bluuebunny/crossref_metadata_2025 huggingface dataset:
Different effects of medications for hypertension on renal function between patients with and without diabetes mellitus undergoing percutaneous coronary intervention: a retrospective single-center cohort study
Authors: Kanda Daisuke , Takumi Takuro , Tokushige Akihiro , Ikeda Yoshiyuki , Ohishi Mitsuru
Published: October 2023

Background

Diabetes mellitus (DM) and hypertension are well-known atherosclerosis risk factors. Furthermore, renal dysfunction is a crucial risk factor for patients with coronary artery disease (CAD), and managing renal function in these patients is complicated because of comorbid conditions and potential side effects during treatment. Therefore, this study aimed to investigate the effect of medications for hypertension on renal function after percutaneous coronary intervention (PCI) between patients with and without DM with statins.

Methods

In 297 consecutive patients undergoing PCI for stable angina pectoris, cystatin C (CysC) was evaluated at baseline and 9 months after PCI, and the percent change in CysC (%CysC) was calculated. The association of worsening renal function (WRF: %CysC ≥ 0) and baseline characteristics, including medications, was assessed.

Results

Among 297 hypertensive patients with statins, 196 and 101 were with and without DM, respectively. Angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker, and β-blocker were prescribed in 56 (29%), 82 (42%), and 91 (46%) patients in the DM group, and 20 (20%), 52 (51%), and 52 (51%) in the non-DM group, respectively. The patients with WRF after PCI were 100 (51%) and 59 (58%) in the DM and non-DM groups (p = 0.261). Additionally, the %CysC had no significant differences between groups [median: 0%, interquartile range (IQR): -7.9% to 8.5% vs. median: 1.1%, IQR: -6.6% to 9.6%, p = 0.521]. Multivariate logistic analysis for WRF using relevant factors from univariate analysis showed that only β-blocker [odds ratio (OR): 2.76, 95% confidence interval (CI): 1.03–7.90, p = 0.048] was independently associated with WRF in the DM group whereas ACEI (OR: 0.07, 95% CI: 0.01–0.47, p = 0.012) was negatively correlated with WRF in the non-DM group.

Conclusion

The β-blocker was the independent risk factor for WRF in patients with DM in the late phase after PCI for stable angina pectoris, while the use of ACEI had a renoprotective effect in patients without DM.
Outbreak detection algorithms based on generalized linear model: a review with new practical examples
Authors: Zareie Bushra , Poorolajal Jalal , Roshani Amin , Karami Manoochehr
Published: October 2023

Public health surveillance serves a crucial function within health systems, enabling the monitoring, early detection, and warning of infectious diseases. Recently, outbreak detection algorithms have gained significant importance across various surveillance systems, particularly in light of the COVID-19 pandemic. These algorithms are approached from both theoretical and practical perspectives. The theoretical aspect entails the development and introduction of novel statistical methods that capture the interest of statisticians. In contrast, the practical aspect involves designing outbreak detection systems and employing diverse methodologies for monitoring syndromes, thus drawing the attention of epidemiologists and health managers. Over the past three decades, considerable efforts have been made in the field of surveillance, resulting in valuable publications that introduce new statistical methods and compare their performance. The generalized linear model (GLM) family has undergone various advancements in comparison to other statistical methods and models. This study aims to present and describe GLM-based methods, providing a coherent comparison between them. Initially, a historical overview of outbreak detection algorithms based on the GLM family is provided, highlighting commonly used methods. Furthermore, real data from Measles and COVID-19 are utilized to demonstrate examples of these methods. This study will be useful for researchers in both theoretical and practical aspects of outbreak detection methods, enabling them to familiarize themselves with the key techniques within the GLM family and facilitate comparisons, particularly for those with limited mathematical expertise.
Efficacy analysis of minimally invasive surgery for Raynaud’s syndrome
Authors: Yu Fengwei , Liu Yongtao , Zhang Chengnian , Pang Botao , Zhang Daijie , Zhao Wei , Li Xuecheng , Yang Weiqiang
Published: October 2023

Background

Raynaud’s syndrome (RS), also referred to as Raynaud’s phenomenon, is a vasospastic disorder causing episodic color changes in extremities upon exposure to cold or stress. These manifestations, either primary Raynaud’s phenomenon (PRP) or associated with connective tissue diseases like systemic sclerosis (SSc) as secondary Raynaud’s phenomenon (SRP), affect the quality of life. Current treatments range from calcium channel blockers to innovative surgical interventions, with evolving efficacy and safety profiles.

Methods

In this retrospective study, patients diagnosed with RS were selected based on complete medical records, ensuring homogeneity between groups. Surgeries involved microscopic excision of sympathetic nerve fibers and stripping of the digital artery’s adventitia. Postoperative care included antibiotics, analgesia, oral nifedipine, and heat therapies. Evaluation metrics such as the VAS pain score and RCS score were collected bi-weekly. Data analysis was conducted using SPSS 26.0, with significance set at p < 0.05.

Results

In total, 15 patients formed the experimental group, with five presenting fingertip soft tissue necrosis and ten showing RS symptoms. Comparative analysis of demographic data between experimental and control groups, both containing 15 participants, demonstrated no significant age and gender difference. However, the “Mean Duration of RP attack” in the experimental group was notably shorter (9.47 min ± 0.31) than the control group (19.33 min ± 1.79). The RS Severity Score also indicated milder severity for the experimental cohort (score: 8.55) compared to the control (score: 11.23). Postoperative assessments at 2, 4, and 6 weeks revealed improved VAS pain scores, RCS scores, and other measures for the experimental group, showing significant differences (p < 0.05). One distinctive case showcased a variation in the common digital nerve and artery course in an RS patient.

Conclusion

Our retrospective analysis on RS patients indicates that microsurgical techniques are safe and effective in the short term. As surgical practices lean towards minimally invasive methods, our data supports this shift. However, extensive, prospective studies are essential for conclusive insights.
Machine learning-based prediction model and visual interpretation for prostate cancer
Authors: Chen Gang , Dai Xuchao , Zhang Mengqi , Tian Zhujun , Jin Xueke , Mei Kun , Huang Hong , Wu Zhigang
Published: October 2023

Background

Most prostate cancers(PCa) rely on serum prostate-specific antigen (PSA) testing for biopsy confirmation, but the accuracy needs to be further improved. We need to continue to develop PCa prediction model with high clinical application value.

Methods

Benign prostatic hyperplasia (BPH) and prostate cancer data were obtained from the Chinese National Clinical Medical Science Data Center for retrospective analysis. The model was constructed using the XGBoost algorithm, and patients’ age, body mass index (BMI), PSA-related parameters and serum biochemical parameters were used as model variables. Using decision analysis curve (DCA) to evaluate the clinical utility of the models. The shapley additive explanation (SHAP) framework was used to analyze the importance ranking and risk threshold of the variables.

Results

A total of 1915 patients were included in this study, including 823 (43.0%) were BPH patients and 1092 (57.0%) were PCa patients. The XGBoost model provided better performance (AUC 0.82) compared with f/tPSA (AUC 0.75),tPSA (AUC 0.68) and fPSA (AUC 0.61), respectively. Based on SHAP values, f/tPSA was the most important variable, and the top five most important biochemical parameter variables were inorganic phosphorus (P), potassium (K), creatine kinase MB isoenzyme (CKMB), low-density lipoprotein cholesterol (LDL-C), and creatinine (Cre). PCa risk thresholds for these risk markers were f/tPSA (0.13), P (1.29 mmol/L), K (4.29 mmol/L), CKMB ( 11.6U/L), LDL-C (3.05mmol/L) and Cre (74.5-99.1umol/L).

Conclusion

The present model has advantages of wide-spread availability and high net benefit, especially for underdeveloped countries and regions. Furthermore, these risk thresholds can assist in the diagnosis and screening of prostate cancer in clinical practice.
Effects of heart failure and coronary artery disease on erectile dysfunction: a two-sample mendelian randomization study
Authors: Shao Kaiyang , Chen Weikang , Li Yaling , Zheng Huiyan , Hu Ruying , Zhang Jianqiao , Sun Ting
Published: October 2023

Background and aims

There are no clear conclusions as to whether heart failure (HF) and coronary heart disease (CAD) increase the risk of erectile dysfunction (ED).In our study, we used Mendelian randomization (MR) analysis to discover a causal relationship between HF, CAD and ED.

Methods

Single nucleotide polymorphisms (SNPs) associated with HF, CAD and ED were obtained from the MRC IEU Open Genome-Wide Association Study (GWAS) database.After a series of screenings, the remaining SNPs were selected as instrumental variables (IVs) for HF and CAD for MR analysis to assess the relationship between genetically predicted HF or CAD and the pathogenesis of ED.Among them, we used the random-effects inverse variance weighted (IVW) method as the primary analysis method.Finally, Cochran’s q-test, funnel plots, MR-Egger regression, Leave-one-out method and MR-PRESSO were used for sensitivity analysis.

Results

In the IVW method, there was no significant causal relationship between genetically predicted HF and CAD and the incidence of ED.(HF: OR = 1.17, 95% CI 0.99–1.39; p = 0.074;CAD: OR = 1.08, 95% CI 0.99–1.17, p = 0.068)。The results of sensitivity analyses supported our conclusion that no horizontal pleiotropism was found.

Conclusion

This study did not find a causal relationship between HF or CAD and ED in European populations, which requires further in-depth research.
A retrospective study of dynamic navigation system-assisted implant placement
Authors: Ma Lijuan , Ye Mingjun , Wu Mingle , Chen Xiaolei , Shen Shan
Published: October 2023

Background

To evaluate the accuracy of implant placement assisted by a dynamic navigation system, as well as its influencing factors and learning curve.

Methods

At Macao We Care Dental Center, 55 cases of implant placement using dynamic navigation were retrospectively evaluated. To evaluate their accuracy, the apex, tip, and angle deviations of preoperatively planned and postoperatively placed implants were measured. The effects of the upper and lower jaws, different sites or lateral locations of dental implants, and the length and diameter of the implants on accuracy were analyzed, as well as the variation in accuracy with the increase in the number of surgical procedures performed by dentists.

Results

The implant had an apex deviation of 1.60 ± 0.94 mm, a tip deviation of 1.83 ± 1.03 mm, and an angle deviation of 3.80 ± 2.09 mm. Statistical differences were observed in the tip deviation of implants at different positions based on three factors: jaw position, lateral location, and tooth position (P < 0.05). The tip deviation of the anterior teeth area was significantly greater than those of the premolar and molar areas. There were no statistically significant differences in apex deviation, tip deviation, or angle deviation between the implants of different diameters and lengths (P > 0.05). There were significant differences in the angle deviation between the final 27 implants and the first 28 implants. Learning curve analysis revealed that angle deviation was negatively correlated with the number of surgical procedures, whereas the regression of apex deviation and tip deviation did not differ statistically.

Conclusions

The accuracy of dynamic navigation-assisted dental implants meets the clinical needs and is higher than that of traditional implants. Different jaw positions, lateral locations, and implant diameters and lengths had no effect on the accuracy of the dental implants guided by the dynamic navigation system. The anterior teeth area had a larger tip deviation than the posterior teeth area did. As the number of dynamic implantation procedures performed by the same implant doctor increased, the angle deviation gradually decreased.
Evaluation of perfusion parameters of gingival inflammation using laser Doppler flowmetry and tissue spectrophotometry– a prospective comparative clinical study
Authors: Katz Marie Sophie , Ooms Mark , Winnand Philipp , Heitzer Marius , Bock Anna , Kniha Kristian , Hölzle Frank , Modabber Ali
Published: October 2023

Background

The aim of this study was to determine the values of different perfusion parameters- such as oxygen saturation, the relative amount of hemoglobin, and blood flow- in healthy subjects compared to patients with gingivitis as a non-invasive measurement method.

Methods

A total of 114 subjects were enrolled in this study and separated into subjects with gingivitis (50) and without gingivitis (64) based on clinical examination. Gingival perfusion was measured at 22 points in the maxilla and mandible using laser Doppler flowmetry and tissue spectrophotometry (LDF-TS) with the “oxygen to see” device. All patients underwent measurement of gingival perfusion, followed by the clinical evaluation (measurement of probing depths, evaluation of bleeding on probing, plaque level, and biotype). Perfusion parameters were compared between the groups, associations between the non-invasive and clinical measurements were analyzed, and theoretical optimal cut-off values for predicting gingivitis were calculated with receiver operating characteristics.

Results

The mean oxygen saturation, mean relative amount of hemoglobin, and mean blood flow all significantly differed between the groups with and without gingivitis (p = 0.005, p < 0.001, and p < 0.001, respectively). The cut-off value for predicting gingivitis was > 40 AU (p < 0.001; sensitivity 0.90, specificity 0.67).

Conclusions

As a non-invasive method, LDF-TS can help determine gingival hyperemia. Flow values above 40 AU indicate a higher risk of hyperemia, which can be associated with inflammation. The LDF-TS method can be used for the objective evaluation of perfusion parameters during routine examinations and can signal the progression of hyperperfusion before any change in clinical parameters is observed.

Trial registration

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the institutional Clinical Research Ethics Committee (Ethik-Kommission der Medizinischen Fakultät der RWTH Aachen, Decision Number 286/20) and retrospectively registered by the German Clinical Trials Register (File Number DRKS00024048, registered on the 15th of October 2021).
A clustered randomized control trial to assess feasibility, acceptability, and impact of implementing the birth companion intervention package in Ethiopia, Kenya, and Nigeria: study protocol
Authors: Berhanu Della , Bekele Gadise , Melesse Hanna , Taddese Felagot , Owira Patricia , Manguro Griffins , Laleye Oluwatosin , Farouk Zubaida , Balogun Mobolanle , Hyre Anne , Mwaura Samuel , Kiptoo Osborn Koech , Wabwile Valentino Muyundo , Mohammed Siraj , Wolde Konjit , Teno Dedefo , Eke Eberechukwu Chinedu , Don-Aki Jennyfer Oluyemisi , Noguchi Lisa , Suhowatsky Stephanie , Doggett Elizabeth , Yenokyan Gayane , Worku Alemayehu
Published: October 2023

Background

A birth companion is a simple and low-cost intervention that can improve both maternal and newborn health outcomes. The evidence that birth companionship improves labor outcomes and experiences of care has been available for many years. Global and national policies exist in support of birth companions. Many countries including Ethiopia, Kenya, and Nigeria have not yet incorporated birth companions into routine practice in health facilities. This paper presents the protocol for a trial that aims to assess if a package of interventions that addresses known barriers can increase the coverage of birth companions.

Methods

This two parallel arm cluster randomized controlled trial will evaluate the impact of a targeted intervention package on scale-up of birth companionship at public sector health facilities in Ethiopia (five study sites encompassing 12 facilities), Kenya (two sites encompassing 12 facilities in Murang’a and 12 facilities in Machakos counties), and Nigeria (two sites encompassing 12 facilities in Kano and 12 facilities in Nasarawa states). Baseline and endline assessments at each site will include 744 women who have recently given birth in the quantitative component. We will interview a maximum of 16 birth companions, 48 health care providers, and eight unit managers quarterly for the qualitative component in each country.

Discussion

Ample evidence supports the contribution of birth companions to positive health outcomes for mothers and newborns. However, limited data are available on effective strategies to improve birth companion coverage and inform scale-up efforts. This trial tests a birth companion intervention package in diverse clinical settings and cultures to identify possible barriers and considerations to increasing uptake of birth companions. Findings from this study may provide valuable evidence for scaling up birth companionship in similar settings.

Trial registration

Trial is registered with ClinicalTrials.gov with identifier: NCT05565196, first posted 04/10/ 2022.
CRISPR-Cas9 assisted non-homologous end joining genome editing system of Halomonas bluephagenesis for large DNA fragment deletion
Authors: Liu Chunyan , Yue Yaxin , Xue Yanfen , Zhou Cheng , Ma Yanhe
Published: October 2023

Background

Halophiles possess several unique properties and have broad biotechnological applications including industrial biotechnology production. Halomonas spp., especially Halomonas bluephagenesis, have been engineered to produce various biopolyesters such as polyhydroxyalkanoates (PHA), some proteins, small molecular compounds, organic acids, and has the potential to become a chassis cell for the next-generation of industrial biotechnology (NGIB) owing to its simple culture, fast growth, contamination-resistant, low production cost, and high production value. An efficient genome editing system is the key for its engineering and application. However, the efficiency of the established CRISPR-Cas-homologous recombination (HR) gene editing tool for large DNA fragments was still relatively low. In this study, we firstly report a CRISPR-Cas9 gene editing system combined with a non-homologous end joining (NHEJ) repair system for efficient large DNA fragment deletion in Halomonas bluephagenesis.

Results

Three different NHEJ repair systems were selected and functionally identified in Halomonas bluephagenesis TD01. The NHEJ system from M. tuberculosis H37Rv (Mt-NHEJ) can functionally work in H. bluephagenesis TD01, resulting in base deletion of different lengths for different genes and some random base insertions. Factors affecting knockout efficiencies, such as the number and position of sgRNAs on the DNA double-strands, the Cas9 protein promoter, and the interaction between the HR and the NHEJ repair system, were further investigated. Finally, the optimized CRISPR-Cas9-NHEJ editing system was able to delete DNA fragments up to 50 kb rapidly with high efficiency of 31.3%, when three sgRNAs on the Crick/Watson/Watson DNA double-strands and the arabinose-induced promoter Para for Cas9 were used, along with the background expression of the HR repair system.

Conclusions

This was the first report of CRISPR-Cas9 gene editing system combined with a non-homologous end joining (NHEJ) repair system for efficient large DNA fragment deletion in Halomonas spp. These results not only suggest that this editing system is a powerful genome engineering tool for constructing chassis cells in Halomonas, but also extend the application of the NHEJ repair system.
Heterologous overproduction of oviedomycin by refactoring biosynthetic gene cluster and metabolic engineering of host strain Streptomyces coelicolor
Authors: Gu Boncheol , Kim Duck Gyun , Kim Do-Kyung , Kim Minji , Kim Hyun Uk , Oh Min-Kyu
Published: October 2023

Background

Oviedomycin is one among several polyketides known for their potential as anticancer agents. The biosynthetic gene cluster (BGC) for oviedomycin is primarily found in Streptomyces antibioticus. However, because this BGC is usually inactive under normal laboratory conditions, it is necessary to employ systematic metabolic engineering methods, such as heterologous expression, refactoring of BGCs, and optimization of precursor biosynthesis, to allow efficient production of these compounds.

Results

Oviedomycin BGC was captured from the genome of Streptomyces antibioticus by a newly constructed plasmid, pCBA, and conjugated into the heterologous strain, S. coelicolor M1152. To increase the production of oviedomycin, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system was utilized in an in vitro setting to refactor the native promoters within the ovm BGC. The target promoters of refactoring were selected based on examination of factors such as transcription levels and metabolite profiling. Furthermore, genome-scale metabolic simulation was applied to find overexpression targets that could enhance the biosynthesis of precursors or cofactors related to oviedomycin production. The combined approach led to a significant increase in oviedomycin production, reaching up to 670 mg/L, which is the highest titer reported to date. This demonstrates the potential of the approach undertaken in this study.

Conclusions

The metabolic engineering approach used in this study led to the successful production of a valuable polyketide, oviedomycin, via BGC cloning, promoter refactoring, and gene manipulation of host metabolism aided by genome-scale metabolic simulation. This approach can be also useful for the efficient production of other secondary molecules encoded by ‘silent’ BGCs.
Epigallocatechin-3-gallate and cancer: focus on the role of microRNAs
Authors: Wang Chunguang , Bai Meiling , Sun Zhiguang , Yao Nan , Zhang Aiting , Guo Shengyu , Asemi Zatollah
Published: October 2023

MicroRNAs (miRNAs) are a group of small non-coding RNAs that affect gene expression. The role of miRNAs in different types of cancers has been published and it was shown that several miRNAs are inappropriately expressed in different cancers. Among the mechanisms that can cause this lack of proper expression are epigenetics, chromosomal changes, polymorphisms or defects in processing proteins. Recent research shows that phytochemicals, including epigallocatechin-3-gallate (EGCG), exert important epigenetic-based anticancer effects such as pro-apoptotic or anti proliferative through miRNA gene silencing. Given that EGCG is able to modulate a variety of cancer-related process i.e., angiogenesis, proliferation, metastasis and apoptosis via targeting various miRNAs such as let-7, miR-16, and miR-210. The discovery of new miRNAs and the differences observed in their expression when exposed to EGCG provides evidence that targeting these miRNAs may be beneficial as a form of treatment. In this review, we aim to provide an overview, based on current knowledge, on how phytochemicals, including epigallocatechin-3-gallate, can be considered as potential miRNAs modulator to improve efficacy of current cancer treatments.
Treatment-seeking behaviours of malaria patients versus non-malaria febrile patients along China-Myanmar border
Authors: Xu Jian-Wei , Deng Dao-Wei , Wei Chun , Zhou Xing-Wu , Li Jian-Xiong
Published: October 2023

Background

Appropriate malaria treatment-seeking behaviour (TSB) is critical for timely detecting malaria, prompt treatment, and prevention of onward transmission of the disease in a community. This study aimed to compare treatment-seeking behaviours between malaria patients and non-malaria febrile patients, and to analyse the factors associated with appropriate TSB along the China-Myanmar border.

Methods

A cross-sectional study was carried out to investigate the appropriate TSB of microscopy-confirmed malaria patients versus non-malaria febrile (NMF) patients. An unconditional logistic regression analysis (LRA) was used to identify factors associated with appropriate TSB.

Results

Among 223 malaria patients and 446 NMF patients, 129 (57.8%) of the malaria patients versus 163 (36.5%) of the NMF patients firstly sought treatment in health facilities without laboratory testing for malaria (P < 0.0001). A total of 85(38.1%) of the malaria patients versus 278 (62.3%) of the NMF patients had appropriate TSB, namely, seeking treatment in health facilities with laboratory testing for malaria within 48 h (P < 0.0001). Multivariate LRA identified that the malaria patients with Chinese nationality had less appropriate TSB compared to those with other nationalities (adjusted odds ratio [AOR]: 0.21, 95% confidence interval CI 0.07–0.68, P = 0.0097), and malaria patients residing in urban areas had more appropriate TSB compared to those living in rural areas (AOR: 2.16, 95%CI 1.06–4.39, P = 0.0337).

Conclusions

TSB was not appropriate in malaria patients. Chinese citizenship and rural residence were two independent factors associated with inappropriate malaria TSB. It is urgently necessary to improve appropriate malaria TSB through effective campaigns of information, education, and communication for malaria control in Myanmar and preventing reestablishment of malaria transmission in Yunnan, China.
Extended-spectrum β-lactamase- producing gram-negative bacterial infections in severely ill COVID-19 patients admitted in a national referral hospital, Kenya
Authors: Mutua Jeniffer Munyiva , Njeru John Mwaniki , Musyoki Abednego Moki
Published: October 2023

Background

Bacterial infections in COVID-19 patients, especially those caused by multidrug-resistant gram-negative strains, are associated with increased morbidity, hospital stay and mortality. However, there is limited data on the epidemiology of extended-spectrum β-lactamase (ESBL)-producing bacteria in COVID-19 patients. Here, we assessed the prevalence and the factors associated with ESBL-producing gram-negative bacterial (GNB) infections among severely ill COVID-19 patients admitted in Kenyatta National Hospital (KNH), Kenya.

Methods

We adopted a descriptive cross-sectional study design for patients admitted between October 2021 and February 2022, purposively recruiting 120 SARS-CoV- 2 infected participants based on clinical presentation. Demographics and clinical characteristics data were collected using structured questionnaires and case report forms. Clinical samples were collected and analyzed by standard microbiological methods in the KNH Microbiology laboratory and the Centre for Microbiology Research, Kenya Medical Research Institute.

Results

GNB infections prevalence was 40.8%, majorly caused by ESBL—producers (67.3%) predominated by Klebsiella pneumoniae (45.5%). Generally, 73% of the ESBL producers harboured our target ESBL genes, mainly CTX-M-type (59%, 17/29) in K. pneumoniae (76.9%, 20/26). GNB harbouring TEM-type (83%, 10/12) and SHV-type (100%, 7/7) genes showed ESBLs phenotypes and inhibitor resistance, mainly involving clavulanate, but most of them remained susceptible to tazobactam (60%, 6/10). SHV-type genes carrying ESBL producers showed resistance to both cefotaxime (CTX) and ceftazidime (CAZ) (K. pneumoniae), CAZ (E. coli) or CTX (E. cloacae complex and K. pneumoniae). About 87% (20/23) of isolates encoding CTX-M-type β-lactamases displayed CTX/ceftriaxone (CRO) resistance phenotype. About 42% of isolates with CTX-M-type β-lactamases only hydrolyzed ceftazidime (CAZ). Isolates with OXA-type β-lactamases were resistant to CTX, CAZ, CRO, cefepime and aztreonam. Patients with comorbidities were 10 times more likely to have an ESBL-producing GNB infection (aOR = 9.86, 95%CI 1.30 – 74.63, p = 0.003).

Conclusion

We report a high prevalence of ESBL-GNB infections in severely ill COVID-19 patients, predominantly due to Klebsiella pneumoniae harbouring CTX-M type ESBL genes. The patient’s underlying comorbidities increased the risk of ESBL-producing GNB infection. In COVID-19 pandemic, enhanced systematic and continuous surveillance of ESBL-producing GNB, strict adherence to infection control measures and antimicrobial stewardship policies are warranted in the current study setting.
Surface antibody changes protein corona both in human and mouse serum but not final opsonization and elimination of targeted polymeric nanoparticles
Authors: Capolla Sara , Colombo Federico , De Maso Luca , Mauro Prisca , Bertoncin Paolo , Kähne Thilo , Engler Alexander , Núñez Luis , Spretz Ruben , Larsen Gustavo , Dal Bo Michele , Toffoli Giuseppe , Macor Paolo
Published: October 2023

Background

Nanoparticles represent one of the most important innovations in the medical field. Among nanocarriers, polymeric nanoparticles (PNPs) attracted much attention due to their biodegradability, biocompatibility, and capacity to increase efficacy and safety of encapsulated drugs. Another important improvement in the use of nanoparticles as delivery systems is the conjugation of a targeting agent that enables the nanoparticles to accumulate in a specific tissue. Despite these advantages, the clinical translation of therapeutic approaches based on nanoparticles is prevented by their interactions with blood proteins. In fact, the so-formed protein corona (PC) drastically alters the biological identity of the particles. Adsorbed activated proteins of the complement cascade play a pivotal role in the clearance of nanoparticles, making them more easily recognized by macrophages, leading to their rapid elimination from the bloodstream and limiting their efficacy. Since the mouse is the most used preclinical model for human disease, this work compared human and mouse PC formed on untargeted PNPs (uPNPs) and targeted PNPs (tPNPs), paying particular attention to complement activation.

Results

Mouse and human serum proteins adsorbed differently to PNPs. The differences in the binding of mouse complement proteins are minimal, whereas human complement components strongly distinguish the two particles. This is probably due to the human origin of the Fc portion of the antibody used as targeting agent on tPNPs. tPNPs and uPNPs mainly activate complement via the classical and alternative pathways, respectively, but this pattern did not affect their binding and internalization in macrophages and only a limited consumption of the activity of the human complement system was documented.

Conclusions

The results clearly indicate the presence of complement proteins on PNPs surface but partially derived from an unspecific deposition rather than an effective complement activation. The presence of a targeting antibody favors the activation of the classical pathway, but its absence allows an increased activation of the alternative pathway. This results in similar opsonization of both PNPs and similar phagocytosis by macrophages, without an impairment of the activity of circulating complement system and, consequently, not enhancing the susceptibility to infection.

Graphical abstract
Harm reduction social work with people who use drugs: a qualitative interview study with social workers in harm reduction services in Sweden
Authors: Richert Torkel , Stallwitz Anke , Nordgren Johan
Published: October 2023

Background

Social work with people who use drugs (PWUD) has traditionally focused on abstinence and rehabilitation. In recent years, harm reduction has gained an increasingly more important role in social work with PWUD, and social workers are key professionals in many harm reduction services. This study investigates how social workers in harm reduction services for PWUD in Sweden understand the concept of harm reduction and how it relates to goals of rehabilitation, and how they assess and deal with dilemmas and challenges in everyday work.

Methods

The study is based on interviews with 22 social workers in harm reduction services for PWUD in the Scania region of Sweden. A thematic analysis in three steps was used in coding and processing the data.

Results

The social workers pointed to similar values between social work and harm reduction and argued for combining the two fields to improve services for PWUD. Three overarching principles for Harm Reduction Social Work (HRSW) were developed based on the social workers accounts: (1) Harm reduction is a prerequisite for rather than a counterpoint to rehabilitation and recovery, (2) motivational work must be non-mandatory and based on the client’s goals, (3) a holistic perspective is crucial for Harm Reduction Social Work. Challenges in doing HRSW concerned restrictive laws, policies, and guidelines, resistance from managers, difficulties in setting boundaries between client autonomy and life-saving interventions, and the risk of normalizing high-risk behaviors.

Conclusions

We use the concept of Harm Reduction Social Work to show how social work with PWUD can have a primary focus on reducing harm and risks, while at the same time it involves a holistic perspective that facilitates motivation and change. The suggested principles of HRSW can provide guidance in practical social work with vulnerable PWUD. Social workers can have important roles in most harm reduction settings and may act to enable recovery.
Cross-walk of the Chronic Liver Disease Questionnaire for Nonalcoholic Steatohepatitis (CLDQ-NASH) and the EuroQol EQ-5D-5L in patients with NASH
Authors: Fishman Jesse , Higgins Victoria , Piercy James , Pike James
Published: October 2023

Background

Nonalcoholic steatohepatitis (NASH) is a chronic progression of nonalcoholic fatty liver disease, which can negatively impact the health-related quality of life (HRQoL) of affected individuals. HRQoL in NASH has been assessed using the disease-specific Chronic Liver Disease Questionnaire for NASH (CLDQ-NASH) and the generic EuroQol EQ-5D-5L. As the performance of these instruments relative to each other is unknown, we performed a cross-walk analysis of CLDQ-NASH to EQ-5D-5L using data from a real-world NASH population.

Methods

Data were drawn from the Adelphi Real World 2019 NASH Disease Specific Programme, a cross-sectional survey of physicians and their patients in the United States. Patients with physician-diagnosed NASH completed a questionnaire that included the CLDQ-NASH and EQ-5D-5L. Mapping from CLDQ-NASH to EQ-5D-5L was done using tenfold cross-validation; performance was assessed using root-mean squared error as accuracy measure. Subgroup analyses compared performance of the models in obese versus non-obese patients and patients with versus without type 2 diabetes (T2D).

Results

Data from 347 patients were included in this analysis. Overall, 2172 models were tested for predicting EQ-5D-5L index score from CLDQ-NASH score. The best model for this mapping was a generalized linear model using Gaussian distribution and a power link. The best model for mapping from CLDQ-NASH domains to the EQ-5D-5L was a fractional logistic model. Models performed better at predicting upper versus lower values of EQ-5D-5L, for non-obese versus obese patients, and for patients without versus with T2D.

Conclusion

We describe a scoring algorithm for cross-walking the CLDQ-NASH to the EQ-5D-5L enabling health status comparisons of HRQoL across studies.
Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer
Authors: Ji Shufeng , Yu Hao , Zhou Dan , Fan Xulong , Duan Yan , Tan Yijiang , Lang Min , Shao Guoli
Published: October 2023

Background

Triple-negative breast cancer (TNBC) development may be associated with tumor immune escape. This study explores whether the CHI3L1/MAF/CTLA4/S100A4 axis affects immune escape in TNBC through interplay with triple-negative breast cancer stem cells (TN-BCSCs).

Objective

The aim of this study is to utilize single-cell transcriptome sequencing (scRNA-seq) to uncover the molecular mechanisms by which the CHI3L1/MAF/CTLA4 signaling pathway may mediate immune evasion in triple-negative breast cancer through the interaction between tumor stem cells (CSCs) and immune cells.

Methods

Cell subsets in TNBC tissues were obtained through scRNA-seq, followed by screening differentially expressed genes in TN-BCSCs and B.C.s (CD44+ and CD24−) and predicting the transcription factor regulated by CHI3L1. Effect of CHI3L1 on the stemness phenotype of TNBC cells investigated. Effects of BCSCs-231-derived CHI3L1 on CTLA4 expression in T cells were explored after co-culture of BCSCs-231 cells obtained from microsphere culture of TN-BCSCs with T cells. BCSCs-231-treated T cells were co-cultured with CD8+ T cells to explore the resultant effect on T cell cytotoxicity. An orthotopic B.C. transplanted tumor model in mice with humanized immune systems was constructed, in which the Role of CHI3L1/MAF/CTLA4 in the immune escape of TNBC was explored.

Results

Eight cell subsets were found in the TNBC tissues, and the existence of TN-BCSCs was observed in the epithelial cell subset. CHI3L1 was related to the stemness phenotype of TNBC cells. TN-BCSC-derived CHI3L1 increased CTLA4 expression in T cells through MAF, inhibiting CD8+ T cell cytotoxicity and inducing immunosuppression. Furthermore, the CTLA4+ T cells might secrete S100A4 to promote the stemness phenotype of TNBC cells.

Conclusions

TN-BCSC-derived CHI3L1 upregulates CTLA4 expression in T cells through MAF, suppressing the function of CD8+ T cells, which promotes the immune escape of TNBC.
Effects of autologous serum on TREM2 and APOE in a personalized monocyte-derived macrophage assay of late-onset Alzheimer’s patients
Authors: Eren Neriman , Gerike Susanna , Üsekes Berk , Peters Oliver , Cosma Nicoleta-Carmen , Hellmann-Regen Julian
Published: October 2023

Background

Age-associated deterioration of the immune system contributes to a chronic low-grade inflammatory state known as “inflammaging” and is implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD). Whether changes in the tissue environment caused by circulatory factors associated with aging may alter the innate immune response is unknown. Monocyte-derived macrophages (Mo-MФs) infiltrating the brain alongside microglia are postulated to play a modulatory role in LOAD and both express triggering receptor expressed on myeloid cells 2 (TREM2). Apolipoprotein E (APOE) acts as a ligand for TREM2, and their role in amyloid beta (Aβ) clearance highlights their importance in LOAD. However, the influence of the patient's own milieu (autologous serum) on the synthesis of TREM2 and APOE in infiltrating macrophages remains unknown.

Objectives

To functionally assess patient-specific TREM2 and APOE synthesis, we designed a personalized assay based on Mo-MФs using monocytes from LOAD patients and matched controls (CO). We assessed the influence of each participant’s own milieu, by examining the effect of short- (1 day) and long- (10 days) term differentiation of the cells in the presence of the donor´s autologous serum (AS) into M1-, M2- or M0-macrophages. Additionally, sex differences and Aβ-uptake ability in short- and long-term differentiated Mo-MФs were assessed.

Results

We showed a time-dependent increase in TREM2 and APOE protein levels in LOAD- and CO-derived cells. While AS did not differentially modulate TREM2 compared to standard fetal calf serum (FCS), AS decreased APOE levels in M2 macrophages but increased levels in M1 macrophages. Interestingly, higher levels of TREM2 and lower levels of APOE were detected in female- than in male- LOAD patients. Finally, we report decreased Aβ-uptake in long-term differentiated CO- and LOAD-derived cells, particularly in APOEε4(+) carriers.

Conclusions

We demonstrate for the first time the suitability of a personalized Mo-MФ cell culture-based assay for studying functional TREM2 and APOE synthesis in a patient's own aged milieu. Our strategy may thus provide a useful tool for future research on diagnostic and therapeutic aspects of personalized medicine.
Evaluating an intervention to improve the safety and experience of transitions from hospital to home for older people (Your Care Needs You): a protocol for a cluster randomised controlled trial and process evaluation
Authors: Lawton Rebecca , Murray Jenni , Baxter Ruth , Richardson Gerry , Cockayne Sarah , Baird Kalpita , Mandefield Laura , Brealey Stephen , O’Hara Jane , Foy Robbie , Sheard Laura , Cracknell Alison , Breckin Edmund , Hewitt Catherine ,   on behalf of the PACT research team
Published: October 2023

Background

Older patients often experience safety issues when transitioning from hospital to home. The ‘Your Care Needs You’ (YCNY) intervention aims to support older people to ‘know more’ and ‘do more’ whilst in hospital so that they are better prepared for managing at home.

Methods

A multi-centre cluster randomised controlled trial (cRCT) will evaluate the effectiveness and cost-effectiveness of the YCNY intervention.

Forty acute hospital wards (clusters) in England from varying medical specialities will be randomised to deliver YCNY or care-as-usual on a 1:1 basis. The primary outcome will be unplanned hospital readmission rates within 30 days of discharge. This will be extracted from routinely collected data of at least 5440 patients (aged 75 years and older) discharged to their own homes during the 4- to 5-month YCNY intervention period. A nested cohort of up to 1000 patients will be recruited to the study to collect secondary outcomes via follow-up questionnaires at 5-, 30- and 90-day post-discharge. These will include measures of patient experience of transitions, patient-reported safety events, quality of life and healthcare resource use. Unplanned hospital readmission rates at 60 and 90 days of discharge will be collected from routine data.

A process evaluation (primarily interviews and observations with patients, carers and staff) will be conducted to understand the implementation of the intervention and the contextual factors that shape this, as well as the intervention’s underlying mechanisms of action. Fidelity of intervention delivery will also be assessed across all intervention wards.

Discussion

This study will establish the effectiveness and cost-effectiveness of the YCNY intervention which aims to improve patient safety and experience for older people during transitions of care. The process evaluation will generate insights about how the YCNY intervention was implemented, what elements of the intervention work and for whom, and how to optimise its implementation so that it can be delivered with high fidelity in routine service contexts.

Trial registration

UK Clinical Research Network Portfolio: 44559; ISTCRN: ISRCTN17062524. Registered on 11/02/2020.
Imaging features and clinical value of 18F-FDG PET/CT for predicting airway involvement in patients with relapsing polychondritis
Authors: Yi Jing-Wei , Huang Jun-Feng , Hou Peng , Lin Zi-Kai , Lin Jin-Sheng , Lin Si-Yan , Wang Min , Li Shi-Yue , Wang Xin-Lu
Published: October 2023

Background

The clinical value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in assessing relapsing polychondritis (RP) with airway involvement remains controversial. This study aimed to investigate PET/CT features of RP with airway involvement and explore its clinical value in predicting disease pattern, severity and prognosis.

Methods

RP patients with airway involvement who underwent PET/CT from January 2010 to July 2022 were retrospectively reviewed. PET/CT features were analyzed both visually and semiquantitatively with the maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG). Patterns of airway involvement on PET were summarized. Correlations of SUVmax and TLG of the airway were made with spirometric indicators and serological inflammatory markers (CRP and ESR). In addition, long-term follow-up was conducted through questionnaires in regard to symptom control, subjective feeling, pulmonary function, and quality of life.

Results

Fifty-two cases were finally included. 18F-FDG PET showed FDG-avid lesions with increased FDG uptake in the airway among 94.2% of the patients. Three patterns (focal, multifocal and diffuse patterns) were identified. TLG of the whole airway was lower in patients with previous therapy (p = 0.046). Bronchoscopy was more sensitive in detecting tracheal abnormalities (90.7% vs.53.5%, p = 0.039) but less sensitive for peripheral airway lesions (65.1% vs. 79.1%, p = 0.046) compared with PET. SUVmax and TLG of the airway positively correlated with spirometry indicators (FEV1%pred, FEV1/FVC, MEF 50%pred, etc.) and serological inflammatory markers. Five patients died during the follow-up, with two deaths related to airway problems. Higher FDG uptake predicted worse subjective feeling, but not with symptom control or pulmonary function.

Conclusion

PET/CT is a valuable tool for RP with airway involvement, particularly in assessing peripheral airway lesions, and PET/CT related parameters are significantly associated with disease patterns, severity, and long-term outcomes.
Plant growth-promoting endophytic fungi of the wild halophytic rice Oryza coarctata
Authors: Airin Arifa Akhter , Arafat Md Iyasir , Begum Rifat Ara , Islam Md Rakibul , Seraj Zeba Islam
Published: October 2023

Background

Plant growth-promoting endophytic fungi (PGPEF) that are associated with halophytes have the potential to boost crop salinity tolerance and productivity. This in turn has the potential of enabling and improving cultivation practices in coastal lands affected by salt stress.

Methods

Endophytic fungi from the wild halophytic rice Oryza coarctata were isolated, characterized, identified, and studied for their effects on all developing stages of rice plant growth and their yields both with and without salt stress.

Key results

In this study, three different fungal endophytes were isolated from the halophytic wild rice Oryza coarctata. Two isolates were identified as Talaromyces adpressus (OPCRE2) and Talaromyces argentinensis (OPCRh1) by ITS region sequencing. The remaining isolate NPCRE2 was confirmed as a novel strain named Aspergillus welwitschiae Ocstreb1 (AwOcstreb1) by whole genome sequencing. These endophytes showed various plant growth-promoting (PGP) abilities in vitro (e.g., IAA, ACC-deaminase and siderophore production, phosphate, and zinc solubilization as well as nitrogen fixation), where AwOcstreb1 was significantly more efficient compared to the other two isolates at high salinity (900 mm). Independent application of these fungi in commercial rice (Oryza sativa) showed significant elevation in plant growth, especially in the case of the AwOcstreb1 inoculants, which had enhanced metabolite and chlorophyll content at the seedling stage in both no-salt control and 100-mm salt-stressed plants. At the same time, AwOcstreb1-treated plants had a significantly lower level of H2O2, electrolyte leakage, and Na+/K+ ratio under saline conditions. Higher expression (1.6 folds) of the SOS1 (salt overly sensitive 1) gene was also observed in these plants under salinity stress. This strain also improved percent fertility, tillering, panicle number, and filled grain number in both no-salt control and 45-mm salt-stressed inoculated plants at the reproductive stage. Consequently, the differences in their yield was 125.16% and 203.96% (p < 0.05) in colonized plants in normal and saline conditions, respectively, compared to uninoculated controls.

Conclusions

We propose that AwOcstreb1 is a potential candidate for an eco-friendly biofertilizer formula to improve the cultivation and yield of rice or any other crop in the highly saline coastal regions of Bangladesh.