bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of infections associated with the use of bispecific antibodies in multiple myeloma: a pooled analysis
Authors: Mazahreh Farah , Mazahreh Liyan , Schinke Carolina , Thanendrarajan Sharmilan , Zangari Maurizio , Shaughnessy John D. , Zhan Fenghuang , van Rhee Frits , Al Hadidi Samer
Published: March 2023

The use of bispecific antibodies (BsAbs) in the treatment of relapsed/refractory multiple myeloma (MM) is showing early promising overall response rates in heavily pretreated patients. Infectious complications related to the use of BsAbs are not well described. We conducted a pooled analysis that included all single-agent BsAbs used in MM with no prior use of different BsAbs. A total of 1185 patients with MM were treated with a BsAb in the studied period (71.6% of the patients treated with an agent targeting B-cell maturation antigen (BCMA). Pooled median follow-up was short at 6.1 months (7.5 vs 5.2 months for BCMA vs non-BCMA BsAbs, respectively). Adverse events of interest included all grade neutropenia in 38.6%, all grade infections in 50% (n = 542/1083), all grade cytokine release syndrome in 59.6% (n = 706/1185), grade III/IV neutropenia in 34.8% (n = 372/1068), grade III/IV infections in 24.5% (n = 272/1110), grade III/IV pneumonia in 10% (n = 52.4/506), and grade III/IV coronavirus disease 2019 in 11.4% (n = 45.4/395) of the patients. Non-BCMA–targeted BsAbs were associated with lower grade III/IV neutropenia (25.3% vs 39.2%) and lower grade III/IV infections (11.9% vs 30%) when compared with BCMA-targeted BsAbs. Hypogammaglobulinemia was reported in 4 studies, with a prevalence of 75.3% (n = 256/340) of the patients, with IV immunoglobulin used in 48% (n = 123/256) of them. Death was reported in 110 patients, of which 28 (25.5%) were reported to be secondary to infections. Certain precautions should be used when using BsAbs to mitigate the risk and/or identify and treat infections promptly.
Correlative analysis on InGaN/GaN nanowires: structural and optical properties of self-assembled short-period superlattices
Authors: Alonso-Orts Manuel , Hötzel Rudolfo , Grieb Tim , Auf der Maur Matthias , Ries Maximilian , Nippert Felix , März Benjamin , Müller-Caspary Knut , Wagner Markus R. , Rosenauer Andreas , Eickhoff Martin
Published: March 2023

The influence of self-assembled short-period superlattices (SPSLs) on the structural and optical properties of InGaN/GaN nanowires (NWs) grown by PAMBE on Si (111) was investigated by STEM, EDXS, µ-PL analysis and k·p simulations. STEM analysis on single NWs indicates that in most of the studied nanostructures, SPSLs self-assemble during growth. The SPSLs display short-range ordering of In-rich and In-poor InxGa1-xN regions with a period of 2–3 nm that are covered by a GaN shell and that transition to a more homogenous InxGa1-xN core. Polarization- and temperature-resolved PL analysis performed on the same NWs shows that they exhibit a strong parallel polarized red-yellow emission and a predominantly perpendicular polarized blue emission, which are ascribed to different In-rich regions in the nanostructures. The correlation between STEM, µ-PL and k·p simulations provides better understanding of the rich optical emission of complex III-N nanostructures and how they are impacted by structural properties, yielding the significant impact of strain on self-assembly and spectral emission.

Graphical abstract
Diagnosis and treatment approaches for simultaneous onset of subarachnoid hemorrhage and thyroid storm: a case report
Authors: Ohya Aimi , Ohtake Makoto , Kawamura Yusuke , Akimoto Taisuke , Iwashita Masayuki , Yamamoto Tetsuya , Takeuchi Ichiro
Published: March 2023

Background

Subarachnoid hemorrhage and thyroid storm are similar in their clinical symptomatology, and diagnosis of these conditions, when they occur simultaneously, is difficult. Here, we report a rare case of concurrent subarachnoid hemorrhage and thyroid storm we encountered at our hospital.

Case presentation

The patient was a 52-year-old woman. While bathing at home, the patient experienced a sudden disturbance of consciousness and was brought to our hospital. The main physical findings upon admittance were Glasgow Coma Scale score of E1V2M4, elevated blood pressure (208/145 mmHg), and tachycardia with atrial fibrillation (180 bpm) along with body temperature of 36.1 °C. Brain computed tomography revealed subarachnoid hemorrhage associated with a ruptured aneurysm of the posterior communicating artery branching from the left internal carotid artery, and aneurysm clipping was performed. Blood tests upon admission revealed high levels of free T3 and free T4 and low levels of thyroid-stimulating hormone. Upon determining that the patient had hyperthyroidism, thiamazole was administered. However, due to continuous impaired consciousness, fever, and persistence of tachycardia, the patient was diagnosed with thyroid storm. Oral potassium iodide and hydrocortisone were added to the treatment. The treatment was successful as the patient’s symptoms improved, and she became lucid.

In this case, we believe that in the presence of untreated hyperthyroidism, the onset of subarachnoid hemorrhage induced thyroid storm. Tachycardia of 130 bpm or higher, which is the diagnostic criterion for thyroid storm, rarely occurs with subarachnoid hemorrhage. Therefore, we believe it is an important factor for recognizing the presence of the thyroid storm. In this case, clipping surgery was prioritized which resulted in a favorable outcome. However, it is possible that invasive surgery may have exacerbated thyroid storm, suggesting that treatment should be tailored as per patient’s condition.

Conclusion

If a pulse rate of 130 bpm or higher is observed alongside subarachnoid hemorrhage, we recommend considering the possibility of concomitant thyroid storm and testing for thyroid hormone. If concomitant thyroid storm is present, we believe that a treatment plan tailored to the patient’s condition is critical, and early diagnosis will lead to a favorable outcome for the patient.
DeltaMSI: artificial intelligence-based modeling of microsatellite instability scoring on next-generation sequencing data
Authors: Swaerts Koen , Dedeurwaerdere Franceska , De Smet Dieter , De Jaeger Peter , Martens Geert A.
Published: March 2023

Background

DNA mismatch repair deficiency (dMMR) testing is crucial for detection of microsatellite unstable (MSI) tumors. MSI is detected by aberrant indel length distributions of microsatellite markers, either by visual inspection of PCR-fragment length profiles or by automated bioinformatic scoring on next-generation sequencing (NGS) data. The former is time-consuming and low-throughput while the latter typically relies on simplified binary scoring of a single parameter of the indel distribution. The purpose of this study was to use machine learning to process the full complexity of indel distributions and integrate it into a robust script for screening of dMMR on small gene panel-based NGS data of clinical tumor samples without paired normal tissue.

Methods

Scikit-learn was used to train 7 models on normalized read depth data of 36 microsatellite loci in a cohort of 133 MMR proficient (pMMR) and 46 dMMR tumor samples, taking loss of MLH1/MSH2/PMS2/MSH6 protein expression as reference method. After selection of the optimal model and microsatellite panel the two top-performing models per locus (logistic regression and support vector machine) were integrated into a novel script (DeltaMSI) for combined prediction of MSI status on 28 marker loci at sample level. Diagnostic performance of DeltaMSI was compared to that of mSINGS, a widely used script for MSI detection on unpaired tumor samples. The robustness of DeltaMSI was evaluated on 1072 unselected, consecutive solid tumor samples in a real-world setting sequenced using capture chemistry, and 116 solid tumor samples sequenced by amplicon chemistry. Likelihood ratios were used to select result intervals with clinical validity.

Results

DeltaMSI achieved higher robustness at equal diagnostic power (AUC = 0.950; 95% CI 0.910–0.975) as compared to mSINGS (AUC = 0.876; 95% CI 0.823–0.918). Its sensitivity of 90% at 100% specificity indicated its clinical potential for high-throughput MSI screening in all tumor types.

Clinical Trial Number/IRBB1172020000040, Ethical Committee, AZ Delta General Hospital.
Amino acid substitutions in specific proteins correlate with farnesol unresponsiveness in Candida albicans
Authors: Mohammadi Sima , Leduc Annie , Charette Steve J. , Barbeau Jean , Vincent Antony T.
Published: March 2023

Background

The quorum-sensing molecule farnesol, in opportunistic yeast Candida albicans, modulates its dimorphic switch between yeast and hyphal forms, and biofilm formation. Although there is an increasing interest in farnesol as a potential antifungal drug, the molecular mechanism by which C. albicans responds to this molecule is still not fully understood.

Results

A comparative genomic analysis between C. albicans strains that are naturally unresponsive to 30 µM of farnesol on TYE plates at 37 °C versus responsive strains uncovered new molecular determinants involved in the response to farnesol. While no signature gene was identified, amino acid changes in specific proteins were shown to correlate with the unresponsiveness to farnesol, particularly with substitutions in proteins known to be involved in the farnesol response. Although amino acid changes occur primarily in disordered regions of proteins, some amino acid changes were also found in known domains. Finally, the genomic investigation of intermediate-response strains showed that the non-response to farnesol occurs gradually following the successive accumulation of amino acid changes at specific positions.

Conclusion

It is known that large genomic changes, such as recombinations and gene flow (losses and gains), can cause major phenotypic changes in pathogens. However, it is still not well known or documented how more subtle changes, such as amino acid substitutions, play a role in the adaptation of pathogens. The present study shows that amino acid changes can modulate C. albicans yeast’s response to farnesol. This study also improves our understanding of the network of proteins involved in the response to farnesol, and of the involvement of amino acid substitutions in cellular behavior.
Transcriptome sequencing leads to an improved understanding of the infection mechanism of Alternaria solani in potato
Authors: Jiang Jia , Guo Xuhao , Tan Huanhuan , Ding Mingya , Liu Fangming , Yang Zhihui , Zhu Jiehua
Published: March 2023

Background

Alternaria solani (A. solani), the main pathogen of potato early blight, causes serious yield reductions every year. The application of fungicides is the most common and effective method of controlling Alternaria-caused diseases. The differentially expressed transcripts of A. solani infecting potato were identified, revealing a group of valuable candidate genes for a systematic analysis to increase the understanding of the molecular pathogenesis of A. solani, and providing scientific data for formulating additional measures to prevent and control potato early blight. In this study, a deep RNA-sequencing approach was applied to gain insights into A. solani pathogenesis. At 3, 4, and 5 days post inoculation (dpi), RNA samples from the susceptible potato cultivar Favorita infected with A. solani strain HWC-168, were sequenced and utilized for transcriptome analysis, and compared to the transcriptome obtained 0 dpi.

Results

A total of 4430 (2167 upregulated, 2263 downregulated), 4736 (2312 upregulated, 2424 downregulated), and 5043 (2411 upregulated, 2632 downregulated) genes were differentially expressed 3, 4 and 5 dpi, respectively, compared with genes analysed at 0 dpi. KEGG enrichment analysis showed that genes involved in the pathways of amino acid metabolism, glucose metabolism, and enzyme activity were significantly differentially expressed at the late infection stage. Correspondingly, symptoms developed rapidly during the late stage of A. solani infection. In addition, a short time-series expression miner (STEM) assay was performed to analyse the gene expression patterns of A. solani and Profile 17 and 19 showed significant change trends 3, 4 and 5 dpi. Both profiles, but especially Profile 17, included enzymes, including transferases, oxidoreductases, hydrolases and carbohydrate-active enzymes (CAZYmes), which may play important roles in late fungal infection. Furthermore, possible candidate effectors were identified through the adopted pipelines, with 137 differentially expressed small secreted proteins identified, including some enzymes and proteins with unknown functions.

Conclusions

Collectively, the data presented in this study show that amino acid metabolism, and glucose metabolism pathways, and specific pathway-related enzymes may be key putative pathogenic factors, and play important roles in late stage A. solani infection. These results contribute to a broader base of knowledge of A. solani pathogenesis in potato, as indicated by the transcriptional level analysis, and provide clues for determining the effectors of A. solani infection.
Analyzing the queuing theory at the emergency department at King Hussein cancer center
Authors: Qandeel Mahmoud Salameh , Al-Qudah Islam Khaleel , Nayfeh Riyad , Aryan Haitham , Ajaj Omar , Alkhatib Hisham , Hamdan Yousef
Published: March 2023

Objectives

This study was conducted in 2022 at King Hussein Cancer Center (KHCC) to analyze the queuing theory approach at the Emergency Department (ED) to estimate patients’ wait times and predict the accuracy of the queuing theory approach.

Methods

According to the statistics, the peak months were July and August, with peak hours from 10 a.m. until 6 p.m. The study sample was a week in July 2022, during the peak days and hours. This study measured patients’ wait times at these three stations: the health informatics desk, triage room, and emergency bed area.

Results

The average number of patients in line at the health informatics desk was not more than 3, and the waiting time was between 1 and 4 min. Since patients were receiving the service immediately in the triage room, there was no waiting time or line because the nurse’s role ended after taking the vital signs and rating the patient’s disease acuity. Using equations of queuing theory and other relativistic equations in the emergency bed area gave different results. The queuing theory approach showed that the average residence time in the system was between 4 and 10 min.

Conclusions

Conversely, relativistic equations (ratios of served patients and departed patients and other related variables) demonstrated that the average residence time was between 21 and 36 min.
Associations between parenthood and dementia in men and women: biology or confounding?
Authors: Basit Saima , Wohlfahrt Jan , Boyd Heather A.
Published: March 2023

Background

High parity and extremes of age at first birth have been linked with increased dementia risk in women, with exposure to pregnancy-associated physiological changes proposed as an explanation. However, confounding by socioeconomic and lifestyle factors could also produce such associations, whereby men would share similar patterns of association. We investigated whether these associations hold for both sexes.

Methods

In a cohort study including all women (N = 2,222,638) and men (N = 2,141,002) ≥ 40 years of age in 1994–2017 in Denmark, we used Cox regression to evaluate associations between number of children, age at first birth, and dementia risk separately for women and men.

Results

During follow-up, 81,413 women and 53,568 men (median age at diagnosis, 83.3 and 80.3 years, respectively) developed dementia. Compared with having one child, having two or more children was associated with modest decreases in overall dementia risk in both sexes (hazard ratio [HR] range 0.82–0.91, Pdifference men vs. women = 0.07). Although the associations between childlessness and overall dementia risk differed statistically for men and women, the association magnitudes differed only slightly (HRmen 1.04, 95% confidence interval [CI] 1.01–1.06; HRwomen 0.99, 95% CI 0.97–1.01; P = 0.002). Associations between age at becoming a parent and overall dementia were also similar for women and men, with the exception of older (≥ 40 years) first-time parents (HRmen 1.00, 95% CI 0.96–1.05; HRwomen 0.92, 95% CI 0.86–0.98; P = 0.01). With few exceptions, sub-analyses by dementia subtype and timing of onset also revealed similar patterns and effect magnitudes for women and men.

Conclusions

Associations between number of children, age at becoming a parent, and dementia risk were similar for both sexes. Lifestyle and socioeconomic factors are more likely to explain the observed associations than normal pregnancy-related physiological changes.
The obstetric and gynecological service providers’ and recipients’ perception and experience of the quality of obstetric triage services during the COVID-19 pandemic in Iran
Authors: Yazdimoghaddam Hamideh , Sadrzadeh Sayyed Majid , Karimi Fatemeh Zahra
Published: March 2023

Background

Enhancing the quality of obstetric triage services requires a clear perception of the current situations and problems, this issue gained more importance during the COVID-19 pandemic. The purpose of this study was to explore the obstetric and gynecological service providers’ and recipients’ perception and experience of the quality of obstetric triage services during the COVID-19 pandemic.

Methods

This research was a qualitative study carried out using conventional content analysis. Participants were selected through purposive sampling, and data collection was conducted using in-depth semi-structured interviews. Data were analyzed using MAXQDA software and conventional content analysis. Validity of the data was approved based on four criteria: credibility, dependability, conformability and transferability.

Results

Five themes emerged through analysis: “unpreparedness to deal with the COVID-19 resulting in disorganized triage”, “threat to the physical and mental health of personnel during the COVID-19 pandemic”, “degradation of the quality of services due to improper triage structure during the COVID-19 pandemic”, “communicating with patients which is neglected during the COVID-19 pandemic” and finally “accountability required to improve the provision of services during the COVID-19 pandemic.

Conclusion

Obstetrics and gynecology service providers and recipients faced formidable challenges in the triage department during this pandemic caused by the complex and ambiguous nature of the Coronavirus. Identifying the problems, barriers and challenges in providing services to patients in this situation especially in triage, can lead to an improvement in the outcome of services.
A study on the quality evaluation index system of smart home care for older adults in the community ——based on Delphi and AHP
Authors: Chen Huaxiao , Zhang Yuwei , Wang Li
Published: March 2023

Background

In the context of the “silver wave” and “technology wave”, smart home care for older adults in the community provide new ways for China and other countries to support ageing in place. Yet, only very few studies have focused on developing a quality index system of smart care. This study attempted to draw on the SERVQUAL model to establish a quality evaluation index system for smart senior care for older adults in the community.

Methods

On the basis of the service quality model, this paper has integrated qualitative and quantitative analyses using the Delphi and Analytic Hierarchy Process (AHP) methods to construct the index system of smart home care in the community and obtain the weights. These were based on literature research and field interviews in Guangzhou and Shenzhen pilot districts.

Results

A quality evaluation indexes system of smart home care for older adults in the community was developed, with 5 primary indices and 33 secondary indices. The weights of the 5 stair indices from high to low were smart emergency assistance 0.332, smart meal assistance 0.272, smart medical assistance 0.229, smart cleaning assistance 0.110 and smart amusement assistance 0.057.

Conclusion

The results from the weight allocation revealed smart emergency assistance, smart meal assistance, and smart medical care assistance were the most important and crucial aspects of community-based smart home care. The study also suggested that “timeliness”, “reliability”, and “ease of use” should be given more attention. It is recommended to use this index system as a regulatory benchmark to guide the government bodies, senior care enterprises and communities to take measures to enhance the quality.
Personalized hypertension treatment recommendations by a data-driven model
Authors: Hu Yang , Huerta Jasmine , Cordella Nicholas , Mishuris Rebecca G. , Paschalidis Ioannis Ch.
Published: March 2023

Background

Hypertension is a prevalent cardiovascular disease with severe longer-term implications. Conventional management based on clinical guidelines does not facilitate personalized treatment that accounts for a richer set of patient characteristics.

Methods

Records from 1/1/2012 to 1/1/2020 at the Boston Medical Center were used, selecting patients with either a hypertension diagnosis or meeting diagnostic criteria (≥ 130 mmHg systolic or ≥ 90 mmHg diastolic, n = 42,752). Models were developed to recommend a class of antihypertensive medications for each patient based on their characteristics. Regression immunized against outliers was combined with a nearest neighbor approach to associate with each patient an affinity group of other patients. This group was then used to make predictions of future Systolic Blood Pressure (SBP) under each prescription type. For each patient, we leveraged these predictions to select the class of medication that minimized their future predicted SBP.

Results

The proposed model, built with a distributionally robust learning procedure, leads to a reduction of 14.28 mmHg in SBP, on average. This reduction is 70.30% larger than the reduction achieved by the standard-of-care and 7.08% better than the corresponding reduction achieved by the 2nd best model which uses ordinary least squares regression. All derived models outperform following the previous prescription or the current ground truth prescription in the record. We randomly sampled and manually reviewed 350 patient records; 87.71% of these model-generated prescription recommendations passed a sanity check by clinicians.

Conclusion

Our data-driven approach for personalized hypertension treatment yielded significant improvement compared to the standard-of-care. The model implied potential benefits of computationally deprescribing and can support situations with clinical equipoise.
Nurses’ perceptions of critically ill patients’ eye care: a qualitative study in Iran
Authors: Mahani Maryam Askaryzadeh , Farokhzadian Jamileh , Bahramnezhad Fatemeh , Nematollahi Monirsadat
Published: March 2023

Background

Despite the high prevalence of ocular complications in patients admitted to the intensive care unit (ICU), eye care, as an important component of the care plan, has not received much attention from nurses. To improve the quality of eye care, the challenges and concerns of ICU nurses should be studied deeply. Thus, the present study aimed at exploring the challenges faced by ICU nurses in taking care of patients admitted to the ICU.

Methods

The present conventional qualitative content analysis study was carried out on 11 nurses and 3 head nurses selected purposefully by observing the maximum variation. The data were collected through face-to-face, in-depth, and semi-structured interviews. All data were recorded, transcribed, and analyzed using the conventional content analysis method proposed by Graneheim and Lundman (Nurse Educ Today 24:105–12, 2004). The Max Q Data software 2020 was run to record the interviews and extract codes from the transcriptions.

Results

The participants’ mean age was 37.14 ± 6.41 years and their average work experience in ICU was 10.29 ± 7.63 years. The core category that emerged from data analysis was “the lack of an evidence-based approach”, which was subdivided into five categories: “education, the missing link”, “nurses’ inadequate professional competence”, “unsafe nursing care”, “organizational requirements”, and “difficulty in eye care evaluation”.

Conclusion

Evidence-based practice plays a minor role in the field of eye care in Iran, despite its critical importance. Thus, the Ministry of Health and Medical Education of Iran is recommended to adapt the clinical guidelines so that more attention is paid to this field.
Exploring staff perspectives on caring for isolated hospitalised patients during the COVID-19 pandemic: a qualitative study
Authors: Digby Robin , Hopper Ingrid , Hughes Leanne , McCaskie Doug , Tuck Michelle , Fallon Kethly , Hunter Peter , Bucknall Tracey
Published: March 2023

Background

Strict isolation of COVID-19 patients to prevent cross infection may inadvertently cause serious adverse outcomes including psychological harm, limitations to care, increased incidence of delirium, deconditioning and reduced quality of life. Previous research exploring the staff perspective of the effect of isolation on patients is limited. The aim of this study is to understand staff perceptions and interpretations of their experiences of the care and treatment of isolated patients and the impact of isolation on patients, families, and staff.

Method

This qualitative, exploratory study is set in a major metropolitan, quaternary hospital in Melbourne, Australia. Data was collected in focus groups with clinical and non-clinical staff and analysed using content analysis. The hospital ethics committee granted approval. Each participant gave informed verbal consent.

Results

Participants included 58 nursing, medical, allied health, and non-clinical staff. Six main themes were identified: 1) Communication challenges during COVID-19; 2) Impact of isolation on family; 3) Challenges to patients’ health and safety; 4) Impact on staff; 5) Challenging standards of care; 6) Contextual influences: policy, decision-makers and the environment.

Conclusion

Isolating patients and restricting visitors resulted in good pandemic management, but staff perceived it came at considerable cost to staff and consumers. Innovative communication technology may facilitate improved connection between all parties. Mental health support is needed for patients, families, and staff. Further research using a co-design model with input from patients, families and staff is recommended to determine appropriate interventions to improve care.

Preventing the spread of infection is essential for good pandemic management, but the cost to consumers and staff must be mitigated. Preparation for future pandemics must consider workforce preparedness, adapted models of care and workflow.
Exhaled biomarkers in adults with non-productive cough
Authors: Emilsson Össur Ingi , Kokelj Spela , Östling Jörgen , Olin Anna-Carin
Published: March 2023

Background

Chronic cough is a common condition but disease mechanisms are not fully understood. Our aim was to study respiratory biomarkers from the small airways in individuals with non-productive cough.

Methods

A cohort of 107 participants answered detailed questionnaires, performed spirometry, exhaled NO measurement, impulse oscillometry, gave blood samples and particles in exhaled air (PEx) samples. Current smokers (N = 38) were excluded. A total of 14 participants reported non-productive cough (cases). A total of 55 participants reported no cough (control group). PEx samples, containing exhaled particles derived from small airways, were collected and analysed with the SOMAscan proteomics platform.

Results

Participants with non-productive cough had similar age, sex, BMI, and inflammation markers in blood tests, as participants without cough. The proteomics analysis found 75 proteins significantly altered among participants with chronic cough compared to controls, after adjusting for sex and investigator performing the PExA measurement (all with p-value < 0.05 and q-value ≤ 0.13, thereof 21 proteins with a q-value < 0.05). These proteins were mostly involved in immune and inflammatory responses, complement and coagulation system, but also tight junction proteins and proteins involved in neuroinflammatory responses.

Conclusions

This exploratory study on proteomics of exhaled particles among individuals with chronic cough found alterations in relative abundance of 75 proteins. The proteins identified are implicated in both pathways known to be implicated in cough, but also potentially new pathways. Further studies are needed to explore the importance of these findings.
Prediabetes and all-cause mortality in young patients undergoing coronary artery angiography: a multicenter cohort study in China
Authors: He Yibo , Lu Hongyu , Ling Yihang , Liu Jin , Yu Sijia , Zhou Ziyou , Chang Tian , Liu Yong , Chen Shiqun , Chen Jiyan
Published: March 2023

Background

The prevalence of prediabetes is increasing in young adults and patients undergoing coronary angiography. However, whether prediabetes is a considerable risk factor for all-cause mortality remains undetermined in young patients undergoing coronary angiography.

Methods

In this study, we retrospectively included 8868 young patients (men aged < 45 years, women aged < 55 years) who underwent coronary angiography (CAG). Patients were categorized as normoglycemic, prediabetes and diabetes according to the HbA1c level or documented history of diabetes. The association of all-cause mortality with diabetes and prediabetes was detected by Cox proportional hazards regression analysis.

Results

A total of 3240 (36.5%) among 8868 young patients receiving CAG were prediabetes and 2218 (25.0%) were diabetes. 728 patients died during a median follow-up of 4.92 years. Compared to the normoglycemic group, prediabetes increased the risk of all-cause mortality in young CAG patients by 24%(adjusted HR: 1.24, 95% CI: 1.04–1.49, p = 0.019) and diabetes increased the risk of all-cause mortality by 46%(adjusted HR:1.46, 95% CI:1.2–1.79, p < 0.001). Subgroup analysis showed that diabetes and prediabetes increased the risk of death mainly in patients without comorbidities.

Conclusion

Prediabetes accounts for more than one-third of the young adults undergoing CAG and was associated with an increased risk of all-cause mortality, active prevention strategy should be considered for these patients.
Curcumin: a natural organic component that plays a multi-faceted role in ovarian cancer
Authors: Liu Xiaoping , Qi Mingming , Li Xidie , Wang Jingjin , Wang Mingyuan
Published: March 2023

Curcumin, a natural organic component obtained from Curcuma longa’s rhizomes, shows abundant anti-tumor, antioxidant and anti-inflammatory pharmacological activities, among others. Notably the anti-tumor activity has aroused widespread attention from scholars worldwide. Numerous studies have reported that curcumin can delay ovarian cancer (OC), increase its sensitivity to chemotherapy, and reduce chemotherapy drugs’ side effects. It has been shown considerable anticancer potential by promoting cell apoptosis, suppressing cell cycle progression, inducing autophagy, inhibiting tumor metastasis, and regulating enzyme activity. With an in-depth study of curcumin’s anti-OC mechanism, its clinical application will have broader prospects. This review summarizes the latest studies on curcumin’s anti-OC activities, and discusses the specific mechanism, hoping to provide references for further research and applications.
The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition
Authors: Rossaint Rolf , Afshari Arash , Bouillon Bertil , Cerny Vladimir , Cimpoesu Diana , Curry Nicola , Duranteau Jacques , Filipescu Daniela , Grottke Oliver , Grønlykke Lars , Harrois Anatole , Hunt Beverley J. , Kaserer Alexander , Komadina Radko , Madsen Mikkel Herold , Maegele Marc , Mora Lidia , Riddez Louis , Romero Carolina S. , Samama Charles-Marc , Vincent Jean-Louis , Wiberg Sebastian , Spahn Donat R.
Published: March 2023

Background

Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management.

Methods

The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma included representatives from six European professional societies and convened to assess and update the previous version of this guideline using a structured, evidence-based consensus approach. Structured literature searches covered the period since the last edition of the guideline, but considered evidence cited previously. The format of this edition has been adjusted to reflect the trend towards concise guideline documents that cite only the highest-quality studies and most relevant literature rather than attempting to provide a comprehensive literature review to accompany each recommendation.

Results

This guideline comprises 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points. While approximately one-third of patients who have experienced severe trauma arrive in hospital in a coagulopathic state, a systematic diagnostic and therapeutic approach has been shown to reduce the number of preventable deaths attributable to traumatic injury.

Conclusion

A multidisciplinary approach and adherence to evidence-based guidelines are pillars of best practice in the management of severely injured trauma patients. Further improvement in outcomes will be achieved by optimising and standardising trauma care in line with the available evidence across Europe and beyond.
Heme biosensor-guided in vivo pathway optimization and directed evolution for efficient biosynthesis of heme
Authors: Zhang Jian , Li Qingbin , Wang Qi , Zhao Jingyu , Zhu Yuan , Su Tianyuan , Qi Qingsheng , Wang Qian
Published: March 2023

Background

Heme has attracted much attention because of its wide applications in medicine and food. The products of genes hemBCDEFY convert 5-aminolevulinic acid to protoporphyrin IX (PPIX; the immediate precursor of heme); protoporphyrin ferrochelatase (FECH) inserts Fe2+ into PPIX to generate heme. Biosynthesis of heme is limited by the need for optimized expression levels of multiple genes, complex regulatory mechanisms, and low enzymatic activity; these problems need to be overcome in metabolic engineering to improve heme synthesis.

Results

We report a heme biosensor-guided screening strategy using the heme-responsive protein HrtR to regulate tcR expression in Escherichia coli, providing a quantifiable link between the intracellular heme concentration and cell survival in selective conditions (i.e., the presence of tetracycline). This system was used for rapid enrichment screening of heme-producing strains from a library with random ribosome binding site (RBS) variants and from a FECH mutant library. Through up to four rounds of iterative evolution, strains with optimal RBS intensities for the combination of hemBCDEFY were screened; we obtained a PPIX titer of 160.8 mg/L, the highest yield yet reported in shaken-flask fermentation. A high-activity FECH variant was obtained from the saturation mutagenesis library. Fed-batch fermentation of strain SH20C, harboring the optimized hemBCDEFY and the FECH mutant, produced 127.6 mg/L of heme.

Conclusion

We sequentially improved the multigene biosynthesis pathway of PPIX and performed in vivo directed evolution of FECH, based on a heme biosensor, which demonstrated the effectiveness of the heme biosensor-based pathway optimization strategy and broadens our understanding of the mechanism of heme synthesis.
EBS-seq: enrichment-based method for accurate analysis of 5-hydroxymethylcytosine at single-base resolution
Authors: Lee Jaywon , Lee Dongin , Kim Hwang-Phill , Kim Tae-You , Bang Duhee
Published: March 2023

Background

A growing body of research has emphasized 5-hydroxymethylcytosine (5hmC) as an important epigenetic mark. High-resolution methods to detect 5hmC require high sequencing depth and are therefore expensive. Many studies have used enrichment-based methods to detect 5hmC; however, conventional enrichment-based methods have limited resolution. To overcome these limitations, we developed EBS-seq, a cost-efficient method for 5hmC detection with single-base resolution that combines the advantages of high-resolution methods and enrichment-based methods.

Results

EBS-seq uses selective labeling of 5hmC, deamination of cytosine and 5-methylcytosine, pull-down of labeled 5hmC, and C-to-T conversion during DNA amplification. Using this method, we profiled 5hmC in HEK293T cells and two colorectal cancer samples. Compared with conventional enrichment-based 5hmC detection, EBS-seq improved 5hmC signals by localizing them at single-base resolution. Furthermore, EBS-seq was able to determine 5hmC levels in CpG-dense regions where distortion of signals can occur, such as CpG islands and CpG shores. Comparing EBS-seq and conventional high-resolution 5hmC detection by ACE-seq, we showed that EBS-seq is more effective at finding 5hmC sites. Using EBS-seq, we found strong associations between gene expression and gene-body 5hmC content in both HEK293T cells and colorectal cancer samples.

Conclusions

EBS-seq is a reliable and cost-efficient method for 5hmC detection because it simultaneously enriches 5hmC-containing DNA fragments and localizes 5hmC signals at single-base resolution. This method is a promising choice for 5hmC detection in challenging clinical samples with low 5hmC levels, such as cancer tissues.
Long-term follow-up of Mycoplasma hyopneumoniae-specific immunity in vaccinated pigs
Authors: Biebaut Evelien , Beuckelaere Lisa , Boyen Filip , Haesebrouck Freddy , Gomez-Duran Charles-Oliver , Devriendt Bert , Maes Dominiek
Published: March 2023

Mycoplasma hyopneumoniaeis the primary agent of enzootic pneumonia in pigs. To minimize the economic losses caused by this disease,M. hyopneumoniaevaccination is commonly practiced. However, the persistence ofM. hyopneumoniaevaccine-induced immunity, especially the cell-mediated immunity, till the moment of slaughter has not been investigated yet. Therefore, on two commercial farms, 25 pigs (n = 50) received a commercial bacterin intramuscularly at 16 days of age. Each month, the presence ofM. hyopneumoniae-specific serum antibodies was analyzed and the proliferation of and TNF-α, IFN-γ and IL-17A production by different T cell subsets in blood was assessed using recall assays. Natural infection withM. hyopneumoniaewas assumed in both farms. However, the studied pigs remainedM. hyopneumoniaenegative for almost the entire trial. Seroconversion was not observed after vaccination and all pigs became seronegative at two months of age. The kinetics of the T cell subset frequencies was similar on both farms.Mycoplasma hyopneumoniae-specific cytokine-producing CD4+CD8+T cells were found in blood of pigs from both farms at one month of age but decreased significantly with increasing age. On the other hand, T cell proliferation after in vitroM. hyopneumoniaestimulation was observed until the end of the fattening period. Furthermore, differences in humoral and cell-mediated immune responses afterM. hyopneumoniaevaccination were not seen between pigs with and without maternally derived antibodies. This study documents the long-termM. hyopneumoniaevaccine-induced immune responses in fattening pigs under field conditions. Further research is warranted to investigate the influence of a natural infection on these responses.
RETRACTED ARTICLE: Loan repayment performance and its determinants: evidence from micro and small enterprises operating in Dire-Dawa, Ethiopia
Authors: Kiros Yitbarek
Published: March 2023

Microfinance Institutions (MFIs) reach a large number of poor people who are not served by formal financial institutions and have been a prime element in the economic growth of countries like Ethiopia. To operate successfully MFIs have to make sure that the loan disbursed has to be repaid to have a sustainable and viable financial operation and contribute their own its share in reducing unemployment and poverty reduction. In light of this, this research study was conducted to investigate the factors affecting loan repayment performance and factors affecting it in Micro and Small Enterprises (MSEs) financed by Microfinance Institutions by taking lender characteristics. Primary data was collected using questionnaires and interviews. A total of 175 Micro and Small Enterprises were selected using purposive sampling. Secondary data was acquired from annual reports and financial statements of Microfinance institutions and other institutions. Descriptive analysis as well as econometric analysis was used to analyze the effect of the literature-driven variables on the loan repayment performance of borrowers. The binary logistic regression result revealed that loan repayment period, grace period, and timeliness of loan release have a statistically significant effect on the loan repayment performances of borrowers. Loan size has a statistically insignificant effect on the loan repayment performance of borrowers.
Standardization of Rehmannia glutinosa (Gaertn.) DC. steam processing and evaluation of its chemical, anti-oxidant, and anti-inflammatory properties
Authors: Chung Yuseong , Rahmat Endang , Nam Hyeon Hwa , Lee Ayeong , Park Jun Hong , Moon Byeong Cheol , Kang Youngmin
Published: March 2023

Rehmannia glutinosa (Gaertn.) DC., belonging to the family Scrophulariaceae, is an important medicinal herb cultivated in East Asia. Traditionally, R. glutinosa is steam processed to increase its efficacy in treating various ailments such as diabetes, hematinic deficiencies and adrenal disorder. However, standardization of processed R. glutinosa is highly needed to increase its quality to fulfill global market demand that is safe and possess high level of efficacy. Therefore, this study aimed to optimize the R. glutinosa steam processing methods by evaluating some key parameters such as steaming temperature, number of steaming times, steaming duration, and additive supplementation. R. glutinosa samples were steam processed at different temperatures (100 °C, 110 °C, and 120 °C), various steaming times (1 to 5 times), several steaming duration (1 to 4 h), and additives supplementation (rice wine, 5% EtOH, 10% EtOH, 20% EtOH, 30% EtOH, and 40% EtOH). As the result, 2 h, 3 replications, and supplementation with 20% EtOH at 120 °C were identified as the optimal conditions for R. glutinosa steam processing. Optimized processed R. glutinosa (SPRR 20%EtOH) resulted in significantly higher content of 5-HMF (7648.60 ± 150.08 µg/g) and iso-verbacoside (203.80 ± 10.72 µg/g) compared with unprocessed R. glutinosa (UPR). Compared to those of other samples, SPRR 20% EtOH samples had higher total flavonoid (55.36 ± 1.68 mg/g) and phenolic (69.24 ± 4.56 mg/g) contents and stronger DPPH antioxidant activity (56%). Furthermore, SPRR 20% EtOH had excellent anti-inflammatory activity, as evidenced by the suppression of inducible nitric oxide synthase (iNOS) caused by activation of nuclear factor-κB (NF-κB) through p-p65 pathway in LPS-stimulated RAW 264.7 cells. These findings will provide a basis towards industrialization of R. glutinosa processing technology that will be very helpful for oriental medication field.
When complex movement yields simple dispersal: behavioural heterogeneity, spatial spread and parasitism in groups of micro-wasps
Authors: Burte Victor , Cointe Melina , Perez Guy , Mailleret Ludovic , Calcagno Vincent
Published: March 2023

Background

Understanding how behavioural dynamics, inter-individual variability and individual interactions scale-up to shape the spatial spread and dispersal of animal populations is a major challenge in ecology. For biocontrol agents, such as the microscopic Trichogramma parasitic wasps, an understanding of movement strategies is also critical to predict pest-suppression performance in the field.

Methods

We experimentally studied the spatial propagation of groups of parasitoids and their patterns of parasitism. We investigated whether population spread is density-dependent, how it is affected by the presence of hosts, and whether the spatial distribution of parasitism (dispersal kernel) can be predicted from the observed spread of individuals. Using a novel experimental device and high-throughput imaging techniques, we continuously tracked the spatial spread of groups of parasitoids over large temporal and spatial scales (8 h; and 6 m, ca. 12,000 body lengths). We could thus study how population density, the presence of hosts and their spatial distribution impacted the rate of population spread, the spatial distribution of individuals during population expansion, the overall rate of parasitism and the dispersal kernel (position of parasitism events).

Results

Higher population density accelerated population spread, but only transiently: the rate of spread reverted to low values after 4 h, in a “tortoise-hare” effect. Interestingly, the presence of hosts suppressed this transiency and permitted a sustained high rate of population spread. Importantly, we found that population spread did not obey classical diffusion, but involved dynamical switches between resident and explorer movement modes. Population distribution was therefore not Gaussian, though surprisingly the distribution of parasitism (dispersal kernel) was.

Conclusions

Even homogenous asexual groups of insects develop behavioural heterogeneities over a few hours, and the latter control patterns of population spread. Behavioural switching between resident and explorer states determined population distribution, density-dependence and dispersal. A simple Gaussian dispersal kernel did not reflect classical diffusion, but rather the interplay of several non-linearities at individual level. These results highlight the need to take into account behaviour and inter-individual heterogeneity to understand population spread in animals.