bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and combinatorial engineering of indole-3-acetic acid synthetic pathways in Paenibacillus polymyxa
Authors: Sun Huimin , Zhang Jikun , Liu Wenteng , E Wenhui , Wang Xin , Li Hui , Cui Yanru , Zhao Dongying , Liu Kai , Du Binghai , Ding Yanqin , Wang Chengqiang 
Published: August 2022

AbstractBackgroundPaenibacillus polymyxais a typical plant growth-promoting rhizobacterium (PGPR), and synthesis of indole-3-acetic acid (IAA) is one of the reasons for its growth-promoting capacity. The synthetic pathways of IAA inP. polymyxamust be identified and modified.ResultsP. polymyxaSC2 and its spontaneous mutant SC2-M1 could promote plant growth by directly secreting IAA. Through metabonomic and genomic analysis, the genespatA,ilvB3, andfusEin the native IPyA pathway of IAA synthesis in strain SC2-M1 were predicted. A novel strong promoterP04420was rationally selected, synthetically analyzed, and then evaluated on its ability to express IAA synthetic genes.Co-expression of three genes,patA,ilvB3, andfusE, increased IAA yield by 60% in strain SC2-M1. Furthermore, the heterogeneous geneiaamof the IAM pathway and two heterogeneous IPyA pathways of IAA synthesis were selected to improve the IAA yield of strain SC2-M1.The genesELJP6_14505,ipdC,andELJP6_00725of the entire IPyA pathway fromEnterobacter ludwigiiJP6 were expressed well by promoterP04420in strain SC2-M1 and increased IAA yield in the engineered strain SC2-M1 from 13 to 31 μg/mL, which was an increase of 138%.ConclusionsThe results of our study help reveal and enhance the IAA synthesis pathways ofP. polymyxaand its future application.
Docetaxel chemotherapy plus androgen-deprivation therapy in high-volume disease metastatic hormone-sensitive prostate cancer in Chinese patients: an efficacy and safety analysis
Authors: Guo Zhuifeng , Lu Xuwei , Yang Fan , Qin Liang , Yang Ning , Wu Jiawen , Wang Hang 
Published: August 2022

Abstract
Objective
To investigate the efficacy and safety of docetaxel chemotherapy combined with androgen-deprivation therapy for patients with high-volume disease metastatic hormone-sensitive prostate cancer.

Methods
153 cases of high-volume disease metastatic hormone-sensitive prostate cancer in Minhang Hospital between January 2018 and December 2019 were analyzed retrospectively, including the number of patients, age, initial PSA level, Gleason score, TNM stage and ECOG score. 90 patients in the endocrine therapy group received continuous ADT, and 63 patients in the combined chemotherapy group received docetaxel plus ADT. The progression-free survival time (time from initiation of prostate cancer treatment to progression to CRPC), PSA response rate, and adverse reactions were compared between the two groups.

Results
All 153 cases were closely followed up for a period of 12.3–35.3 months, with a median follow-up time of 23.5 months. The median time to reach the lowest point of PSA in the two groups was 6.3 months and 7.9 months (P = 0.018) in the combination chemotherapy group and the ADT group alone, with 27 (42.9%) and 12 (13.3%) cases in the two groups Within 12 months of treatment, PSA decreased to below 0.2 ng/ml (P = 0.02), and progression-free survival was 16.9 months (6.5–28.5 months) and 11.2 months (4.3–22.7 months) in the two groups. (P < 0.001). There were 18 cases (28.6%) and 54 cases (60%) in the two groups with disease progression (P < 0.001). There were 6 cases (9.5%) and 15 cases (16.7%) in the combination chemotherapy group and the ADT group died of prostate cancer and related complications, respectively. All 63 cases in the combined chemotherapy group completed 6 cycles of chemotherapy. 39 (61.9%) cases experienced varying degrees of neutropenia, of which 12 (19%) experienced grade 3–4 neutropenia, with 6 cases (9.5%) developed febrile neutropenia. 30 cases (47.6%) had toxic reactions in the digestive system, and 3 case (4.3%) had grade 3 liver dysfunction. 27 cases (42.8%) had skin and mucosal toxicity. 9 cases (14.3%) had mild fluid retention. No blood and digestive toxicity were observed in the ADT group. 33 cases (52.4%) and 48 (53.3%) of the two groups had symptoms of afternoon hot flashes and fatigue, (P = 0.961).

Conclusion
Docetaxel chemotherapy combined with endocrine therapy could be one of effective treatments for delaying castration resistance of HVD-mHSPC, which could prolong PFS effectively and obtain a higher PSA response rate, high safety under close monitoring, and controllable adverse reactions.
Multifaceted roles of extracellular RNAs in different diseases
Authors: Sohail Abdullah Muhammad , Khawar Muhammad Babar , Afzal Ali , Hassan Ali , Shahzaman Sara , Ali Ahmed 
Published: August 2022

AbstractExtracellular RNAs (exRNAs) are novel circulating factors that can be used as biomarkers in various diseases. Their unique and diverse kinds, as well as their role as biomarkers, make them significant biomarkers. There has been immense work carried out since the discovery of exRNAs in circulation and other biological fluids to catalog and determine whether exRNAs may be utilized as indicators for health and illness. In this review, we aim to understand the current state of exRNAs in relation to various diseases and their potential as biomarkers. We will also review current issues and challenges faced in using exRNAs, with clinical and lab trials, that can be used as viable markers for different diseases.
The morphogenesis of the rabbit meibomian gland in relation to sex hormones: Immunohistochemical and transmission electron microscopy studies
Authors: El-Desoky Sara M. M. , Abdellah Nada 
Published: August 2022

AbstractRabbits have been proposed as a model for the human meibomian gland (MG), a large specific sebaceous gland in the eyelid that consists of secretory acini arranged laterally and related to the central duct via short ductules, with the central duct continuing as an excretory duct to open at the free margin of the lid. First detected at embryonic day 18 as an aggregation of mesenchymal cells in the tarsal plate, it completes its development approximately 2 weeks postnatal when the separation of the eyelids is completed. The Transmission electron microscopy supports the meibocytes’ gradient maturation to the meibum’s synthesis. While the differentiating cells, their cytoplasm, are well packed with lipid droplets, the basal cells are characterized by a high nuclear to cytoplasm ratio. The androgen and estrogen receptor proteins are expressed in the basal cell and the meibocytes, and increase in age increases in the expression of these proteins. Additionally, the cytokeratin (CK14) is expressed in the basal and differentiating cells of the acini and the ductal epithelium. Therefore, the duct cells of the MG are common in all stem cells. These data concluded that the MG plays a major role in maintaining the health of the ocular surface and preservation of visual acuity. Any abnormalities in the structure of the MG lead to its dysfunction and changes in lipid secretion.
DeepLabCut increases markerless tracking efficiency in X-ray video analysis of rodent locomotion
Authors: Kirkpatrick Nathan J. , Butera Robert J. , Chang Young-Hui 
Published: August 2022

ABSTRACT
Despite the prevalence of rat models to study human disease and injury, existing methods for quantifying behavior through skeletal movements are problematic owing to skin movement inaccuracies associated with optical video analysis, or require invasive implanted markers or time-consuming manual rotoscoping for X-ray video approaches. We examined the use of a machine learning tool, DeepLabCut, to perform automated, markerless tracking in bi-planar X-ray videos of locomoting rats. Models were trained on 590 pairs of video frames to identify 19 unique skeletal landmarks of the pelvic limb. Accuracy, precision and time savings were assessed. Machine-identified landmarks deviated from manually labeled counterparts by 2.4±0.2 mm (n=1710 landmarks). DeepLabCut decreased analysis time by over three orders of magnitude (1627×) compared with manual labeling. Distribution of these models may enable the processing of a large volume of accurate X-ray kinematics locomotion data in a fraction of the time without requiring surgically implanted markers.
Elevated shock index and modified shock index are associated with mortality and major adverse cardiac events in patients with acute myocardial infarction: A systematic review and meta-analysis
Authors: Pramudyo Miftah , Putra Iwan Cahyo Santosa , Kamarullah William , Prameswari Hawani Sasmaya , Saboe Aninka , Akbar Mohammad Rizki 
Published: August 2022

Background Blood pressure (BP) and heart rate (HR) have been studied extensively to predict unfavourable outcomes in patients suffering from an acute myocardial infarction (AMI). Shock index (SI) and modified shock index (MSI) are two new emerging parameters that incorporate BP and HR into their calculations, thereby improving the predictive value of each HR and BP alone in AMI patients. Thus, our aim was to determine the prognostic utility of SI and MSI in AMI patients. Methods We searched PubMed, ProQuest, EBSCO Host, and Europe PMC from conception to May 2022. Studies were eligible if they evaluated the relationship of SI and MSI with all-cause mortality and major adverse cardiac events. Results A total of 16 studies involving 80,195 participants met the inclusion criteria and were included in this meta-analysis. Our study revealed significantly higher all-cause mortality risk for patients with high SI and MSI compared to patients with low indices, regardless of the periods of outcomes, study population, or diverse cut-off values. Moreover, both increased SI and MSI also predicted higher major adverse cardiac events rates. Conclusions According to our findings, both SI and MSI in the emergency department can predict all-cause mortality and major adverse cardiac events in patients with acute myocardial infarction. Given this growing body of evidence, as well as the fact that SI and MSI are very simple objective indices derived from two readily available vital signs, they should be used in daily clinical practice to risk stratify patients presenting with acute myocardial infarction. PROSPER registration CRD42022329558.
“In principio”: The Metaphysical Exegesis of John 1:1 by Albert the Great, Bonaventure and Thomas Aquinas
Authors: Nannini Andrea , Trepczyński Marcin 
Published: August 2022

„In principio”: metafizyczna egzegeza J 1,1 Alberta Wielkiego, Bonawentury i Tomasza z Akwinu
Artykuł przedstawia interpretacje słów „in principio” (Jan 1,1) zaproponowane przez Alberta Wielkiego, Bonawenturę i Tomasza z Akwinu w ich komentarzach do Ewangelii wg św. Jana. Ujęcia tych autorów różnią się. Albert używa pojęć pierwszej zasady oraz intelektu, który działa powszechnie i wytwarza swoje światło. Bonawentura buduje swoją interpretację na Augustyńskim rozróżnieniu między początkiem bez początku i początkiem z początku. Akwinata tworzy zaś ramę pojęciową opartą na teoriach metafizycznych. Wszystkie te ujęcia ujawniają metafizyczny charakter dokonanej przez tych autorów egzegezy pierwszego zdania Janowej Ewangelii. Owo metafizyczne nastawienie umożliwiło im zastosowanie zaawansowanych pojęć i stanowi jeden z powodów, by ich egzegezę określić jako “analityczną”.
Biological sample donation and informed consent for neurobiobanking: Evidence from a community survey in Ghana and Nigeria
Authors: Singh Arti , Arulogun Oyedunni , Akinyemi Joshua , Nichols Michelle , Calys-Tagoe Benedict , Ojebuyi Babatunde , Jenkins Carolyn , Obiako Reginald , Akpalu Albert , Sarfo Fred , Wahab Kolawole , Sunday Adeniyi , Owolabi Lukman F. , Adigun Muyiwa , Afolami Ibukun , Olorunsogbon Olorunyomi , Ogunronbi Mayowa , Melikam Ezinne Sylvia , Laryea Ruth , Asibey Shadrack , Oguike Wisdom , Melikam Lois , Sule Abdullateef , Titiloye Musibau A. , Yahaya Isah Suleiman , Bello Abiodun , Kalaria Rajesh N. , Jegede Ayodele , Owolabi Mayowa , Ovbiagele Bruce , Akinyemi Rufus 
Published: August 2022

Introduction
Genomic research and neurobiobanking are expanding globally. Empirical evidence on the level of awareness and willingness to donate/share biological samples towards the expansion of neurobiobanking in sub-Saharan Africa is lacking.

Aims
To ascertain the awareness, perspectives and predictors regarding biological sample donation, sharing and informed consent preferences among community members in Ghana and Nigeria.

Methods
A questionnaire cross-sectional survey was conducted among randomly selected community members from seven communities in Ghana and Nigeria.

Results
Of the 1015 respondents with mean age 39.3 years (SD 19.5), about a third had heard of blood donation (37.2%, M: 42.4%, F: 32.0%, p = 0.001) and a quarter were aware of blood sample storage for research (24.5%; M: 29.7%, F: 19.4%, p = 0.151). Two out of ten were willing to donate brain after death (18.8%, M: 22.6%, F: 15.0%, p<0.001). Main reasons for unwillingness to donate brain were; to go back to God complete (46.6%) and lack of knowledge related to brain donation (32.7%). Only a third of the participants were aware of informed consent (31.7%; M: 35.9%, F: 27.5%, p<0.001). Predictors of positive attitude towards biobanking and informed consent were being married, tertiary level education, student status, and belonging to select ethnic groups.

Conclusion
There is a greater need for research attention in the area of brain banking and informed consent. Improved context-sensitive public education on neurobiobanking and informed consent, in line with the sociocultural diversities, is recommended within the African sub region.
Cost-effectiveness of the add-on exenatide to conventional treatment in patients with Parkinson’s disease when considering the coexisting effects of diabetes mellitus
Authors: Chen Hsuan-Chih , Wang Chen-Yu , Chen Hsiu-Hsi , Liou Horng- Huei 
Published: August 2022

Objective
This study aims to investigate the cost-effectiveness of the add-on exenatide to conventional pharmacotherapy in patients with Parkinson’s disease (PD) when considering the coexistence of diabetes mellitus (DM).

Methods
We used the Keelung and Community-based Integrated Screening databases to understand the medical utilisation in the Hoehn and Yahr stages of patients with PD. A Markov model with 1-year cycle length and 50-year time horizon was used to assess the cost-effectiveness of add-on exenatide to conventional pharmacotherapy compared to conventional pharmacotherapy alone. All costs were adjusted to the value of the new Taiwanese dollar (NT$) as of the year 2020. One-way sensitivity and probability analyses were performed to test the robustness of the results.

Results
From a societal perspective, the add-on exenatide brought an average of 0.39 quality-adjusted life years (QALYs) gained, and a cost increment of NT$104,744 per person in a 50-year horizon compared to conventional pharmacotherapy. The incremental cost-effectiveness ratio (ICER) was NT$268,333 per QALY gained. As the ICER was less than the gross domestic product per capita (NT$839,558), the add-on exenatide was considered to be very cost-effective in the two models, according to the World Health Organization recommendation. Add-on exenatide had a 96.9% probability of being cost-effective in patients with PD, and a 100% probability of being cost-effective in patients with PD and DM.

Conclusion
Add-on exenatide is cost-effective in PD combined with DM. Considering that DM may be a risk factor for neurodegenerative diseases, exenatide provides both clinical benefits and cost-effectiveness when considering both PD and DM.
Association between folic acid use during pregnancy and gestational diabetes mellitus: Two population-based Nordic cohort studies
Authors: Pazzagli Laura , Segovia Chacón Silvia , Karampelias Christos , Cohen Jacqueline M. , Bröms Gabriella , Kieler Helle , Odsbu Ingvild , Selmer Randi , Andersson Olov , Cesta Carolyn E. 
Published: August 2022

Introduction
Inconsistent results have been reported on the association between folic acid use in pregnancy and risk of GDM. The aim of this study was to estimate the association between folic acid use and GDM in two population-based Nordic cohorts.

Material and methods
Two cohort studies were conducted using data from the national population registers in Norway (2005–2018, n = 791,709) and Sweden (2006–2016, n = 1,112,817). Logistic regression was used to estimate the associations between GDM and self-reported folic acid use and prescribed folic acid use, compared to non-users, adjusting for covariates. To quantify how potential unmeasured confounders may affect the estimates, E-values were reported. An exposure misclassification bias analysis was also performed.

Results
In Norwegian and Swedish cohorts, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for maternal self-reported folic acid use were 1.10 (1.06–1.14) and 0.89 (0.85–0.93), with E-values of 1.43 (1.31) and 1.50 (1.36), respectively. For prescribed folic acid use, ORs were 1.33 (1.15–1.53) and 1.56 (1.41–1.74), with E-values of 1.99 (1.57) and 2.49 (2.17), in Norway and Sweden respectively.

Conclusions
The slightly higher or lower odds for GDM in self-reported users of folic acid in Norway and Sweden respectively, are likely not of clinical relevance and recommendations for folic acid use in pregnancy should remain unchanged. The two Nordic cohorts showed different directions of the association between self-reported folic acid use and GDM, but based on bias analysis, exposure misclassification is an unlikely explanation since there may still be differences in prevalence of use and residual confounding. Prescribed folic acid is used by women with specific comorbidities and co-medications, which likely underlies the higher odds for GDM.
Intra- and post-operative risk of retinal breaks during vitrectomy for macular hole and vitreomacular traction
Authors: Jairath Neil K. , Paulus Yannis M. , Yim Angela , Zhou Yunshu , Parekh Bela J. , Jairath Ruple , Musch David C. , Rosenthal Julie M. 
Published: August 2022

Background/Objective
To evaluate the development of intra- and post-operative retinal breaks after pars plana vitrectomy (PPV) for macular hole (MH) and/or vitreomacular traction (VMT).

Subjects/Methods
Medical records of patients who underwent PPV at Kellogg Eye Center between 1/1/2005–6/30/2018, were evaluated in three groups: group 1, MH/VMT (n = 136); group 2, epiretinal membrane (ERM) without VMT (n = 270); and group 3, diagnostic vitrectomy (DV) or vitreous opacities (n = 35). Statistical analyses were conducted using SAS.

Results
20.6% of patients with MH/VMT, 8.5% of patients with ERM, and 5.7% of patients with DV or vitreous opacities had either intra-operative or post-operative breaks. Indication of MH/VMT versus ERM was a significant predictor for this outcome (p = .0112). The incidence of retinal breaks was higher in operations using 23-gauge versus 25-gauge PPV (25.0% vs. 7.4%, p < .0001).

Conclusions
The presence of MH and/or VMT is a significant risk factor for retinal breaks from PPV, as is use of 23-gauge vitrectomy.
Network diffusion model predicts neurodegeneration in limb-onset Amyotrophic Lateral Sclerosis
Authors: Bhattarai Anjan , Chen Zhaolin , Chua Phyllis , Talman Paul , Mathers Susan , Chapman Caron , Howe James , Lee C. M. Sarah , Lie Yenni , Poudel Govinda R. , Egan Gary F. 
Published: August 2022

Objective
Emerging evidences suggest that the trans-neural propagation of phosphorylated 43-kDa transactive response DNA-binding protein (pTDP-43) contributes to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). We investigated whether Network Diffusion Model (NDM), a biophysical model of spread of pathology via the brain connectome, could capture the severity and progression of neurodegeneration (atrophy) in ALS.

Methods
We measured degeneration in limb-onset ALS patients (n = 14 at baseline, 12 at 6-months, and 9 at 12 months) and controls (n = 12 at baseline) using FreeSurfer analysis on the structural T1-weighted Magnetic Resonance Imaging (MRI) data. The NDM was simulated on the canonical structural connectome from the IIT Human Brain Atlas. To determine whether NDM could predict the atrophy pattern in ALS, the accumulation of pathology modelled by NDM was correlated against atrophy measured using MRI. In order to investigate whether network spread on the brain connectome derived from healthy individuals were significant findings, we compared our findings against network spread simulated on random networks.

Results
The cross-sectional analyses revealed that the network diffusion seeded from the inferior frontal gyrus (pars triangularis and pars orbitalis) significantly predicts the atrophy pattern in ALS compared to controls. Whereas, atrophy over time with-in the ALS group was best predicted by seeding the network diffusion process from the inferior temporal gyrus at 6-month and caudal middle frontal gyrus at 12-month. Network spread simulated on the random networks showed that the findings using healthy brain connectomes are significantly different from null models.

Interpretation
Our findings suggest the involvement of extra-motor regions in seeding the spread of pathology in ALS. Importantly, NDM was able to recapitulate the dynamics of pathological progression in ALS. Understanding the spatial shifts in the seeds of degeneration over time can potentially inform further research in the design of disease modifying therapeutic interventions in ALS.
Impact of human mobility and networking on spread of COVID-19 at the time of the 1st and 2nd epidemic waves in Japan: An effective distance approach
Authors: Nohara Yasuhiro , Manabe Toshie 
Published: August 2022

Background
The influence of human mobility to the domestic spread of COVID-19 in Japan using the approach of effective distance has not yet been assessed.

Methods
We calculated the effective distance between prefectures using the data on laboratory-confirmed cases of COVID-19 from January 16 to August 23, 2020, that were times in the 1st and the 2nd epidemic waves in Japan. We also used the aggregated data on passenger volume by transportation mode for the 47 prefectures, as well as those in the private railway, bus, ship, and aviation categories. The starting location (prefecture) was defined as Kanagawa and as Tokyo for the 1st and the 2nd waves, respectively. The accuracy of the spread models was evaluated using the correlation between time of arrival and effective distance, calculated according to the different starting locations.

Results
The number of cases in the analysis was 16,226 and 50,539 in the 1st and 2nd epidemic waves, respectively. The relationship between arrival time and geographical distance shows that the coefficient of determination was R2 = 0.0523 if geographical distance Dgeo and time of arrival Ta set to zero at Kanagawa and was R2 = 0.0109 if Dgeo and Ta set to zero at Tokyo. The relationship between arrival time and effective distance shows that the coefficient of determination was R2 = 0.3227 if effective distance Deff and Ta set to zero at Kanagawa and was R2 = 0.415 if Deff and time of arrival Ta set to zero at Tokyo. In other words, the effective distance taking into account the mobility network shows the spatiotemporal characteristics of the spread of infection better than geographical distance. The correlation of arrival time to effective distance showed the possibility of spreading from multiple areas in the 1st epidemic wave. On the other hand, the correlation of arrival time to effective distance showed the possibility of spreading from a specific area in the 2nd epidemic wave.

Conclusions
The spread of COVID-19 in Japan was affected by the mobility network and the 2nd epidemic wave is more affected than those of the 1st epidemic. The effective distance approach has the impact to estimate the domestic spreading COVID-19.