bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
Thyrotoxicosis as a rare presentation in acute suppurative thyroiditis: a case report
Authors: Seyedjavadeyn Zeynab , Miratashi Yazdi Seyed Amir , Samimiat Alireza , Vahedi Matin 
Published: October 2023

Abstract
Background
Acute suppurative thyroiditis is a rare and potentially life-threatening disease. A few cases of acute suppurative thyroiditis associated with thyrotoxicosis have been reported in adults. We report a case of acute suppurative thyroiditis that was associated with thyrotoxicosis.

Case presentation
We report the case of a 49-year-old Iranian female presented with a painful neck swelling for a week. Computed tomography showed a well-defined gas-filled collection in the left thyroid lobe with an enhancing margin. The patient underwent two-phase surgery, first left thyroid abscess drainage and then total thyroidectomy. The result of histopathology examination was multinodular goiter with abscess formation without malignancy.

Conclusion
Abscess formation and thyrotoxicosis is a very rare condition that occurs at the same time in acute suppurative thyroiditis. Despite antibiotic therapy being the first line of treatment, surgery is also required when antibiotic therapy fails.