bluuebunny/crossref_metadata_2025_split huggingface dataset:
The predictive role of sickness absence spell durations in associations with inpatient- and specialized outpatient care among a population-based Swedish twin sample
Authors: Ropponen Annina , Wang Mo , Narusyte Jurgita , Kärkkäinen Sanna , Blom Victoria , Svedberg Pia 
Published: April 2021

Abstract
Background
The associations between a sickness absence spell duration and patient care have been rarely studied. An assumption is that associations would differ by spell duration and by the patient care type, inpatient- or specialized outpatient, due to severity of diseases and/or conditions. We aimed to investigate sickness absence spells in various spell durations as a predictor for subsequent inpatient- and specialized outpatient care separately, and to study if familial confounding plays a role in these associations.

Methods
We followed a population-based sample of Swedish twins born 1925–90 with national registers from 2001 for first incident sickness absence spell (days to calculate spell duration categorized into ≤30 days, 31–90 days, 91–180 days and ≥ 181 days), or no sickness absence, and for inpatient- and specialized outpatient care until 2013 (n = 24,975). Cox proportional hazards models were applied for hazard ratios (HR) with 95% confidence intervals (CI) while accounting for covariates and familial confounding.

Results
First incident sickness absence spell across all duration categories was associated with an increased risk of inpatient- (age- and sex adjusted HR 1.28 to 6.05) or specialized outpatient care (HR 1.17–2.50), both in comparison to those without any sickness absence or the shortest sickness absence spell category (1–30 days). The associations remained statistically significant while controlling for covariates or familial confounding.

Conclusions
First incident sickness absence spell increases the risk of inpatient care or specialized outpatient care regardless of the duration of the sickness absence spell. Hence, incident sickness absence spells should be noted and targeted to actions at workplaces as well as in primary and occupational health care.
Determinants of health care use among homeless individuals: evidence from the Hamburg survey of homeless individuals
Authors: Hajek André , Bertram Franziska , Heinrich Fabian , van Rüth Victoria , Ondruschka Benjamin , Kretzler Benedikt , Schüler Christine , Püschel Klaus , König Hans-Helmut 
Published: April 2021

Abstract
Background
To identify the determinants of health care use among homeless individuals.

Methods
Data were taken from the Hamburg survey of homeless individuals (n = 100 individuals in the here used model, mean age 44.8 years, SD 12.5) focusing on homeless individuals in Hamburg, Germany. The number of physician visits in the past 3 months and hospitalization in the preceding 12 months were used as outcome measures. Drawing on the Andersen model of health care use as a conceptual framework, predisposing characteristics, enabling resources and need factors as well as psychosocial variables were included as correlates.

Results
Negative binomial regressions showed that increased physician visits were associated with being female (IRR: 4.02 [95% CI: 1.60–10.11]), absence of chronic alcohol consume (IRR: 0.26 [95% CI: 0.12–0.57]) and lower health-related quality of life (IRR: 0.97 [95% CI: 0.96–0.98]). Furthermore, logistic regressions showed that the likelihood of hospitalization was positively associated with lower age (OR: 0.93 [95% CI: 0.89–0.98]), having health insurance (OR: 8.11 [2.11–30.80]) and lower health-related quality of life (OR: 0.97 [95% CI: 0.94–0.99]).

Conclusions
Our study showed that predisposing characteristics (both age and sex), enabling resources (i.e., health insurance) and need factors in terms of health-related quality of life are main drivers of health care use among homeless individuals. This knowledge may assist in managing health care use.
Victorian healthcare experience survey 2016–2018; evaluation of interventions to improve the patient experience
Authors: Wong Eunice , Mavondo Felix , Horvat Lidia , McKinlay Louise , Fisher Jane 
Published: April 2021

Abstract
Background
Patient experience is recognised as a quality of care indicator and increasingly health services are working on achieving set targets and improving their performance. Interventions at the point of care targeting communication with patients, patient engagement in care processes and discharge planning are associated with better patient experience. However, their efficacy and application to different contexts are still unclear. The aims were to describe the interventions implemented by health services to improve patient experience, their impact on overall patient experiences and specific experiences in areas of communication, discharge planning, patient education on treatment/tests, the physical environment and access to care.

Methods
Secondary data analysis of the Victorian Healthcare Experience inpatient surveys reported in September 2016 and 2018 and content analysis of interventions published in the Victorian Quality Account for 2017 from 59 public health services in Victoria, Australia. The interventions were categorised using an adapted taxonomy of professional interventions by the Cochrane EPOC Review Group. Univariate tests and confirmatory factor analysis were conducted to test measure invariance across the 2016 and 2018 groups and examine the association between each of the intervention categories on overall patient experience measure and specific outcome measures.

Results
This study found that the overall patient experience was consistent (93%) between 2016 and 2018 samples. In comparing impact, a single intervention rather than none or multiple interventions in communication, respect and dignity and treatment and disease education areas were associated with a higher level of the overall patient experience. Interventions in waiting time, access to service, care continuity and emotional support categories were associated with a decrease in overall patient experience.

Conclusion
This study found that to improve the overall patient experience, more focus is needed on evidence-based interventions in dignity and respect and emotional support. Furthermore, the choice of interventions should be guided by evidence of their efficacy and prioritising implementing one intervention well, provides more gains.
Toceranib phosphate-associated nephrotic syndrome in a dog: a case report
Authors: Remerowski Shannon M. , Herrera Chamisa L. , Donnelly Lindsay L. 
Published: April 2021

Abstract
Background
Nephrotic syndrome (NS) is rare in dogs and is characterized by concurrent clinical findings of proteinuria, hyperlipidemia, hypoalbuminemia, and edema. NS has been reported in humans receiving tyrosine kinase inhibitors (TKI) and in dogs receiving masitinib. This is the first report of NS in a dog receiving toceranib phosphate.

Case presentation
An 8-year-old, female, spayed Labrador retriever was diagnosed with a 10 cm mast cell tumor on the left lateral abdomen. After completion of a 12-week vinblastine and prednisone protocol, she began treatment with toceranib phosphate (2.6 mg/kg by mouth, every other day). Proteinuria was documented prior to starting toceranib. On day 426 after diagnosis (day 328 of toceranib phosphate treatment), the dog was evaluated for diarrhea, lethargy and anorexia. On physical examination, dependent edema was noted on the ventral chest and abdomen, and sterile neutrophilic inflammation was aspirated from a 2.3 cm splenic nodule. The following laboratory values were reported: albumin < 1.5 g/dL; cholesterol 378 mg/dl and urine protein to creatinine ratio of 3.79. The patient was diagnosed with NS, and treatment with toceranib phosphate was discontinued. Low-dose aspirin was started in addition to an increased dosage of enalapril (0.47 mg/kg q12hr). No other therapy was instituted. The dog improved clinically, and laboratory values returned to near normal over the 8-week follow-up. She was euthanized 1399 days after discontinuing toceranib phosphate with progressive disease.

Conclusions
Nephrotic syndrome is a potential adverse event associated with the drug toceranib phosphate which may be reversible with discontinuation of treatment. Careful monitoring of urine protein, serum biochemistry, blood pressure and patient weight is advisable during treatment with toceranib phosphate.
Biochemical and synergistic properties of a novel alpha‐amylase from Chinese nong‐flavor Daqu
Authors: Chen Lanchai , Yi Zhuolin , Fang Yang , Jin Yanling , He Kaize , Xiao Yao , Zhao Dong , Luo Huibo , He Hui , Sun Qun , Zhao Hai 
Published: April 2021

Abstract
Background
Daqu is the most important fermentation starter for Chinese liquor, with large number of microbes and enzymes being openly enriched in the Daqu system over thousands of years. However, only a few enzymes have been analyzed with crude protein for total liquefying power and saccharifying power of Daqu. Therefore, the complex enzymatic system present in Daqu has not been completely characterized. Moreover, their pivotal and complicated functions in Daqu are completely unknown.

Results

In this study, a novel α-amylase NFAmy13B, from GH13_5 subfamily (according to the Carbohydrate-Active enZYmes Database, CAZy) was successfully heterologous expressed by Escherichia coli from Chinese Nong-flavor (NF) Daqu. It exhibited high stability ranging from pH 5.5 to 12.5, and higher specific activity, compared to other GH13_5 fungal α-amylases. Moreover, NFAmy13B did not show activity loss and retained 96% residual activity after pre-incubation at pH 11 for 21 h and pH 12 for 10 h, respectively. Additionally, 1.25 mM Ca2+ significantly improved its thermostability. NFAmy13B showed a synergistic effect on degrading wheat starch with NFAmy13A (GH13_1), another α-amylase from Daqu. Both enzymes could cleave maltotetraose and maltopentaose in same degradation pattern, and only NFAmy13A could efficiently degrade maltotriose. Moreover, NFAmy13B showed higher catalytic efficiency on long-chain starch, while NFAmy13A had higher catalytic efficiency on short-chain maltooligosaccharides. Their different catalytic efficiencies on starch and maltooligosaccharides may be caused by their discrepant substrate-binding region.

Conclusions
This study mined a novel GH13_5 fungal α-amylase (NFAmy13B) with outstanding alkali resistance from Nong-flavor (NF) Daqu. Furthermore, its synergistic effect with NFAmy13A (GH13_1) on hydrolyzing wheat starch was confirmed, and their possible contribution in NF Daqu was also speculated. Thus, we not only provide a candidate α-amylase for industry, but also a useful strategy for further studying the interactions in the complex enzyme system of Daqu.
Phosphonates enantiomers receiving with fungal enzymatic systems
Authors: Serafin-Lewańczuk Monika , Brzezińska-Rodak Małgorzata , Lubiak-Kozłowska Katarzyna , Majewska Paulina , Klimek-Ochab Magdalena , Olszewski Tomasz K. , Żymańczyk-Duda Ewa 
Published: April 2021

Abstract
Background
Phosphonates derivatives are in the area of interests because of their unique chemical-physical features. These compounds manifest variety of biological interactions within the sensitive living cells, including impact on particular enzymes activities. Biological “cause and effect” interactions are based upon the specific matching between the structures and/or compounds and this is usually the result of proper optical configurations of particular chiral moieties. Presented research is targeted to the phosphonates with the heteroatom incorporated in their side functionalities. Such molecules are described as possible substrates of bioconversion for the first time lately and this field is not fully explored.

Results
Presented research is targeted to the synthesis of pure hetero-phosphonates enantiomers. The catalytic activity of yeasts and moulds were tested towards two substrates: the thienyl and imidazole phosphonates to resolve their racemic mixtures. Biotransformations conditions differed depending on the outcome, what included changing of following parameters: type of cultivation media, bioprocess duration (24–72 h), additional biocatalyst pre-treatment (24–48 h starvation step triggering the secondary metabolism). (S)-1-amino-1-(3-thienyl)methylphosphonate was produced with the assistance of R. mucilaginosa or A. niger (e.e. up to 98% and yield up to 100%), starting from the 3 mM of substrate racemic mixture. Bioconversion of racemic mixture of 3 mM of (1-amino-1-(4-imidazole)methylphosphonic acid) resulted in the synthesis of S-isomer (up to 95% of e.e.; 100% of yield) with assistance of R. mucilaginosa. 24 h biotransformation was conducted with biomass preincubated under 48-hour starvation conditions. Such stereoselective resolution of the racemic mixtures of substrates undergoes under kinetic control with the conversion of one from the enantiomers.

Conclusions
Composition of the culturing media and pre-incubation in conditions of nutrient deficiency were significant factors influencing the results of kinetic resolution of racemic mixtures of phosphonic substrates and influencing the economic side of the biocatalysis e.g. by determining the duration of whole biocatalytic process.

Graphical abstract
Down-regulation of cylindromatosis protein phosphorylation by BTK inhibitor promotes apoptosis of non-GCB-diffuse large B-cell lymphoma
Authors: Xu Xin , Wei Ting , Zhong Weijie , Ang Rosalind , Lei Ye , Zhang Hui , Li Qingshan 
Published: April 2021

AbstractBackgroundNon-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB-DLBCL) has worse clinical outcome than GCB-DLBCL, and some relapsed/refractory non-GCB-DLBCL (R/R non-GCB-DLBCL) are even resistant to CD20 monoclonal antibody (rituximab). Bruton’s tyrosine kinase inhibitors (BTKis) are new drugs for B-cell lymphoma. BTKis can promote apoptosis of DLBCL by inactivating nuclear transcription factor κB (NFκB) signaling pathway. Cylindromatosis (CYLD) is a tumor suppressor and ubiquitinase. CYLD can inactivate NFκB signaling pathway through ubiquitination and regulate the apoptosis of hematological tumors. The ubiquitination of CYLD can be regulated by phosphorylation, suggesting that the regulation of CYLD phosphorylation can be a potential mechanism to promote the apoptosis of hematological tumors. Therefore, we hypothesized that BTKis could promote the apoptosis of non-GCB-DLBCL by regulating the phosphorylation of CYLD, especially in rituximab resistant cases, and we proved this hypothesis through both in vivo and in vitro experiments.MethodsThe baseline expression levels of CYLD phosphorylation in non-GCB-DLBCL patients and cell lines were detected by Western Blotting. The non-GCB-DLBCL cell lines were treated with BTKis, and apoptosis induced by BTKis treatment was detected by Western blotting, cell viability assay and Annexin V assay. To verify whether the effect of BTKis on apoptosis in non-GCN-DLBCL cells is CYLD dependent, the expression of CYLD was knocked down by lentiviral shRNAs. To verify the effect of BTKis on the phosphorylation of CYLD and the apoptosis in vivo and in rituximab resistant non-GCB-DLBCL, the xeograft model and rituximab resistant non-GCB-DLBCL cells were generated by tumor cell inoculation and escalation of drug concentrations, respectively.ResultsBTKis induced apoptosis by down-regulating CYLD phosphorylationin in non GCB-DLBCL, xenograft mouse model, and rituximab-resistant cells, and this effect could be enhanced by rituximab. Knocking-down CYLD reversed apoptosis which was induced by BTKis. BTKis induced CYLD-dependent apoptosis in non-GCB-DLBCL including in rituximab-resistant cells.ConclusionsThe present results indicated that CYLD phosphorylation is a potential clinical therapeutic target for non-GCB-DLBCL, especially for rituximab-resistant relapsed/refractory cases.
Role of tumor mutation burden-related signatures in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma
Authors: Tang Rong , Liu Xiaomeng , Wang Wei , Hua Jie , Xu Jin , Liang Chen , Meng Qingcai , Liu Jiang , Zhang Bo , Yu Xianjun , Shi Si 
Published: April 2021

AbstractBackgroundHigh tumor mutation burden (TMB) has gradually become a sensitive biomarker for predicting the response to immunotherapy in many cancers, including lung, bladder and head and neck cancers. However, whether high TMB predicts the response to immunotherapy and prognosis in pancreatic ductal adenocarcinoma (PDAC) remained obscure. Hence, it is significant to investigate the role of genes related to TMB (TRGs) in PDAC.MethodsThe transcriptome and mutation data of PDAC was downloaded from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA). Five independent external datasets of PDAC were chosen to validate parts of our results. qRT-PCR and immunohistochemical staining were also performed to promote the reliability of this study.ResultsThe median overall survival (OS) was significantly increased in TMB_low group compared with the counterpart with higher TMB score after tumor purity adjusted (P = 0.03). 718 differentially expressed TRGs were identified and functionally enriched in some oncogenic pathways. 67 TRGs were associated with OS in PDAC. A prognostic model for the OS was constructed and showed a high predictive accuracy (AUC = 0.849). We also found TMB score was associated with multiple immune components and signatures in tumor microenvironment. In addition, we identified a PDAC subgroup featured with TMBlowMicrosatellite instabilityhigh(MSIhigh) was associated with prolonged OS and a key molecule, ANKRD55, potentially mediating the survival benefits.ConclusionThis study analyzed the biological function, prognosis value, implications for mutation landscape and potential influence on immune microenvironment of TRGs in PDAC, which contributed to get aware of the role of TMB in PDAC. Future studies are expected to investigate how these TRGs regulate the initiation, development or repression of PDAC.
Hereditary angioedema due to C1 inhibitor deficiency in Belarus: epidemiology, access to diagnosis and seven novel mutations in SERPING1 gene
Authors: Guryanova Irina , Suffritti Chiara , Parolin Debora , Zanichelli Andrea , Ishchanka Nastassia , Polyakova Ekaterina , Belevtsev Mikhail , Perego Francesca , Cicardi Marco , Zharankova Yulia , Konoplya Natalya , Caccia Sonia , Gidaro Antonio 
Published: April 2021

Abstract
Background
Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease. Few states in developing countries have an adequate management of HAE, but none of them belongs to the former USSR area. This study analyses data from C1-INH-HAE patients from Belarus.

Methods
Data about clinical characteristics, genetics, access to diagnosis and treatment were collected from 2010 by the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology in Minsk. A questionnaire about attacks, prophylactic (LTP) and on-demand therapy (ODT) was administered to patients.

Results
We identified 64 C1-INH-HAE patients belonging to 26 families, 27 (42.2%) of which were diagnosed in the last 3 years. The estimated minimal prevalence was 1:148,000. Median age at diagnosis was 29 years, with diagnostic delay of 19 years. Thirty-eight patients answered a questionnaire about therapy. Eleven patients did not use any treatment to resolve HAE attacks. Twenty-seven patients underwent ODT: 9 with appropriate treatments, and 18 with inappropriate treatments. Nine patients used LTP with attenuated androgens and 1 with tranexamic acid. Thirty-two patients answered a questionnaire about attacks and triggers: 368 angioedema attacks were reported, with an average of 10 attacks per year. We found 24 different SERPING1 variants: 9 missenses, 6 in splice sites, 6 small deletions, 2 nonsense, 1 large deletion; 7 have not been previously described. De novo variants were found in 11 patients.

Conclusions
C1-INH-HAE diagnosis and management in Belarus is improved as seen from the high number of new diagnosis in the last 3 years. Next steps will be to reduce the diagnostic delay and to promote the LTP and ODT.
Ethical and legal issues in psychedelic harm reduction and integration therapy
Authors: Pilecki Brian , Luoma Jason B. , Bathje Geoff J. , Rhea Joseph , Narloch Vilmarie Fraguada 
Published: April 2021

AbstractPsychedelic-assisted therapy may represent an upcoming paradigm shift in the treatment of mental health problems as recent clinical trials have demonstrated strong evidence of their therapeutic benefits. While psychedelics are currently prohibited substances in most countries, the growing popularity of their therapeutic potential is leading many people to use psychedelics on their own rather than waiting for legal medical access. Therapists therefore have an ethical duty to meet this need by providing support for clients using psychedelics. However, incorporating psychedelics into traditional psychotherapy poses some risk given their prohibited status and many therapists are unsure of how they might practice in this area. This paper explicates such risks and describes ways in which therapists can mitigate them and strive to practice within legal and ethical boundaries. A harm reduction approach will be emphasized as a useful framework for conducting therapy around clients' use of psychedelics. It is argued that therapists can meet with clients before and after their own personal psychedelic experiences in order to help clients minimize risk and maximize benefit. Common clinical scenarios in this growing clinical area will also be discussed.
Intragenerational social mobility and self-rated oral health in the british cohort study
Authors: Mohd Khairuddin Aina Najwa , Bernabé Eduardo , Delgado-Angulo Elsa Karina 
Published: April 2021

Abstract
Background
Most studies on social mobility and oral health have focused on movement between generations (intergenerational mobility) rather than movement within an individual’s own lifetime (intragenerational mobility). The aim of this study was to investigate the association between intragenerational social mobility from early to middle adulthood and self-rated oral health.

Methods
This study used data from 6524 participants of the 1970 British Birth Cohort Study, an ongoing population-based birth cohort of individuals born in England, Scotland and Wales. Participants’ socioeconomic position was indicated by occupational social class at age 26 and 46 years (the first and latest adult waves, respectively). Self-rated oral health was measured at age 46 years. The association between social mobility and adult oral health was assessed using conventional regression models and diagonal reference models, adjusting for gender, ethnicity, country of residence and residence area.

Results
Over a fifth of participants (22.2%) reported poor self-rated oral health at age 46 years. In conventional regression analysis, the odds ratios for social mobility varied depending on whether they were adjusted for social class of origin or destination. In addition, all social trajectories had greater odds of reporting poor oral health than non-mobile adults in class I/II. In diagonal reference models, both upward (Odds Ratio 0.79; 95% CI 0.63–0.99) and downward mobility (0.90; 95% CI 0.71–1.13) were inversely associated with poor self-rated oral health. The origin weight was 0.48 (95% CI 0.33–0.63), suggesting that social class of origin was as important as social class of destination.

Conclusion
This longitudinal analysis showed that intragenerational social mobility from young to middle adulthood was associated with self-rated oral health, independent of previous and current social class.