bluuebunny/crossref_metadata_2025_split huggingface dataset:
A critical interpretive synthesis of migrants’ experiences of the Australian health system
Authors: Lakin Kimberly , Kane Sumit 
Published: January 2023

AbstractWhile the health of and healthcare use by migrants has received significant scholarly and policy attention in Australia, current debates highlight that a critical examination of the theoretical underpinnings of these inquiries and responses is needed. We conducted a systematic review and critical interpretive synthesis (CIS) to critically examine how the policy and scholarly literature conceptualises migrants’ interactions with and experiences of the Australian health system. Guided by PRISMA, we searched for literature without imposing any limits. We also searched key State and Federal Government websites for relevant policy documents. Our initially broad inclusion criteria became refined as the CIS progressed. We prioritised the likely relevance and theoretical contribution of the papers to our inquiry over methodological quality. The CIS of 104 papers revealed that the Australian scholarly literature and policy documents consistently homogenise and reduce migrants according to an assumed, (1) cultural identity, (2) linguistic affiliation, and/or (3) broad geographic origin. Based on these three critiques and drawing on the theoretical literature, we propose a synthesising argument on how the Australian literature could better conceptualise migrants’ experiences of the Australian health system. We contend that both research and policy should explicitly recognise and engage with the multifaceted and shifting ways that migrants define themselves, generally, and during their encounters with destination country health systems. Engagement with this notion is necessary for also understanding how aspects of migrants’ identities are dynamically co-constructed during their interactions with the health system. These understandings have implications for improving the design and implementation of policies and programs directed at improving the responsiveness of Australia’s health system to the needs and expectations of migrant communities specifically, and destination countries broadly.
The diagnostic accuracy of 332 incisional biopsies in patients with malignant tumors in the musculoskeletal system
Authors: Dirks Michael , Ewerbeck Nicolas K. , Ballhause Tobias M. , Weiß Sebastian , Luebke Andreas , Schlickewei Carsten , Frosch Karl-Heinz , Priemel Matthias 
Published: January 2023

Abstract
Background
It is known that specimen collection followed by histopathological workup is the core of evidence-based medical therapy of musculoskeletal tumors. There exist many controversies about how a biopsy should be performed. While some centers recommend minimal invasive biopsy procedures, mostly the core needle biopsy (CNB), others prefer the incisional biopsy.

Purpose of the study
This study aimed to determine the accuracy of incisional biopsy for malignant tumors in the musculoskeletal system. Moreover, advantages and disadvantages to other biopsy methods are discussed.

Methods
This retrospective, single-center study about 844 incisional biopsies (benign and malignant) analysis the diagnostic accuracy of 332 malignant tumors, concerning the final histopathological result. In addition, surgical complications are analyzed to find the best way to plan and treat patients timely and correct. Secondary endpoints are the patients age, the pure operation time, as well as the type of tumor, and the subsequent therapy.

Results
In summary, incisional biopsy corresponded a sensitivity of 100% for malignancy in 844 incisional biopsies and a specificity of 97.6% in 332 malignant tumors, but it features greater operative expense (incision/suture 23.5 min) and the risk of general anesthesia.

Conclusion
The method of biopsy should be tailored to the individual patient and the experience of the center performing the procedure.
Identification and characterization of two SERPINC1 mutations causing congenital antithrombin deficiency
Authors: Wang Han-lu , Ruan Dan-dan , Wu Min , Ji Yuan-yuan , Hu Xing-xing , Wu Qiu-yan , Zhang Yan-ping , Lin Bin , Hu Ya-nan , Wang Hang , Tang Yi , Fang Zhu-ting , Luo Jie-wei , Liao Li-sheng , Gao Mei-zhu 
Published: January 2023

Abstract
Background
Antithrombin (AT) is the main physiological anticoagulant involved in hemostasis. Hereditary AT deficiency is a rare autosomal dominant thrombotic disease mainly caused by mutations in SERPINC1, which was usually manifested as venous thrombosis and pulmonary embolism. In this study, we analyzed the clinical characteristics and screened for mutant genes in two pedigrees with hereditary AT deficiency, and the functional effects of the pathogenic mutations were evaluated.

Methods
Candidate gene variants were analyzed by next-generation sequencing to screen pathogenic mutations in probands, followed by segregation analysis in families by Sanger sequencing. Mutant and wild-type plasmids were constructed and transfected into HEK293T cells to observe protein expression and cellular localization of SERPINC1. The structure and function of the mutations were analyzed by bioinformatic analyses.

Results
The proband of pedigree A with AT deficiency carried a heterozygous frameshift mutation c.1377delC (p.Asn460Thrfs*20) in SERPINC1 (NM000488.3), a 1377C base deletion in exon 7 resulting in a backward shift of the open reading frame, with termination after translation of 20 residues, and a different residue sequence translated after the frameshift. Bioinformatics analysis suggests that the missing amino acid sequence caused by the frameshift mutation might disrupt the disulfide bond between Cys279 and Cys462 and affect the structural function of the protein. This newly discovered variant is not currently included in the ClinVar and HGMD databases. p.Arg229* resulted in a premature stop codon in exon 4, and bioinformatics analysis suggests that the truncated protein structure lost its domain of interaction with factor IX (Ala414 site) after the deletion of nonsense mutations. However, considering the AT truncation protein resulting from the p.Arg229* variant loss a great proportion of the molecule, we speculate the variant may affect two functional domains HBS and RCL and lack of the corresponding function. The thrombophilia and decreased-AT-activity phenotypes of the two pedigrees were separated from their genetic variants. After lentiviral plasmid transfection into HEK293T cells, the expression level of AT protein decreased in the constructed c.1377delC mutant cells compared to that in the wild-type, which was not only reduced in c.685C > T mutant cells but also showed a significant band at 35 kDa, suggesting a truncated protein. Immunofluorescence localization showed no significant differences in protein localization before and after the mutation.

Conclusions
The p.Asn460Thrfs*20 and p.Arg229* variants of SERPINC1 were responsible for the two hereditary AT deficiency pedigrees, which led to AT deficiency by different mechanisms. The p.Asn460Thrfs*20 variant is reported for the first time.
Klf4-Sirt3/Pparα-Lcad pathway contributes to high phosphate-induced lipid degradation
Authors: Yu Angen , Xu Yichuang , Hogstrand Christer , Zhao Tao , Tan Xiao-Ying , Wei Xiaolei , Song Yu-Feng , Luo Zhi 
Published: January 2023

Abstract
Background
Phosphorus commonly reduces lipid deposition in the vertebrates. However, the underlying mechanisms involved in the process remain unclear.

Methods
Yellow catfish were given three experimental diets with dietary phosphate levels of 3.22, 6.47 and 7.99 g Pi kg− 1, respectively, for 8 weeks. The contents of triglyceride, non-esterified free fatty acids, adenosine triphosphate, nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide, enzymatic activities, mRNA and protein expression were determined in the intestinal tissues. Hematoxylin and eosin, Oil Red O staining, and transmission electron microscope were performed for intestinal tissues. Primary intestinal epithelial cells were isolated from yellow catfish intestine. Western blot analysis, Immunoprecipitation assays, Immunofluorescence staining, and RNA extraction and quantitative real-time PCR were decided. Luciferase reporter assays and electrophoretic mobility shift assay were used to evaluate the function of Sirt3, PPARα and Lcad promoters.

Results
High dietary phosphate intake activated intestinal phosphate absorption and excretion, and reduced lipid deposition through increasing lipolysis in the intestine. Moreover, phosphate incubation increased the mRNA and protein expression of krüppel like factor 4 (klf4), silent mating-type information regulation 2 homolog 3 (sirt3), peroxisome proliferator activated receptor alpha (pparα) and long chain acyl-CoA dehydrogenase (lcad) in the intestinal epithelial cells (IECs), and klf4 knockdown attenuated the phosphate-induced increase of protein levels of Sirt3, Pparα and Lcad. Further investigation found that Klf4 overexpression increased the activity of sirt3 and pparα promoters, which in turn reduced the acetylation and protein level of Lcad.

Conclusion
Dietary Pi excess induced lipid degradation by the activation of the Klf4-Sirt3/Pparα-Lcad pathway in the intestine and primary IECs.

Graphical Abstract
Association between radiotherapy and risk of second primary malignancies in patients with resectable lung cancer: a population-based study
Authors: Zhou Bolun , Zang Ruochuan , Song Peng , Zhang Moyan , Bie Fenglong , Bai Guangyu , Li Yuan , Huai Qilin , Han Yuning , Gao Shugeng 
Published: January 2023

Abstract
Background
The most common form of treatment for non-metastatic lung cancer is surgery-based combination therapy, which may also include adjuvant radiotherapy or chemotherapy. Second primary malignancies (SPMs) are uncommon but significant radiation side effects in patients with resectable lung cancer, and SPMs have not been adequately investigated. Our study aims to assess the correlations of radiotherapy with the development of SPMs in patients with resectable lung cancer.

Methods
We screened for any primary malignancy that occurred more than five years after the diagnosis of resectable lung cancer. Based on the large cohort of the Surveillance, Epidemiology and End Results database, radiotherapy-correlated risks were estimated using the Poisson regression analysis and the cumulative incidence of SPMs was calculated using Fine-Gray competing risk regression analysis.

Results
Among the 62,435 patients with non-metastatic lung cancer undergoing surgery, a total of 11,341 (18.16%) patients have received radiotherapy. Our findings indicated that radiotherapy was substantially related to a high risk of main second solid malignancies (RR = 1.21; 95%CI, 1.08 to 1.35) and a negligible risk of main second hematologic malignancies (RR = 1.08; 95%CI, 0.84 to 1.37). With the greatest number of patients, the risk of acquiring a second primary gastrointestinal cancer was the highest overall (RR = 1.77; 95 percent CI, 1.44 to 2.15). The cumulative incidence and standardized incidence ratios of SPMs revealed similar findings. Furthermore, the young and the elderly may be more vulnerable, and the highest risk of acquiring most SPMs was seen more than ten years after lung cancer diagnosis. Additionally, more attention should be paid to the second primary gastrointestinal cancer in young individuals with resectable lung cancer.

Conclusion
After receiving radiotherapy, an increased risk of developing second primary solid and gastrointestinal cancers was observed for patients with resectable lung cancer. The prevention of SPMs associated with radiotherapy requires further attention.
D-Mannose prevents bone loss under weightlessness
Authors: Gu Ranli , Liu Hao , Hu Menglong , Zhu Yuan , Liu Xuenan , Wang Feilong , Wu Likun , Song Danyang , Liu Yunsong 
Published: January 2023

Abstract
Background
Astronauts undergo significant microgravity-induced bone loss during space missions, which has become one of the three major medical problems hindering human's long-term space flight. A risk-free and antiresorptive drug is urgently needed to prevent bone loss during space missions. D-mannose is a natural C-2 epimer of D-glucose and is abundant in cranberries. This study aimed to investigate the protective effects and potential mechanisms of D-mannose against bone loss under weightlessness.

Methods
The hind legs of tail-suspended (TS) rats were used to mimic weightlessness on Earth. Rats were administered D-mannose intragastrically. The osteoclastogenic and osteogenic capacity of D-mannose in vitro and in vivo was analyzed by micro-computed tomography, biomechanical assessment, bone histology, serum markers of bone metabolism, cell proliferation assay, quantitative polymerase chain reaction, and western blotting. RNA-seq transcriptomic analysis was performed to detect the underlying mechanisms of D-mannose in bone protection.

Results
The TS rats showed lower bone mineral density (BMD) and poorer bone morphological indices. D-mannose could improve BMD in TS rats. D-mannose inhibited osteoclast proliferation and fusion in vitro, without apparent effects on osteoblasts. RNA-seq transcriptomic analysis showed that D-mannose administration significantly inhibited the cell fusion molecule dendritic cell-specific transmembrane protein (DC-STAMP) and two indispensable transcription factors for osteoclast fusion (c-Fos and nuclear factor of activated T cells 1 [NFATc1]). Finally, TS rats tended to experience dysuria-related urinary tract infections (UTIs), which were suppressed by treatment with D-mannose.

Conclusion
D-mannose protected against bone loss and UTIs in rats under weightlessness. The bone protective effects of D-mannose were mediated by inhibiting osteoclast cell fusion. Our findings provide a potential strategy to protect against bone loss and UTIs during space missions.
Cross-cultural diversity analysis: traditional knowledge and uses of freshwater fish species by indigenous peoples of southern Punjab, Pakistan
Authors: Iqbal Khalid Javed , Umair Muhammad , Altaf Muhammad , Hussain Tanveer , Ahmad Rana Manzoor , Abdeen Sayed Muhammad Zain Ul , Pieroni Andrea , Abbasi Arshad Mahmood , Ali Shahzad , Ashraf Sana , Amjad Naila , Khan Abdul Majid , Bussmann Rainer W. 
Published: January 2023

Abstract
Background
Fisheries have tremendous cultural and educational importance in human societies. The world is undergoing fast environmental and cultural changes, and local knowledge is being lost. Understanding how people interpret environmental change and develop practices in response to such change is essential to comprehend human resource use. This study was planned with the intent to document and conserve the knowledge about the uses of the freshwater fish fauna among the residents in South Punjab, Pakistan.

Methods
Semi-structured interviews and questionnaires were conducted to collect data from informers (N = 88). Principal component analysis, relative frequency citation, fidelity level, relative popularity level, rank-order priority, and similarity index were used to analyze the fish data.

Results
Overall, a total of 43 species of fishes were utilized in the study region, but only 26 species were utilized ethnomedicinally to treat a variety of illnesses such as asthma, body weakness, burn, chicken pox, cold, cough, eyesight, hepatitis, impotence, joint pain, night blindness, skin burn, spleen treatment, stomach infection, and weakness. The uses of fishes were analyzed employing various indices. The highest use value (UV) of 0.86 was calculated for spotted snakehead (Channa punctata), whereas the lowest UV of 0.05 was attained by karail fish (Securicula gora). Moreover, Channa punctata, Cyprinus carpio, Labeo rohita, Oreochromis niloticus, Wallago attu, Hypophthalmichthys molitrix, Rita rita, Sperata seenghala, Notopterus notopterus, Labeo dyocheilus, Systomus sarana, Puntius punjabensis, Securicula gora, Ompok bimaculatus, and Ompok pabda were the most popular species with RPL = 1.0. Out of the total, 20 species had a “zero” similarity index, while the ethnomedicinal use of 12 species (i.e., Labeo dyocheilus, Labeo boggut, Systomus sarana, Puntius punjabensis, Aspidoparia morar, Securicula gora, Crossocheilus diplochilus, Mastacembelus armatus, Ompok bimaculatus, Ompok pabda, Labeo gonius, and Sperata seenghala) was documented for the first time for a variety of diseases (i.e., body weakness, stomach infection, skin burn, joint pain, impotence, asthma, spleen treatment, and chicken pox).

Conclusion
Our findings showed that the local people of the study area hold noteworthy traditional knowledge about the medicinal and cultural uses of fish species. Furthermore, a comprehensive analysis of active chemicals and in vivo and/or in vitro activities of chemicals derived from ichthyofauna with the highest FC as well as UVs could be interesting for research on new drugs.
Health-related quality of life and patient-reported symptoms after postoperative proton beam radiotherapy of cervical and endometrial cancer: 2-year results of the prospective phase II APROVE-trial
Authors: Meixner Eva , Wark Antje , Forster Tobias , Weykamp Fabian , Lang Kristin , König Laila , Lindel Katja , Oelmann-Avendano Jan Tobias , Krisam Johannes , Schneeweiss Andreas , Ellerbrock Malte , Mielke Thomas , Hörner-Rieber Juliane , Herfarth Klaus , Debus Jürgen , Arians Nathalie 
Published: January 2023

Abstract
Introduction
The APROVE-trial investigated the tolerability of postoperative proton beam therapy in women with cervical or endometrial cancer. The present analysis evaluated the secondary endpoints of health-related quality of life (HRQOL) and patient-reported symptoms.

Methods
25 patients were included in this prospective phase-II-trial and treated with postoperative radiotherapy using protons alone or in combination with chemotherapy. To attain general and gynecologic-specific HRQOL measures, the EORTC-QLQ-C30 questionnaires combined with -QLQ-CX24 for cervical and -QLQ-EN24 for endometrial cancer were assessed at baseline, at the end of RT and up to 2 years after radiotherapy. The results were compared to an age-matched norm reference population. Symptoms were assessed using Common Terminology Criteria for Adverse Events (CTCAE) and institutional patient-reported symptoms grading.

Results
Scores regarding global health status were markedly impaired at baseline (mean: 58.0 ± 20.1) compared to reference population data, but significantly (p = 0.036) improved and evened out to comparable norm values 2 years after proton therapy (mean: 69.9 ± 19.3). Treatment caused acute and long-term worsening of pain (p = 0.048) and gastrointestinal symptoms (p = 0.016) for women with endometrial cancer, but no higher-grade CTCAE ≥ 3° toxicity was observed. Dosimetric evaluation of rectum, sigmoid, large and small bowel showed no correlation with the reported gastrointestinal symptoms. After 2 years, fatigue had significantly improved (p = 0.030), whereas patients with cervical cancer experienced more often lymphedema (p = 0.017). Scores for endometrial cancer pertaining to sexual activity (p = 0.048) and body image (p = 0.022) had improved post treatment; in the latter this effect persisted after 2 years.

Conclusion
Proton beam therapy in the adjuvant setting was well tolerated with only low-grade side effects concerning gastrointestinal symptoms, lymphedema and pain. Overall quality of life was impaired at baseline, but patients were able to recover to values comparable to norm population 2 years after proton therapy. Larger studies are needed to confirm whether the benefit of proton therapy translates into a clinical effect. Sexual dysfunction remains an important issue.
Trial registration: The trial was registered at https://clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03184350, 09th June 2017).
Patient Assessment Chronic Illness Care (PACIC) and its associations with quality of life among Swiss patients with systemic sclerosis: a mixed methods study
Authors: Kocher Agnes , Simon Michael , Dwyer Andrew A. , Blatter Catherine , Bogdanovic Jasmina , Künzler-Heule Patrizia , Villiger Peter M. , Dan Diana , Distler Oliver , Walker Ulrich A. , Nicca Dunja 
Published: January 2023

AbstractBackgroundThe Chronic Care Model (CCM) is a longstanding and widely adopted model guiding chronic illness management. Little is known about how CCM elements are implemented in rare disease care or how patients’ care experiences relate to health-related quality of life (HRQoL). We engaged patients living with systemic sclerosis (SSc) to assess current care according to the CCM from the patient perspective and their HRQoL.MethodsWe employed an explanatory sequential mixed methods design. First, we conducted a cross-sectional quantitative survey (n = 101) using the Patient Assessment of Chronic Illness Care (PACIC) and Systemic Sclerosis Quality of Life (SScQoL) questionnaires. Next, we used data from individual patient interviews (n = 4) and one patient focus group (n = 4) to further explore care experiences of people living with SSc with a focus on the PACIC dimensions.ResultsThe mean overall PACIC score was 3.0/5.0 (95% CI 2.8–3.2, n = 100), indicating care was ‘never’ to ‘generally not’ aligned with the CCM. Lowest PACIC subscale scores related to ‘goal setting/tailoring’ (mean = 2.5, 95% CI 2.2–2.7) and ‘problem solving/contextual counselling’ (mean = 2.9, 95% CI 2.7–3.2). No significant correlations were identified between the mean PACIC and SScQoL scores. Interviews revealed patients frequently encounter major shortcomings in care including ‘experiencing organized care with limited participation’, ‘not knowing which strategies are effective or harmful’ and ‘feeling left alone with disease and psychosocial consequences’. Patients often responded to challenges by ‘dealing with the illness in tailored measure’, ‘taking over complex coordination of care’ and ‘relying on an accessible and trustworthy team’.ConclusionsThe low PACIC mean overall score is comparable to findings in patients with common chronic diseases. Key elements of the CCM have yet to be systematically implemented in Swiss SSc management. Identified gaps in care related to lack of shared decision-making, goal-setting and individual counselling-aspects that are essential for supporting patient self-management skills. Furthermore, there appears to be a lack of complex care coordination tailored to individual patient needs.
Single-cell transcriptomics unveils xylem cell development and evolution
Authors: Tung Chia-Chun , Kuo Shang-Che , Yang Chia-Ling , Yu Jhong-He , Huang Chia-En , Liou Pin-Chien , Sun Ying-Hsuan , Shuai Peng , Su Jung-Chen , Ku Chuan , Lin Ying-Chung Jimmy 
Published: January 2023

AbstractBackgroundXylem, the most abundant tissue on Earth, is responsible for lateral growth in plants. Typical xylem has a radial system composed of ray parenchyma cells and an axial system of fusiform cells. In most angiosperms, fusiform cells comprise vessel elements for water transportation and libriform fibers for mechanical support, while both functions are performed by tracheids in other vascular plants such as gymnosperms. Little is known about the developmental programs and evolutionary relationships of these xylem cell types.ResultsThrough both single-cell and laser capture microdissection transcriptomic profiling, we determine the developmental lineages of ray and fusiform cells in stem-differentiating xylem across four divergent woody angiosperms. Based on cross-species analyses of single-cell clusters and overlapping trajectories, we reveal highly conserved ray, yet variable fusiform, lineages across angiosperms. Core eudicotsPopulus trichocarpaandEucalyptus grandisshare nearly identical fusiform lineages, whereas the more basal angiospermLiriodendron chinensehas a fusiform lineage distinct from that in core eudicots. The tracheids in the basal eudicotTrochodendron aralioides, an evolutionarily reversed trait, exhibit strong transcriptomic similarity to vessel elements rather than libriform fibers.ConclusionsThis evo-devo framework provides a comprehensive understanding of the formation of xylem cell lineages across multiple plant species spanning over a hundred million years of evolutionary history.