bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reverse shoulder arthroplasty versus hemiarthroplasty versus non-surgical treatment for older adults with acute 3- or 4-part fractures of the proximal humerus: study protocol for a randomised controlled trial (PROFHER-2: PROximal Fracture of Humerus Evaluation by Randomisation – Trial Number 2)
Authors: Rangan Amar , Gwilym Stephen , Keding Ada , Corbacho Belen , Kottam Lucksy , Arundel Catherine , Coleman Elizabeth , DiMascio Livio , Hewitt Catherine , Jones Valerie , Kassam Jamila , McDaid Catriona , Mitchell Natasha , Mott Andrew , O’Carroll Grace , Tharmanathan Puvan , Torgerson David 
Published: April 2023

Abstract
Background
Proximal humerus fractures (PHF) are common and painful injuries, with the majority resulting from falls from a standing height. As with other fragility fractures, its age-specific incidence is increasing. Surgical treatment with hemiarthroplasty (HA) and reverse shoulder arthroplasty (RSA) have been increasingly used for displaced 3- and 4-part fractures despite a lack of good quality evidence as to whether one type of arthroplasty is superior to the other, and whether surgery is better than non-surgical management. The PROFHER-2 trial has been designed as a pragmatic, multicentre randomised trial to compare the clinical and cost-effectiveness of RSA vs HA vs Non-Surgical (NS) treatment in patients with 3- and 4-part PHF.

Methods
Adults over 65 years of age presenting with acute radiographically confirmed 3- or 4-part fractures, with or without associated glenohumeral joint dislocation, who consent for trial participation will be recruited from around 40 National Health Service (NHS) Hospitals in the UK. Patients with polytrauma, open fractures, presence of axillary nerve palsy, pathological (other than osteoporotic) fractures, and those who are unable to adhere to trial procedures will be excluded. We will aim to recruit 380 participants (152 RSA, 152 HA, 76 NS) using 2:2:1 (HA:RSA:NS) randomisation for 3- or 4-part fractures without joint dislocation, and 1:1 (HA:RSA) randomisation for 3- or 4-part fracture dislocations. The primary outcome is the Oxford Shoulder Score at 24 months. Secondary outcomes include quality of life (EQ-5D-5L), pain, range of shoulder motion, fracture healing and implant position on X-rays, further procedures, and complications. Independent Trial Steering Committee and Data Monitoring Committee will oversee the trial conduct, including the reporting of adverse events and harms.

Discussion
The PROFHER-2 trial is designed to provide a robust answer to guide the treatment of patients aged 65 years or over who sustain 3- and 4-part proximal humeral fractures. The pragmatic design and recruitment from around 40 UK NHS hospitals will ensure immediate applicability and generalisability of the trial findings. The full trial results will be made available in a relevant open-access peer-reviewed journal.

Trial registration
ISRCTN76296703. Prospectively registered on 5th April 2018
Impact of the COVID-19 pandemic on a clinical trial of pneumococcal vaccine scheduling (PVS) in rural Gambia
Authors: Hossain Ilias , Osei Isaac , Lobga Galega , Wutor Baleng M. , Olatunji Yekini , Adefila Williams , Adeshola Banjo , Isa Yasir , Nguyen Cattram , Sonko Kemo , Ceesay Lamin , Baldeh Bubacarr , Barrow Omar , Young Benjamin , Ceesay Saidina , Nyassi Abdoullah , Sarwar Golam , Barjo Ousman , M.Drammeh Momodou , Salaudeen Rasheed , Mackenzie Grant 
Published: April 2023

AbstractThe COVID-19 pandemic represents an unprecedented challenge for clinical research. The Pneumococcal Vaccine Schedules (PVS) study is a non-inferiority, interventional trial in which infants resident in 68 geographic clusters are randomised to two different schedules for pneumococcal vaccination. From September 2019 onwards, all infants resident in the study area became eligible for trial enrolment at all Expanded Programme on Immunisation (EPI) clinics in the study area. Surveillance for clinical endpoints is conducted at all 11 health facilities in the study area. PVS is conducted as a collaboration between the Medical Research Council Unit The Gambia (MRCG) at LSHTM and the Gambian Ministry of Health (MoH). The COVID-19 pandemic caused many disruptions to PVS. MRCG instructed interventional studies that participant enrolment be suspended on 26 March 2020, and a public health emergency was declared in The Gambia on 28 March 2020. Enrolment in PVS restarted on 1 July 2020 and was suspended again on 5 August 2020 after The Gambia experienced a sharp increase in COVID-19 cases in late July 2020 and restarted again on 1 September 2020. During periods of suspended enrolment of infants at EPI clinics, PVS continued safety surveillance at health facilities, albeit with disruptions. During the periods of suspended enrolment, infants who had been enrolled before 26 March 2020 continued to receive the PCV schedule to which they had been randomly allocated based on their village of residence, whereas all other infants received the standard PCV schedule. Throughout 2020 and 2021, the trial faced numerous technical and operational challenges: disruption to MoH delivery of EPI services and clinical care at health facilities; episodes of staff illness and isolation; disruption of MRCG transport, procurement, communications and human resource management; and also a range of ethical, regulatory, sponsorship, trial monitoring and financial challenges. In April 2021, a formal review concluded that the pandemic had not compromised the scientific validity of PVS and that the trial should continue as per protocol. The continuing challenges that COVID-19 poses to PVS, and other clinical trials will persist for some time.
Radiomics model to classify mammary masses using breast DCE-MRI compared to the BI-RADS classification performance
Authors: Debbi Kawtar , Habert Paul , Grob Anaïs , Loundou Anderson , Siles Pascale , Bartoli Axel , Jacquier Alexis 
Published: April 2023

Abstract
Background
Recent advanced in radiomics analysis could help to identify breast cancer among benign mammary masses. The aim was to create a radiomics signature using breast DCE-MRI extracted features to classify tumors and to compare the performances with the BI-RADS classification.

Material and methods
From September 2017 to December 2019 images, exams and records from consecutive patients with mammary masses on breast DCE-MRI and available histology from one center were retrospectively reviewed (79 patients, 97 masses). Exclusion criterion was malignant uncertainty. The tumors were split in a train-set (70%) and a test-set (30%). From 14 kinetics maps, 89 radiomics features were extracted, for a total of 1246 features per tumor. Feature selection was made using Boruta algorithm, to train a random forest algorithm on the train-set. BI-RADS classification was recorded from two radiologists.

Results
Seventy-seven patients were analyzed with 94 tumors, (71 malignant, 23 benign). Over 1246 features, 17 were selected from eight kinetic maps. On the test-set, the model reaches an AUC = 0.94 95 CI [0.85–1.00] and a specificity of 33% 95 CI [10–70]. There were 43/94 (46%) lesions BI-RADS4 (4a = 12/94 (13%); 4b = 9/94 (10%); and 4c = 22/94 (23%)). The BI-RADS score reached an AUC = 0.84 95 CI [0.73–0.95] and a specificity of 17% 95 CI [3–56]. There was no significant difference between the ROC curves for the model or the BI-RADS score (p = 0.19).

Conclusion
A radiomics signature from features extracted using breast DCE-MRI can reach an AUC of 0.94 on a test-set and could provide as good results as BI-RADS to classify mammary masses.
Adrenocortical tumors in children: Sri Lankan experience from a single center, and a mini review
Authors: Naotunna Naotunna Palliya Guruge Chamidri Ra , Siriwardana Harankaha Vidanalage Dinendra Nisha , Lakmini Balagamage Chamila , Gamage Dilhara Senani , Gunarathna Sandani , Samarasinghe Malik , Gunasekara Sanjeewa , Atapattu Navoda 
Published: April 2023

Abstract
Background
Pediatric adrenocortical tumors include both benign adenomas and highly virulent malignant tumors. However, they are very rare among children. The aim of this study is to evaluate the clinicopathological data of children presenting with adrenocortical tumors and assess their survival in a South Asian population.

Case presentation
This is a retrospective cohort study that includes patients diagnosed with adrenocortical tumors from August 2020 to August 2022 followed-up at Lady Ridgeway Hospital. Seven children were diagnosed with adrenal cortical tumors. Their ages ranged from 10 months to 6.5 years. Five of them were boys. All displayed signs of peripheral precocious puberty. One boy phenotypically had features of Beckwith–Wiedemann syndrome. The median time for diagnosis after the onset of symptoms was 4.4 months. The preoperative diagnosis was based on clinical manifestations, elevated dehydroepiandrosterone sulfate levels, and suprarenal masses on computed tomography. All five boys had right-sided suprarenal masses, while the two girls had them on the left side. All underwent surgery for tumor resection. The diagnosis was confirmed based on the histopathology of the adrenal specimens. Four children had a Wieneke score of 4 or more, suggesting the possibility of adrenocortical carcinoma; however, only two of them behaved as malignant tumors. To date, two children have developed local recurrences within a very short period.

Conclusion
Adrenocortical tumors are uncommon in children, and treatment options are limited. To identify early recurrences, routine clinical, radiological, and biochemical examinations at least once every 6–8 weeks is important.
Evaluation of safety and efficacy of autologous oral mucosa-derived epithelial cell sheet transplantation for prevention of anastomotic restenosis in congenital esophageal atresia and congenital esophageal stenosis
Authors: Fujino Akihiro , Fuchimoto Yasushi , Mori Teizaburo , Kano Motohiro , Yamada Yohei , Ohno Michinobu , Baba Yoshiyuki , Isogawa Nobutaka , Arai Katsuhiro , Yoshioka Takako , Abe Makoto , Kanai Nobuo , Takagi Ryo , Maeda Masanori , Umezawa Akihiro 
Published: April 2023

Abstract
Background
We performed the first autologous oral mucosa-derived epithelial cell sheet transplantation therapy in a patient with refractory postoperative anastomotic stricture in congenital esophageal atresia (CEA) and confirmed its safety. In this study, patients with CEA and congenital esophageal stenosis were newly added as subjects to further evaluate the safety and efficacy of cell sheet transplantation therapy.

Methods
Epithelial cell sheets were prepared from the oral mucosa of the subjects and transplanted into esophageal tears created by endoscopic balloon dilatation (EBD). The safety of the cell sheets was confirmed by quality control testing, and the safety of the transplantation treatment was confirmed by 48-week follow-up examinations.

Results
Subject 1 had a stenosis resected because the frequency of EBD did not decrease after the second transplantation. Histopathological examination of the resected stenosis revealed marked thickening of the submucosal layer. Subjects 2 and 3 did not require EBD for 48 weeks after transplantation, during which time they were able to maintain a normal diet by mouth.

Conclusions
Subjects 2 and 3 were free of EBD for a long period of time after transplantation, confirming that cell sheet transplantation therapy is clearly effective in some cases. In the future, it is necessary to study more cases; develop new technologies such as an objective index to evaluate the efficacy of cell sheet transplantation therapy and a device to achieve more accurate transplantation; identify cases in which the current therapy is effective; and find the optimal timing of transplantation; and clarify the mechanism by which the current therapy improves stenosis.
Trial registration: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393.
Menstrual blood-derived endometrial stem cells alleviate neuroinflammation by modulating M1/M2 polarization in cell and rat Parkinson’s disease models
Authors: Li Han , Wei Jinghui , Zhang Zhigang , Li Junyao , Ma Yaokai , Zhang Ping , Lin Juntang 
Published: April 2023

AbstractBackgroundNeuroinflammation is closely related to the development of Parkinson's disease (PD). Because of the extensive sources, non-invasive and periodical collection method, human menstrual blood-derived endometrial stem cells (MenSCs) have been explored as a promising tool for treatment of PD. This study aimed to investigate if MenSCs could inhibit neuroinflammation in PD rats by regulating M1/M2 polarization and to excavate the underlying mechanisms.MethodsMenSCs were co-cultured with 6-OHDA-exposed microglia cell lines. Then the morphology of microglia cells and the level of inflammatory factors were assessed by immunofluorescence and qRT-PCR. After MenSCs were transplanted into the brain of PD rats, animal motor function, the expression of tyrosine hydroxylase, and the level of inflammatory factors in the cerebrospinal fluid (CSF) and serum were detected to evaluate the therapeutic potential of MenSCs. Meanwhile, the expression of M1/M2 phenotype related genes was detected by qRT-PCR. One protein array kit containing 1000 kinds of factors was used to detect the protein components in the conditioned medium of MenSCs. Finally, bioinformatic analysis was performed to analyze the function of factors secreted by MenSCs and the signal pathways involved in.ResultsMenSCs could suppress 6-OHDA-induced microglia cell activation and significantly decrease inflammation in vitro. After transplantation into the brain of PD rats, MenSCs improved animal motor function, which was indicated by the increased movement distance, ambulatory episodes, exercise time on the rotarod, and less contralateral rotation. Additionally, MenSCs reduced the loss of dopaminergic neurons and down-regulated the level of pro-inflammatory factors in the CSF and serum. Moreover, q-PCR and WB results showed the transplantation of MenSCs significantly down-regulated the expression of M1 phenotype cell markers and meanwhile up-regulated the expression of M2 phenotype cell markers in the brain of PD rats. 176 biological processes including inflammatory response, negative regulation of apoptotic process, and microglial cell activation were enriched by GO-BP analysis. 58 signal pathways including PI3K/Akt and MAPK were enriched by KEGG analysis.ConclusionsIn conclusion, our results provide preliminary evidence for the anti-inflammation capacity of MenSCs by regulating M1/M2 polarization. We firstly demonstrated the biological process of factors secreted by MenSCs and the signal pathways involved in using protein array and bioinformatic analysis.
Principles and requirements for nanomaterial representations to facilitate machine processing and cooperation with nanoinformatics tools
Authors: Blekos Kostas , Chairetakis Kostas , Lynch Iseult , Marcoulaki Effie 
Published: April 2023

AbstractEfficient and machine-readable representations are needed to accurately identify, validate and communicate information of chemical structures. Many such representations have been developed (as, for example, the Simplified Molecular-Input Line-Entry System and the IUPAC International Chemical Identifier), each offering advantages specific to various use-cases. Representation of the multi-component structures of nanomaterials (NMs), though, remains out of scope for all the currently available standards, as the nature of NMs sets new challenges on formalizing the encoding of their structure, interactions and environmental parameters. In this work we identify a set of principles that a NM representation should adhere to in order to provide “machine-friendly” encodings of NMs, i.e. encodings that facilitate machine processing and cooperation with nanoinformatics tools. We illustrate our principles by showing how the recently introduced InChI-based NM representation, might be augmented, in principle, to also encode morphology and mixture properties, distributions of properties, and also to capture auxiliary information and allow data reuse.
Smoking is associated with elevated blood level of volatile organic compounds: a population-based analysis of NHANES 2017–2018
Authors: Wu Guangjie , Gong Shiwei , He Yan , Liu Dong 
Published: April 2023

Abstract
Background
The study aims to explore the association between cigarette smoking with blood exposure to volatile organic compounds using population data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018.

Methods
Based on the data of NHANES 2017–2018, we identified 1117 participants aged 18 to 65 years, who had complete VOCs testing data and filled out the Smoking-Cigarette Use and Volatile Toxicant questionnaires. The participants consisted of 214 dual-smoking persons, 41 E-cigarette smokers, 293 combustible-cigarette smokers and 569 non-smokers. We used One-way ANOVA and Welch’s ANOVA to compare differences of VOCs concentration among 4 groups and multivariable regression model to confirm the factors associated with VOCs concentration.

Results
In dual-smoking and combustible-cigarette smokers, blood concentration of 2,5-Dimethylfuran, Benzene, Benzonitrile, Furan, Isobutyronitrile were higher than non-smokers. When compared with people who never smoked, E-cigarette smokers had similar blood concentrations of VOCs. Blood concentrations of Benzene, Furan, and Isobutyronitrile were significant higher in combustible-cigarette smokers than in E-cigarette smokers. In the multivariable regression model, dual-smoking and combustible-cigarette smoking were associated with elevated blood concentrations of several VOCs except 1,4-Dichlorobenzene, while E-cigarette smoking was only associated with elevated 2,5-Dimethylfuran concentration.

Conclusions
Smoking, mainly dual-smoking and combustible-cigarette smoking, is associated with elevated blood concentration of VOCs, while the effect is weak in E-cigarette smoking.
Maternal zinc alleviates tert-butyl hydroperoxide-induced mitochondrial oxidative stress on embryonic development involving the activation of Nrf2/PGC-1α pathway
Authors: Huang Liang , Gao Wei , He Xuri , Yuan Tong , Zhang Huaqi , Zhang Xiufen , Zheng Wenxuan , Wu Qilin , Liu Ju , Wang Wence , Yang Lin , Zhu Yongwen 
Published: April 2023

Abstract
Background
Mitochondrial dysfunction induced by excessive mitochondrial reactive oxygen species (ROS) damages embryonic development and leads to growth arrest.

Objective
The purpose of this study is to elucidate whether maternal zinc (Zn) exert protective effect on oxidative stress targeting mitochondrial function using an avian model.

Result
In ovo injected tert-butyl hydroperoxide (BHP) increases (P < 0.05) hepatic mitochondrial ROS, malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHdG), and decreases (P < 0.05) mitochondrial membrane potential (MMP), mitochondrial DNA (mtDNA) copy number and adenosine triphosphate (ATP) content, contributing to mitochondrial dysfunction. In vivo and in vitro studies revealed that Zn addition enhances (P < 0.05) ATP synthesis and metallothionein 4 (MT4) content and expression as well as alleviates (P < 0.05) the BHP-induced mitochondrial ROS generation, oxidative damage and dysfunction, exerting a protective effect on mitochondrial function by enhancing antioxidant capacity and upregulating the mRNA and protein expressions of Nrf2 and PGC-1α.

Conclusions
The present study provides a new way to protect offspring against oxidative damage by maternal Zn supplementation through the process of targeting mitochondria involving the activation of Nrf2/PGC-1α signaling.

Graphical Abstract
The networked micro-decision context: a new lens on transformative urban governance
Authors: Long Le Anh Nguyen , Krause Rachel M. , Arnold Gwen , Swanson Ryan , Fatemi S. Mohsen 
Published: April 2023

AbstractRecent large-scale societal disruptions, from the COVID-19 pandemic to intensifying wildfires and weather events, reveal the importance of transforming governance systems so they can address complex, transboundary, and rapidly evolving crises. Yet current knowledge of the decision-making dynamics that yield transformative governance remains scant. Studies typically focus on the aggregate outputs of government decisions, while overlooking their micro-level underpinnings. This is a key oversight because drivers of policy change, such as learning or competition, are prosecuted by people rather than organizations. We respond to this knowledge gap by introducing a new analytical lens for understanding policymaking, aimed at uncovering how characteristics of decision-makers and the structure of their relationships affect their likelihood of effectuating transformative policy responses. This perspective emphasizes the need for a more dynamic and relational view on urban governance in the context of transformation.
Force-free and autonomous active Brownian ratchets
(a)
Authors: Rein Constantin , Kolář Martin , Kroy Klaus , Holubec Viktor 
Published: April 2023

Abstract
Autonomous active Brownian ratchets rectify active Brownian particle motion solely by means of a spatially modulated but stationary activity, without external forces. We argue that such ratcheting requires at least a two-dimensional geometry. The underlying principle is similar to the ratcheting induced by steric obstacles in microswimmer baths: suitably polarized swimmers get channeled, while the others get trapped in low-activity regions until they lose direction. The maximum current is generally reached in the limit of large propulsion speeds, in which the rectification efficiency vanishes. Maximum efficiency is attained at intermediate activities and numerically found to be on the order of a few percent, for ratchets with simple wedge-shaped low-activity regions.
Low Vitamin D Levels Are Associated With Long COVID Syndrome in COVID-19 Survivors
Authors: di Filippo Luigi , Frara Stefano , Nannipieri Fabrizio , Cotellessa Alice , Locatelli Massimo , Rovere Querini Patrizia , Giustina Andrea 
Published: April 2023

Abstract

Context
Long COVID is an emerging syndrome affecting 50% to 70% of COVID-19 survivors that still lacks predicting factors.

Objective
Due to the extraskeletal effects of vitamin D, we retrospectively assessed the association between 25(OH) vitamin D levels and long COVID in COVID-19 survivors 6 months after hospitalization.

Methods
Long COVID was defined according to NICE guidelines. Fifty long COVID and 50 non–long-COVID subjects matched on a 1:1 basis were enrolled from an outpatient clinic post-COVID cohort seen from August to November 2020. Therapies/comorbidities affecting calcium/vitamin D/bone metabolism, and/or admission to the intensive care unit during hospitalization were exclusion criteria. 25(OH) Vitamin D was measured at hospital admission and 6 months after discharge.

Results
We observed lower 25(OH) vitamin D levels, evaluated at follow-up, in subjects with long COVID than those without (20.1 vs 23.2 ng/mL, P = .03). Regarding the affected health areas evaluated in the entire cohort, we observed lower 25(OH) vitamin D levels in those with neurocognitive symptoms at follow-up (n = 7) than those without (n = 93) (14.6 vs 20.6 ng/mL, P = .042). In patients presenting vitamin D deficiency (&lt;20 ng/mL), both at admission and at follow-up (n = 42), those affected by long COVID (n = 22) presented lower 25(OH) vitamin D levels at follow-up than those not affected (n = 20) (12.7 vs 15.2 ng/mL, P = .041). In multiple regression analyses, lower 25(OH) vitamin D levels at follow-up were the only variable significantly associated with long COVID in our cohort (P = .008, OR 1.09, CI 1.01-1.16).

Conclusion
COVID-19 survivors with long COVID have lower 25(OH) vitamin D levels than matched patients without long COVID. Our data suggest that vitamin D levels should be evaluated in COVID-19 patients after hospital discharge. The role of vitamin D supplementation as a preventive strategy of COVID-19 sequelae should be tested in randomized controlled trials.