bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving care for cancer-related and other forms of lymphoedema in low- and middle-income countries: a qualitative study
Authors: Torgbenu Eric , Luckett Tim , Buhagiar Mark , Requena Cecilia Mauricio , Phillips Jane L. 
Published: April 2022

AbstractBackgroundLymphoedema is a common, distressing and debilitating condition that can be related to cancer and its treatment or other conditions. Little is known about current practices in the diagnosis, assessment and management of lymphoedema in low- and middle-income countries (LMIC).AimTo describe current practices in diagnosing, assessing and managing cancer-related and other forms of lymphoedema in LMIC, and related barriers and facilitators.MethodsAn exploratory-descriptive qualitative study. Participants were lymphoedema experts or health care professionals identified via published lymphoedema papers and professional organizations respectively. Sampling was purposive to ensure a diversity of perspectives and experience. Data collection was via semi-structured telephone/video interviews, and questions canvassed participants’ experiences and perceptions of lymphoedema care in LMIC. Interviews were audio-recorded and transcribed verbatim. Analysis proceeded via inductive coding before mapping codes to the World Health Organization’s (WHO) Innovative Care for Chronic Conditions Framework.ResultsNineteen participants were interviewed, most of whom were physiotherapists (n = 11). Ten participants worked permanently in a LMIC, while the remainder were based in a high-income country (HIC) and had been involved in initiatives to improve lymphoedema care across multiple LMIC. Participants indicated that management of cancer versus non-cancer related lymphoedema was similar, but that pathways to care were more straight-forward for those receiving cancer care, leading to earlier diagnosis. Key facilitators to optimizing lymphoedema care in LMIC included: 1) joining forces to overcome lymphoedema-related stigma; 2) building workforce capabilities; and 3) partnering with patients and families to support self-management. Ideas for building workforce included developing health professional knowledge, supporting a commitment to multidisciplinary team care, and adapting HIC guidelines for lymphoedema care to LMIC. Partnering with patients and families to support self-management involved following the person-centred approach, establishing clear communication, promoting adherence to management, adapting management to available resources, and involving patient family and friends in lymphoedema care.ConclusionRaising community and health professional awareness regarding lymphoedema and its management is a key first step to improving care outcomes. Resources for clinicians and patients/families developed for lymphoedema care in HIC need to be adapted for low resource settings.
Non-compliance with a nurse’s advice to visit the primary care provider: an exploratory secondary analysis of the TRIAGE-trial
Authors: Homburg Ines , Morreel Stefan , Verhoeven Veronique , Monsieurs Koenraad G. , Meysman Jasmine , Philips Hilde , De Graeve Diana 
Published: April 2022

Abstract
Background
During the cluster randomised TRIAGE-trial, a nurse advised 13% of low-risk patients presenting at an emergency department in Belgium to visit the adjacent general practitioner cooperative. Patients had the right to refuse this advice. This exploratory study examines the characteristics of refusers by uncovering the determinants of non-compliance and its impact on costs, as charged on the patient’s invoice.

Methods
Bivariate analyses with logistic regressions and T-tests were used to test the differences in patient characteristics, patient status, timing characteristics, and costs between refusers and non-refusers. A chi-square automatic interaction detection analysis was used to find the predictors of non-compliance.

Results
23.50% of the patients refused the advice to visit the general practitioner cooperative. This proportion was mainly influenced by the nurse on duty (non-compliance rates per nurse ranging from 2.9% to 52.8%) and the patients’ socio-economic status (receiving increased reimbursement versus not OR 1.37, 95%CI: 0.96 to 1.95). Additionally, non-compliance was associated (at the 0.10 significance level) with being male, not living nearby and certain reasons for encounter. Fewer patients refused when the nurse perceived crowding level as quiet relative to normal, and more patients refused during the evening. The mean cost was significantly higher for patients who refused, which was a result of more extensive examination and higher out-of-pocket expenses at the ED.

Conclusions
The nurse providing the advice to visit the general practitioner cooperative has a central role in the likelihood of patients’ refusal. Interventions to reduce non-compliance should aim at improving nurse-patient communication. Special attention may be required when managing patients with a lower socio-economic status. The overall mean cost was higher for refusers, illustrating the importance of compliance.

Trial registration
The trial was registered on registration number NCT03793972 on 04/01/2019.
Plant metabolomics: a new strategy and tool for quality evaluation of Chinese medicinal materials
Authors: Xiao Qi , Mu Xinlu , Liu Jiushi , Li Bin , Liu Haitao , Zhang Bengang , Xiao Peigen 
Published: April 2022

AbstractThe present quality control method of Chinese medicinal materials (CMM) has obvious deficiency, which cannot be compatible with the multi-target and multi-component characteristics and production process of CMM. Plant metabolomics with a huge impetus to comprehensively characterize the metabolites and clarify the complexity and integrity of CMM, has been widely used in the research of CMM. This article comprehensively reviewed the application of plant metabolomics in the quality control of CMM. It introduced the concept, technique, and application examples, discussed the prospects, limitations, improvements of plant metabolomics. MS and NMR, as important techniques for plant metabolomics, are mainly highlighted in the case references. The purpose of this article is to clarify the advantage of plants metabolomics for promoting the optimization of the CMM quality control system and proposing a system approach to realize the overall quality control of CMM based on plant metabolomics combined with multidisciplinary method.
Multimarker synaptic protein cerebrospinal fluid panels reflect TDP-43 pathology and cognitive performance in a pathological cohort of frontotemporal lobar degeneration
Authors: Cervantes González Alba , Irwin David J. , Alcolea Daniel , McMillan Corey T. , Chen-Plotkin Alice , Wolk David , Sirisi Sònia , Dols-Icardo Oriol , Querol-Vilaseca Marta , Illán-Gala Ignacio , Santos-Santos Miguel Angel , Fortea Juan , Lee Edward B. , Trojanowski John Q. , Grossman Murray , Lleó Alberto , Belbin Olivia 
Published: April 2022

Abstract
Background
Synapse degeneration is an early event in pathological frontotemporal lobar degeneration (FTLD). Consequently, a surrogate marker of synapse loss could be used to monitor early pathologic changes in patients with underlying FTLD. The aim of this study was to evaluate the relationship of antemortem cerebrospinal fluid (CSF) levels of 8 synaptic proteins with postmortem global tau and TDP-43 burden and cognitive performance and to assess their diagnostic capacity in a neuropathological FTLD cohort.

Methods
We included patients with a neuropathological confirmation of FTLD-Tau (n = 24, mean age-at-CSF 67 years ± 11), FTLD-TDP (n = 25, 66 years ± 9) or AD (n = 25, 73 years ± 6) as well as cognitively normal controls (n = 35, 69 years ± 7) from the Penn FTD Center and ADRC. We used a semi-quantitative measure of tau and TDP-43 inclusions to quantify pathological burden across 16 brain regions. Statistical methods included Spearman rank correlations, one-way analysis of covariance, ordinal regression, step-wise multiple linear regression and receiver-operating characteristic curves.

Result
CSF calsyntenin-1 and neurexin-2a were correlated in all patient groups (rs = .55 to .88). In FTLD-TDP, we observed low antemortem CSF levels of calsyntenin-1 and neurexin-2a compared to AD (.72-fold, p = .001, .77-fold, p = .04, respectively) and controls (.80-fold, p = .02, .78-fold, p = .02, respectively), which were inversely associated with post-mortem global TDP-43 burden (regression r2 = .56, p = .007 and r2 = .57, p = .006, respectively). A multimarker panel including calsyntenin-1 was associated with TDP-43 burden (r2 = .69, p = .003) and MMSE score (r2 = .19, p = .03) in FTLD. A second multimarker synaptic panel, also including calsyntenin-1, was associated with MMSE score in FTLD-tau (r2 = .49, p = .04) and improved diagnostic performance to discriminate FTLD-Tau and FTLD-TDP neuropathologic subtypes (AUC = .83).

Conclusion
These synaptic panels have potential in the differential diagnosis of FTLD neuropathologic subtypes and as surrogate markers of cognitive performance in future clinical trials targeting TDP-43 or tau.
Adaptive antitumor immune response stimulated by bio-nanoparticle based vaccine and checkpoint blockade
Authors: Bai Xuewei , Zhou Yanmei , Yokota Yuki , Matsumoto Yoshihiro , Zhai Bo , Maarouf Nader , Hayashi Hikaru , Carlson Rolf , Zhang Songhua , Sousa Aryanna , Sun Bei , Ghanbari Hossein , Dong Xiaoqun , Wands Jack R. 
Published: April 2022

Abstract
Background
Interactions between tumor and microenvironment determine individual response to immunotherapy. Triple negative breast cancer (TNBC) and hepatocellular carcinoma (HCC) have exhibited suboptimal responses to immune checkpoint inhibitors (ICIs). Aspartate β-hydroxylase (ASPH), an oncofetal protein and tumor associated antigen (TAA), is a potential target for immunotherapy.

Methods
Subcutaneous HCC and orthotopic TNBC murine models were established in immunocompetent BALB/c mice with injection of BNL-T3 and 4 T1 cells, respectively. Immunohistochemistry, immunofluorescence, H&E, flow cytometry, ELISA and in vitro cytotoxicity assays were performed.

Results
The ASPH-MYC signaling cascade upregulates PD-L1 expression on breast and liver tumor cells. A bio-nanoparticle based λ phage vaccine targeting ASPH was administrated to mice harboring syngeneic HCC or TNBC tumors, either alone or in combination with PD-1 blockade. In control, autocrine chemokine ligand 13 (CXCL13)-C-X-C chemokine receptor type 5 (CXCR5) axis promoted tumor development and progression in HCC and TNBC. Interactions between PD-L1+ cancer cells and PD-1+ T cells resulted in T cell exhaustion and apoptosis, causing immune evasion of cancer cells. In contrast, combination therapy (Vaccine+PD-1 inhibitor) significantly suppressed primary hepatic or mammary tumor growth (with distant pulmonary metastases in TNBC). Adaptive immune responses were attributed to expansion of activated CD4+ T helper type 1 (Th1)/CD8+ cytotoxic T cells (CTLs) that displayed enhanced effector functions, and maturation of plasma cells that secreted high titers of ASPH-specific antibody. Combination therapy significantly reduced tumor infiltration of immunosuppressive CD4+/CD25+/FOXP3+ Tregs. When the PD-1/PD-L1 signal was inhibited, CXCL13 produced by ASPH+ cancer cells recruited CXCR5+/CD8+ T lymphocytes to tertiary lymphoid structures (TLSs), comprising effector and memory CTLs, T follicular helper cells, B cell germinal center, and follicular dendritic cells. TLSs facilitate activation and maturation of DCs and actively recruit immune subsets to tumor microenvironment. These CTLs secreted CXCL13 to recruit more CXCR5+ immune cells and to lyse CXCR5+ cancer cells. Upon combination treatment, formation of TLSs predicts sensitivity to ICI blockade. Combination therapy substantially prolonged overall survival of mice with HCC or TNBC.

Conclusions
Synergistic antitumor efficacy attributable to a λ phage vaccine specifically targeting ASPH, an ideal TAA, combined with ICIs, inhibits tumor growth and progression of TNBC and HCC.
Effectiveness of an app-based intervention to reduce substance use, gambling, and digital media use in vocational school students: study protocol for a randomized controlled trial
Authors: Arnaud Nicolas , Weymann Johanna , Lochbühler Kirsten , Pietsch Benjamin , Rossa Monika , Kraus Ludwig , Thomasius Rainer , Hanewinkel Reiner , Morgenstern Matthis 
Published: April 2022

Abstract
Background
Substance-related and addictive disorders are among the most common mental disorders in adolescence and young adulthood. Vocational school students are a risk group for problematic substance use and addictive behavior. However, the availability of evidence-based prevention concepts and programs is underdeveloped in the vocational school setting.

Methods/design
A two-arm cluster randomized waitlist-controlled trial will be conducted to evaluate the effectiveness of an app-based intervention to decrease substance use, gambling, and digital media use in vocational school students in Germany. Vocational students will participate in an app-based intervention that is designed to support voluntary commitment to abstain from or reduce substance or digital media use over a period of 2 weeks. The “education-as-usual” control arm will have access to the intervention after data collection is completed. One of the primary outcome measures will be the use of alcohol, nicotine, and digital media 30 days after the intervention. Several secondary outcome measures will also be included, such as cannabis consumption, gambling, symptoms of stress, physical activity, mindfulness, well-being, impulsivity and sensation seeking, and readiness to change. A total of 4500 vocational students from 225 classes will be recruited and randomized across three German federal states.

Discussion
This study protocol describes the design of an RCT testing the effectiveness of an app-based intervention to reduce addictive behaviors in vocational school students. It is expected that this approach will be feasible for and effective in the vocational school setting and that the study provides comprehensive information on the key factors involved in temporary abstaining or reducing substance or digital media use.

Trial registration
German Clinical Trials Register DRKS00023788. Registered on 20 January 2021
The effect of glycerol as a cryoprotective agent in the cryopreservation of adipose tissue
Authors: Zhang Pei-Qi , Tan Poh-Ching , Gao Yi-Ming , Zhang Xiao-Jie , Xie Yun , Zheng Dan-Ning , Zhou Shuang-Bai , Li Qing-Feng 
Published: April 2022

Abstract
Background
Long-term preservation of adipose tissue is crucial for clinical applications. Researchers should consider both efficiency and biosafety when choosing a cryoprotective agent (CPA) for adipose tissue preservation. Glycerol has been applied as a nontoxic CPA for multiple tissues but not adipose tissue. We aimed to evaluate the efficacy of glycerol as a CPA for adipose tissue cryopreservation.

Methods
Fresh human adipose tissues were obtained from patients who underwent liposuction and divided into 1 mL samples. Each sample was randomly mixed with 1 mL of CPA: 60–100% glycerol, 0.25 mol/L trehalose or DMSO + FBS and cryopreserved in − 196 °C liquid nitrogen for one month. After thawing and elution, the tissues were immediately evaluated for activity and structural integrity in vitro. Then, 0.2 mL of each sample was transplanted subdermally to the nude mouse dorsum and harvested after one month for histological examination to assess the effect of the cryopreserved fat in transplantation.

Results
After cryopreservation, the samples treated with DMSO + FBS, trehalose, 60% and 70% glycerol had a more integrated structure than the samples in other groups. Tissues preserved with 70% glycerol had the highest G3PDH activity of 24.41 ± 0.70, comparable to 24.76 ± 0.48 in fresh tissue (p > 0.05). Adipose-derived stem cells (ASC) viability, proliferation and differentiation capability were also better preserved in 70% glycerol group. In vivo analysis showed that tissue preserved with 70% glycerol had a retention rate of 52.37 ± 7.53%, significantly higher than other groups. Histological observation demonstrated better structural integrity and viability in 70% glycerol group. Compared to the DMSO + FBS and trehalose groups, the glycerol groups showed lower tissue inflammation.

Conclusion
Glycerol (70%) is efficient in adipose tissue cryopreservation. Glycerol-based CPAs, which are nontoxic and show biosafety, are a promising solution for clinical tissue cryopreservation.
Human primitive mesenchymal stem cell-derived retinal progenitor cells improved neuroprotection, neurogenesis, and vision in rd12 mouse model of retinitis pigmentosa
Authors: Brown Christina , Agosta Patrina , McKee Christina , Walker Keegan , Mazzella Matteo , Alamri Ali , Svinarich David , Chaudhry G. Rasul 
Published: April 2022

Abstract
Background
Currently, there is no treatment for retinal degenerative diseases (RDD) such as retinitis pigmentosa (RP). Stem cell-based therapies could provide promising opportunities to repair the damaged retina and restore vision. Thus far, primarily adult mesenchymal stem cells (MSCs) have been investigated in preclinical and clinical studies, and the results have not been convincing. We applied a new approach in which primitive (p) MSC-derived retinal progenitor cells (RPCs) were examined to treat retinal degeneration in an rd12 mouse model of RP.

Methods
Well-characterized pMSCs and RPCs labeled with PKH26 were intravitreally injected into rd12 mice. The vision and retinal function of transplanted animals were analyzed using electroretinography. Animals were killed 4 and 8 weeks after cell transplantation for histological, immunological, molecular, and transcriptomic analyses of the retina.

Results
Transplanted RPCs significantly improved vision and retinal thickness as well as function in rd12 mice. pMSCs and RPCs homed to distinct retinal layers. pMSCs homed to the retinal pigment epithelium, and RPCs migrated to the neural layers of the retina, where they improved the thickness of the respective layers and expressed cell-specific markers. RPCs induced anti-inflammatory and neuroprotective responses as well as upregulated the expression of genes involved in neurogenesis. The transcriptomic analysis showed that RPCs promoted neurogenesis and functional recovery of the retina through inhibition of BMP and activation of JAK/STAT and MAPK signaling pathways.

Conclusions
Our study demonstrated that RPCs countered inflammation, provided retinal protection, and promoted neurogenesis resulting in improved retinal structure and physiological function in rd12 mice.
Short-term responses of herbaceous vegetation to bush clearing in semi-arid rangelands of South Africa
Authors: Mndela Mthunzi , Madakadze Ignacio C. , Nherera-Chokuda Florence V. , Dube Sikhalazo , Ramoelo Abel , Mangwane Mziwanda , Tjelele Julius T. 
Published: April 2022

AbstractBush thickening reduces herbaceous species diversity and forage production, leading to a decline in grazing capacity. Hence, altering the micro-climate and woody-grass competition in bush-encroached rangelands using bush clearing is instrumental for the restoration of herbaceous vegetation. The short-term recovery potential of herbaceous species composition, basal cover and biomass production was assessed following bush clearing at Makapaanstad, North West province, South Africa. The mean density was 6908 woody plants ha−1, with Vachellia tenuispina encroaching at 6301 plants ha−1. Paired observations were conducted in bush-cleared sites (where woody plants were cut using saws, with stumps treated with picloram at 1% concentration) and uncleared sites (where the woody cover was left intact). Forty-nine different herbaceous species were recorded, with grasses being more abundant in cleared (62%) than in uncleared sites (50%). Herbaceous species showed interspecific responses, with Brachiaria eruciformis and Panicum coloratum colonising in cleared sites, whereas the frequency of other species remained comparable between cleared and uncleared sites. Graminoids, largely bunch grasses, had a significantly greater basal cover in cleared (496 cm2 m−2) compared to uncleared (301 cm2 m−2) sites. Likewise, total biomass production was significantly (p = 0.05) higher in cleared (760 kg DM ha−1) than in uncleared (636 kg DM ha−1) sites. The principal component analysis (PCA) showed that most herbaceous species were associated with soils having high total nitrogen and nitrite. Seedlings of forbs (r2 = 0.81), grasses (r2 = 0.97) and succulents (r2 = 0.98) were highly associated with nitrate-rich soils. Our results revealed that even at a short term, bush clearing is important for the restoration of herbaceous vegetation.
Evaluation of the importance of mixing during preparation of antibiotic infusions
Authors: Barzel Ina , Jessurun Janique Gabriëlle , Bahmany Soma , van der Kuy Paul Hugo Marie , Koch Birgit Catharina Peter , Hunfeld Nicole Geertruida Maria 
Published: April 2022

Abstract
Background
The mixing step after medication addition to the infusion bag is frequently omitted during the preparation of drug infusions. However, the importance of mixing when preparing antibiotic infusions is still unknown.

Methods
The primary aim of this study was to assess the importance of the mixing step by comparing the concentrations of unmixed antibiotic infusions (cefuroxime, flucloxacillin, meropenem, and vancomycin) with the declared concentration at regular intervals during infusion. The secondary aim was to compare concentrations between preparation sites (hospital pharmacy versus clinical ward). Infusion bags were run through electronic infusion pumps. For cefuroxime, flucloxacillin, and meropenem, samples were collected 1, 15, and 20 min after starting the administration (infusion duration: 30 min). For vancomycin, samples were collected after 1, 60, and 110 min (infusion duration: 120 min). Vancomycin concentrations were measured using the Architect c4000 analyser and other concentrations using a validated UPC2-MS–MS multimethod.

Results
The median concentrations of the four antibiotics were comparable to the declared concentration at all three time points. No significant differences were found between preparation sites.

Conclusions
Spontaneous mixing occurred in the examined antibiotic solutions during normal handling.