bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical practice of palliative sedation in patients dying from COVID-19: a retrospective chart review
Authors: Rijpstra Maaike , Kuip Evelien , Hasselaar Jeroen , Vissers Kris 
Published: April 2023

Abstract
Background
Clinical experts experienced challenges in the practice of palliative sedation (PS) during the COVID-19 pandemic. Rapid deterioration in patients’ situation was observed while the indications for starting PS seemed to differ compared to other terminal patients. It is unclear to which extent clinical trajectories of PS differ for these COVID patients compared to regular clinical practice of PS.

Objectives
To describe the clinical practice of PS in patients with COVID versus non-COVID patients.

Methods
A retrospective analysis of data from a Dutch tertiary medical centre was performed. Charts of adult patients who died with PS during hospitalisation between March ’20 and January ‘21 were included.

Results
During the study period, 73 patients received PS and of those 25 (34%) had a COVID infection. Refractory dyspnoea was reported as primary indication for starting PS in 84% of patients with COVID compared to 33% in the other group (p < 0.001). Median duration of PS was significantly shorter in the COVID group (5.8 vs. 17.1 h, p < 0.01). No differences were found for starting dosages, but median hourly dose of midazolam was higher in the COVID group (4.2 mg/hr vs. 2.4 mg/hr, p < 0.001). Time interval between start PS and first medication adjustments seemed to be shorter in COVID patients (1.5 vs. 2.9 h, p = 0.08).

Conclusion
PS in COVID patients is characterized by rapid clinical deterioration in all phases of the trajectory. What is manifested by earlier dose adjustments and higher hourly doses of midazolam. Timely evaluation of efficacy is recommended in those patients.
Frequency of human papilomavirus and associated factors in gypsy and quilombola women
Authors: de Ribamar Ross José , Marinelli Natália Pereira , Vidal Flavia Castello Branco , da Costa Fraga Elamary , do Desterro Soares Brandão Nascimen Maria , Safádi Marco Aurélio Palazzi 
Published: April 2023

Abstract
Background
The prevalence of Human Papillomavirus (HPV) infection in the general population is widely known, however, there are still few studies related to this infection in minority groups, Thus, the objective is to analyze the frequency of human papillomavirus and associated factors in quilombola and gypsy women.

Methods
Cross-sectional research with 145 quilombola and gypsy women from Caxias, Maranhão. Two Pap smear collections were performed and a questionnaire with 46 questions was applied between January, 2020 and March, 2021. Descriptive analysis and Odds Ratio with 95% confidence interval were performed. The research was approved by the ethics committee.

Results
There were 09 cases of atypia. The frequency of human papillomavirus was 41.37%, with a higher risk in quilombolas 55 (91.70%). Multiple infections were prevalent (53%) with high-risk genotypes 21 (35%). Types 16 and 18 together accounted for 42.85% of cases.

Conclusions
The frequency of human papillomavirus infection was higher than those recorded in the Northeast and Brazil, and therefore type 16 predominated. Due to limitations, the virus lineages and sublineages were not evaluated. Quilombola women had a higher rate of infection than gypsies.
Contributing factors for urban-rural inequalities in unmet need for family planning among reproductive-aged women in Ethiopia: a Blinder-Oaxaca decomposition analysis
Authors: Teferi Henok Mulatu , Schröders Julia 
Published: April 2023

Abstract
Background
Unmet need for family planning (FP) is a global public health concern, particularly in low- and middle-income countries. In Ethiopia, although several studies have assessed unmet needs for FP, there have only been few empirical investigations into regional inequalities and their contributory factors. This study assessed urban-rural inequalities in unmet FP needs among reproductive-aged women in Ethiopia and particularly examined the contribution of material, cultural-behavioral, and psychosocial factors therein.

Methods
A cross sectional study was conducted among 8811 reproductive-aged women derived from the nationally representative 2019 Ethiopian Performance Monitoring for Action (PMA) data. The outcome variable was unmet need for FP. The exposure variable was place of residence (urban or rural). Contributing factors were categorized into material, psychosocial and cultural-behavioral factors. Blinder-Oaxaca decomposition analysis was used to assess urban-rural inequalities in unmet need for FP as well as to disentangle the contributory factors in percentage points.

Result
In our study, 13.8% of reproductive-aged women in Ethiopia reported unmet FP needs. Urban-rural inequalities therein accounted for 6.8% points. Disparities in FP needs between urban and rural areas were mostly explained by psychosocial factors (81.0%) followed by material (21.0%), and cultural-behavioral (3.2%) factors. While women who were living with a partner (39.1%, p < 0.01) and multiparas (51%, p < 0.01) contributed to increasing inequalities, attending family planning counseling services with a healthcare provider (-1.7%, p = 0.03) reduced the gap in unmet need for FP between urban and rural areas. Women from the poorest and poor category contributed 14.1% (p = 0.02) and 11.1% (p = 0.04), respectively. Being from a Muslim religion also contributed to the disparity by 7.3% (p < 0.01).

Conclusion
This study showed that among reproductive-aged women in Ethiopia, inequalities in unmet FP needs show distinct urban-rural patterning. Most inequalities could be attributed to psychosocial factors, mainly parity and marital status, followed by material and cultural-behavioral factors. Policymakers should target these modifiable psychosocial factors to reduce urban-rural inequalities in unmet need for FP in Ethiopia.
Physicians’ and nurses’ experience of using the Abbey Pain Scale (APS) in people with advanced cancer: a qualitative content analysis
Authors: Tegenborg Sussi , Fransson Per , Martinsson Lisa 
Published: April 2023

Abstract
Background
The Abbey Pain Scale (APS), an observational scale used to assess pain in people with end-stage dementia, is also widely used in Sweden to assess pain in patients with advanced cancer. It is unclear whether the APS is appropriate in this context. This study aims to explore physicians’ and nurses’ experiences of using a Swedish translation of the APS (the APS-SE) in people with advanced cancer.

Methods
Conventional qualitative content analysis was used to analyse interviews with physicians (n = 6) and nurses (n = 6) working in oncology and specialised palliative care about their experiences of using the APS-SE.

Results
Three categories were created: fills a need, not always on target, and does not fully suit the clinical situation. Participants reported that although the APS-SE provides support in a challenging situation, it sometimes misses the mark: it does not distinguish well between pain and other types of suffering and its pain score tends not to reflect professionals’ intuitive perceptions of patients’ suffering. Some parts of the APS-SE were not considered useful, and others were perceived as ethically questionable.

Conclusion
Health professionals greatly need an observational pain assessment tool for people with advanced cancer. The APS-SE is helpful in this context, but participants did not perceive it as ideal. Its problems seem inherent to the original APS rather than related to its translation from English to Swedish. Further research is needed to provide a more suitable pain assessment tool for patients with advanced cancer.
Medical device regulation (MDR) in health technology enterprises – perspectives of managers and regulatory professionals
Authors: Huusko Juhamatti , Kinnunen Ulla-Mari , Saranto Kaija 
Published: April 2023

Abstract
Background
In the European Union (EU), there are over half a million medical devices, varying from pacemakers to software. Medical devices play an important role in health care as they are used in diagnosis, prevention, monitoring, prediction, prognosis, treatment, or to alleviate disease. Medical devices are regulated in the EU by the Medical Device Regulation (MDR), which came into force on 25 April 2017 and into application on 26 May 2021. The demand for regulation arose from the need to establish a transparent, robust, predictable, and sustainable regulatory framework. This study aims to examine how the managers and regulatory professionals in health technology enterprises perceived the application of the MDR and what were their information needs regarding the MDR.

Methods
A link to an online questionnaire was sent to 405 managers and regulatory professionals representing health technology enterprises in Finland. The study included 74 respondents. Descriptive statistics were used to describe and summarise the characteristics of the dataset.

Results
Information related to the MDR was fragmented and the necessary information was sought from multiple information sources, while the Finnish Medicines Agency (Fimea) was regarded as the most important source of information and training provider. To some extent, the managers and regulatory professionals expressed their dissatisfaction with the performance of Fimea. The managers and regulatory professionals were not very familiar with the ICT systems provided by the EU. The size of an enterprise affected how many medical devices it manufactures and generally affected the views about the MDR.

Conclusions
The managers and regulatory professionals understood the role of the MDR regarding the safety and transparency of medical devices. The available information regarding the MDR did not properly fit the needs of users and there seemed to be a gap in information quality. The managers and regulatory professionals had some difficulties understanding the available information. Based on our findings, we believe it is paramount to evaluate the challenges faced by Fimea and how it could improve its performance. To some extent, the MDR is regarded as a burden for smaller enterprises. It is important to highlight the benefits of ICT systems and to develop them to better meet the information needs of enterprises.
Diagnostic groups of hospital stays and outpatient visits during 10 years before Alzheimer’s disease
Authors: Mäklin Kiira , Lampela Pasi , Lin Julian , Sirpa Hartikainen , Tolppanen Anna-Maija 
Published: April 2023

Abstract
Background
Alzheimer’s disease (AD) is a major determinant of healthcare costs and increase in the healthcare service use occur already before the AD diagnosis. However, little is known how the different diagnosis categories contribute to this increase in healthcare use. We investigated how the hospitalizations and specialized healthcare outpatient visits from different diagnosis categories, based on the International Classification of Diseases (ICD-10) chapters, contribute to increased specialized healthcare service use during ten-year period preceding AD diagnosis.

Methods
A register-based nationwide cohort of 42,934 community-dwelling persons who received clinically verified AD diagnosis in between 2008 and 2011 in Finland and 1:1 age, sex and hospital district- matched comparison cohort were included. Hospitalizations and specialized healthcare visits were categorized by the main diagnosis, according to the ICD-10 chapters. AD and dementia were separated to their own category. The number of persons with visits and stays was calculated for every 6 months, irrespective of the frequency of visits/stays individual had during that time window. Furthermore, the relative distribution of the diagnosis categories was computed.

Results
AD cohort was more likely to have visits and stays during the 10-year period (OR 1.19, 95% CI 1.17–1.21). The number of persons with visits and stays peaked in AD cohort from 1.5 years before the diagnosis when the differences in relative distribution of different diagnosis categories also became evident. The largest differences were observed for visits/stays with cognitive disorders, symptoms of unspecified diseases and psychiatric disorders diagnoses, and those with missing diagnosis codes in the last time window before AD diagnosis.

Conclusions and implications
Increased healthcare service use before AD diagnosis does not seem to arise from differences in specific diagnosis categories of ICD-10 such as diseases of the circulatory system, but from the higher frequency of visits and stays among persons with AD across diagnosis categories. Based on the relative distribution of diagnosis categories, the steep increase in healthcare service use just before and during the diagnostic process is likely due to prodromal symptoms and visits related to cognition.
High-efficient production of mushroom polyketide compounds in a platform host Aspergillus oryzae
Authors: Han Haiyan , Yu Chunyan , Qi Jianzhao , Wang Pengchao , Zhao Peipei , Gong Wenbing , Xie Chunliang , Xia Xuekui , Liu Chengwei 
Published: April 2023

Abstract
Background
Orsellinic acid (2,4-dihydroxy-6-methylbenzoic acid, OA) and its structural analog o-Orsellinaldehyde, have become widely used intermediates in clinical drugs synthesis. Although the research on the biosynthesis of such compounds has made significant progress, due to the lack of suitable hosts, there is still far from the industrial production of such compounds based on synthetic biology.

Results
With the help of genome mining, we found a polyketide synthase (PKS, HerA) in the genome of the Hericium erinaceus, which shares 60% amino acid sequence homology with ArmB from Armillaria mellea, an identified PKS capable of synthesizing OA. To characterize the function of HerA, we cloned herA and heterologously expressed it in Aspergillus oryzae, and successfully detected the production of OA. Subsequently, the introduction of an incomplete PKS (Pks5) from Ustilago maydis containing only three domains (AMP-ACP-R), which was into herA-containing A. oryzae, the resulted in the production of o-Orsellinaldehyde. Considering the economic value of OA and o-Orsellinaldehyde, we then optimized the yield of these compounds in A. oryzae. The screening showed that when maltose was used as carbon source, the yields of OA and o-Orsellinaldehyde were 57.68 mg/L and 15.71 mg/L respectively, while the yields were 340.41 mg/Kg and 84.79 mg/Kg respectively in rice medium for 10 days.

Conclusions
Herein, we successfully expressed the genes of basidiomycetes using A. oryzae heterologous host. As a fungus of ascomycetes, which not only correctly splices genes of basidiomycetes containing multiple introns, but also efficiently produces their metabolites. This study highlights that A. oryzae is an excellent host for the heterologous production of fungal natural products, and has the potential to become an efficient chassis for the production of basidiomycete secondary metabolites in synthetic biology.

Graphical Abstract
TGF-β signaling promotes cervical cancer metastasis via CDR1as
Authors: Zhong Guanglei , Zhao Qian , Chen Zhiliao , Yao Tingting 
Published: April 2023

Abstract
Background
Due to the lack of effective treatment, metastasis is the main cause of cancer related deaths. TGF-β pathway has been reported related to cervical cancer metastasis. However, mechanism is still unclear.

Methods
After agonist of TGF-β treatment, RNA sequencing revealed the expression profiles of circRNA in cervical cancer. In situ hybridization was used to analysis relationship between CDR1as and prognosis. Real-time PCR, Western blot, RNA interference, Transwell assay, Wound healing assay, RNA pulldown assay and RIP assays were performed in vitro. And in vivo cervical cancer model (including foot pad model and subcutaneous tumor formation) was also performed.

Results
CDR1as was found upregulated obviously following TGF-β activation. In situ hybridization showed CDR1as was positively correlated with lymph node metastasis and shortened survival length. Simultaneously, overexpression of CDR1as promoted cervical cancer metastasis in vitro and in vivo. It was also found that CDR1as could facilitate the orchestration of IGF2BP1 on the mRNA of SLUG and stabilize it from degradation. Silencing IGF2BP1 hampers CDR1as related metastasis in cervical cancer. Additionally, effective CDR1as has been proven to activate TGF-β signaling factors known to promote EMT, including P-Smad2 and P-Smad3.

Conclusions
Our study proved TGF-β signaling may promote cervical cancer metastasis via CDR1as.
Baseline characteristics of people experiencing homelessness with a recent drug overdose in the PHOENIx pilot randomised controlled trial
Authors: Lowrie Richard , McPherson Andrew , Mair Frances S. , Stock Kate , Jones Caitlin , Maguire Donogh , Paudyal Vibhu , Duncan Clare , Blair Becky , Lombard Cian , Ross Steven , Hughes Fiona , Moir Jane , Scott Ailsa , Reilly Frank , Sills Laura , Hislop Jennifer , Farmer Natalia , Lucey Sharon , Wishart Stephen , Provan George , Robertson Roy , Williamson Andrea 
Published: April 2023

Abstract
Background
Drug-related deaths in Scotland are the highest in Europe. Half of all deaths in people experiencing homelessness are drug related, yet we know little about the unmet health needs of people experiencing homelessness with recent non-fatal overdose, limiting a tailored practice and policy response to a public health crisis.

Methods
People experiencing homelessness with at least one non-fatal street drug overdose in the previous 6 months were recruited from 20 venues in Glasgow, Scotland, and randomised into PHOENIx plus usual care, or usual care. PHOENIx is a collaborative assertive outreach intervention by independent prescriber NHS Pharmacists and third sector homelessness workers, offering repeated integrated, holistic physical, mental and addictions health and social care support including prescribing. We describe comprehensive baseline characteristics of randomised participants.

Results
One hundred and twenty-eight participants had a mean age of 42 years (SD 8.4); 71% male, homelessness for a median of 24 years (IQR 12–30). One hundred and eighteen (92%) lived in large, congregate city centre temporary accommodation. A quarter (25%) were not registered with a General Practitioner. Participants had overdosed a mean of 3.2 (SD 3.2) times in the preceding 6 months, using a median of 3 (IQR 2–4) non-prescription drugs concurrently: 112 (87.5%) street valium (benzodiazepine-type new psychoactive substances); 77 (60%) heroin; and 76 (59%) cocaine. Half (50%) were injecting, 50% into their groins. 90% were receiving care from Alcohol and Drug Recovery Services (ADRS), and in addition to using street drugs, 90% received opioid substitution therapy (OST), 10% diazepam for street valium use and one participant received heroin-assisted treatment. Participants had a mean of 2.2 (SD 1.3) mental health problems and 5.4 (SD 2.5) physical health problems; 50% received treatment for physical or mental health problems. Ninety-one per cent had at least one mental health problem; 66% had no specialist mental health support. Participants were frail (70%) or pre-frail (28%), with maximal levels of psychological distress, 44% received one or no daily meal, and 58% had previously attempted suicide.

Conclusions
People at high risk of drug-related death continue to overdose repeatedly despite receiving OST. High levels of frailty, multimorbidity, unsuitable accommodation and unmet mental and physical health care needs require a reorientation of services informed by evidence of effectiveness and cost-effectiveness.

Trial registration UK Clinical Trials Registry identifier: ISRCTN 10585019.
Preoperative anemia and long-term survival in patients undergoing colorectal cancer surgery: a retrospective cohort study
Authors: Deng Yixu , Weng Meilin , zhang Jun 
Published: April 2023

Abstract
Background
The impact of preoperative anemia on a survival outcome and the importance of correcting preoperative anemia in patients with colorectal cancer (CRC) remain controversial. This study aimed to explore how preoperative anemia affects the long-term survival of patients undergoing colorectal cancer surgery.

Methods
This was a retrospective cohort study in which adult patients underwent surgical resection for colorectal cancer between January 1, 2008, and December 31, 2014, at a large tertiary cancer center. A total of 7436 patients were enrolled in this study. Anemia was defined according to the diagnostic criteria of China (hemoglobin level < 110 g/L for women and < 120 g/L for men). The median follow-up time was 120.5 months (10.0 years). Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce selection bias. Overall survival (OS) and disease-free survival (DFS) were compared between patients with and without preoperative anemia using the Kaplan–Meier estimator and the weighted log-rank test based on IPTW. Univariate and multivariate Cox proportional hazards models were used to assess factors associated with OS and DFS. Multivariable Cox regression was also used to assess red blood cell (RBC) transfusion associations between preoperative anemia and outcomes.

Results
After IPTW adjustment, clinical profiles were similar, except that tumor location and TNM stage remained imbalanced between the preoperative anemia and preoperative non-anemia groups (p < 0.001). IPTW analysis showed that the 5-year OS rate (71.3 vs. 78.6%, p < 0.001) and the 5-year DFS rate (63.9 vs. 70.9%, p < 0.001) were significantly lower in the preoperative anemia group. Multivariate analysis showed that preoperative anemia was associated with poorer OS and DFS, while RBC transfusion may improve OS (hazard ratio [HR] 0.54, p = 0.054) and DFS (HR 0.50, p = 0.020) in CRC patients with preoperative anemia.

Conclusions
Preoperative anemia is an independent risk factor for survival in patients undergoing colorectal surgery. Strategies to reduce preoperative anemia in patients with CRC should be considered.
Combined treatment with glucosamine and chondroitin sulfate improves rheumatoid arthritis in rats by regulating the gut microbiota
Authors: Wang Xuesong , Liu Dongsong , Li Dan , Yan Jiai , Yang Ju , Zhong Xiaohui , Xu Qin , Xu Yuanze , Xia Yanping , Wang Qinyue , Cao Hong , Zhang Feng 
Published: April 2023

Abstract
Background
To investigate the ameliorative effects of glucosamine (GS), chondroitin sulphate (CS) and glucosamine plus chondroitin sulphate (GC) on rheumatoid arthritis (RA) in rats, and to explore the mechanism of GS, CS and GC in improving RA based on the gut microbiota.

Methods
RA rat models were effectively developed 14 days after CFA injection, and then garaged with GS, CS and GC. Body weight and paw volume of rats were monitored at multiple time points at the beginning of CFA injection. Until D36, serum and ankle tissue specimens were used to measure levels of circulating inflammatory factors (TNF-α, IL-1β, MMP-3, NO and PGE2) and local inflammatory indicators (TLR-4 and NF-κB). On D18, D25, and D36, intergroup gut microbiota was compared using 16S rRNA gene sequencing and bioinformatics analysis. We also performed the correlation analysis of gut bacteria, joint swelling and inflammatory indicators.

Results
GC, rather than GS and CS, could reduce right paw volumes, levels of TLR-4 and NF-κB in synovial tissues. In addition, enriched genera in RA model rats screened out by LEfSe analysis could be inhibited by GC intervention, including potential LPS-producing bacteria (Enterobacter, Bacteroides, Erysipelotrichaceae_unclassified and Erysipelotrichaceae_uncultured) and some other opportunistic pathogens (Esherichia_Shigella, Nosocomiicoccus, NK4A214_group, Odoribacter, Corynebacterium and Candidatus_Saccharimonas.etc.) that positively correlated with pro-inflammatory cytokines, right paw volume, and pathology scores. Furthermore, the gut microbiota dysbiosis was observed to recover before alleviating joint swelling after interventions.

Conclusions
GC could inhibit potential LPS-producing bacteria and the activation of TLR-4/NF-κB pathway in RA rats, thus alleviating RA-induced joint injury.