bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol of a prospective single-arm multicenter clinical study to assess the safety and performance of the aXess hemodialysis graft: The pivotal study
Authors: De Vriese An S , D’Haeninck Annick , Mendes Artur , Ministro Augusto , Krievins Dainis , Kingsmore David , Mestres Gaspar , Villanueva Gonzalo , Rodrigues Hugo , Turek Jakub , Zieliński Maciej , De Letter Jan , Coelho Andreia , Loureiro Luís Alvarenga , Tozzi Matteo , Menegolo Mirko , Alija Palma Fariñas , Theodoridis Panagiotis G , Gibbs Paul , Ebrahimi Reze , Nauwelaers Sigi , Kakkos Stavros K , Matoussevitch Vladimir , Moll Frans , Gargiulo Mauro 
Published: May 2023

Background: Arteriovenous grafts (AVGs) are used for patients deemed unsuitable for the creation of an autogenous arteriovenous fistula (AVF) or unable to await maturation of the AVF before starting hemodialysis. However, AVGs are prone to infection and thrombosis resulting in low long-term patency rates. The novel aXess Hemodialysis Graft consists of porous polymeric biomaterial allowing the infiltration by cells and the growth of neotissue, while the graft itself is gradually absorbed, ultimately resulting in a fully functional natural blood vessel. The Pivotal Study will examine the long-term effectiveness and safety of the aXess Hemodialysis Graft. Methods: The Pivotal Study is a prospective, single-arm, multicenter study that will be conducted in 110 subjects with end-stage renal disease who are not deemed suitable for the creation of an autogenous vascular access. The primary efficacy endpoint will be the primary patency rate at 6 months. The primary safety endpoint will be the freedom from device-related serious adverse events at 6 months. The secondary endpoints will include the procedural success rate, time to first cannulation, patency rates, the rate of access-related interventions to maintain patency, the freedom from device-related serious adverse events and the rate of access site infections. Patients will be followed for 60 months. An exploratory Health Economic and Outcomes Research sub-study will determine potential additional benefits of the aXess graft to patients, health care institutions, and reimbursement programs. Discussion: The Pivotal study will examine the long-term performance and safety of the aXess Hemodialysis Graft and compare the outcome measures with historical data obtained with other graft types and autogenous AVFs. Potential advantages may include superior long-term patency rates and lower infection rates versus currently available AVGs and a shorter time to first cannulation compared to an autologous AVF. As such, the aXess Hemodialysis Graft may fulfill an unmet clinical need in the field of hemodialysis access.
The effects of upper limb exercise training on upper limb muscle strength in people with chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials
Authors: Karagiannis Christos , Savva Christos , Korakakis Vasileios , Ploutarchou George , Adamide Tonia , Georgiou Andreas , Xanthos Theodoros 
Published: May 2023

Background: Upper limb (UL) muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). UL muscle dysfunction is associated with muscle weakness, dyspnea, and exercise intolerance. Although upper limb exercise training (ULET) is typically incorporated in pulmonary rehabilitation programs, its effects on UL muscle strength remains unclear. Objectives: The purpose of this systematic review was to investigate the effectiveness of ULET, in UL muscle strength of people with COPD. Design: This is systematic review and meta-analysis study. Data Sources and Methods: Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Protocols 2020 guidelines were used for this study. PubMed, Cochrane, CINAHL Plus and SPORTDiscus and clinicaltrials.gov registry were searched from inception to July 2022. Included studies were randomized controlled trials, assessing the effectiveness in muscle strength of ULET, compared with other types of upper or lower limb exercise or no exercise. The quality and risk of bias were assessed using the Physiotherapy Evidence Database (PEDro) scale and certainty of evidence with the Grading of Recommendations, Assessment, Development, and Evaluations approach. Treatment effects of ULET were calculated using standardized mean differences and 95% confidence intervals. Results: Twenty-four studies, with a total sample of 882 patients, were included. Most studies were of moderate quality and high risk of bias. Very low to low certainty evidence indicates a significant difference in UL muscle strength in favor of resistance ULET, compared with lower limb exercise alone or no exercise. No significant differences were found in different types of ULET comparisons. Conclusion: The results of this review showed that resistance ULET could improve UL muscle strength in people with COPD. Most studies, however, were of moderate quality and high risk of bias. Further studies with larger sample sizes, better methodological quality, and standardized training protocols are needed to confirm these findings.
Systematic Review on Environmental Design for Adaptive and Problem Behaviors of People With Intellectual and Developmental Disabilities
Authors: Ellis Natalie , Yi Ye Ji 
Published: May 2023

Objectives: The presented systematic review explores the empirical studies regarding environmental design strategies that support adaptive behaviors while improving problem behaviors of people with intellectual and developmental disabilities (IDD). Background: People with IDD perceive and interact with their environment differently from people without disabilities. Design research has not always considered these differences, and environmental design solutions are not commonly found. Methods: The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocols. The study reports the findings from the systematic review of 32 peer-reviewed studies published in EBSCO, ERIC, ProQuest, PsycINFO, MEDLINE CINAHL, Consumer Health Complete (EBSCOhost), and Psychology and Behavioral Sciences Collection between 1990 and 2020. In addition, quality assessment tools appraised the study’s quality. Results: The review identified 26 design strategies. Five themes qualitatively organized these environmental attributes: coherence, affordance, control, stimulation, and restoration. Conclusion: The evidence indicates that adequately designed physical environments can support the adaptive behaviors of people with IDD while alleviating behavioral problems. Design features not supported by strong empirical evidence should be further addressed in future studies.
Key Thresholds and Relative Contributions of Knee Geometry, Anteroposterior Laxity, and Body Weight as Risk Factors for Noncontact ACL Injury
Authors: Zeitlin Jacob , Fontana Mark A. , Parides Michael K. , Nawabi Danyal H. , Wickiewicz Thomas L. , Pearle Andrew D. , Beynnon Bruce D. , Imhauser Carl W. 
Published: May 2023

Background: Limited data exist regarding the association of tibiofemoral bony and soft tissue geometry and knee laxity with risk of first-time noncontact anterior cruciate ligament (ACL) rupture. Purpose: To determine associations of tibiofemoral geometry and anteroposterior (AP) knee laxity with risk of first-time noncontact ACL injury in high school and collegiate athletes. Study Design: Cohort study; Level of evidence, 2. Methods: Over a 4-year period, noncontact ACL injury events were identified as they occurred in 86 high school and collegiate athletes (59 female, 27 male). Sex- and age-matched control participants were selected from the same team. AP laxity of the uninjured knee was measured using a KT-2000 arthrometer. Magnetic resonance imaging was taken on ipsilateral and contralateral knees, and articular geometries were measured. Sex-specific general additive models were implemented to investigate associations between injury risk and 6 features: ACL volume, meniscus–bone wedge angle in the lateral compartment of the tibia, articular cartilage slope at the middle region of the lateral compartment of the tibia, femoral notch width at the anterior outlet, body weight, and AP displacement of the tibia relative to the femur. Importance scores (in percentages) were calculated to rank the relative contribution of each variable. Results: In the female cohort, the 2 features with the highest importance scores were tibial cartilage slope (8.6%) and notch width (8.1%). In the male cohort, the 2 top-ranked features were AP laxity (5.6%) and tibial cartilage slope (4.8%). In female patients, injury risk increased by 25.5% with lateral middle cartilage slope becoming more posteroinferior from –6.2° to –2.0° and by 17.5% with lateral meniscus–bone wedge angle increasing from 27.3° to 28.2°. In males, an increase in AP displacement from 12.5 to 14.4 mm in response to a 133-N anterior-directed load was associated with a 16.7% increase in risk. Conclusion: Of the 6 variables studied, there was no single dominant geometric or laxity risk factor for ACL injury in either the female or male cohort. In males, AP laxity >13 to 14 mm was associated with sharply increased risk of noncontact ACL injury. In females, lateral meniscus–bone wedge angle >28° was associated with a sharply decreased risk of noncontact ACL injury.
Admission blood pressure and clinical outcomes in patients with acute ischaemic stroke treated with intravenous alteplase and endovascular treatment versus endovascular treatment alone: A MR CLEAN-NO IV substudy
Authors: van den Berg Sophie A , Uniken Venema Simone M , LeCouffe Natalie E , Postma Alida A , Lycklama à Nijeholt Geert J , Rinkel Leon A , Treurniet Kilian M , Kappelhof Manon , Bruggeman Agnetha E , van Kranendonk Katinka R , Majoie Charles BLM , Dippel Diederik WJ , van der Worp H Bart , Coutinho Jonathan M , Nederkoorn Paul J , Roos Yvo BWEM 
Published: May 2023

Introduction: High systolic blood pressure (SBP) is associated with poor functional outcome. We analysed whether the association of SBP with outcomes after endovascular treatment (EVT) is modified by prior intravenous thrombolysis (IVT). Patients and methods: This was a post-hoc analysis of MR CLEAN-NO IV, a randomised trial of IVT with alteplase followed by EVT versus EVT alone, within 4.5 h from stroke onset. SBP was recorded on hospital admission. The primary outcome was 90-day modified Rankin Scale (mRS) score and secondary outcomes included symptomatic intracranial haemorrhage (sICH) and successful reperfusion (eTICI 2b-3), analysed with (ordinal) logistic regression. Estimates were calculated per 10 mmHg change in SBP. We assessed whether IVT modified the associations of SBP with these outcomes using multiplicative interaction terms. Results: Of 539 randomised patients, 266 received IVT. The association of SBP with mRS score was J-shaped, with an inflection point at 150 mmHg. Using 150 mmHg as a reference point, SBPs higher than 150 mmHg were associated with poor functional outcome (acOR: 1.23, 95% CI: 1.09–1.38), but lower SBPs were not (acOR: 1.14, 95% CI: 0.99–1.30). Higher SBP was not associated with the risk of sICH (aOR: 1.09, 95% CI: 0.93–1.27) nor with the probability of successful reperfusion (aOR: 1.00, 95% CI: 0.91–1.10). Our main result was that we found no effect modification by IVT ( p-values for interaction, mRS = 0.94; sICH = 0.26; successful reperfusion = 0.58). Discussion and conclusion: There was no effect modification of IVT with SBP for any of the clinical outcomes. Therefore, the level of SBP (if ⩽185/110 mmHg) should not guide IVT decisions in patients otherwise eligible for both IVT and EVT within the 4.5-h time window. Trial registration: ISRCTN80619088, https://www.isrctn.com/ISRCTN80619088 .
The rapid detection of procalcitonin in septic serum using immunoaffinity MALDI chips
Authors: Dvorak Josef , Novakova Jana , Kraftova Lucie , Studentova Vendula , Matejovic Martin , Radej Jaroslav , Karvunidis Thomas , Horak Jan , Kralovcova Marcela , Hrabak Jaroslav , Kalaninova Zuzana , Volny Michael , Novak Petr , Pompach Petr 
Published: May 2023

Abstract
Background
Sepsis is a common worldwide health condition with high mortality. It is caused by a dysregulated immune response to the pathogen. Severe infections resulting in sepsis can be also determined by monitoring several bloodstream biomarkers, one of them being pro-hormone procalcitonin (PCT). PCT concentration in the bloodstream correlates well with sepsis and in severe cases increases up to a thousand times from the healthy physiological values in a short time. In this study, we developed a rapid technique for PCT detection by MALDI-TOF mass spectrometry, that uses in-situ enrichment directly on the specialized immuno MALDI chips that are utilized as MALDI plates. The method’s ability to detect PCT was confirmed by comparing the results with LC–MS bottom-up workflow. The new method detects intact PCT by its m/z and uncovers its alternations in septic serum.

Methods
The MALDI chips used for the detection of PCT were prepared by ambient ion soft landing of anti-PCT antibody on an ITO glass slide. The chips were used for the development of the rapid MALDI-TOF MS method. A parallel method based on affinity enrichment on magnetic beads followed by LC–MS/MS data-dependent peptide microsequencing was used to prove PCT presence in the sample. All samples were also tested by ELISA to determine PCT concentration prior to analyzing them by mass spectrometry methods.

Results
The MALDI chip method was optimized using recombinant PCT spiked into the human serum. The PCT detection limit was 10 ng/mL. The optimized method was used to analyze 13 sera from patients suffering sepsis. The PCT results were confirmed by LC–MS/MS. The measurement of the intact PCT by the MALDI chip method revealed that sera of patients with severe sepsis have other forms of PCT present, which show post-processing of the primary sequence by cleavage of PCT, resulting in the formation of N and C termini fragments.

Conclusions
Procalcitonin from human serum was successfully enriched and detected using immunoaffinity MALDI chips. The intact PCT was characterized in 13 septic patients. The method is more specific compared to non-MS-based immunoaffinity techniques and allows observation of different variants of PCT in septic patients.
Patient experience and repeatability of measurements made with the Pentacam HR in patients with keratoconus
Authors: Gustafsson Ingemar , Bizios Dimitrios , Ivarsen Anders , Hjortdal Jesper Ø 
Published: May 2023

Abstract
Background
To investigate whether the repeatability of measurements with the Pentacam HR in patients with keratoconus is improved by patients gaining more experience of the measurement situation. Such an improvement could enhance the accuracy with which progressive keratoconus can be detected.

Methods
Four replicate measurements were performed on Day 0 and on Day 3. Parameters commonly used in the diagnosis of progressive keratoconus were included in the analysis, namely the flattest central keratometry value (K1), the steepest central keratometry value (K2), the maximum keratometry value (Kmax), and the parameters A, B and C from the Belin ABCD Progression Display. In addition, quality parameters used by the Pentacam HR to assess the quality of the measurements were included, namely the analysed area (front + back), 3D (front + back), XY, Z, and eye movements.

Results
Neither the diagnostic parameters nor the quality parameters showed any statistically significant improvement on Day 3 compared to Day 0. The quality parameter “eye movements” deteriorated significantly with increasing Kmax.

Conclusion
Gaining experience of the measurement situation did not increase the accuracy of the measurements. Further investigations should be performed to determine whether the increasing number of eye movements with increasing disease severity has a negative effect on the repeatability of the measurements.
To what extent classic socio-economic determinants explain trends of anaemia in tribal and non-tribal women of reproductive age in India? Findings from four National Family Heath Surveys (1998–2021)
Authors: Ghosal Jyoti , Bal Madhusmita , Ranjit‬ Manoranjan , Das Arundhuti , Behera Manas Ranjan , Satpathy Sudhir Kumar , Dutta Ambarish , Pati Sanghamitra 
Published: May 2023

AbstractBackgroundDespite unprecedented socio-economic growth experienced by Indians in the past few decades, and a long history of anti-anaemia public health measures, prevalence of anaemia in Indian non-pregnant women of reproductive age group (NPWRA) has not declined. This warrants a firm understanding of what explains the anaemia situation over time, preferably by sub-populations. Therefore, we aimed to examine the trends of anaemia in tribal NPWRA (least privileged) and compare with the trends in the NPWRA of general caste (most privileged) between 1998 to 2021. Additionally, the study also explored explanation of any decline and tribal/general narrowing of these trends.MethodsWe studied four rounds of National Family Health Survey (1998–99, 2005–06, 2015–16, 2019–21). We examined the trend of anaemia (haemoglobin < 12 g/dl) and its possible determinants in tribal and general NPWRA and estimated the portion of “decline” and “narrowing” that could be explained by theunderlyingandintermediatedeterminants (wealth, education, residence, parity and food security) using multiple logistic regression.ResultsThe distribution of determinants improved over 23 years in both the groups but more in tribals. But anaemia either remained unchanged or increased in both except 7.1 points decline in tribals between 2006–2016, leading also to 7 points narrowing of tribal/general gap. The modest attenuation of beta coefficients representing the change of anaemia prevalence (log of odds) in tribals from -0.314(-0.377, -0.251) to -0.242(-0.308, -0.176) after adjustment with determinants could explain only 23% of the decline. Similarly, only 7% of the narrowing of the tribal/general anaemia gap could be explained.ConclusionsThe structural determinants wealth, education, food security, parity and urban amenities improved immensely in India but anaemia did not decline in this 23-year period. This implies that the “usual suspects” – the structural determinants are not the main drivers of anaemia in the country. The main driver may be absolute and/or functional deficiency status of micronutrients including iron attributable to inadequate uptake and absorption of these elements from Indian diets; and therefore, their effects are noticeable in every socio-economic stratum of India. Future research for aetiologies and new interventions for anaemia alleviation in India may focus on these factors.
Oxidative stress gene expression, DNA methylation, and gut microbiota interaction trigger Crohn’s disease: a multi-omics Mendelian randomization study
Authors: Xu Shu , Li Xiaozhi , Zhang Shenghong , Qi Cancan , Zhang Zhenhua , Ma Ruiqi , Xiang Liyuan , Chen Lianmin , Zhu Yijun , Tang Ce , Bourgonje Arno R. , Li Miaoxin , He Yao , Zeng Zhirong , Hu Shixian , Feng Rui , Chen Minhu 
Published: May 2023

Abstract
Background
Oxidative stress (OS) is a key pathophysiological mechanism in Crohn’s disease (CD). OS-related genes can be affected by environmental factors, intestinal inflammation, gut microbiota, and epigenetic changes. However, the role of OS as a potential CD etiological factor or triggering factor is unknown, as differentially expressed OS genes in CD can be either a cause or a subsequent change of intestinal inflammation. Herein, we used a multi-omics summary data-based Mendelian randomization (SMR) approach to identify putative causal effects and underlying mechanisms of OS genes in CD.

Methods
OS-related genes were extracted from the GeneCards database. Intestinal transcriptome datasets were collected from the Gene Expression Omnibus (GEO) database and meta-analyzed to identify differentially expressed genes (DEGs) related to OS in CD. Integration analyses of the largest CD genome-wide association study (GWAS) summaries with expression quantitative trait loci (eQTLs) and DNA methylation QTLs (mQTLs) from the blood were performed using SMR methods to prioritize putative blood OS genes and their regulatory elements associated with CD risk. Up-to-date intestinal eQTLs and fecal microbial QTLs (mbQTLs) were integrated to uncover potential interactions between host OS gene expression and gut microbiota through SMR and colocalization analysis. Two additional Mendelian randomization (MR) methods were used as sensitivity analyses. Putative results were validated in an independent multi-omics cohort from the First Affiliated Hospital of Sun Yat-sen University (FAH-SYS).

Results
A meta-analysis from six datasets identified 438 OS-related DEGs enriched in intestinal enterocytes in CD from 817 OS-related genes. Five genes from blood tissue were prioritized as candidate CD-causal genes using three-step SMR methods: BAD, SHC1, STAT3, MUC1, and GPX3. Furthermore, SMR analysis also identified five putative intestinal genes, three of which were involved in gene–microbiota interactions through colocalization analysis: MUC1, CD40, and PRKAB1. Validation results showed that 88.79% of DEGs were replicated in the FAH-SYS cohort. Associations between pairs of MUC1–Bacillus aciditolerans and PRKAB1–Escherichia coli in the FAH-SYS cohort were consistent with eQTL–mbQTL colocalization.

Conclusions
This multi-omics integration study highlighted that OS genes causal to CD are regulated by DNA methylation and host-microbiota interactions. This provides evidence for future targeted functional research aimed at developing suitable therapeutic interventions and disease prevention.
Production of a 135-residue long N-truncated human keratinocyte growth factor 1 in Escherichia coli
Authors: Kim Young Su , Lee Hye-Jeong , Handoko Gabriella Aphrodita , Kim Jaehui , Kim Seong-Bo , Won Minho , Park Jung-Ho , Ahn Jungoh 
Published: May 2023

Abstract
Background
Palifermin (trade name Kepivance®) is an amino-terminally truncated recombinant human keratinocyte growth factor 1 (KGF-1) with 140 residues that has been produced using Escherichia coli to prevent and treat oral mucositis following radiation or chemotherapy. In this study, an amino-terminally shortened KGF-1 variant with 135 residues was produced and purified in E. coli, and its cell proliferation activity was evaluated.

Results
We expressed soluble KGF-1 fused to thioredoxin (TRX) in the cytoplasmic fraction of E. coli to improve its production yield. However, three N-truncated forms (KGF-1 with 140, 138, and 135 residues) were observed after the removal of the TRX protein from the fusion form by cleavage of the human enterokinase light chain C112S (hEKL C112S). The shortest KGF-1 variant, with 135 residues, was expressed by fusion with TRX via the hEKL cleavage site in E. coli and purified at high purity (> 99%). Circular dichroism spectroscopy shows that purified KGF-1135 had a structure similar to that of the KGF-1140 as a random coiled form, and MCF-7 cell proliferation assays demonstrate its biological activity.

Conclusions
We identified variations in N-terminus-truncated KGF-1 and selected the most stable form. Furthermore, by a simple two-step purification, highly purified KGF-1135 was obtained that showed biological activity. These results demonstrate that KGF-1135 may be considered an alternative protein to KGF-1.