS-CoV-2 in the intestines for 45 days. In the current case, it was not possible to determine if fecal-oral transfer to the family occurred, and more research is needed to establish the potential risk of the fecal-oral transmission route.
Validity of the patient health questionnaire 9-item in autistic youths: a pilot study
Authors: Pilunthanakul Thanita , Goh Tze Jui , Fung Daniel Shuen Sheng , Sultana Rehena , Allen John Carson , Sung Min 
Published: November 2021

Abstract
Background
Autistic adolescents have greater predisposition to depression and suicidality than neurotypical adolescents. Early detection is essential for timely treatment. The Patient Health Questionnaire 9-item (PHQ-9) is a brief screen for depression. The study examines the validity of the PHQ-9 for detecting major depressive disorder (MDD) in autistic youths.

Methods
English speaking youths aged 10–18 years, with DSM-IV/DSM-5/ICD-10 diagnosis of Autism Spectrum Disorder (ASD), and their parents presenting to a child psychiatric service were invited to participate between May 2018 to August 2020. Participants completed the respective self- and parent-rated PHQ-9 independently. MDD was verified using the MINI-Kid (Mini-International Neuropsychiatric Interview, Kid version).

Results
One hundred one youth, mean (SD) age 14.6 (2.3), were enrolled. 27 (27%) met criteria for current MDD. Mean total PHQ-9 scores, percentage ratings for severity of symptoms of depression, functional impairment, dysthymia and suicidality were compared. Areas under the ROC curve and statistically optimal cutoffs were determined. Parents rated depressive symptoms severity lower than their children. The PHQ-9 displayed low sensitivity with high false negative rates at conventional, adjusted and proposed cutoffs.

Conclusions
Future studies should improve on the validity and reliability of existing depression screening tools, or develop more appropriate screening methods of depression, for autistic youths.
The interaction of adverse childhood experiences and gender as risk factors for depression and anxiety disorders in US adults: a cross-sectional study
Authors: Whitaker Robert C. , Dearth-Wesley Tracy , Herman Allison N. , Block Amy E. , Holderness Mary Howard , Waring Nicholas A. , Oakes J. Michael 
Published: November 2021

Abstract
Background
Exposure to adverse childhood experiences (ACEs) and being female are distinct risk factors for having a major depressive episode (MDE) or an anxiety disorder (AD) in adulthood, but it is unclear whether these two risk factors are synergistic. The purpose of this study was to determine whether exposure to ACEs and being female are more than additive (synergistic) in their association with MDE and AD in US adults.

Methods
We pooled cross-sectional survey data in the Midlife in the United States study from two nationally-representative cohorts of English-speaking US adults. Data from the first cohort were collected in 2004–2006 and from the second in 2011–2014. Data from both cohorts included the 12-month prevalence of MDE and AD (generalized anxiety disorder or panic disorder) assessed with the Composite International Diagnostic Interview Short Form, gender (here termed female and male), and the count of five categories of exposure to ACEs: physical, sexual, or emotional abuse; household alcohol or substance abuse; and parental separation or divorce.

Results
Of the 5834 survey respondents, 4344 (74.5%) with complete data on ACEs were included in the analysis. Mean (SD) age was 54.1 (13.8) years and 53.9% were female. The prevalences of MDE, AD, and exposure to 3–5 categories of ACEs were 13.7, 10.0, and 12.5%, respectively. After adjusting for covariates (age, race, and current and childhood socioeconomic disadvantage), for those with both risk factors (female and 3–5 ACEs) the prevalence of MDE was 26.9%. This was 10.2% (95% CI: 1.8, 18.5%) higher than the expected prevalence based on the additive associations of the two risk factors. The adjusted prevalence of AD among females with 3–5 ACEs was 21.9%, which was 11.4% (95% CI: 4.0, 18.9%) higher than the expected prevalence.

Conclusions
For both MDE and AD, there was synergy between the two risk factors of exposure to ACEs and being female. Identification and treatment of MDE and AD may benefit from understanding the mechanisms involved in the synergistic interaction of gender with ACEs.
Symptoms, impacts, and suitability of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT™) questionnaire in patients with sarcoidosis-associated pulmonary hypertension (SAPH): a qualitative interview study
Authors: Currie Brooke M. , Davies Evan W. , Beaudet Amélie , Stassek Larissa , Kleinman Leah , Baughman Robert P. 
Published: November 2021

Abstract
Background
Sarcoidosis-associated pulmonary hypertension (SAPH) is a prevalent and serious complication of sarcoidosis. No SAPH-specific self-report instruments for assessing SAPH symptoms and their impact on patients are available to date. This study sought to determine whether the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT™) questionnaire is suitable for use in patients with SAPH.

Methods
Patients diagnosed with SAPH participated in qualitative one-on-one telephone interviews to better understand SAPH symptoms and their impacts on patients’ lives and to determine the appropriateness of the PAH-SYMPACT™ for use in patients with SAPH. The interviews comprised concept elicitation, completion of the PAH-SYMPACT™, and cognitive debriefing. Interview transcripts were analyzed by content analysis.

Results
Eleven patients with SAPH were interviewed between August 2019 and June 2020. In the concept elicitation, all 11 participants endorsed shortness of breath and nine participants (82%) rated it as their “most bothersome or severe” symptom. Impacts endorsed by all 11 participants were difficulty walking uphill or up stairs and difficulty in performing daily activities. Cognitive debriefing indicated that the PAH-SYMPACT™ items were relevant and understandable to most participants and reflected their experiences of SAPH. Participants indicated that no key symptoms or impacts of SAPH were missing. They also reported that the PAH-SYMPACT™ instructions and response options were clear, and that it would be feasible to complete the 11 symptom items and one oxygen use item as part of their daily schedule.

Conclusions
This study suggests the PAH-SYMPACT™ is suitable for assessing symptoms and their impact in patients with SAPH. However, larger longitudinal studies are needed to confirm that it is fit for use in this patient population and that it can be used to reliably detect temporal changes in patients’ symptom status.
Trial registration Not applicable.
Effect of local somatosensory stimulus on postural sway during sit-to-stand movement in the elderly
Authors: Annor Peter , Kwak Kiyoung , Kim Huigyun , Kim Dongwook 
Published: November 2021

Abstract
Background
Sit-to-stand (STS) is a complex movement that requires successful postural control. Aging is a normal part of human life that leads to weakness of sensory capabilities, resulting in diminished postural control. Therefore, STS movement is a challenging task for the elderly. Local tendon vibration (LTV) can be utilized to assist STS of the elderly by improving postural control. Many studies have revealed that the LTV has various physiological positive effect. However, previous studies did not consider subjects’ individual difference for properties of applied LTV. Also, there are almost no studies to assist and to improve elder’s STS movement. Thus, the purpose of this study was to examine the influence of lower limb LTV on postural sway during STS in the elderly, and to examine whether a specific vibration frequency can increase postural control in the elderly.

Results
The common characteristic differences between the elderly and younger population during STS movement were analyzed. In addition, the effect of vibration on the center of mass (COM) and the center of pressure (COP) variable responses in young adults and the elderly were investigated. As a result, the elderly exhibit larger COP sway area and higher COP mediolateral (ML) displacement than the young adults. In addition, the elderly generally have lower COM velocities in all directions compared to the young adults. It was found that COP and COM related to postural stability are affected when LTV of the 180 Hz, 190 Hz and 250 Hz is applied to the elderly. Particularly, the 190 Hz vibration induced significant reduction in COP sway area and COP ML displacement.

Conclusions
These results mean that the LTV contributes to stability of elders’ STS movement by reducing postural sway. Furthermore, a reduction of postural sway depends on frequency of the LTV. These findings suggest that individual response to characteristics of vibration must be considered, and imply that the LTV can be used as rehabilitation therapy to improve postural control in the elderly, and utilized in motion assistive devices to deliver apt vibration frequencies.

Trial registration
CRIS, KCT0005434, Registered 25 September 2020, Retrospectively registered, https://cris.nih.go.kr/cris/index/index.do
Design of a new lyoprotectant increasing freeze-dried Lactobacillus strain survival to long-term storage
Authors: Bodzen Aurore , Jossier Audrey , Dupont Sébastien , Mousset Pierre-Yves , Beney Laurent , Lafay Sophie , Gervais Patrick 
Published: November 2021

Abstract
Background
Stabilization of freeze-dried lactic acid bacteria during long-term storage is challenging for the food industry. Water activity of the lyophilizates is clearly related to the water availability and maintaining a low aw during storage allows to increase bacteria viability. The aim of this study was to achieve a low water activity after freeze-drying and subsequently during long-term storage through the design of a lyoprotectant. Indeed, for the same water content as sucrose (commonly used lyoprotectant), water activity is lower for some components such as whey, micellar casein or inulin. We hypothesized that the addition of these components in a lyoprotectant, with a higher bound water content than sucrose would improve lactobacilli strains survival to long-term storage. Therefore, in this study, 5% whey (w/v), 5% micellar casein (w/v) or 5% inulin (w/v) were added to a 5% sucrose solution (w/v) and compared with a lyoprotectant only composed of 5% sucrose (w/v). Protective effect of the four lyoprotectants was assessed measuring Lactiplantibacillus plantarum CNCM I-4459 survival and water activity after freeze-drying and during 9 months storage at 25 °C.

Results
The addition whey and inulin were not effective in increasing Lactiplantibacillus plantarum CNCM I-4459 survival to long-term-storage (4 log reduction at 9 months storage). However, the addition of micellar casein to sucrose increased drastically the protective effect of the lyoprotectant (3.6 log i.e. 0.4 log reduction at 9 months storage). Comparing to a lyoprotectant containing whey or inulin, a lyoprotectant containing micellar casein resulted in a lower water activity after freeze-drying and its maintenance during storage (0.13 ± 0.05).

Conclusions
The addition of micellar casein to a sucrose solution, contrary to the addition of whey and inulin, resulted in a higher bacterial viability to long-term storage. Indeed, for the same water content as the others lyoprotectants, a significant lower water activity was obtained with micellar casein during storage. Probably due to high bound water content of micellar casein, less water could be available for chemical degradation reactions, responsible for bacterial damages during long-term storage. Therefore, the addition of this component to a sucrose solution could be an effective strategy for dried bacteria stabilization during long-term storage.