bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictable Rehabilitation of Bone Deficiencies: Hygiene, Functional and Aesthetic Perspectives
Authors: Sethi Ashok , Kaus Thomas 
Published: June 2023

The aim of this article is to describe a method for correcting bone deficiencies which may compromise aesthetic, functional or oral hygiene maintenance of implant supported restorations. The generic causes of these deficiencies are mentioned. The use of autogenous block bone grafts is described alongside methods for managing the hard and soft tissues at both the recipient and donor sites. The biomechanical advantage conferred with the use of grafts in reducing the crown:implant ratio is emphasised. The sources of intraoral bone grafts are identified and the risks of damage to adjacent anatomical structures and their avoidance are addressed. The principles of healing are briefly described with an emphasis on the increasing predictability of contact healing, as opposed to gap healing. The impact and inherent risks associated with the supplementary use of membranes for containment is also addressed. Clinical cases have been used to illustrate procedures and outcomes. Previously published data is referenced.
Barriers to the integration of palliative care in Ghana: evidence from a tertiary health facility
Authors: Okyere Joshua , Kissah-Korsah Kwaku 
Published: June 2023

Background: Integration of palliative care (PC) in cancer management is critical to improving the overall quality of life of cancer patients and their families. Nevertheless, only a few people in need of PC services actually receive them. Objective: The study explored the barriers to the successful integration of PC in cancer management in Ghana. Design: The design was an exploratory descriptive qualitative research design. Methods: In all, we conducted 13 interviews with service providers (7), patients (4) and caregivers (2). An inductive thematic analysis was carried out. Data were managed using QSR NVivo 12. Results: Our study reveals the different levels of barriers that adversely affect the successful integration of PC and cancer management. Emerging from the findings are patient- and family-level barriers (denial of the primary diagnosis and understanding of PC and financial constraints), service provider–level barriers (healthcare providers’ misunderstanding of PC and late referrals), and institutional and policy-level barriers (infrastructural and logistical constraints, non-inclusion of PC in the National Health Insurance Scheme, low staff strength). Conclusion: We conclude that different levels of barriers are encountered in the integration of PC in cancer management. There is a need for policymakers to develop comprehensive guidelines and protocols for the integration of PC into cancer management. These guidelines should address the various levels of factors that serve as barriers to PC integration. The guidelines should also emphasise the importance of early referral for PC and educate service providers on the benefits of PC for patients with life-limiting illnesses. Our findings underscore a need to include PC services and medication in the benefits package of the health insurance scheme to reduce the financial burden on patients and their families. In addition, continuous professional training of all cadre of service providers is needed to facilitate PC integration.
Incidence, clinical presentation, risk factors, outcomes, and biomarkers in de novo late acute GVHD
Authors: Akahoshi Yu , Spyrou Nikolaos , Hogan William J. , Ayuk Francis , DeFilipp Zachariah , Weber Daniela , Choe Hannah K. , Hexner Elizabeth O. , Rösler Wolf , Etra Aaron M. , Sandhu Karamjeet , Yanik Gregory A. , Chanswangphuwana Chantiya , Kitko Carrie L. , Reshef Ran , Kraus Sabrina , Wölfl Matthias , Eder Matthias , Bertrand Hannah , Qayed Muna , Merli Pietro , Grupp Stephan A. , Aguayo-Hiraldo Paibel , Schechter Tal , Ullrich Evelyn , Baez Janna , Beheshti Rahnuma , Gleich Sigrun , Kowalyk Steven , Morales George , Young Rachel , Kwon Deukwoo , Nakamura Ryotaro , Levine John E. , Ferrara James L. M. , Chen Yi-Bin 
Published: June 2023

Abstract
Late acute graft-versus-host disease (GVHD) is defined as de novo acute GVHD presenting beyond 100 days after allogeneic hematopoietic cell transplantation (HCT) without manifestations of chronic GVHD. Data are limited regarding its characteristics, clinical course, and risk factors because of underrecognition and changes in classification. We evaluated 3542 consecutive adult recipients of first HCTs at 24 Mount Sinai Acute GVHD International Consortium (MAGIC) centers between January 2014 and August 2021 to better describe the clinical evolution and outcomes of late acute GVHD. The cumulative incidence of classic acute GVHD that required systemic treatment was 35.2%, and an additional 5.7% of patients required treatment for late acute GVHD. At the onset of symptoms, late acute GVHD was more severe than classic acute GVHD based on both clinical and MAGIC algorithm probability biomarker parameters and showed a lower overall response rate on day 28. Both clinical and biomarker grading at the time of treatment stratified the risk of nonrelapse mortality (NRM) in patients with classic and late acute GVHD, respectively, but long-term NRM and overall survival did not differ between patients with classic and late acute GVHD. Advanced age, female-to-male sex mismatch, and the use of reduced intensity conditioning were associated with the development of late acute GVHD, whereas the use of posttransplant cyclophosphamide–based GVHD prevention was protective mainly because of shifts in GVHD timing. Because overall outcomes were comparable, our findings, although not definitive, suggest that similar treatment strategies, including eligibility for clinical trials, based solely on clinical presentation at onset are appropriate.
Impact of detectable monoclonal protein at diagnosis on outcomes in marginal zone lymphoma: a multicenter cohort study
Authors: Epperla Narendranath , Zhao Qiuhong , Karmali Reem , Torka Pallawi , Shea Lauren , Oh Timothy S. , Anampa-Guzmán Andrea , Reves Heather , Tavakkoli Montreh , Greenwell Irl Brian , Hansinger Emily , Umyarova Elvira , Annunzio Kaitlin , Sawalha Yazeed , Christian Beth , Thomas Colin , Barta Stefan K. , Geethakumari Praveen Ramakrishnan , Bartlett Nancy L. , Grover Natalie S. , Olszewski Adam J. 
Published: June 2023

Abstract
Given the paucity of data surrounding the prognostic relevance of monoclonal paraprotein (M-protein) in marginal zone lymphoma (MZL), we sought to evaluate the impact of detecting M-protein at diagnosis on outcomes in patients with MZL in a large retrospective cohort. The study included 547 patients receiving first-line therapy for MZL. M-protein was detectable at diagnosis in 173 (32%) patients. There was no significant difference in the time from diagnosis to initiation of any therapy (systemic and local) between the M-protein and no M-protein groups. Patients with M-protein at diagnosis had significantly inferior progression-free survival (PFS) compared with those without M-protein at diagnosis. After adjusting for factors associated with inferior PFS in univariate models, presence of M-protein remained significantly associated with inferior PFS (hazard ratio, 1.74; 95% confidence interval, 1.20-2.54; P = .004). We observed no significant difference in the PFS based on the type or quantity of M-protein at diagnosis. There were differential outcomes in PFS based on the first-line therapy in patients with M-protein at diagnosis, in that, those receiving immunochemotherapy had better outcomes compared with those receiving rituximab monotherapy. The cumulative incidence of relapse in stage 1 disease among the recipients of local therapy was higher in the presence of M-protein; however, this did not reach statistical significance. We found that M-protein at diagnosis was associated with a higher risk of histologic transformation. Because the PFS difference related to presence of M-protein was not observed in patients receiving bendamustine and rituximab, immunochemotherapy may be a preferred approach over rituximab monotherapy in this group and needs to be explored further.
Donor bone marrow–derived macrophage engraftment into the central nervous system of patients following allogeneic transplantation
Authors: Loeb Anisha M. , Pattwell Siobhan S. , Meshinchi Soheil , Bedalov Antonio , Loeb Keith R. 
Published: June 2023

Abstract
Hematopoietic stem cell transplantation is a well-known treatment for hematologic malignancies, wherein nascent stem cells provide regenerating marrow and immunotherapy against the tumor. The progeny of hematopoietic stem cells also populate a wide spectrum of tissues, including the brain, as bone marrow–derived macrophages similar to microglial cells. We developed a sensitive and novel combined immunohistochemistry (IHC) and XY fluorescence in situ hybridization assay to detect, quantify, and characterize donor cells in the cerebral cortices of 19 female patients who underwent allogeneic stem cell transplantation. We showed that the number of male donor cells ranged from 0.14% to 3.0% of the total cells or from 1.2% to 25% of microglial cells. Using tyramide-based fluorescent IHC, we found that at least 80% of the donor cells expressed the microglial marker ionized calcium-binding adapter molecule-1, consistent with bone marrow–derived macrophages. The percentage of donor cells was related to pretransplantation conditioning; donor cells from radiation-based myeloablative cases averaged 8.1% of microglial cells, whereas those from nonmyeloablative cases averaged only 1.3%. The number of donor cells in patients conditioned with busulfan- or treosulfan-based myeloablation was similar to that in total body irradiation-based conditioning; donor cells averaged 6.8% of the microglial cells. Notably, patients who received multiple transplantations and those with the longest posttransplantation survival had the highest level of donor engraftment, with donor cells averaging 16.3% of the microglial cells. Our work represents the largest study characterizing bone marrow–derived macrophages in patients after transplantation. The efficiency of engraftment observed in our study warrants future research on microglial replacement as a therapeutic option for disorders of the central nervous system.
Mild COVID-19 has no detrimental effect on semen quality
Authors: Edimiris Philippos , Doehmen Cornelius , Müller Lisa , Andrée Marcel , Baston-Buest Dunja Maria , Buest Sebastian , Adams Ortwin , Krüssel Jan-Steffen , Bielfeld Alexandra Petra 
Published: June 2023

Abstract
Background
As of today, the effect of coronavirus disease 2019 (COVID-19) on male fertility remains unclear. Studies published so far have partly contradictory results, likely due to very small sample sizes and heterogeneous populations.
To gain a deeper understanding of the impact of COVID-19 on male fertility, we performed a prospective case–control study, in which we examined the ejaculate of 37 subjects, including 25 subjects in the acute phase of mild COVID-19 and 12 subjects who did not suffer from COVID-19. Determination of semen parameters, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) qPCR, and infectivity analysis were performed in the acute phase of the disease and in series.

Results
Semen parameter values did not differ significantly between subjects with mild COVID-19 and the control group. The serial examination of semen parameters revealed no significant changes between 4, 18, and 82 days after the onset of symptoms. SARS-CoV-2 RNA or infectious particles could not be detected in any ejaculate.

Conclusion
Mild COVID-19 seems to have no detrimental effect on semen parameter values.
Nanoliposomal VEGF-R2 peptide vaccine acts as an effective therapeutic vaccine in a murine B16F10 model of melanoma
Authors: Zahedipour Fatemeh , Zamani Parvin , Mashreghi Mohammad , Astaneh Mojgan , Sankian Mojtaba , Amiri Atefeh , Jamialahmadi Khadijeh , Jaafari Mahmoud Reza 
Published: June 2023

Abstract
Background
The vascular endothelial growth factor receptor-2 (VEGFR-2) plays an important role in melanoma development and progression. Peptide vaccines have shown great potential in cancer immunotherapy by targeting VEGFR-2 as a tumor-associated antigen and boosting the immune response against both tumor cells and tumor endothelial cells. Despite this, the low efficiency of peptide vaccines has resulted in moderate therapeutic results in the majority of studies. Enhancing the delivery of peptide vaccines using nanoliposomes is an important strategy for improving the efficacy of peptide vaccines. In this regard, we designed VEGFR-2-derived peptides restricted to both mouse MHC I and human HLA-A*02:01 using immunoinformatic tools and selected three peptides representing the highest binding affinities. The peptides were encapsulated in nanoliposomal formulations using the film method plus bath sonication and characterized for their colloidal properties.

Results
The mean diameter of peptide-encapsulated liposomes was around 135 nm, zeta potential of − 17 mV, and encapsulation efficiency of approximately 70%. Then, vaccine formulations were injected subcutaneously in mice bearing B16F10-established melanoma tumors and their efficiency in triggering immunological, and anti-tumor responses was evaluated. Our results represented that one of our designed VEGFR-2 peptide nanoliposomal formulations (Lip-V1) substantially activated CD4+ (p < 0.0001) and CD8+ (P < 0.001) T cell responses and significantly boosted the production of IFN-γ (P < 0.0001) and IL-4 (P < 0.0001). Furthermore, this formulation led to a significant decrease in tumor volume (P < 0.0001) and enhanced survival (P < 0.05) in mice.

Conclusion
Our findings suggest that the nanoliposomal formulation containing VEGFR-2 peptides could be a promising therapeutic vaccination approach capable of eliciting strong antigen-specific immunologic and anti-tumor responses.
Multivariate analysis of seed chemical diversity among wild fenugreek (Trigonella monantha C. A. Mey.) ecotypes
Authors: Hasaroeih Neda Esamaeilinejad , Ghanavati Farangis , Moradi Foad , Kohpalkani Jahangir Abbasi , Rahimizadeh Majid 
Published: June 2023

Abstract
Background
Wild fenugreek (Trigonella monantha), a multi-purpose annual plant, has traditionally been used as a food, forage, and medicinal plant. However, the knowledge of the diversity of its chemical characteristics is limited. In this study, 40 wild fenugreek ecotypes collected from their natural habitats in Iran and grown together in field conditions, were analyzed for their seed chemical properties.

Results
The ecotypes were cultivated in a randomized complete block design (RCBD) with three replications. The results of ANOVA revealed a significant difference among the ecotypes for all measured characters (P < 0.01). The results showed a high level of diversity among the ecotypes based on the measured characters, including antioxidant activity (48.19 to 86.85%), phenol (0.82 to 1.51 mg gallic acid per g dry weight), flavonoid (1.07 to 3.11 mg quercetin per g dry weight), trigonelline (0.02 to 0.08 mmol/l), 4-hydroxyisoleucine (0.197 to 0.906 mg/g), sucrose (0.13 to 3.77 mM), glucose (1.07 to 12.1 mM), and fructose (13.3 to 45.5 mM). The cluster analysis divided the ecotypes into four groups and the PCA analysis showed that the three first components explained 73% of the total variance among the ecotypes. Also, heat map correlation revealed that many positive and negative correlations were observed among the measured characters. The results did not show a relationship between the amounts of compounds and the place of sample collection.

Conclusions
The present study suggests considerable diversity in the seed chemical compositions of the wild fenugreek ecotypes. Therefore, many ecotypes could be useful for medicinal purposes, as well as for human nutrition.
Effects of an individualised exercise programme plus Behavioural Change Enhancement (BCE) strategies for managing fatigue in frail older adults: a cluster randomised controlled trial
Authors: Liu Justina Y. W. , Yin Yue-Heng , Kor Patrick P. K. , Kwan Rick Y. C. , Lee Paul H. , Chien Wai Tong , Siu Parco M. , Hill Keith D. 
Published: June 2023

Abstract
Background
To the best of our knowledge, although ageing-induced fatigue could cause adverse outcomes such as frailty, there is currently no intervention for it. This study evaluated the effects of an individualised exercise programme with/without BCE strategies on reducing fatigue in older adults.

Methods
A three-armed cluster-randomised controlled trial (RCT) was conducted with 184 participants (mean age: 79.1 ± 6.4; mean frailty score: 2.8 + 0.8) from 21 community centres (ClinicalTrials.gov: NCT03394495). They were randomised into either: the COMB group (n = 64), receiving 16 weeks of exercise training plus the BCE programme; the EXER group (n = 65), receiving exercise training and health talks; or the control group (n = 55), receiving only health talks. Fatigue was assessed using the Multi-dimensional Fatigue Inventory (range: 20 to 100, with higher scores indicating higher fatigue levels) at baseline, and immediately, 6 months, and 12 months post-intervention.

Results
The GEE analyses showed significant interaction (time x group) between the COMB and control groups immediately (p < 0.001), 6 months (p < 0.001), and 12 months (p < 0.001) post-intervention. Comparing the COMB and EXER groups, there was a significant interaction immediately (p = 0.013) and at 12 months post-intervention (p = 0.007). However, no significant difference was seen between the EXER group and control group at any time point.

Conclusions
The COMB intervention showed better immediate and sustainable effects (i.e., 12 months after the intervention) on reducing fatigue in frail older adults than exercise training or health education alone.

Trial registration
ClinicalTrials.gov (NCT03394495), registered on 09/01/2018.
The L-shaped correlation between systolic blood pressure and short-term and long-term mortality in patients with cerebral hemorrhage
Authors: Xu Jiang , Xie Zhiping , Chen Kang , Lan Shihai , Liao Gang , Xu Shan , Yang Xuanyong , Luo Hai 
Published: June 2023

Abstract
Background
A large amount of evidence has shown the necessity of lowering blood pressure (BP) in patients with acute cerebral hemorrhage, but whether reducing BP contributes to lower short-term and long-term mortality in these patients remains uncertain.

Aims
We aimed to explore the association between BP, including systolic and diastolic BP, during intensive care unit (ICU) admission and 1-month and 1-year mortality after discharge of patients with cerebral hemorrhage.

Methods
A total of 1085 patients with cerebral hemorrhage were obtained from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Maximum and minimum values of systolic and diastolic BP in these patients during their ICU stay were recorded, and endpoint events were defined as the 1-month mortality and 1-year mortality after the first admission. Multivariable adjusted models were performed for the association of BP with the endpoint events.

Results
We observed that patients with hypertension were likely to be older, Asian or Black and had worse health insurance and higher systolic BP than those without hypertension. The logistic regression analysis showed inverse relationships between systolic BP-min (odds ratio (OR) = 0.986, 95% CI 0.983–0.989, P < 0.001) and diastolic BP-min (OR = 0.975, 95% CI 0.968–0.981, P < 0.001) and risks of 1-month, as well as 1-year mortality when controlling for confounders including age, sex, race, insurance, heart failure, myocardial infarct, malignancy, cerebral infarction, diabetes and chronic kidney disease. Furthermore, smooth curve analysis suggested an approximate L-shaped association of systolic BP with the risk of 1-month mortality and 1-year mortality. Reducing systolic BP in the range of 100–150 mmHg has a lower death risk in these patients with cerebral hemorrhage.

Conclusion
We observed an L-shaped association between systolic BP levels and the risks of 1-month and 1-year mortality in patients with cerebral hemorrhage, which supported that lowering BP when treating an acute hypertensive response could reduce short-term and long-term mortality.
Development and internal validation of a non-invasive clinical tool to predict sufficient omega-3 levels in early pregnancy
Authors: Fu Joanna YX , Wang Carol A , Liu Ge , Mead Elyse , Phung Jason , Makrides Maria , Pennell Craig E 
Published: June 2023

Abstract
Background
Complications from preterm birth (PTB) are the leading cause of death and disability in those under five years. Whilst the role of omega-3 (n-3) supplementation in reducing PTB is well-established, growing evidence suggests supplementation use in those replete may increase the risk of early PTB. Aim: To develop a non-invasive tool to identify individuals with total n-3 serum levels above 4.3% of total fatty acids in early pregnancy.

Methods
We conducted a prospective observational study recruiting 331 participants from three clinical sites in Newcastle, Australia. Eligible participants (n = 307) had a singleton pregnancy between 8 and 20 weeks’ gestation at recruitment. Data on factors associated with n-3 serum levels were collected using an electronic questionnaire; these included estimated intake of n-3 (including food type, portion size, frequency of consumption), n-3 supplementation, and sociodemographic factors. The optimal cut-point of estimated n-3 intake that predicted mothers with total serum n-3 levels likely above 4.3% was developed using multivariate logistic regression, adjusting for maternal age, body mass index, socioeconomic status, and n-3 supplementation use. Total serum n-3 levels above 4.3% was selected as previous research has demonstrated that mothers with these levels are at increased risk of early PTB if they take additional n-3 supplementation during pregnancy. Models were evaluated using various performance metrics including sensitivity, specificity, area under receiver operator characteristic (AUROC) curve, true positive rate (TPR) at 10% false positive rate (FPR), Youden Index, Closest to (0,1) Criteria, Concordance Probability, and Index of Union. Internal validation was performed using 1000-bootstraps to generate 95% confidence intervals for performance metrics generated.

Results
Of 307 eligible participants included for analysis, 58.6% had total n-3 serum levels above 4.3%. The optimal model had a moderate discriminative ability (AUROC 0.744, 95% CI 0.742–0.746) with 84.7% sensitivity, 54.7% specificity and 37.6% TPR at 10% FPR.

Conclusions
Our non-invasive tool was a moderate predictor of pregnant women with total serum n-3 levels above 4.3%; however, its performance is not yet adequate for clinical use.

Trial registration
This trial was approved by the Hunter New England Human Research Ethics Committee of the Hunter New England Local Health District (Reference 2020/ETH00498 on 07/05/2020 and 2020/ETH02881 on 08/12/2020).