bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Do Governance Conditions Influence Knowledge Diaspora Engagement in the Development Agenda of Ethiopia?
Authors: Bogale Mekonnen , Yesigat Abate , Jibat Nega , Hadis Sebsib , Tafese Tibebu 
Published: December 2024

Abstract
Generating evidence of knowledge diaspora engagement governance conditions is crucial for informed decision-making, yet there is a lack of research of this topic in the Ethiopian context. This study aimed to investigate how governance conditions influence knowledge diaspora engagement in Ethiopia’s development agenda. Qualitative methods, including key informant interviews and focus group discussions with purposely selected stakeholders (such as ministries, diaspora coordinating offices, universities, teaching and referral hospitals and diaspora associations), were employed to generate and analyse the evidence. The study found that, despite the political will, a formal diaspora policy, diaspora coordinating offices and the diaspora’s cultural attachment to their country of origin, actual engagement remains limited. The reasons for this include political instability, incoherent policies, weak collaboration among agencies, lack of engagement strategies, corruption, unnecessarily restrictive bureaucratic service delivery and inadequate monitoring mechanisms. Addressing gaps in the governance conditions would improve the diaspora engagement, thereby enabling Ethiopia to harness the full potential of its knowledge diaspora for national development.
Spine X-ray image segmentation based on deep learning and marker controlled watershed
Authors: Xiao Yating , Chen Yan , Zhang Yong , Zhang Runjie , Cui Guangyu , Song Yufeng , Zhang Quan 
Published: December 2024

Background The development of automatic methods for vertebral segmentation provides the objective analysis of each vertebra in the spine image, which is important for the diagnosis of various spinal diseases. However, vertebrae have inter-class similarity and intra-class variability, and some adjacent vertebrae exhibit adhesion. Objective To solve the adhesion problem of adjacent vertebrae and ensure that the boundary between adjacent vertebrae can be accurately demarcated, we propose an image segmentation method based on deep learning and marker controlled watershed. Methods This method consists of a dual-path model of localization path and segmentation path to achieve automatic vertebral segmentation. For the vertebral localization path, a high-resolution network (HRNet) is used to locate vertebral center. Moreover, based on spine posture, a new bone direction loss (BD-Loss) is designed to constrain HRNet. For the vertebral segmentation path, we proposed a VU-Net network to achieve vertebral preliminary segmentation. Additionally, a position information perception module (PIPM) is introduced to realize the guidance of HRNet to VU-Net. Finally, we novelly use the outputs of HR-Net and VU-Net deep learning networks to initialize the marker controlled watershed algorithm to suppress the adhesion of adjacent vertebrae and achieve vertebral fine segmentation. Results The proposed method was evaluated on two spine X-ray datasets using four metrics. The first dataset contains sagittal images of the cervical spine, while the second dataset contains coronal images of the whole spine, both with different health conditions. Our method achieved Recall of 96.82% and 94.38%, Precision of 97.24% and 98.14%, Dice coefficient of 97.03% and 96.22%, Intersection over Union of 94.24% and 92.72% on the cervical spine and whole spine datasets respectively, outperforming current state-of-the-art techniques.
Long-term efficacy and safety of danicopan as add-on therapy to ravulizumab or eculizumab in PNH with significant EVH
Authors: Kulasekararaj Austin , Griffin Morag , Piatek Caroline , Shammo Jamile , Nishimura Jun-ichi , Patriquin Christopher , Schrezenmeier Hubert , Barcellini Wilma , Panse Jens , Gaya Anna , Patel Yogesh , Liu Peng , Filippov Gleb , Sicre de Fontbrune Flore , Risitano Antonio , Lee Jong Wook 
Published: December 2024

Abstract
Complement C5 inhibitor treatment with ravulizumab or eculizumab for paroxysmal nocturnal hemoglobinuria (PNH) improves outcomes and survival. Some patients remain anemic due to clinically significant extravascular hemolysis (cs-EVH; hemoglobin [Hb] ≤9.5 g/dL and absolute reticulocyte count [ARC] ≥120 × 109/L). In the phase 3 ALPHA trial, participants received oral factor D inhibitor danicopan (150 mg 3 times daily) or placebo plus ravulizumab or eculizumab during the 12-week, double-blind treatment period 1 (TP1); those receiving placebo switched to danicopan during the subsequent 12-week, open-label TP2 and continued during the 2-year long-term extension (LTE). There were 86 participants randomized in the study, of whom 82 entered TP2, and 80 entered LTE. The primary end point was met, with Hb improvements from baseline at week 12 (least squares mean change, 2.8 g/dL) with danicopan. For participants switching from placebo to danicopan at week 12, improvements in mean Hb were observed at week 24. Similar trends were observed for the proportion of participants with ≥2 g/dL Hb increase, ARC, proportion of participants achieving transfusion avoidance, and Functional Assessment of Chronic Illness Therapy–Fatigue scale scores. Improvements were maintained up to week 72. No new safety signals were observed. The breakthrough hemolysis rate was 6 events per 100 patient-years. These long-term data demonstrate sustained efficacy and safety of danicopan plus ravulizumab/eculizumab for continued control of terminal complement activity, intravascular hemolysis, and cs-EVH in PNH. This trial was registered at www.clinicaltrials.gov as #NCT04469465.
Prediction of miRNA-disease associations based on PCA and cascade forest
Authors: Zhang Chuanlei , Li Yubo , Dong Yinglun , Chen Wei , Yu Changqing 
Published: December 2024

Abstract
Background
As a key non-coding RNA molecule, miRNA profoundly affects gene expression regulation and connects to the pathological processes of several kinds of human diseases. However, conventional experimental methods for validating miRNA-disease associations are laborious. Consequently, the development of efficient and reliable computational prediction models is crucial for the identification and validation of these associations.

Results
In this research, we developed the PCACFMDA method to predict the potential associations between miRNAs and diseases. To construct a multidimensional feature matrix, we consider the fusion similarities of miRNA and disease and miRNA-disease pairs. We then use principal component analysis(PCA) to reduce data complexity and extract low-dimensional features. Subsequently, a tuned cascade forest is used to mine the features and output prediction scores deeply. The results of the 5-fold cross-validation using the HMDD v2.0 database indicate that the PCACFMDA algorithm achieved an AUC of 98.56%. Additionally, we perform case studies on breast, esophageal and lung neoplasms. The findings revealed that the top 50 miRNAs most strongly linked to each disease have been validated.

Conclusions
Based on PCA and optimized cascade forests, we propose the PCACFMDA model for predicting undiscovered miRNA-disease associations. The experimental results demonstrate superior prediction performance and commendable stability. Consequently, the PCACFMDA is a potent instrument for in-depth exploration of miRNA-disease associations.
The median effective dose of ciprofol combined with sufentanil in suppressing the laryngeal mask airway insertion response in both young and older adult patients
Authors: Zhou Xuelei , Zhao Li , Mao Wei , Chen Linlin , Liu Xianchun , Li Linji 
Published: December 2024

Abstract
Background
Ciprofol, a novel intravenous anesthetic, exhibits similar sedation mechanisms and pharmacokinetic properties to propofol. However, ciprofol demonstrates greater potency and is associated with reduced injection pain compared to propofol. Given the varying sensitivities to anesthetic agents across different age groups, this study aims to determine the median effective dose (ED50) of ciprofol required to suppress the laryngeal mask airway (LMA) insertion response in both young and older adult patients, as well as to assess its potential adverse reactions.

Methods
In this study, 46 patients scheduled for surgery under general anesthesia with LMA insertion were recruited. Upon entering the operating room, patients were intravenously administered ciprofol (0.4 mg·kg− 1) and sufentanil (0.3 µg·kg− 1), followed by LMA insertion after three minutes. To derive robust confidence intervals for both ED50 and ED95, we performed an analysis using a logistic regression model combined with bootstrap resampling.

Results
In the young adult group, the ED50 and ED95 of ciprofol for suppressing the LMA insertion response were 0.38 mg·kg− 1 (95% CI, 0.35–0.41) and 0.46 mg·kg− 1 (95%CI, 0.40–0.56), respectively. In the older adult group, the respective ED50 and ED95 were 0.29 mg·kg− 1 (95% CI, 0.26–0.32) and 0.37 mg·kg− 1 (95% CI, 0.30–0.78). Regarding adverse reactions, although there were differences in the incidence of injection pain, hypotension, and bradycardia between the young and older groups, no statistically significant differences were observed between the two groups.

Conclusion
In this study, significant differences were observed in the ED50 of ciprofol for suppressing the LMA insertion response between young and older adult patients. The ED50 of ciprofol for young adult patients was 0.38 mg·kg− 1 (95% CI, 0.35–0.41), while for older adult patients it was0.29 mg·kg− 1 (95% CI, 0.26–0.32).

Trial registration
This study was registered on February 17, 2024, with the China Clinical Trial Registration Center (www.chictr.org.cn; Registration Number: ChiCTR2400080891).
Acute kidney injury and in-hospital outcomes after transcatheter aortic valve replacement in patients without chronic kidney disease: insights from the national inpatient sample
Authors: Ye Congyan , Ma Xueping , Shi Bo , Yan Rui , Fu Shizhe , Wang Kairu , Yan Ru , Jia Shaobin , Yang Shengping , Cong Guangzhi 
Published: December 2024

Abstract
Background
Acute kidney injury (AKI) complicates transcatheter aortic valve replacement (TAVR), leading to higher mortality. The incidence and effects of AKI on clinical outcomes in patients undergoing TAVR without chronic kidney disease (CKD) are unclear. We aimed to determine the association between AKI and in-hospital outcomes in patients with TAVR using propensity score matching (PSM).

Methods
Using International Classification of Diseases-10th Revision codes, we queried the National Inpatient Sample for TAVR performed between 2016 and 2021. Patients were divided into two groups according to perioperative AKI development. Patients with CKD or on permanent hemodialysis at baseline were excluded. We conducted 1:1 PSM to assemble a cohort of patients with similar baseline characteristics. Multivariate logistic regression was used to assess the association between AKI and in-hospital outcomes. Sensitivity analysis was conducted to evaluate the robustness of our inferences.

Results
Of 47,372 unweighted patient admissions for TAVR, 1617 (3.41%) had a concomitant diagnosis of AKI. The incidence of AKI decreased from 4.82 to 3.18% from 2016 to 2021 (P-trend < 0.01). Before PSM, patients with AKI had a significantly higher rate of in-hospital mortality compared with those without AKI (6.12% vs. 0.48%, respectively; odds ratio [OR] 8.59, 95% confidence interval [CI] 6.32–11.68). Using the PSM algorithm, 1579 well-matched patients were included in each group. After PSM, an association was observed between patients with TAVR and concomitant AKI and a higher risk of in-hospital mortality (6.21% vs. 1.08%, respectively; OR 5.96; 95% CI 3.54–10.04). In subgroup analyses stratified according to age (≤ 80 and > 80 years), sex (male/female), and hypertension status, consistent associations were observed between AKI and the risk of in-hospital mortality. AKI patients were at higher risk for acute myocardial infarction (OR 1.78, 95% CI 1.35–2.34), major bleeding (OR 1.62, 95% CI 1.13–2.33), blood transfusion (OR 1.65, 95% CI 1.28–2.11), and cardiogenic shock (OR 3.73, 95% CI 2.77–5.01). No significant betweengroup differences were observed in stroke (P = 0.12).

Conclusion
AKI was a strong predictor of in-hospital mortality in patients undergoing TAVR without CKD and was associated with higher post-procedure complication rates.
Effect of the Norwegian agreement on a more inclusive working life on use of sick leave and pregnancy benefits among pregnant women: a cohort study
Authors: Hasting Rachel Louise , Hoff Rune , Merkus Suzanne L , Gran Jon Michael , Mehlum Ingrid S 
Published: December 2024

Abstract
Background
We aimed to estimate the effect of the voluntary Norwegian Agreement on a More Inclusive Working Life (IA Agreement) on use of sickness absence (SA) and pregnancy benefits among pregnant women.

Methods
Pregnant women (n = 112,486) with a birth during 1.12.2003–31.12.2010 were followed from 6 to 37 gestational weeks in a continuous time multistate model with the following states: work, full SA, graded SA, pregnancy benefits, maternity leave, and other. Women working in IA companies were compared to those in non-IA companies regarding incidence and duration of SA and pregnancy benefits. Differences between groups with respect to calendar year, age, civil status, education, industry, and number of employees in the company were adjusted for using inverse probability of treatment weighting. Absolute differences in probabilities over time, expected length of stay (ELOS) in each state and differences in ELOS between IA and non-IA were calculated. 95% confidence intervals (CI) were generated using bootstrapping (1,000 repetitions).

Results
Adjusted analyses suggest that women working in IA companies were more likely to be in full SA in the first and last trimesters, but less likely between 14 and 28 weeks, than those in non-IA companies. The probability of being in work mirrored this, with women in IA companies tending to spend half a day more in work (ELOS difference 0.55, 95% CI -1.79, 3.02). Differences were not statistically significant. The use of graded SA was slightly higher (ELOS difference 0.46, 95% CI -0.87, 1.72) and the use of pregnancy benefits slightly lower (ELOS difference − 0.43, 95% CI -1.32, 0.42) among those in IA companies compared to non-IA companies.

Conclusions
Women in IA companies tended to spend more time in work and graded SA, but less time on pregnancy benefits. Differences in full SA varied during pregnancy and were most positive mid-pregnancy. This indicates that IA measures could be more effective for conditions experienced at this point. However, effects were small and not statistically significant, which may indicate the IA Agreement has not focused much on pregnant women.

Key terms
IA Agreement, MBRN, MoBa, multistate models, pregnancy, pregnancy benefits, sickness absence, work participation.
Inactivation of the conserved protease LonA increases production of xylanase and amylase in Bacillus subtilis
Authors: Wang Biwen , Kes Mariah B. M. J. , van Saparoea Anna C. H. van den Berg , Dugar Gaurav , Luirink Joen , Hamoen Leendert W. 
Published: December 2024

Abstract
Background
Bacillus subtilis is widely used for industrial enzyme production due to its capacity to efficiently secrete proteins. However, secretion efficiency of enzymes varies widely, and optimizing secretion is crucial to make production commercially viable. Previously, we have shown that overexpression of the xylanase XynA lowers expression of Clp protein chaperones, and that inactivation of CtsR, which regulates and represses clp transcription, increases the production of XynA. In the current study, we examined whether the same is the case for overexpression of the α-amylase AmyM from Geobacillus stearothermophilus by B. subtilis, and why XynA shows a different timing of secretion compared to AmyM.

Results
Transcriptome analyses revealed that B. subtilis cells overexpressing AmyM exhibited a distinct profile compared to XynA overexpressing cells, however there were also similarities and in both cases expression of CtsR controlled genes was downregulated. In contrast to XynA, inactivation of CtsR did not improve AmyM production. Upregulation of other protein chaperones, including GroEL/ES and DnaJ/K, by inactivating their transcriptional repressor HrcA, had almost no effect on XynA yields and in fact considerably lowered that of AmyM. Despite using the same promoter, the production of XynA peaks well before AmyM reaches its optimal secretion rate. Transcriptome and ribosome profiling indicated that this is neither related to transcription nor to translation regulation. We show that the reduced secretion in the stationary phase is partially due to the activity of secreted proteases, but also due to the activity of the intracellular protease LonA. The absence of this protein resulted in a 140% and 20% increased production for XynA and AmyM, respectively.

Conclusion
The combination of transcriptome and ribosome profiling offered important information to determine at which cellular level production bottlenecks occurred. This helped us to identify LonA protease as an important factor influencing enzyme production yields in B. subtilis.
Evaluation of effectiveness of bacteriophage purification methods
Authors: Binte Mohamed Yakob Adil Siti Saleha , Tucci Joseph , Irving Helen , Cianciarulo Cassandra , Kabwe Mwila 
Published: December 2024

AbstractThe use of bacteriophages for therapy has increased over the last decade. While there is need for clear regulatory pathways for bacteriophage approval for mainstream use in clinical practice, practitioners and patients have been able to access bacteriophage therapy under compassionate grounds and through magistral preparations. However, there is currently no standard for purifying these bacteriophages to ensure safety, and good manufacturing practice certification may not be achieved in these emergency uses. In this study, we employed an Interleukin Receptor Associated Kinase (IRAK) 3 knockout monocyte-based assay to evaluate the endotoxin removal efficacy of three common bacteriophage purification methods: Triton X-100 exposure, CsCl density gradient ultracentrifugation, and Pierce™ High-Capacity Endotoxin Removal Resin spin columns. In our experiments we tested these purification methods on three different bacteriophage morphotypes: siphovirus, podovirus and myovirus. We showed that the lowest endotoxin levels and immune responses were achieved when purifying bacteriophages with Triton-X treatment. The results from purifying with CsCl density gradient ultracentrifugation were comparable, and these were both significantly better than purification with Pierce™ High-Capacity Endotoxin Removal Resin spin columns. We also showed that Triton X-100 purification resulted in the lowest loss of bacteriophage titres. Finally, of the bacteriophages tested here, it did not appear that virus morphology affected efficacy of endotoxin removal.
Pulsatilla chinensis functions as a novel antihyperlipidemic agent by upregulating LDLR in an ERK-dependent manner
Authors: Song Wei-fang , Wang Rui-jun , Yao Rui-xin , Jiang Qiu-yan , Feng Juan , Luo Kun , Di Zheng-han , Ma Cheng-mei , Xie Lan 
Published: December 2024

Abstract
Background
Pulsatilla chinensis (PC) is a traditional Chinese medicine (TCM) known for its beneficial activities. It has been historically used to treat dysentery, vaginal trichomoniasis, bacterial infections, and malignant tumors. The therapeutic potential of PC in the management of hypercholesterolemia remains largely unexplored.

Methods
A high-throughput screening based on high-throughput sequencing was conducted in HepG2 cells to construct gene expression profiles for several hundred TCMs. In vivo evaluation of the efficacy of PC was performed using rats with hypercholesterolemia. Transcriptome analysis was carried out on PC-treated rat livers and HepG2 cells to investigate the mechanism of action of PC in vitro. The findings were further validated using RT-qPCR and western blot techniques.

Results
PC was identified as similar to Rhizoma Coptidis based on signature genes related to metabolism. Administration of PC via gavage in rats with hypercholesterolemia for 11 weeks resulted in substantially reduced serum total cholesterol and low-density lipoprotein (LDL) cholesterol and ameliorated fatty liver. Transcriptome analysis revealed that PC regulated various pathways associated with lipid metabolism. The LDL receptor (LDLR), a key player in cholesterol metabolism, was upregulated by PC both in vivo and in vitro. It was discovered that PC achieved this upregulation by activating extracellular regulated protein kinase (ERK) signaling in HepG2 cells. To uncover the major bioactive components responsible for the anti- hypercholesterolemia effect of PC, two major saponins, named Pulsatilla saponin D (PCD) and PC anemoside B4 (PCB4), were assessed. PCD, but not PCB4, was identified as the active ingredient responsible for the upregulation of LDLR by PC.

Conclusion
These findings demonstrated that PC acts as an antihypercholesterolemic agent by upregulating LDLR in an ERK-dependent manner and holds potential in the treatment of hypercholesterolemia.
Quality of life after idiopathic multicentric Castleman disease in China: a cross-sectional, multi-center survey of patient reported outcome and caregiver reported outcome
Authors: Chen Jia , Zhang Miao-yan , Gao Yu-han , Zhang Lu , Li Jian 
Published: December 2024

AbstractThe majority of multicentric Castleman disease (MCD) patients in China are of the idiopathic subtype (iMCD) with systemic manifestations. However, the impact of iMCD on life quality, mental and psychological status, social function, and caregiving burden is poorly understood. To address this gap, a cross-sectional web-based survey was conducted with 178 iMCD patients and 82 caregivers, including 42 patient-caregiver dyads. Patient-reported outcome measurements were performed using four self-administered questionnaires (MCD-SS, SF-36, PHQ-9, and WPAI:GH). Caregiver-reported outcome measurements were performed using three questionnaires (SF-36, Zarit-22, CRA) to assess the caregiving burden. Correlation analysis was performed in patient-caregiver dyads. Patients reported a median of nine symptoms by MCD-SS, with a high mean score of 4.34 for the Fatigue domain. Their SF-36 scores indicated significant declines in physical and mental health compared to the Chinese general population (p < 0.001). Based on PHQ-9, around 65% of patients exhibited depressive symptoms, with 28.6% of them experiencing mild to severe major depression. Only 47.2% (84/178) of the patients were employed, and 28.5% experienced impaired work time. Caregivers also reported lower SF-36 scores than the general population (p < 0.05) and expressed feeling of self-criticism, lack of family support and financial problems. Correlations were observed between patients’ symptom burden, mental health impairment and caregiving burden (correlation coefficient: 0.31 ~ 0.55). Our study concluded that fatigue and depressive symptoms significantly impact the life quality and social well-being of iMCD patients. The disease also affect the physical and mental health of caregivers, leading to feelings of guilt and a lack of family support.