bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Isavuconazonium Sulfate and Posaconazole Delayed Release Tablets on Tacrolimus Dose-to-Concentration Ratios
Authors: Sweiss Helen , Kincaide Elisabeth , Levine Deborah , Hall Reed 
Published: December 2022

Introduction Limited evidence exists on the effect of isavuconazonium sulfate and posaconazole delayed release tablets on tacrolimus dose-to-concentration ratios in lung transplant recipients. Project Aims The purpose of this evaluation was to assess the impact of novel triazoles on tacrolimus dose-to-concentration ratios. Design This retrospective review included lung transplant recipient ≥18 years of age from January 1, 2017 to October 1, 2020 who received either posaconazole delayed release tablets or isavuconazonium sulfate for. A paired analysis evaluated outcomes pre-triazole and post-triazole initiation. Results Forty-one patients met evaluation criteria for inclusion. A total of 34 of 41 patients received posaconazole delayed release tablets. Of these patients, 22 of 34 were transitioned from previous triazole to posaconazole delayed release tablets and experienced a 47% reduction in tacrolimus dose-to-concentration ratio. Twelve patients were newly initiated on posaconazole delayed release tablets and experienced a 50% reduction in tacrolimus dose-to-concentration ratios. Although not statistically significant, a 30% reduction in tacrolimus dose-to-concentration ratio was observed when transitioning to isavuconazonium sulfate from previous triazole therapy. Conclusion Limited data exists to provide guidance on tacrolimus dose adjustments with initiation and conversion of novel triazoles, however, this evaluation provides more knowledge on the drug interaction with novel triazoles and tacrolimus.
Specific multimorbidity patterns modify the impact of an exercise intervention in older hospitalized adults
Authors: Martínez-Velilla Nicolas , Galbete Arkaitz , Roso-Llorach Albert , Zambom-Ferraresi Fabricio , Sáez de Asteasu Mikel L , Izquierdo Mikel , Vetrano Davide L , Calderón-Larrañaga Amaia 
Published: December 2022

Background Different multimorbidity patterns present with different prognoses, but it is unknown to what extent they may influence the effectiveness of an individualized multicomponent exercise program offered to hospitalized older adults. Methods This study is a secondary analysis of a randomized controlled trial conducted in the Department of Geriatric Medicine of a tertiary hospital. In addition to the standard care, an exercise-training multicomponent program was delivered to the intervention group during the acute hospitalization period. Multimorbidity patterns were determined through fuzzy c-means cluster analysis, over 38 chronic diseases. Functional, cognitive and affective outcomes were considered. Results Three hundred and six patients were included in the analyses (154 control; 152 intervention), with a mean age of 87.2 years, and 58.5% being female. Four patterns of multimorbidity were identified: heart valves and prostate diseases (26.8%); metabolic diseases and colitis (20.6%); psychiatric, cardiovascular and autoimmune diseases (16%); and an unspecific pattern (36.6%). The Short Physical Performance Battery (SPPB) test improved across all patterns, but the intervention was most effective for patients in the metabolic/colitis pattern (2.48-point difference between intervention/control groups, 95% CI 1.60-3.35). Regarding the Barthel Index and the Mini Mental State Examination (MMSE), the differences were significant for all multimorbidity patterns, except for the psychiatric/cardio/autoimmune pattern. Differences concerning quality of life were especially high for the p sychiatric/cardio/autoimmune pattern (16.9-point difference between intervention/control groups, 95% CI 4.04, 29.7). Conclusions Patients in all the analyzed multimorbidity patterns improved with this tailored program, but the improvement was highest for those in the metabolic pattern. Understanding how different chronic disease combinations are associated with specific functional and cognitive responses to a multicomponent exercise intervention may allow further tailoring such interventions to older patients’ clinical profile.
Nontuberculous mycobacteria infection and pulmonary disease in bronchiectasis
Authors: Suska Kseniia , Amati Francesco , Sotgiu Giovanni , Gramegna Andrea , Mantero Marco , Ori Margherita , Ferrarese Maurizio , Codecasa Luigi Ruffo , Stainer Anna , Blasi Francesco , Aliberti Stefano 
Published: December 2022

BackgroundAlthough interest in nontuberculous mycobacteria (NTM) infection has increased in the last decades, published data vary according to different geographical areas, diagnostic facilities and quality of study design. This study aims at assessing both prevalence and incidence of NTM infection and NTM pulmonary disease (NTM-PD) among adults with bronchiectasis, to describe patients’ characteristics, therapeutic options and clinical outcomes.MethodsBronchiectasis adults who had been tested for NTM were enrolled at the Bronchiectasis Program of the Policlinico Hospital in Milan, Italy, from 2016 to 2018.ResultsAmong the 373 patients enrolled, 26.1% had at least one respiratory sample positive for NTM and 12.6% reached a diagnosis of NTM-PD. Incidence rates for NTM infection and NTM-PD were 13 (95% CI 10–16) and 4 (95% CI 2–6) per 100 person-years, respectively. The most prevalent NTM species causing NTM-PD wereM. intracellulare(38.3%),M. avium(34.0%),M. abscessus(8.5%) andM. kansasii(8.5%). Once treatment for NTM-PD was initiated, a favourable outcome was documented in 52.2% of the patients, while a negative outcome was recorded in 32.6%, including recurrence (17.4%), treatment failure (10.9%), re-infection (2.2%) and relapse (2.2%). Treatment halted was experienced in 11 (23.9%) patients.ConclusionsNTM infection is frequent in bronchiectasis patients and the presence of NTM-PD is relevant. The low success rate of NTM-PD treatment in bronchiectasis patients requires a call to action to identify new treatment modalities and new drugs to improve patients’ outcomes.
Genome-wide identification of BBX gene family and their expression patterns under salt stress in soybean
Authors: Shan Binghui , Bao Guohua , Shi Tianran , Zhai Lulu , Bian Shaomin , Li Xuyan 
Published: December 2022

Abstract
Background
BBX genes are key players in the regulation of various developmental processes and stress responses, which have been identified and functionally characterized in many plant species. However, our understanding of BBX family was greatly limited in soybean.

Results
In this study, 59 BBX genes were identified and characterized in soybean, which can be phylogenetically classified into 5 groups. GmBBXs showed diverse gene structures and motif compositions among the groups and similar within each group. Noticeably, synteny analysis suggested that segmental duplication contributed to the expansion of GmBBX family. Moreover, our RNA-Seq data indicated that 59 GmBBXs showed different transcript profiling under salt stress, and qRT-PCR analysis confirmed their expression patterns. Among them, 22 GmBBXs were transcriptionally altered with more than two-fold changes by salt stress, supporting that GmBBXs play important roles in soybean tolerance to salt stress. Additionally, Computational assay suggested that GmBBXs might potentially interact with GmGI3, GmTOE1b, GmCOP1, GmCHI and GmCRY, while eight types of transcription factors showed potentials to bind the promoter regions of GmBBX genes.

Conclusions
Fifty-nine BBX genes were identified and characterized in soybean, and their expression patterns under salt stress and computational assays suggested their functional roles in response to salt stress. These findings will contribute to future research in regard to functions and regulatory mechanisms of soybean BBX genes in response to salt stress.
Celiac disease and upper secondary school achievement in Sweden A retrospective cohort study
Authors: Johansson Katarina , Norström Fredrik , Green Peter H. R. , Ivarsson Anneli , Richter Sundberg Linda , Själander Anders , Myleus Anna 
Published: December 2022

Abstract
Background
Both undiagnosed celiac disease and some chronic childhood diseases are associated with lower academic achievement. However, there is little knowledge of achievements in those diagnosed with celiac disease. Our aim was to investigate school achievements in upper secondary school among Swedish adolescents with celiac disease.

Methods
We performed a retrospective cohort study using register data. We analyzed choice of upper secondary school program, completion of upper secondary school including achievements of basic eligibility for college/university, and final grade in individuals with celiac disease diagnosed before 15 years of age, born 1991–97. We compared with the Swedish population of the same birth years. Analyses were adjusted for sex, year of birth, living region at 17 years of age, and parental education as well as income.

Results
The cohort included 734 074 individuals, whereof 3 257 (62% females) with celiac disease. There was no significant difference in choice of upper secondary school program. No significant difference was found in completion or achieving basic eligibility for college/university in adjusted analyses. The mean final grade in the celiac disease group was 13.34 (standard deviation 4.85) compared to 12.78 (standard deviation 5.01) in the reference population (p < 0.001), out of a maximum of 20. The effect of celiac disease on final grade remained in adjusted analyses (p = 0.012).

Conclusions
We found that diagnosed celiac disease does not negatively affect school achievements in upper secondary school. This finding suggests the diagnosis, treatment and follow-up programs of celiac disease could reverse potential deleterious academic processes.
The effect of sleep disturbance on the association between work–family conflict and burnout in nurses: a cross-sectional study from South Korea
Authors: Han Sujeong , Kwak Sungjung 
Published: December 2022

Abstract
Background
Sleep disturbances can lead to work–family conflicts and affect the mental health of nurses. This study aimed to investigate the mediating effect of sleep disturbance on the association between work–family conflict (WFC) and burnout in nurses.

Methods
Responses to a questionnaire from 156 nurses working in a hospital in South Korea were analyzed. Multiple linear regression analysis and PROCESS Macro Model 4 were used to analyze the mediating effect of sleep disturbance on the relationship between WFC and burnout. A bootstrapping approach was used to test the statistical significance of the indirect parameter effects.

Results
The WFC of nurses had a positive correlation with sleep disturbance and burnout. Moreover, sleep disturbance completely mediated the association between WFC and burnout.

Conclusions
Nursing administrators should pay careful attention to WFCs that interfere with nurses’ sleep and reduce their sleep quality, and design suitable working schedules that minimize the effects of WFC. In addition, hospital administrators should improve shift scheduling to ensure good sleep quality and reduce the health effects of WFC among nurses.
Impact of the 24-hour time target policy for emergency departments in South Korea: a mixed method study in a single medical center
Authors: Park Sookyung , Chang Hansol , Jung Weon , Lee Se Uk , Hwang Sung Yeon , Yoon Hee , Cha Won Chul , Shin Tae Gun , Sim Min Seob , Jo Ik Joon , Kim Taerim 
Published: December 2022

Abstract
Background
In South Korea, after the spread of the Middle East Respiratory Syndrome epidemic was aggravated by long stays in crowded emergency departments (EDs), a 24-hour target policy for EDs was introduced to prevent crowding and reduce patients' length of stay (LOS). The policy requires at least 95% of all patients to be admitted, discharged or transferred from an ED within 24 hours of arrival. This study analyzes the effects of the 24-hour target policy on ED LOS and compliance rates and describes the consequences of the policy.

Methods
A mixed-methods approach was applied to a retrospective observational study of ED visits combined with a survey of medical professionals. The primary measure was ED LOS, and the secondary measure was policy compliance rate which refers to the proportion of patient visits with a LOS shorter than 24 hours. Patient flow, quality of care, patient safety, staff workload, and staff satisfaction were also investigated through surveys. Mann–Whitney U and χ2 tests were used to compare variables before and after the introduction of the policy.

Results
The median ED LOS increased from 3.9 hours (interquartile range [IQR] = 2.1–7.6) to 4.5 hours (IQR = 2.5–8.5) after the policy was introduced. This was likely influenced by the average monthly number of patients, which greatly increased from 4819 (SD = 340) to 5870 (SD = 462) during the same period. The proportion of patients with ED LOS greater than 24 hours remained below5% only after 6 months of policy implementation, but the number of patients whose disposition was decided at 23 hours increased by 4.84 times. Survey results suggested that patient flow and quality of care improved slightly, while the workload of medical staff worsened.

Conclusions
After implementing the 24-hour target policy, the proportion of patients whose ED LOS exceeded 24 hours decreased, even though the median ED LOS increased. However, the unintended consequences of the policy were observed such as increased medical professional workload and abrupt expulsion of patients before 24 hours.
Re-evaluation of the myoepithelial cells roles in the breast cancer progression
Authors: Shams Anwar 
Published: December 2022

AbstractOver the past decades, luminal epithelial cell lineage has gained considerable attraction as the functionally milk-secreting units and as the most fruitful acreage for breast cancer launching. Recognition of the effective involvement of the myoepithelial cells in mammary gland development and in hampering tumorigenesis has renewed the interest in investigating the biological roles of this second main mammary lineage. The human breast is made up of an extensively branching ductal system intervening by copious lobular units. The ductal system is coated by a chain of luminal epithelial cells (LECs) situated on a layer of myoepithelial cells (MECs) and encompassed by a distinguished basement membrane. Ductal contractility during lactation is a well-known function delivered by the MECs however this is not the only assignment mediated by these cellular populations. It has been well appreciated that the MECs exhibit a natural paracrine power in defeating cancer development and advancement. MECs were found to express numerous proteinase inhibitors, anti-angiogenic factors, and tumour suppressors proteins. Additionally, MECs contributed effectively to maintaining the right luminal cells' polarization and further separating them from the adjacent stroma by making an integrated fence. Indeed, disruption of the MECs layer was reported to facilitate the invasion of the cancer cells to the surrounding stroma. Nonetheless, MECs were also found to exhibit cancer-promoting effects and provoke tumour invasion and dissemination by displaying distinct cancer chemokines. Herein in this review, we aimed to address the roles delivered by MECs in breast cancer progression and decipher the molecular mechanisms regulating proper MECs’ physiology, integrity, and terminal differentiation.
Graphical Abstract
Modern thromboprophylaxis protocol based on guidelines applied in a respiratory intensive care unit: a single-center prospective cohort study
Authors: Tang Xiao , Lyu Wen-Rui , Jin Yu , Wang Rui , Li Xu-Yan , Li Ying , Zhang Chun-Yan , Zhao Wei , Tong Zhao-Hui , Sun Bing 
Published: December 2022

Abstract
Background
Critically ill patients in intensive care units (ICUs) are at high risk of venous thromboembolism (VTE). This study aimed to explore the prophylaxis effect under a guideline-based thromboprophylaxis protocol among critically ill patients in a respiratory ICU.

Methods
For this single-center prospective cohort study, we followed the thromboprophylaxis protocol, which was drawn up based on relevant guidelines and Chinese experts’ advice. Clinical data were entered into an electronic case report form and analyzed. Multivariate logistic regression was conducted to explore independent risk factors of VTE event under this protocol.

Results
From August 1, 2014, to December 31, 2020, 884 patients underwent thromboprophylaxis according to this protocol; 10.5% of them received mechanical prophylaxis, 43.8% received pharmacological prophylaxis, and 45.7% received pharmacological combined with mechanical prophylaxis. The proportion of VTE events was 14.3% for patients who received the thromboprophylaxis protocol, of which 0.1% had pulmonary thromboembolism (PTE), 2.0% had proximal deep vein thrombosis (DVT), and 12.1% had isolated distal DVT. There was no significant difference between different thromboprophylaxis measures. Cirrhosis (OR 5.789, 95% CI [1.402, 23.894], P = 0.015), acute asthma exacerbation (OR 39.999, 95% CI [4.704, 340.083], P = 0.001), and extracorporeal membrane oxygenation treatment (OR 22.237, 95%CI [4.824, 102.502], P < 0.001) were independent risk factors for proximal DVT under thromboprophylaxis.

Conclusions
The thromboprophylaxis protocol based on guidelines applied in the ICU was practicable and could help decrease the proportion of PTE and proximal DVT events. The risk factors of VTE events happening under the thromboprophylaxis protocol require more attention.

Trial registration
ClinicalTrials.gov: NCT02213978.
Efficient biosynthesis of pinosylvin from lignin-derived cinnamic acid by metabolic engineering of Escherichia coli
Authors: Hu Yueli , Zhang Chen , Zou Lihua , Zheng Zhaojuan , Ouyang Jia 
Published: December 2022

Abstract
Background
The conversion of lignin-derived aromatic monomers into valuable chemicals has promising potential to improve the economic competitiveness of biomass biorefineries. Pinosylvin is an attractive pharmaceutical with multiple promising biological activities.

Results
Herein, Escherichia coli was engineered to convert the lignin-derived standard model monomer cinnamic acid into pinosylvin by introducing two novel enzymes from the wood plant: stilbene synthase from Pinus pinea (PpSTS) and 4-Coumarate-CoA ligase from Populus trichocarpa (Ptr4CL4). The expression of Ptr4CL4 drastically improved the production of pinosylvin (42.5 ± 1.1 mg/L), achieving values 15.7-fold higher than that of Ptr4CL5 (another 4-Coumarate-CoA ligase from Populus trichocarpa) in the absence of cerulenin. By adjusting the expression strategy, the optimized engineered strain produced pinosylvin at 153.7 ± 2.2 mg/L with an extremely high yield of 1.20 ± 0.02 mg/mg cinnamic acid in the presence of cerulenin, which is 83.9% ± 1.17 of the theoretical yield. This is the highest reported pinosylvin yield directly from cinnamic acid to date.

Conclusion
Our work highlights the feasibility of microbial production of pinosylvin from cinnamic acid and paves the way for converting lignin-related aromatics to valuable chemicals.
Fixed-point results for generalized contraction in K-sequentially complete ordered dislocated fuzzy quasimetric spaces
Authors: Shoaib Abdullah , Khaliq Kheeba 
Published: December 2022

AbstractThe ambition of this work is to introduce the notion of left (right) K-sequentially complete ordered dislocated fuzzy quasimetric spaces and to define a relevant Hausdorff metric on compact sets. A new approach, given in (Shoaib et al. in Filomat 34(2):323–338, 2020) has been used to obtain fixed-point results for multivalued mappings fulfilling generalized contraction in the latest framework. For the authenticity of our result, an example is formulated.
Exploring the experiences of clients receiving opioid use disorder treatment at a methadone clinic in Kenya: a qualitative study
Authors: Kiburi Sarah Kanana , Mwangi Jackline , Maina Geoffrey 
Published: December 2022

Abstract
Background
Assessing the experiences of individuals on methadone treatment is essential to help evaluate the treatment program’s effectiveness. This study aimed to explore the experiences of patients receiving methadone treatment at a clinic in Nairobi, Kenya.

Method
This study employed an exploratory qualitative study design. Through purposive sampling, participants were enrolled from individuals attending a methadone clinic for at least 2 years. Semi-structured individual interviews were used to collect data on substance use and experience before methadone treatment and experiences after starting methadone treatment, including benefits and challenges. Interviews were transcribed, and NVIVO 12 software was used to code the data using the preidentified analytical framework. Thematic analyses were utilized to identify cross-cutting themes between these two data sets. Seventeen participants were enrolled.

Results
Seventeen participants were enrolled comprising 70% males, with age range from 23 to 49 years and more than half had secondary education. The interview data analysis identified four themes, namely: (a) the impact of opioid use before starting treatment which included adverse effects on health, legal problems and family dysfunction; (b) learning about methadone treatment whereby the majority were referred from community linkage programs, family and friends; (c) experiences with care at the methadone treatment clinic which included benefits such as improved health, family reintegration and stigma reduction; and (d) barriers to optimal methadone treatment such as financial constraints.

Conclusion
The findings of this study show that clients started methadone treatment due to the devastating impact of opioid use disorder on their lives. Methadone treatment allowed them to regain their lives from the adverse effects of opioid use disorder. Additionally, challenges such as financial constraints while accessing treatment were reported. These findings can help inform policies to improve the impact of methadone treatment.
Inhibition of glycogen synthase kinase-3-beta (GSK3β) blocks nucleocapsid phosphorylation and SARS-CoV-2 replication
Authors: Shapira Tirosh , Vimalanathan Selvarani , Rens Celine , Pichler Virginia , Peña-Díaz Sandra , Jordana Grace , Rees William , Winkler Dirk F. H. , Sarai Iqbal , Steiner Theodore , Jean François , Pelech Steven , Av-Gay Yossef 
Published: December 2022

AbstractGSK3β has been proposed to have an essential role in Coronaviridae infections. Screening of a targeted library of GSK3β inhibitors against both SARS-CoV-2 and HCoV-229E to identify broad-spectrum anti-Coronaviridae inhibitors resulted in the identification of a high proportion of active compounds with low toxicity to host cells. A selected lead compound, T-1686568, showed low micromolar, dose-dependent activity against SARS-CoV-2 and HCoV-229E. T-1686568 showed efficacy in viral-infected cultured cells and primary 2D organoids. T-1686568 also inhibited SARS-CoV-2 variants of concern Delta and Omicron. Importantly, while inhibition by T-1686568 resulted in the overall reduction of viral load and protein translation, GSK3β inhibition resulted in cellular accumulation of the nucleocapsid protein relative to the spike protein. Following identification of potential phosphorylation sites of Coronaviridae nucleocapsid, protein kinase substrate profiling assays combined with Western blotting analysis of nine host kinases showed that the SARS-CoV-2 nucleocapsid could be phosphorylated by GSK3β and PKCa. GSK3β phosphorylated SARS-CoV-2 nucleocapsid on the S180/S184, S190/S194 and T198 phospho-sites, following previous priming in the adjacent S188, T198 and S206, respectively. Such inhibition presents a compelling target for broad-spectrum anti-Coronaviridae compound development, and underlies the mechanism of action of GSK3β host-directed therapy against this class of obligate intracellular pathogens.