bluuebunny/crossref_metadata_2025 huggingface dataset:
Spirit-Filled World: Religious Dis/Continuity in African Pentecostalism
Authors: Kgatle Mookgo Solomon
Published: January 2024

African Pentecostalism is in continuity with popular religion in linking African challenges and problems to the spirit world. However, Allan Anderson, a leading Pentecostal theologian, argues that this continuity should be studied simultaneously with the discontinuity between African Pentecostalism and certain popular religions. Based on this argument, there exists a tension between continuity with certain popular religions in African Pentecostalism on the one hand, and discontinuity with certain aspects of it on the other hand—hence the concept “dis/continuity.” Seeking a balance, this review article explores Anderson’s text in regards to both the context of African Pentecostalism’s continuity with popular religion, where there is connection between people’s challenges and the spirit world, and the context of discontinuity, where African Pentecostalism is delinked from certain aspects of popular religion based on the very different ways in which African Pentecostalism addresses people’s various problems. In summary, while African traditional religions as an expression of popular religion use different mediums to find solutions, African Pentecostalism uses the power of the Holy Spirit for the same.
Grundzüge der Außereuropäischen Christentumsgeschichte: Asien, Afrika, und Lateinamerika 1450–2000 (Main Features of the Non-European History of Christianity: Asia, Africa, and Latin America, 1450–2000)
Authors: Ward Kevin
Published: January 2024

Professor Klaus Koschorke’s pioneering work Grundzüge der Außereuropäischen Christentumsgeschichte: Asien, Afrika, und Lateinamerika 1450–2000 (Main features of the non-European history of Christianity: Asia, Africa, and Latin America, 1450–2000) provides an overview of the historical development of Christianity in the Global South between 1450 and 2000. Koschorke emphasized the “polycentric” nature of Christianity—the fact that, for the gospel to be successful, it must become deeply embedded in the local cultures it encounters, producing forms of Christianity that are distinctive from those of Europe or North America, and in which indigenous evangelism, theology, and discipleship flourish. Koschorke also highlights the importance of relationships between the churches of South America, Asia, and Africa, the Black Atlantic, networks of co-operation throughout the Indian and Pacific Oceans that are as important as Western missionary movements in identifying Christianity as a world religion.
World Christianity 2024: Fragmentation and Unity
Authors: Zurlo Gina A. , Johnson Todd M. , Crossing Peter F.
Published: January 2024

This article marks the 40th year of including statistical information on World Christianity and mission in the International Bulletin of Mission Research. This year’s focus is on organizations that address the global fragmentation of Christianity by promoting dialogue among Christians. We identify here some of the larger umbrella organizations that seek to represent or bring together portions of four traditions (Catholics, Independents, Orthodox, Protestants), two movements within these traditions (Evangelicals, Pentecostals/Charismatics), and 47,000 denominations. These include the World Council of Churches, the World Evangelical Alliance, the Lausanne Movement, the World Pentecostal Fellowship, Empowered21, and the Global Christian Forum.
The China Mission in the Early Seventeenth Century: The Link between Higher Administration and On-the-Ground Missions
Authors: Xie Jingzhen
Published: January 2024

Adopting an accommodationist strategy with a positive attitude, the mission in China had a breakthrough when Matteo Ricci reached the Ming Court in 1601. Valentin Carvaglio’s Lettre de la Chine de l’an 1601 reports on this historical moment and testifies that the Jesuits’ intelligent, discreet, and humble presence under the guidance of the policy was an effective strategy. However, after Ricci’s death, the high profile adopted by the mission and tensions between Carvaglio and Nicholas Longobardi caused setbacks. This article seeks to provide a deeper understanding of how new mission directions and tensions between the administration from above and missions on the ground can impact mission.
Cranio-Orbital Oncoplastic Reconstruction in Pediatric Population: Single-Institution’s Experience of 10 Cases
Authors: Skochdopole Anna J. , Layon Sarah A. , Hashemi Ammar S. A. , Yim Nicholas H. , McCarter Jacob H. , Chelius Daniel C. , Pederson William C. , Buchanan Edward P.
Published: January 2024

Background:

Pediatric cranio-orbital tumors have several etiologies and given the broad spectrum of pathology, it is difficult to predict the extent of resection. Reconstruction in children and adolescents is particularly challenging due to potential craniofacial growth and the relatively limited availability of donor sites. In this review, we analyze 10 pediatric and adolescent cases from a single institution, discuss the existing literature, and propose a reconstruction algorithm for managing these complex defects.

Methods:

A retrospective chart review was performed to identify pediatric and adolescent patients with cranio-orbital tumors who underwent tumor resection and reconstruction at our institution between January 2012 and July 2022.

Results:

A total of 10 patients underwent oncoplastic reconstruction of defects of either the cranium alone or combination of cranium and orbit, with a mean age of 12.4 years (range: 2-20). The defects involved the parietal (n = 3, 30%), parietooccipital (n = 1; 10%), temporoparietal (n = 1; 10%), occipital (n = 1, 10%), and fronto-orbital (n = 4; 40%) regions. Cranioplasty was performed with split-thickness bone grafts, exchange cranioplasty, or alloplastic materials. A pericranial flap was used to isolate intracranial and extracranial contents in 2 cases. Free flaps were utilized for additional soft tissue coverage in 2 cases. Complications included free flap venous thrombosis, CSF leak, hardware exposure, sagittal sinus injury, superior sagittal sinus thrombosis, vertical diplopia, and hypertropia.

Conclusion:

The goals of oncoplastic reconstruction for cranio-orbital defects in pediatric and adolescent patients align with those in adults. However, reconstructive surgeons must consider age-specific differences, such as growth potential and limited donor sites. Effective reconstruction can be achieved through meticulous planning, clear communication, and a multidisciplinary approach.
Simulated site amplification for Central and Eastern North America: Data set development and amplification models
Authors: Ilhan Okan , Hashash Youssef MA , Stewart Jonathan P , Rathje Ellen M , Nikolaou Sissy , Campbell Kenneth W
Published: January 2024

This article presents a suite of response spectrum (RS) and Fourier amplitude spectrum (FAS) site amplification models for Central and Eastern North America (CENA). The amplification database used in model development was produced through large-scale one-dimensional site response analyses and overcomes limitations of prior databases by providing broader coverage of anticipated site conditions. New amplification functions conditioned on either VS30 or site natural period ( Tnat) as the primary independent variable are provided, the latter of which better captures features of the computed site amplification from the simulated database (i.e. model dispersion is reduced). Models for standard deviation also are developed. RS and FAS linear amplification functions that adjust the reference condition of VS = 3000 m/s to VS30 = 760 m/s, and account for amplification for profiles either with a sharp VS impedance or a more gradual increase in VS are also developed.
Applying the EHA/EBMT grading for ICAHT after CAR-T: comparative incidence and association with infections and mortality
Authors: Rejeski Kai , Wang Yucai , Hansen Doris K. , Iacoboni Gloria , Bachy Emmanuel , Bansal Radhika , Penack Olaf , Müller Fabian , Bethge Wolfgang , Munoz Javier , Mohty Razan , Bücklein Veit L. , Barba Pere , Locke Frederick L. , Lin Yi , Jain Michael D. , Subklewe Marion
Published: January 2024

Cytopenias represent the most common side effect of CAR T-cell therapy (CAR-T) and can predispose for severe infectious complications. Current grading systems, such as the Common Terminology Criteria for Adverse Events (CTCAE), neither reflect the unique quality of post–CAR-T neutrophil recovery, nor do they reflect the inherent risk of infections due to protracted neutropenia. For this reason, a novel EHA/EBMT consensus grading was recently developed for Immune Effector Cell-Associated HematoToxicity (ICAHT). In this multicenter, observational study, we applied the grading system to a large real-world cohort of 549 patients treated with BCMA- or CD19-directed CAR-T for refractory B-cell malignancies (112 multiple myeloma [MM], 334 large B-cell lymphoma [LBCL], 103 mantle cell lymphoma [MCL]) and examined the clinical sequelae of severe (≥3°) ICAHT. The ICAHT grading was strongly associated with the cumulative duration of severe neutropenia (r = 0.92, P < .0001), the presence of multilineage cytopenias, and the use of platelet and red blood cell transfusions. We noted an increased rate of severe ICAHT in patients with MCL vs those with LBCL and MM (28% vs 23% vs 15%). Severe ICAHT was associated with a higher rate of severe infections (49% vs 13%, P < .0001), increased nonrelapse mortality (14% vs 4%, P < .0001), and inferior survival outcomes (1-year progression-free survival: 35% vs 51%, 1-year overall survival: 52% vs 73%, both P < .0001). Importantly, the ICAHT grading demonstrated superior capacity to predict severe infections compared with the CTCAE grading (c-index 0.73 vs 0.55, P < .0001 vs nonsignificant). Taken together, these data highlight the clinical relevance of the novel grading system and support the reporting of ICAHT severity in clinical trials evaluating CAR-T therapies.
Regression algorithms-driven mechanical properties prediction of angle bracket connection on cross-laminated timber structures
Authors: Wu Zhe , Chen Lin , Xiong Haibei
Published: January 2024

The construction of structures using cross-laminated timber (CLT) has grown in popularity as a result of its environmentally friendly and high-strength characteristics. The primary function of angle bracket connections is to resist the force of CLT structures under horizontal forces, which is essential to ensure the seismic resilience and ductility of CLT structures. A regression algorithms-driven method for predicting the mechanical performance of angle bracket connections is introduced in this study. As input parameters, the geometric dimensions of the angle bracket connector, the connection method of the connector with the wall and floor slabs, and the properties of the CLT panel are utilized to predict the yield load, the maximal load, the initial stiffness, and the ductility ratio of the angle bracket connection. Prediction models were developed using the collected data from 110 angle bracket experiments, and each prediction model's performance was discussed in depth. Lastly, the permutation importance and SHapley Additive exPlanations (SHAP) value analysis were used to interpret the prediction models. The results showed that the extreme gradient boosting (XGB) algorithm could accurately predict the maximum and yielding load of the angle bracket connection, with R2 reaching 0.968 and 0.939. Furthermore, in predicting the initial stiffness of the angle bracket, the XGB algorithm performed the best with an average ratio of predicted to actual values of 0.985. The results indicated that this study proposed an accurate and efficient method for angle bracket connection to predicting its mechanical properties and confirmed the trustworthiness and feasibility of the prediction models.
Evaluation of the causal effects of blood metabolites on irritable bowel syndrome: Mendelian randomization
Authors: Zeng Yu , Liu Huabing , Pei Zhihui , Li Rui , Liu Zuihui , Liao Chuanwen
Published: January 2024

Background

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain, discomfort, and changes in bowel habits. The mechanism underlying IBS remains unclear, and little evidence exists for clarifying the causal relationship between blood metabolites and IBS.

Methods

We conducted a Mendelian randomization (MR) study using two samples. Exposure data for 7824 Europeans were extracted from a genome-wide association study (GWAS) on metabolite levels. The IBS GWAS data from the GWAS database were used for the initial analysis. The primary analysis of causal relationships was conducted using inverse-variance weighting (IVW) with MR-Egger and weighted medians as supplementary analyses. Sensitivity analyses were performed using a combination of the Cochran’s Q test, MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier, and leave-one-out analysis. For significant associations, replication and meta-analyses were performed using additional independent IBS case GWAS data released by the FinnGen Consortium R9. To identify the metabolites, score regression, confounding analysis, and reverse MR were performed to further assess the causal relationships between the metabolites.

Results

After rigorous screening, we identified four known metabolites to be associated with IBS (stearate, odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.59–0.92; arginine, OR: 1.36, 95% CI: 1.07–1.74; 1-palmitoylglycerol, OR:1.49, 95% CI: 1.07–2.07; 1-palmitoylglycerophosphoinositol, OR: 0.84, 95% CI: 0.71–0.99).

Conclusions

MR analysis revealed a causal relationship between the four metabolites and IBS, providing preliminary evidence for the pathogenesis of IBS. Our results provide novel insights into the potential biomarkers of IBS.
Endoscopic gastrointestinal bypass anastomosis using deformable self-assembled magnetic anastomosis rings (DSAMARs) in a pig model
Authors: Zhang Miaomiao , Mao Jianqi , Ma Jia , Xu Shuqin , Lyu Yi , Yan Xiaopeng
Published: January 2024

Background

To investigate the feasibility of a deformable self-assembled magnetic anastomosis ring (DSAMAR), designed and developed by us, for endoscopic gastrointestinal bypass anastomosis.

Methods

Ten experimental pigs were used as model animals. The DSAMAR comprises 10 trapezoidal magnetic units, arranged in a straight line under the constraint of a guide wire. When the desired anastomosis site is reached under the guidance of an endoscope, the catheter pushes the magnetic unit along the guide wire. The linear DSAMAR can be assembled into a circular DSAMAR. Two DSAMARs were inserted, one at the end of the duodenum and the other into the stomach successively. They attracted each other and compressed the wall of the stomach and duodenum to establish gastrointestinal bypass anastomosis. The experimental pigs were euthanized 4 weeks after the operation, and the gastrointestinal bypass anastomosis specimens were obtained. The anastomosis formation was evaluated by the naked eye and histology.

Results

Gastrointestinal bypass anastomosis with DSAMARs was successfully performed. The average operation time under an endoscope was 70.30 ± 19.05 min (range: 43–95 min). The DSAMARs were discharged through the anus 10–17 days after surgery. There were no complications such as gastrointestinal bleeding, perforation, anastomotic fistula, and gastrointestinal obstruction during and after the operation. Gastroscopy and gross specimen of the anastomosis showed a well-formed magnetic anastomosis. Histological observation showed good continuity of the serous membrane and the mucosa of magnetic anastomosis.

Conclusion

The DSAMAR is a safe and feasible device for fashioning gastrointestinal bypass anastomosis in this animal model.
Improving health literacy through group antenatal care: results from a cluster randomized controlled trial in Ghana
Authors: Lori Jody R. , Kukula Vida Ami , Liu Liya , Apetorgbor Veronica E.A. , Ghosh Bidisha , Awini Elizabeth , Lockhart Nancy , Amankwah Georgina , Zielinski Ruth , Moyer Cheryl A. , Williams John
Published: January 2024

Background

Although the majority of Ghanaian women receive antenatal care (ANC), many exhibit low health literacy by misinterpreting and incorrectly operationalizing ANC messages, leading to poor maternal and newborn health outcomes. Prior research in low-resource settings has found group antenatal care (G-ANC) feasible for women and providers. This study aims to determine the effect of G-ANC on increasing maternal health literacy. We hypothesized that pregnant women randomized into G-ANC would exhibit a greater increase in maternal health literacy than women in routine, individual ANC.

Methods

A 5-year cluster randomized controlled trial was conducted in 14 rural and peri-urban health facilities in the Eastern Region of Ghana. Facilities were paired based on patient volume and average gestational age at ANC enrollment and then randomized into intervention (G-ANC) vs. control (routine, individual ANC); 1761 pregnant women were recruited. Data collection occurred at baseline (T0) and post-birth (T2) using the Maternal Health Literacy scale, a 12-item composite scale to assess maternal health literacy. Logistic regression compared changes in health literacy from T0 to T2.

Results

Overall, women in both the intervention and control groups improved their health literacy scores over time (p < 0.0001). Women in the intervention group scored significantly higher on 3 individual items and on overall composite scores (p < 0.0001) and were more likely to attend 8 or more ANC visits.

Conclusion

While health literacy scores improved for all women attending ANC, women randomized into G-ANC exhibited greater improvement in overall health literacy post-birth compared to those receiving routine individual care. Life-saving information provided during ANC must be presented in an understandable format to prevent women and newborns from dying of preventable causes.

Trial Registry

Ethical approval for the study was obtained from the Institutional Review Boards of the University of Michigan (HUM#00161464) and the Ghana Health Service (GHS-ERC: 016/04/19).
The role of dairy consumption in the relationship between wealth and early life physical growth in India: evidence from multiple national surveys
Authors: George Franciosalgeo , Rajeev L Naga , Bandyopadhyay Sulagna , Baby Jeswin , Sinha Srishti , Sachdev Harshpal Singh , Kurpad Anura V , Thomas Tinku
Published: January 2024

Introduction

Prevalence of undernutrition continues to be high in India and low household wealth is consistently associated with undernutrition. This association could be modified through improved dietary intake, including dairy consumption in young children. The beneficial effect of dairy on child growth has not been explored at a national level in India. The present analyses aimed to evaluate the direct and indirect (modifying association of household level per adult female equivalent milk and milk product consumption) associations between household wealth index on height for age (HAZ) and weight for age (WAZ) in 6-59 months old Indian children using data from of nationally representative surveys.

Methods

Two triangulated datasets of two rounds of National Family Health Survey, (NFHS-3 and 4) and food expenditure (National Sample Survey, NSS61 and 68) surveys, were produced by statistical matching of households using Non-Iterative Bayesian Approach to Statistical Matching technique. A Directed Acyclic Graph was constructed to map the pathways in the relationship of household wealth with HAZ and WAZ based on literature. The direct association of wealth index and its indirect association through per adult female equivalent dairy consumption on HAZ and WAZ were estimated using separate path models for each round of the surveys.

Results

Wealth index was directly associated with HAZ and WAZ in both the rounds, but the association decreased from NFHS-3 (βHAZ: 0.145; 95% CI: 0.129, 0.16) to NFHS-4 (βHAZ: 0.102; 95%CI: 0.093, 0.11). Adult female equivalent milk intake (increase of 10gm/day) was associated with higher HAZ (β_NFHS-3=0.001;95% CI: 0, 0.002; β_NFHS-4=0.002;95% CI: 0.002, 0.003) but had no association with WAZ. The indirect association of wealth with HAZ through dairy consumption was 2-fold higher in NFHS-4 compared to NFHS-3.

Conclusions

The analysis of triangulated survey data shows that household level per- adult female equivalent dairy consumption positively modified the association between wealth index and HAZ, suggesting that regular inclusion of milk and milk products in the diets of children from households across all wealth quintiles could improve linear growth in this population.
DAIR in treating chronic PJI after total knee arthroplasty using continuous local antibiotic perfusion therapy: a case series study
Authors: Zenke Yukichi , Motojima Yasuhito , Ando Kohei , Kosugi Kenji , Hamada Daishi , Okada Yasuaki , Sato Naohito , Shinohara Daichi , Suzuki Hitoshi , Kawasaki Makoto , Sakai Akinori
Published: January 2024

Background

Antimicrobial agents are administered via intramedullary antibiotic perfusion (iMAP)/intrasoft tissue antibiotic perfusion (iSAP) to infected lesions to control osteoarticular and soft tissue infections. Continuous local antibiotic perfusion (CLAP) has been reported to be useful. This study aimed to investigate the outcomes of DAIR combined with CLAP for chronic PJI after total knee arthroplasty performed at our hospital.

Subjects and methods

Six patients (male; one case, female; five cases, mean age 79.5 years (70–94)) underwent CLAP for chronic PJI after TKA at our hospital between July 2020 and June 2022. They were followable for at least one year after surgery. Seven months (17–219), with a mean follow-up of 24.3 months (12–36). In addition to direct debridement and insert exchange, systemic antimicrobial treatment, and CLAP with gentamicin were performed using NPWT. We investigated the organisms causing the inflammation, the duration of iMAP/iSAP implantation, the maximum daily dose of GM, the maximum GM blood concentration, and the presence or absence of GM-induced adverse events.

Result

Two of six patients had a recurrence of infection at five weeks and five months after initial CLAP and required repeat CLAP treatment, but all patients could preserve their components. The organisms responsible for the flare-ups were MSSA in three cases: ESBL-producing E. coli, mixed MSSA and streptococcal infection, Klebsiella pneumonia in one case each, and unknown pathogens in one case. CLAP therapy for all patients was administered eight times in 6 cases: iMAP, mean: 10.0 days (5–16); iSAP, mean: 19.3 days (15–28); GM dose, mean: 162.5 mg/day (80–240); and GM blood concentration, mean: 1.4 µg/mL (0.2-5.0). Adverse events included one case of reversible acute kidney injury during CLAP in a patient with recurrent infection.

DAIR with CLAP for chronic post-TKA infection can be a useful treatment option to preserve components and allow the infection to subside, provided the implant is not markedly loosened.
The association between plain water intake and periodontitis in the population aged over 45: a cross-sectional study based on NHANES 2009–2014
Authors: Li Xianxian , Wang Lili , Yang Luming , Liu Xianghong , Liu Henglang , Mu Yandong
Published: January 2024

Background

Numerous studies have demonstrated the impact of beverage consumption on overall health and oral health. Specifically, high consumption of sugar-sweetened beverages and coffee has been associated with an increased risk of metabolic disorders and periodontitis. Conversely, high intake of plain water has been linked to various health benefits, including weight management and reduced energy intake. However, no previous studies have explored the potential association between plain water intake and the risk of periodontitis.

Objectives

Our objective was to investigate the relationship between plain water consumption and periodontitis in a middle-aged and elderly population.

Methods

The present cross-sectional study was conducted among participants aged ≥ 45 in the 2009–2014 National Health and Nutrition Examination Surveys. Multivariable regression analysis, subgroup analysis and smooth fitting tests were conducted to explore the independent relationship between plain water intake and periodontitis.

Results

A total of 5,882 participants were enrolled,62.02% have periodontitis. Periodontitis patients have lower plain water intake. The multivariable regression tests showed that the risk of periodontitis decreased with increased plain water intake quartiles (Q4 OR = 0.78; 95%CI 0.62–0.96) after fully adjustment. Subgroup analysis and interaction tests showed that gender, age, smoking, diabetes, hypertension or BMI does not significantly interact with the association. However, the relation was significant in males (Q4 OR = 0.64; 95%CI 0.47–0.86) but not in females (Q4 OR = 0.97;95% CI 0.71–1.31). In the smoothed curve fits stratified by gender, the curve for male participants displayed as a U-shape, with an optimal plain water intake at 1200 ml/day. For males drinking plain water less than 1200 ml/day, the risk of periodontitis decreased by 24% with each increase of 500 ml plain water intake (OR = 0.76, 95%CI 0.66–0.87, p < 0.001).

Conclusions

Together, the results showed that plain water intake is negatively associated with periodontitis risk in US middle aged and elderly population. Further studies are needed to investigate the mechanism unites this association. Attention should be given to adequate plain water intake when considering dietary suggestions to the population at high risk of developing periodontitis, especially for men.
Challenges of using evidence in managerial decision-making of the primary health care system
Authors: Hedayatipour Marjan , Etemadi Sina , Hekmat Somayeh Noori , Moosavi Alisadat
Published: January 2024

Background

Managerial Evidence-Based Decision-Making [EBDM] in the primary is a systematic approach that directs the decision-maker in a conscientious, explicit, and judicious utilization of reliable and best evidence based on the professional experiences and preferences of stakeholders and patients from various sources. This study aimed to investigate the challenges primary healthcare managers encounter while undertaking decision-making processes.

Method

A systematic review was conducted in 2022 with the aim of identifying and collecting all qualitative articles pertaining to evidence-based decision-making in the primary healthcare system. To achieve this, a meticulous search was conducted using the relevant keywords, including primary health care and evidence-based decision making, as well as their corresponding synonyms, across the databases Web of Science, Scopus, and Pubmed. Importantly, there were no limitations imposed on the timeframe for the search. To carefully analyze and consolidate the findings of this systematic review, the meta-synthesis approach was employed.

Results

A total of 22 articles were assessed in this systematic review study. The results revealed the main categories including evidence nature, EBDM barriers, utilizing evidence, decision-makers ability, organizational structure, evidence-based, EBDM support, communication for EBDM, evidence sides, EBDM skill development, public health promotion, and health system performance improvement.

Conclusion

The primary healthcare system is crucial in improving health outcomes and ensuring access to healthcare services for all individuals. This study explored the utilization of evidence-based EBDM within the primary healthcare system. We identified five key dimensions: causal, contextual, and intervening conditions, strategies, and consequences of EBDM as a core phenomenon. The findings will help policymakers and administrators comprehend the importance of evidence-based decision-making, ultimately leading to enhanced decision quality, community well-being, and efficiency within the healthcare system. EBDM entails considering the best reliable evidence, and incorporating community preferences while also exploiting the professional expertise and experiences of decision-makers. This systematic review has the potential to provide guidance for future reforms and enhance the quality of decision-making at the managerial level in primary healthcare.
RNA-seq reveals multifaceted gene expression response to Fab production in Escherichia coli fed-batch processes with particular focus on ribosome stalling
Authors: Vazulka Sophie , Schiavinato Matteo , Tauer Christopher , Wagenknecht Martin , Cserjan-Puschmann Monika , Striedner Gerald
Published: January 2024

Background

Escherichia coli is a cost-effective expression system for production of antibody fragments like Fabs. Various yield improvement strategies have been applied, however, Fabs remain challenging to produce. This study aimed to characterize the gene expression response of commonly used E. coli strains BL21(DE3) and HMS174(DE3) to periplasmic Fab expression using RNA sequencing (RNA-seq). Two Fabs, Fabx and FTN2, fused to a post-translational translocation signal sequence, were produced in carbon-limited fed-batch cultivations.

Results

Production of Fabx impeded cell growth substantially stronger than FTN2 and yields of both Fabs differed considerably. The most noticeable, common changes in Fab-producing cells suggested by our RNA-seq data concern the cell envelope. The Cpx and Psp stress responses, both connected to inner membrane integrity, were activated, presumably by recombinant protein aggregation and impairment of the Sec translocon. The data additionally suggest changes in lipopolysaccharide synthesis, adjustment of membrane permeability, and peptidoglycan maturation and remodeling. Moreover, all Fab-producing strains showed depletion of Mg2+, indicated by activation of the PhoQP two-component signal transduction system during the early stage and sulfur and phosphate starvation during the later stage of the process. Furthermore, our data revealed ribosome stalling, caused by the Fabx amino acid sequence, as a contributor to low Fabx yields. Increased Fabx yields were obtained by a site-specific amino acid exchange replacing the stalling sequence. Contrary to expectations, cell growth was not impacted by presence or removal of the stalling sequence. Considering ribosome rescue is a conserved mechanism, the substantial differences observed in gene expression between BL21(DE3) and HMS174(DE3) in response to ribosome stalling on the recombinant mRNA were surprising.

Conclusions

Through characterization of the gene expression response to Fab production under industrially relevant cultivation conditions, we identified potential cell engineering targets. Thereby, we hope to enable rational approaches to improve cell fitness and Fab yields. Furthermore, we highlight ribosome stalling caused by the amino acid sequence of the recombinant protein as a possible challenge during recombinant protein production.
Immunofluorescence study of cytoskeleton in endothelial cells induced with malaria sera
Authors: Wongsawat Mathusorn , Glaharn Supattra , Srisook Charit , Dechkhajorn Wilanee , Chaisri Urai , Punsawad Chuchard , Techarang Tachpon , Chotivanich Kesinee , Krudsood Srivicha , Viriyavejakul Parnpen
Published: January 2024

Background

Endothelial cells (ECs) play a major role in malaria pathogenesis, as a point of direct contact of parasitized red blood cells to the blood vessel wall. The study of cytoskeleton structures of ECs, whose main functions are to maintain shape and provide strength to the EC membrane is important in determining the severe sequelae of Plasmodium falciparum malaria. The work investigated the cytoskeletal changes (microfilaments-actin, microtubules-tubulin and intermediate filaments-vimentin) in ECs induced by malaria sera (Plasmodium vivax, uncomplicated P. falciparum and complicated P. falciparum), in relation to the levels of pro-inflammatory cytokines.

Methods

Morphology and fluorescence intensity of EC cytoskeleton stimulated with malaria sera were evaluated using immunofluorescence technique. Levels of tumour necrosis factor (TNF) and interferon (IFN)-gamma (γ) were determined using enzyme-linked immunosorbent assay (ELISA). Control experimental groups included ECs incubated with media alone and non-malaria patient sera. Experimental groups consisted of ECs incubated with malaria sera from P. vivax, uncomplicated P. falciparum and complicated P. falciparum. Morphological scores of cytoskeletal alterations and fluorescence intensity were compared across each experiment group, and correlated with TNF and IFN-γ.

Results

The four morphological changes of cytoskeleton included (1) shrinkage of cytoskeleton and ECs with cortical condensation, (2) appearance of eccentric nuclei, (3) presence of “spiking pattern” of cytoskeleton and EC membrane, and (4) fragmentation and discontinuity of cytoskeleton and ECs. Significant damages were noted in actin filaments compared to tubulin and vimentin filaments in ECs stimulated with sera from complicated P. falciparum malaria. Morphological damages to cytoskeleton was positively correlated with fluorescence intensity and the levels of TNF and IFN-γ.

Conclusions

ECs stimulated with sera from complicated P. falciparum malaria showed cytoskeletal alterations and increased in fluorescence intensity, which was associated with high levels of TNF and IFN-γ. Cytoskeletal changes of ECs incubated with complicated P. falciparum malaria sera can lead to EC junctional alteration and permeability changes, which is mediated through apoptotic pathway. The findings can serve as a basis to explore measures to strengthen EC cytoskeleton and alleviate severe malaria complications such as pulmonary oedema and cerebral malaria. In addition, immunofluorescence intensity of cytoskeleton could be investigated as potential prognostic indicator for malaria severity.
The 4th NextGen Therapies for SJIA and MAS: part 1 the elephant in the room: diagnostic/classification criteria for systemic juvenile idiopathic arthritis and adult-onset still’s disease
Authors: Nigrovic Peter A. , de Benedetti Fabrizio , Kimura Yukiko , Lovell Daniel J. , Vastert Sebastiaan J.
Published: January 2024

Currently, the criteria used to classify patients with SJIA are different from those used for AOSD. However, it has been recognized that the existing terms are too narrow, subdividing the Still’s population unnecessarily between pediatric-onset and adult-onset disease and excluding an appreciable group of children in whom overt arthritis is delayed or absent. Government regulators and insurers rely upon the guidance of subject experts to provide disease definitions, and when these definitions are flawed, to provide new and better ones. The classification session at the NextGen 2022 conference helped to serve this purpose, establishing the need for a revised definitional system that transcends the fault lines that remain in existing definitions.
Diagnostic value and role of serum miR-15a-5p in patients with schizophrenia
Authors: Xu Zhen , Yang Ruidong , Chen Guanwen , Jiang Mingjun
Published: January 2024

Background

More and more studies have confirmed that the heredity plays an important role in mental disorders, especially microRNA. The objective of this research was to explore the level of miR-15a-5p in patients with schizophrenia (SZ), and to evaluate the feasibility of this miRNA as a diagnostic marker of SZ.

Methods

The serum level of miR-15a-5p in patients with SZ and healthy people was detected by RT-qPCR. ROC curve was established to evaluate the clinical diagnostic significance of miR-15a-5p in SZ. Pearson correlation coefficient was used to evaluate the correlation between miR-15a-5p level and PANSS score. Logistic regression was used to assess the risk factors of SZ. A rat model of SZ was established, and the effects of miR-15a-5p on the behavior of SZ rats were observed through water maze test and open field test.

Results

The serum level of miR-15a-5p in patients with SZ was significantly increased, and ROC analysis revealed that miR-15a-5p had clinical diagnostic value in SZ. High level of miR-15a-5p was positively correlated with the positive symptom, negative symptom and general psychopathology subscore of patients. Logistic regression results showed that miR-15a-5p was a risk factor affecting the occurrence of SZ. Animal studies showed that the serum level of miR-15a-5p was elevated in the SZ rats, and inhibiting the expression of miR-15a-5p has a positive effect on improving the cognitive function and anxiety behavior of SZ rats.

Conclusions

Serum miR-15a-5p is a risk factor for SZ, which is of great significance for the diagnosis of SZ.
The positional consistency between guidewire and cannulated or solid screw in robot-assisted spinal internal fixation surgery
Authors: Zhao Jingwei , Zhang Yunxian , Fan Mingxing , Han Xiaoguang , Liu Bo , He Da , Tian Wei
Published: January 2024

Background

This study aimed to investigate the positional consistency between the guidewire and the screw in spinal internal fixation surgery.

Methods

This study involved 64 patients who underwent robot-assisted thoracic or lumbar pedicle screw fixation surgery. Guidewires were inserted with the assistance of the Tirobot. Either cannulated screws or solid screws were inserted. Guidewire and screw accuracy was measured using CT images based on the Gertzbein and Robbins scale. The positional consistency between guidewire and screw was evaluated based on the fused CT images, which could graphically and quantitatively demonstrate the consistency. The consistency was evaluated based on a grading system that considered the maximum distance and angulation between the centerline of the guidewire and the screw in the region of the pedicle.

Results

A total of 322 screws were placed including 206 cannulated ones and 116 solid ones. Based on the Gertzbein and Robbins scale, 97.5% of the guidewires were grade A, and 94.1% of the screws were grade A. Based on our guidewire-screw consistency scale, 85% in cannulated group, and 69.8% in solid group, were grade A. Both solid and cannulated screws may alter trajectory compared to the guidewires. The positional accuracy and guidewire-screw consistency in the solid screw group is significantly worse than that in the cannulated screw group. The cortical bone of the pedicle has a positive guide effect on either solid or cannulated screws.

Conclusion

The pedicle screws may alter trajectory despite the guidance of the guidewires. Solid screws show worse positional accuracy and guidewire-screw consistency compared with cannulated screws.

Trial registration The study was retrospectively registered and approved by our center’s institutional review board.
Use of health services and perceived need for information and follow-up after percutaneous coronary intervention
Authors: Hjertvikrem Nina , Brørs Gunhild , Instenes Irene , Helmark Charlotte , Pettersen Trond Røed , Rotevatn Svein , Zwisler Ann Dorthe O. , Norekvål Tone Merete ,   the CONCARDPCI Investigators
Published: January 2024

Objective

Few patients achieve full control of their coronary artery disease (CAD) risk factors. Follow-up, such as cardiac rehabilitation, is important to increase adherence to lifestyle changes and treatment, to improve the patient’s risk profile, and to treat established complications of CAD clinical events. However, the type of follow-up patients receive varies. Therefore, the aim of this research note was to describe and compare patients’ self-reported use of health services, the type of follow-up patients reported to prefer, and the type of information patients reported to be important, in two countries with different follow-up practices after PCI.

Results

We included 3417 patients in Norway and Denmark, countries with different follow-up strategies after PCI. The results showed large differences between the countries regarding health services used. In Denmark the most frequently used health services were consultations at outpatient clinics followed by visits to the general practitioner and visits to the fitness centre, whereas in Norway visits to the general practitioner were most common, followed by rehospitalisation and no follow-up used. However, patients found the same type of follow-up and information important in both countries. Patients’ perceived need for follow-up and information decreased over time, suggesting a need for early follow-up when the patients are motivated.

Trial registration: NCT03810612 (18/01/2019).
De novo KAT6B mutation causes Say–Barber–Biesecker–Young–Simpson variant of Ohdo syndrome in an Iranian boy: a case report
Authors: Davarnia Behzad , Panahi Mohammad , Rahimi Bahareh , Anari Hassan , Farajollahi Reza , Rodbaneh Ehsan Abbaspour , Jeddi Farhad
Published: January 2024

Background

Say–Barber–Biesecker–Young–Simpson (SBBYS) (OMIM #603736, Ohdo syndrome variant) is a rare type of severe blepharophimosis intellectual disability syndrome, which is generally characterized by a global developmental delay, distinctive facial features, and intellectual disability with multiple congenital anomalies, including skeletal involvement, missing, or underdeveloped kneecaps, and genital anomalies, in affected males. It has been shown that mutations in the KAT6B gene, which is a lysine acetyltransferase-encoding gene, have been associated with SBBYS syndrome. All the known variants are dominant de novo mutations that result in protein truncation.

Case presentation

A 14-year-old Iranian Azeri boy with an intellectual disability, distinct dysmorphic facial features such as open-mouth expression, sparse medial eyebrows, widely spaced upward-slanted eyes, epicanthal folds, broad nasal bridge, low-set ears, anteverted ears, short philtrum, hypertelorism, microphthalmia is presented in this case study. Cryptorchidism was reported. Neurologically, the patient presented with poor eye contact, hypotonia, and speech difficulties. In the skeletal X-ray, underdeveloped kneecaps with some new features were observed.

Conclusion

We present the first case of SBBYS syndrome in association with some new anomaly features in the Iranian population. Based on this diagnosis, we could provide the patient with a suitable plan of management as well as appropriate genetic counseling for his family.
DBPP-Predictor: a novel strategy for prediction of chemical drug-likeness based on property profiles
Authors: Gu Yaxin , Wang Yimeng , Zhu Keyun , Li Weihua , Liu Guixia , Tang Yun
Published: January 2024

Evaluation of chemical drug-likeness is essential for the discovery of high-quality drug candidates while avoiding unwarranted biological and clinical trial costs. A high-quality drug candidate should have promising drug-like properties, including pharmacological activity, suitable physicochemical and ADMET properties. Hence, in silico prediction of chemical drug-likeness has been proposed while being a challenging task. Although several prediction models have been developed to assess chemical drug-likeness, they have such drawbacks as sample dependence and poor interpretability. In this study, we developed a novel strategy, named DBPP-Predictor, to predict chemical drug-likeness based on property profile representation by integrating physicochemical and ADMET properties. The results demonstrated that DBPP-Predictor exhibited considerable generalization capability with AUC (area under the curve) values from 0.817 to 0.913 on external validation sets. In terms of application feasibility analysis, the results indicated that DBPP-Predictor not only demonstrated consistent and reasonable scoring performance on different data sets, but also was able to guide structural optimization. Moreover, it offered a new drug-likeness assessment perspective, without significant linear correlation with existing methods. We also developed a free standalone software for users to make drug-likeness prediction and property profile visualization for their compounds of interest. In summary, our DBPP-Predictor provided a valuable tool for the prediction of chemical drug-likeness, helping to identify appropriate drug candidates for further development.
Müller glial cells located in the peripheral retina are more susceptible to high pressure: implications for glaucoma
Authors: Pereiro Xandra , Ruzafa Noelia , Azkargorta Mikel , Elortza Félix , Acera Arantxa , Ambrósio António Francisco , Santiago Ana Raquel , Vecino Elena
Published: January 2024

Background

Glaucoma, a progressive neurodegenerative disease, is a leading cause of irreversible vision loss worldwide. This study aims to elucidate the critical role of Müller glia (MG) in the context of retinal ganglion cell (RGC) death, particularly focusing on the influence of peripheral MG sensitivity to high pressure (HP).

Methods

Co-cultures of porcine RGCs with MG were isolated from both the central and peripheral regions of pig retinas and subjected to both normal and HP conditions. Mass spectrometry analysis of the MG-conditioned medium was conducted to identify the proteins released by MG under all conditions.

Results

Peripheral MG were found to secrete a higher quantity of neuroprotective factors, effectively promoting RGC survival under normal physiological conditions. However, under HP conditions, co-cultures with peripheral MG exhibited impaired RGC survival. Moreover, under HP conditions, peripheral MG significantly upregulated the secretion of proteins associated with apoptosis, oxidative stress, and inflammation.

Conclusions

This study provides robust evidence suggesting the involvement of MG in RGC death in glaucoma, thus paving the way for future therapeutic investigations.
Activation of senescence in critically ill patients: mechanisms, consequences and therapeutic opportunities
Authors: Martín-Vicente Paula , López-Martínez Cecilia , Rioseras Beatriz , Albaiceta Guillermo M.
Published: January 2024

Whereas aging is a whole-organism process, senescence is a cell mechanism that can be triggered by several stimuli. There is increasing evidence that critical conditions activate cell senescence programs irrespective of patient’s age. In this review, we briefly describe the basic senescence pathways and the consequences of their activation in critically ill patients. The available evidence suggests a paradigm in which activation of senescence can be beneficial in the short term by rendering cells resistant to apoptosis, but also detrimental in a late phase by inducing a pro-inflammatory and pro-fibrotic state. Senescence can be a therapeutic target. The use of drugs that eliminate senescent cells (senolytics) or the senescence-associated phenotype (senomorphics) will require monitoring of these cell responses and identification of therapeutic windows to improve the outcome of critically ill patients.