bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surface-anchored microbial enzyme-responsive solid lipid nanoparticles enabling colonic budesonide release for ulcerative colitis treatment
Authors: Zhang Yipeng , Wang Liying , Wang Zi-Dan , Zhou Quan , Zhou Xuefei , Zhou Tianhua , Guan Yi-Xin , Liu Xiangrui 
Published: May 2023

AbstractColon-targeted oral drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC), which is a disease with high relapse and remission rates associated with immune system inflammation and dysregulation localized within the lining of the large bowel. However, the success of current available approaches used for colon-targeted therapy is limited. Budesonide (BUD) is a corticosteroid drug, and its rectal and oral formulations are used to treat UC, but the inconvenience of rectal administration and the systemic toxicity of oral administration restrict its long-term use. In this study, we designed and prepared colon-targeted solid lipid nanoparticles (SLNs) encapsulating BUD to treat UC by oral administration. A negatively charged surfactant (NaCS-C12) was synthesized to anchor cellulase-responsive layers consisting of polyelectrolyte complexes (PECs) formed by negatively charged NaCS and cationic chitosan onto the SLNs. The release rate and colon-specific release behavior of BUD could be easily modified by regulating the number of coated layers. We found that the two-layer BUD-loaded SLNs (SLN-BUD-2L) with a nanoscale particle size and negative zeta potential showed the designed colon-specific drug release profile in response to localized high cellulase activity. In addition, SLN-BUD-2L exhibited excellent anti-inflammatory activity in a dextran sulfate sodium (DSS)-induced colitis mouse model, suggesting its potential anti-UC applications.
How to exclude pulmonary embolism in patients hospitalized with COVID-19: a comparison of predictive scores
Authors: Vielhauer Jakob , Benesch Christopher , Pernpruner Anna , Johlke Anna-Lena , Hellmuth Johannes Christian , Muenchhoff Maximilian , Scherer Clemens , Fink Nicola , Sabel Bastian , Schulz Christian , Mayerle Julia , Mahajan Ujjwal Mukund , Stubbe Hans Christian 
Published: May 2023

Abstract
Background
Pulmonary embolism (PE) is an important complication of Coronavirus disease 2019 (COVID-19). COVID-19 is associated with respiratory impairment and a pro-coagulative state, rendering PE more likely and difficult to recognize. Several decision algorithms relying on clinical features and D-dimer have been established. High prevalence of PE and elevated Ddimer in patients with COVID-19 might impair the performance of common decision algorithms. Here, we aimed to validate and compare five common decision algorithms implementing age adjusted Ddimer, the GENEVA, and Wells scores as well as the PEGeD- and YEARS-algorithms in patients hospitalized with COVID-19.

Methods
In this single center study, we included patients who were admitted to our tertiary care hospital in the COVID-19 Registry of the LMU Munich. We retrospectively selected patients who received a computed tomography pulmonary angiogram (CTPA) or pulmonary ventilation/perfusion scintigraphy (V/Q) for suspected PE. The performances of five commonly used diagnostic algorithms (age-adjusted D-dimer, GENEVA score, PEGeD-algorithm, Wells score, and YEARS-algorithm) were compared.

Results
We identified 413 patients with suspected PE who received a CTPA or V/Q confirming 62 PEs (15%). Among them, 358 patients with 48 PEs (13%) could be evaluated for performance of all algorithms. Patients with PE were older and their overall outcome was worse compared to patients without PE. Of the above five diagnostic algorithms, the PEGeD- and YEARS-algorithms performed best, reducing diagnostic imaging by 14% and 15% respectively with a sensitivity of 95.7% and 95.6%. The GENEVA score was able to reduce CTPA or V/Q by 32.2% but suffered from a low sensitivity (78.6%). Age-adjusted D-dimer and Wells score could not significantly reduce diagnostic imaging.

Conclusion
The PEGeD- and YEARS-algorithms outperformed other tested decision algorithms and worked well in patients admitted with COVID-19. These findings need independent validation in a prospective study.
A mentored hands-on training model for scaling up implementation and intervention research in India: “connecting the dots”
Authors: Ransing Ramdas , Hawk Mary , McDonald Margaret , Jones Jacquelyn , Bhatia Triptish , Verma Vijay , Shah Gyan D. , Brar Jaspreet , Egan James Erin , Konsale Prasad , Kaur Jasmine , Singh Ravinder , Singh Harpreet , Dhaliwal R. S. , Wood Joel , Nimgaonkar Vishwajit , Deshpande Smita , Swaminathan Soumya 
Published: May 2023

AbstractDespite the high burden of mental disorders in low- and middle-income countries (LMICs), less than 25% of those in need have access to appropriate services, in part due to a scarcity of locally relevant, evidence-based interventions and models of care. To address this gap, researchers from India and the United States and the Indian Council of Medical Research (ICMR) collaboratively developed a “Grantathon” model to provide mentored research training to 24 new principal investigators (PIs). This included a week-long didactic training, a customized web-based data entry/analysis system and a National Coordination Unit (NCU) to support PIs and track process objectives. Outcome objectives were assessed via scholarly output including publications, awards received and subsequent grants that were leveraged. Multiple mentorship strategies including collaborative problem-solving approaches were used to foster single-centre and multicentre research. Flexible, approachable and engaged support from mentors helped PIs overcome research barriers, and the NCU addressed local policy and day-to-day challenges through informal monthly review meetings. Bi-annual formal review presentations by all PIs continued through the COVID-19 pandemic, enabling interim results reporting and scientific review, also serving to reinforce accountability. To date, more than 33 publications, 47 scientific presentations, 12 awards, two measurement tools, five intervention manuals and eight research grants have been generated in an open-access environment. The Grantathon is a successful model for building research capacity and improving mental health research in India that could be adopted for use in other LMICs.
Clinical features, treatment, and outcomes of celiac-associated arthritis: a retrospective cohort study
Authors: Altaffer Ana Luiza , Weiss Pamela 
Published: May 2023

Abstract
Background
Although arthritis is recognized as an extra-intestinal manifestation of celiac disease, little is known about the clinical course and outcomes of pediatric celiac-associated arthritis. This study describes clinical characteristics, treatments, and outcomes of children with celiac-associated arthritis.

Methods
This was a retrospective cohort study of children with celiac disease seen in pediatric rheumatology clinic between 2004 and 2021 for joint complaints. Data was abstracted from electronic health records. Patient demographics and clinical manifestations were evaluated using standard descriptive statistics. Physician- and patient-reported outcomes were evaluated at the index visit, 6-month follow-up, and last recorded visit, and were compared using Wilcoxon signed-rank tests.

Results
Twenty-nine patients with celiac disease were evaluated for joint complaints, and 13 were diagnosed with arthritis. Their mean age was 8.9 years (SD 5.9), and 61.5% were female. Celiac disease diagnosis was made before arthritis diagnosis in only 2 cases (15.4%). Initial testing that led to the celiac disease diagnosis was obtained by the rheumatologist in 6 cases (46.2%). Only 8 patients (61.5%) had concomitant GI symptoms, and of these, 3 patients had BMI z-scores <-1.64 and 1 had impaired linear growth. Arthritis presentation was most often oligoarticular (76.9%) and asymmetric (84.6%). Most cases required systemic therapy (n = 11, 84.6%) with DMARDs, biologics, or both. Of the 10 patients who required systemic therapy and reported compliance with the gluten-free diet, 3 (30%) were able to stop systemic medications. Two of 3 patients who cleared celiac serologies came off systemic medications. Statistically significant improvement was noted in the number of joints involved (p = 0.02) and physician global assessment of disease activity (p = 0.03) between the index and final visit.

Conclusions
Rheumatologists play an important role in the identification of celiac disease, as arthritis was the presenting symptom in most cases and was not always associated with GI symptoms or poor growth. The arthritis was most often oligoarticular and asymmetric. Most children required systemic therapy. The gluten-free diet may not be sufficient to manage arthritis, but antibody clearance may be an indicator of higher likelihood of disease control off medications. Outcomes are promising with a combination of diet and medical therapy.
Role of macrophage autophagy in postoperative pain and inflammation in mice
Authors: Mitsui Kazuha , Hishiyama Sohei , Jain Aakanksha , Kotoda Yumi , Abe Masako , Matsukawa Takashi , Kotoda Masakazu 
Published: May 2023

Abstract
Background
Postoperative pain and inflammation are significant complications following surgery. Strategies that aim to prevent excessive inflammation without hampering natural wound-healing are required for the management of postoperative pain and inflammation. However, the knowledge of the mechanisms and target pathways involved in these processes is lacking. Recent studies have revealed that autophagy in macrophages sequesters pro-inflammatory mediators, and it is therefore being recognized as a crucial process involved in regulating inflammation. In this study, we tested the hypothesis that autophagy in macrophages plays protective roles against postoperative pain and inflammation and investigated the underlying mechanisms.

Methods
Postoperative pain was induced by plantar incision under isoflurane anesthesia in mice lacking macrophage autophagy (Atg5flox/flox LysMCre +) and their control littermates (Atg5flox/flox). Mechanical and thermal pain sensitivity, changes in weight distribution, spontaneous locomotor activity, tissue inflammation, and body weight were assessed at baseline and 1, 3, and 7 days after surgery. Monocyte/macrophage infiltration at the surgical site and inflammatory mediator expression levels were evaluated.

Results
Atg5flox/flox LysMCre + mice compared with the control mice exhibited lower mechanical and thermal pain thresholds and surgical/non-surgical hindlimb weight-bearing ratios. The augmented neurobehavioral symptoms observed in the Atg5flox/flox LysMCre + mice were associated with more severe paw inflammation, higher pro-inflammatory mediator mRNA expression, and more monocytes/macrophages at the surgical site.

Conclusion
The lack of macrophage autophagy augmented postoperative pain and inflammation, which were accompanied by enhanced pro-inflammatory cytokine secretion and surgical-site monocyte/macrophage infiltration. Macrophage autophagy plays a protective role in postoperative pain and inflammation and can be a novel therapeutic target.
A systematic review of the applications of markerless motion capture (MMC) technology for clinical measurement in rehabilitation
Authors: Lam Winnie W. T. , Tang Yuk Ming , Fong Kenneth N. K. 
Published: May 2023

Abstract
Background
Markerless motion capture (MMC) technology has been developed to avoid the need for body marker placement during motion tracking and analysis of human movement. Although researchers have long proposed the use of MMC technology in clinical measurement—identification and measurement of movement kinematics in a clinical population, its actual application is still in its preliminary stages. The benefits of MMC technology are also inconclusive with regard to its use in assessing patients’ conditions. In this review we put a minor focus on the method’s engineering components and sought primarily to determine the current application of MMC as a clinical measurement tool in rehabilitation.

Methods
A systematic computerized literature search was conducted in PubMed, Medline, CINAHL, CENTRAL, EMBASE, and IEEE. The search keywords used in each database were “Markerless Motion Capture OR Motion Capture OR Motion Capture Technology OR Markerless Motion Capture Technology OR Computer Vision OR Video-based OR Pose Estimation AND Assessment OR Clinical Assessment OR Clinical Measurement OR Assess.” Only peer-reviewed articles that applied MMC technology for clinical measurement were included. The last search took place on March 6, 2023. Details regarding the application of MMC technology for different types of patients and body parts, as well as the assessment results, were summarized.

Results
A total of 65 studies were included. The MMC systems used for measurement were most frequently used to identify symptoms or to detect differences in movement patterns between disease populations and their healthy counterparts. Patients with Parkinson’s disease (PD) who demonstrated obvious and well-defined physical signs were the largest patient group to which MMC assessment had been applied. Microsoft Kinect was the most frequently used MMC system, although there was a recent trend of motion analysis using video captured with a smartphone camera.

Conclusions
This review explored the current uses of MMC technology for clinical measurement. MMC technology has the potential to be used as an assessment tool as well as to assist in the detection and identification of symptoms, which might further contribute to the use of an artificial intelligence method for early screening for diseases. Further studies are warranted to develop and integrate MMC system in a platform that can be user-friendly and accurately analyzed by clinicians to extend the use of MMC technology in the disease populations.
Low-cost and automated phenotyping system “Phenomenon” for multi-sensor in situ monitoring in plant in vitro culture
Authors: Bethge Hans , Winkelmann Traud , Lüdeke Patrick , Rath Thomas 
Published: May 2023

AbstractBackgroundThe current development of sensor technologies towards ever more cost-effective and powerful systems is steadily increasing the application of low-cost sensors in different horticultural sectors. In plant in vitro culture, as a fundamental technique for plant breeding and plant propagation, the majority of evaluation methods to describe the performance of these cultures are based on destructive approaches, limiting data to unique endpoint measurements. Therefore, a non-destructive phenotyping system capable of automated, continuous and objective quantification of in vitro plant traits is desirable.ResultsAn automated low-cost multi-sensor system acquiring phenotypic data of plant in vitro cultures was developed and evaluated. Unique hardware and software components were selected to construct a xyz-scanning system with an adequate accuracy for consistent data acquisition. Relevant plant growth predictors, such as projected area of explants and average canopy height were determined employing multi-sensory imaging and various developmental processes could be monitored and documented. The validation of the RGB image segmentation pipeline using a random forest classifier revealed very strong correlation with manual pixel annotation. Depth imaging by a laser distance sensor of plant in vitro cultures enabled the description of the dynamic behavior of the average canopy height, the maximum plant height, but also the culture media height and volume. Projected plant area in depth data by RANSAC (random sample consensus) segmentation approach well matched the projected plant area by RGB image processing pipeline. In addition, a successful proof of concept for in situ spectral fluorescence monitoring was achieved and challenges of thermal imaging were documented. Potential use cases for the digital quantification of key performance parameters in research and commercial application are discussed.ConclusionThe technical realization of “Phenomenon” allows phenotyping of plant in vitro cultures under highly challenging conditions and enables multi-sensory monitoring through closed vessels, ensuring the aseptic status of the cultures. Automated sensor application in plant tissue culture promises great potential for a non-destructive growth analysis enhancing commercial propagation as well as enabling research with novel digital parameters recorded over time.
The genetic spectrum of congenital ocular motor apraxia type Cogan: an observational study, continued
Authors: Schröder Simone , Yigit Gökhan , Li Yun , Altmüller Janine , Büttel Hans-Martin , Fiedler Barbara , Kretzschmar Christoph , Nürnberg Peter , Seeger Jürgen , Serpieri Valentina , Valente Enza Maria , Wollnik Bernd , Boltshauser Eugen , Brockmann Knut 
Published: May 2023

Abstract
Background
The term congenital ocular motor apraxia (COMA), coined by Cogan in 1952, designates the incapacity to initiate voluntary eye movements performing rapid gaze shift, so called saccades. While regarded as a nosological entity by some authors, there is growing evidence that COMA designates merely a neurological symptom with etiologic heterogeneity. In 2016, we reported an observational study in a cohort of 21 patients diagnosed as having COMA. Thorough re-evaluation of the neuroimaging features of these 21 subjects revealed a previously not recognized molar tooth sign (MTS) in 11 of them, thus leading to a diagnostic reassignment as Joubert syndrome (JBTS). Specific MRI features in two further individuals indicated a Poretti–Boltshauser syndrome (PTBHS) and a tubulinopathy. In eight patients, a more precise diagnosis was not achieved. We pursued this cohort aiming at clarification of the definite genetic basis of COMA in each patient.

Results
Using a candidate gene approach, molecular genetic panels or exome sequencing, we detected causative molecular genetic variants in 17 of 21 patients with COMA. In nine of those 11 subjects diagnosed with JBTS due to newly recognized MTS on neuroimaging, we found pathogenic mutations in five different genes known to be associated with JBTS, including KIAA0586, NPHP1, CC2D2A, MKS1, and TMEM67. In two individuals without MTS on MRI, pathogenic variants were detected in NPHP1 and KIAA0586, arriving at a diagnosis of JBTS type 4 and 23, respectively. Three patients carried heterozygous truncating variants in SUFU, representing the first description of a newly identified forme fruste of JBTS. The clinical diagnoses of PTBHS and tubulinopathy were confirmed by detection of causative variants in LAMA1 and TUBA1A, respectively. In one patient with normal MRI, biallelic pathogenic variants in ATM indicated variant ataxia telangiectasia. Exome sequencing failed to reveal causative genetic variants in the remaining four subjects, two of them with clear MTS on MRI.

Conclusions
Our findings indicate marked etiologic heterogeneity in COMA with detection of causative mutations in 81% (17/21) in our cohort and nine different genes being affected, mostly genes associated with JBTS. We provide a diagnostic algorithm for COMA.
Surgical treatments for postamputation pain: study protocol for an international, double-blind, randomised controlled trial
Authors: Pettersen Emily , Sassu Paolo , Reinholdt Carina , Dahm Peter , Rolfson Ola , Björkman Anders , Innocenti Marco , Pedrini Francesca Alice , Breyer Juan Manuel , Roche Aidan , Hart Andrew , Harrington Lorraine , Ladak Adil , Power Hollie , Hebert Jacqueline , Ortiz-Catalan Max 
Published: May 2023

Abstract
Background
Painful conditions such as residual limb pain (RLP) and phantom limb pain (PLP) can manifest after amputation. The mechanisms underlying such postamputation pains are diverse and should be addressed accordingly. Different surgical treatment methods have shown potential for alleviating RLP due to neuroma formation — commonly known as neuroma pain — and to a lesser degree PLP. Two reconstructive surgical interventions, namely targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI), are gaining popularity in postamputation pain treatment with promising results. However, these two methods have not been directly compared in a randomised controlled trial (RCT). Here, we present a study protocol for an international, double-blind, RCT to assess the effectiveness of TMR, RPNI, and a non-reconstructive procedure called neuroma transposition (active control) in alleviating RLP, neuroma pain, and PLP.

Methods
One hundred ten upper and lower limb amputees suffering from RLP will be recruited and assigned randomly to one of the surgical interventions (TMR, RPNI, or neuroma transposition) in an equal allocation ratio. Complete evaluations will be performed during a baseline period prior to the surgical intervention, and follow-ups will be conducted in short term (1, 3, 6, and 12 months post-surgery) and in long term (2 and 4 years post-surgery). After the 12-month follow-up, the study will be unblinded for the evaluator and the participants. If the participant is unsatisfied with the outcome of the treatment at that time, further treatment including one of the other procedures will be discussed in consultation with the clinical investigator at that site.

Discussion
A double-blind RCT is necessary for the establishment of evidence-based procedures, hence the motivation for this work. In addition, studies on pain are challenging due to the subjectivity of the experience and the lack of objective evaluation methods. Here, we mitigate this problem by including different pain evaluation methods known to have clinical relevance. We plan to analyse the primary variable, mean change in NRS (0–10) between baseline and the 12-month follow-up, using the intention-to-treat (ITT) approach to minimise bias and keep the advantage of randomisation. The secondary outcomes will be analysed on both ITT and per-protocol (PP). An adherence protocol (PP population) analysis will be used for estimating a more realistic effect of treatment.

Trial registration
ClinicalTrials.gov NCT05009394.
Assessing the efficiency of health systems in achieving the universal health coverage goal: evidence from Sub-Saharan Africa
Authors: Arhin Kwadwo , Oteng-Abayie Eric Fosu , Novignon Jacob 
Published: May 2023

Abstract
Objective
Universal health coverage (UHC) is a major pathway to save many people from catastrophic and impoverishing healthcare spending and address the inequality in health and healthcare. The objective of this paper is to assess the efficiency with which health systems in sub-Saharan Africa (SSA) are utilizing healthcare resources to progress towards achieving the UHC goal by 2030.

Methods
The study followed the guidelines proposed by the World Health Organization (WHO) and World Bank joint UHC monitoring framework and the computational operationalization approach proposed by Wagstaff et al. (2015) to estimate the UHC index for each of the 30 selected SSA countries. The bootstrapping output-oriented data envelopment analysis (DEA) was used to estimate the bias-corrected technical efficiency scores and examine the environmental factors that influence health system efficiency.

Results
The estimated UHC levels ranged from a minimum of 52% to a maximum of 81% $$(SD=8.6\%)$$

(
S
D
=
8.6
%
)

with a median coverage of 66%. The average bias-corrected efficiency score was 0.81 $$\left(95\% CI:0.77-0.85\right)$$

95
%
C
I
:
0.77
-
0.85

. The study found that education, governance quality, public health spending, external health funding, and prepayment arrangements that pool funds for health had a positive significant effect on health system efficiency in improving UHC, while out-of-pocket payment had a negative impact.

Conclusion
The results show that health systems in SSA can potentially enhance UHC levels by at least 19% with existing healthcare resources if best practices are adopted. Policymakers should aim at improving education, good governance, and healthcare financing architecture to reduce out-of-pocket payments and over-reliance on donor funding for healthcare to achieve UHC.