bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning derivation of four computable 24-h pediatric sepsis phenotypes to facilitate enrollment in early personalized anti-inflammatory clinical trials
Authors: Qin Yidi , Kernan Kate F. , Fan Zhenjiang , Park Hyun-Jung , Kim Soyeon , Canna Scott W. , Kellum John A. , Berg Robert A. , Wessel David , Pollack Murray M. , Meert Kathleen , Hall Mark , Newth Christopher , Lin John C. , Doctor Allan , Shanley Tom , Cornell Tim , Harrison Rick E. , Zuppa Athena F. , Banks Russell , Reeder Ron W. , Holubkov Richard , Notterman Daniel A. , Michael Dean J. , Carcillo Joseph A. 
Published: May 2022

AbstractBackgroundThrombotic microangiopathy-inducedthrombocytopenia-associated multiple organ failureand hyperinflammatorymacrophage activation syndromeare important causes of late pediatric sepsis mortality that are often missed or have delayed diagnosis. The National Institutes of General Medical Science sepsis research working group recommendations call for application of new research approaches in extant clinical data sets to improve efficiency of early trials of new sepsis therapies. Our objective is to apply machine learning approaches to derive computable 24-h sepsis phenotypes to facilitate personalized enrollment in early anti-inflammatory trials targeting these conditions.MethodsWe applied consensus,k-means clustering analysis to our extant PHENOtyping sepsis-induced Multiple organ failure Study (PHENOMS) dataset of 404 children. 24-hour computable phenotypes are derived using 25 available bedside variables including C-reactive protein and ferritin.ResultsFour computable phenotypes (PedSep-A, B, C, and D) are derived. Compared to all other phenotypes, PedSep-A patients (n = 135; 2% mortality) were younger and previously healthy, with the lowest C-reactive protein and ferritin levels, the highest lymphocyte and platelet counts, highest heart rate, and lowest creatinine (p < 0.05); PedSep-B patients (n = 102; 12% mortality) were most likely to be intubated and had the lowest Glasgow Coma Scale Score (p < 0.05); PedSep-C patients (n = 110; mortality 10%) had the highest temperature and Glasgow Coma Scale Score, least pulmonary failure, and lowest lymphocyte counts (p < 0.05); and PedSep-D patients (n = 56, 34% mortality) had the highest creatinine and number of organ failures, including renal, hepatic, and hematologic organ failure, with the lowest platelet counts (p < 0.05). PedSep-D had the highest likelihood of developingthrombocytopenia-associated multiple organ failure(Adj OR 47.51 95% CI [18.83–136.83],p < 0.0001) andmacrophage activation syndrome(Adj OR 38.63 95% CI [13.26–137.75],p < 0.0001).ConclusionsFour computable phenotypes are derived, with PedSep-D being optimal for enrollment in early personalized anti-inflammatory trials targeting thrombocytopenia-associated multiple organ failure and macrophage activation syndrome in pediatric sepsis. A computer tool for identification of individual patient membership (www.pedsepsis.pitt.edu) is provided. Reproducibility will be assessed at completion of two ongoing pediatric sepsis studies.
Rehabilitation for life: the effect on physical function of rehabilitation and care in older adults after hip fracture—study protocol for a cluster-randomised stepped-wedge trial
Authors: Ipsen Jonas Ammundsen , Pedersen Lars T. , Viberg Bjarke , Nørgaard Birgitte , Suetta Charlotte , Bruun Inge H. 
Published: May 2022

Abstract
Background
A hip fracture is a serious event for older adults, given that approximately 50% do not regain their habitual level of physical function, and the mortality rate is high, as is the number of readmissions. The gap in healthcare delivery, as separated into two financial and self-governing sectors, might be a contributing cause of inferior rehabilitation and care for these patients. Therefore, we aim to assess the effect of continuous and progressive rehabilitation and care across sectors for older adults after hip fracture.

Methods/design
The project is designed as a stepped-wedge cluster randomised controlled trial. The study population of patients are older adults 65 years of age and above discharged after a hip fracture and healthcare professionals in primary and secondary care (municipalities and hospitals). Healthcare professionals from different sectors (hospital and municipalities) will be engaged in the empowerment-orientated praxis, through a workshop for healthcare professionals with knowledge sharing to the older adults using a digital health application (app). The rehabilitation intervention consists of 12 weeks of progressive resistance exercises initiated 1–2 days after discharge. To improve communication across sectors, a videoconference involving the patient and physiotherapists from both sectors will be conducted. On day, 3 after discharge, an outreach nurse performs a thorough assessment including measurement of vital signs. A hotline to the hospital for medical advice is a part of the intervention. The intervention is delivered as an add-on to the usual rehabilitation and care, and it involves one regional hospital and the municipalities within the catchment area of the hospital. The primary outcome is a Timed Up and Go Test 8 weeks post-surgery.

Discussion
Using a stepped-wedge design, the intervention will be assessed as well as implemented in hospital and municipalities, hopefully for the benefit of older adults after hip fracture. Furthermore, the collaboration between the sectors is expected to improve.

Trial registration
The study is approved by the Regional Scientific Ethics Committees of Southern Denmark (S-20200070) and the Danish Data Protection Agency (20-21854). Registered 9 of June 2020 at ClinicalTrials.gov, NCT04424186.
Risk factors and surgical prognosis in patients with aortic valve involvement caused by Takayasu arteritis
Authors: Shi Xuemei , Du Juan , Li Taotao , Gao Na , Fang Wei , Chen Suwei , Qiao Zhiyu , Li Chengnan , Zhu Junming , Pan Lili 
Published: May 2022

Abstract
Objective
Aortic valve involvement is not uncommon in patients with Takayasu arteritis (TAK) and leading to poor prognosis. The aim of our study was to explore the risk factors of aortic valve involvement and to evaluate the prognosis in TAK patients with aortic valve involvement.

Method
In this retrospective study, 172 TAK patients were divided into groups with or without aortic valve involvement to identify the risk factors. Patients who underwent aortic valve surgical treatment were followed up to assess cumulative incidence of postoperative adverse events.

Results
A total of 92 TAK patients (53.49%) had aortic valvular lesion. The infiltration of inflammatory cells was found in surgical specimens of aortic valve. Numano type IIb, elevated high-sensitivity C-reactive protein (hs-CRP) level, and dilation of ascending aorta and aortic root were statistically associated with aortic valvular lesion in TAK patients (OR [95%CI] 6.853 [1.685–27.875], p=0.007; 4.896 [1.646–14.561], p=0.004; 4.509 [1.517–13.403], p=0.007; 9.340 [2.188–39.875], p=0.003). The 1-, 5-, and 7-year cumulative incidence of postoperative adverse events were 14.7%, 14.7%, and 31.8%, respectively. Surgical methods (p=0.024, hazard ratio (HR) 0.082) and postoperatively anti-inflammatory therapy (p=0.036, HR 0.144) were identified as potential predictors of postoperative adverse events.

Conclusions
Regularly echocardiogram screening is suggested in patients with Numano type IIb and aggressive treatment should be performed early in TAK patients. As for TAK patients with aortic valve surgery, aortic root replacement seems to be the preferred option and regular anti-inflammatory therapy may reduce the occurrence of adverse events of them.
Subclinical carotid artery atherosclerosis and cognitive function in older adults
Authors: Lin Felice , Pa Judy , Karim Roksana , Hodis Howard N. , Han S. Duke , Henderson Victor W. , St. John Jan A. , Mack Wendy J. 
Published: May 2022

Abstract
Background
The combined effects of increased life expectancy and the considerable number of persons reaching old age will magnify the dementia epidemic in the USA. Demonstration that subclinical atherosclerosis precedes and is associated with cognitive impairment suggests a modifiable risk factor for age-associated cognitive impairment and dementia. The purpose of this study is to determine whether subclinical atherosclerosis as measured by carotid artery intima-media thickness (CIMT) is associated with changes in cognitive function over time in older adults.

Methods
This study combined longitudinal data from three clinical trials conducted between 2000 and 2013: the B-Vitamin Atherosclerosis Intervention Trial (BVAIT), the Women’s Isoflavone Soy Health (WISH) trial, and the Early versus Late Intervention Trial with Estradiol (ELITE). Participants were recruited from the general population in the Greater Los Angeles area and were free of cardiovascular disease and diabetes; no cognitive or psychiatric exclusion criteria were specified. The same standardized protocol for ultrasound image acquisition and measurement of CIMT was used in all trials. CIMT measurements performed at baseline and 2.5 years were used in these analyses. Cognitive function was assessed at baseline and 2.5 years using a battery of 14 standardized cognitive tests. All clinical trials were conducted at the University of Southern California Atherosclerosis Research Unit, Los Angeles, and had at least 2.5 years of cognitive follow-up.

Results
A total of 308 men and 1187 women, mean age of 61 years, were included in the combined longitudinal dataset for the primary analysis. No associations were found between CIMT and cognitive function at baseline or at 2.5 years. There was a weak inverse association between CIMT measured at baseline and change in global cognition assessed over 2.5 years (β (SE) = − 0.056 (0.028) units per 0.1 mm CIMT, 95% CI − 0.110, − 0.001, p = 0.046). No associations between CIMT at baseline and changes in executive function, verbal memory, or visual memory were found.

Conclusions
In this sample of healthy older adults, our findings suggest an association between subclinical atherosclerosis and change in global cognitive function over 2.5 years. Stronger associations were observed longitudinally over 2.5 years than cross-sectionally. When analysis was stratified by age group (<65 and ≥65 years old), the inverse association remained statistically significant for participants in the older age group. Subclinical atherosclerosis of the carotid artery may be a modifiable correlate of cognitive decline in middle and older age.

Trial registration
BVAIT, NCT00114400. WISH, NCT00118846. ELITE, NCT00114517.
Autologous conditioned serum (Orthokine) injection for treatment of classical trigeminal neuralgia: results of a single-center case series
Authors: Aghamohammadi Dawood , Sharifi Shahrzad , Shakouri Seyed Kazem , Eslampour Yashar , Dolatkhah Neda 
Published: May 2022

Abstract
Background
Despite some advances, treatment of trigeminal neuralgia remains a significant challenge. This study determines the efficacy and safety of autologous conditioned serum (Orthokine) injection into the foramen oval to treat refractory trigeminal neuralgia.

Case presentation
This is a consecutive case series from the Pain and Palliative Care Department of Imam Reza University Hospital, Tabriz, Iran. Eleven Iranian patients, eligible according to the inclusion and exclusion criteria, aged 45.64 ± 11.58 years (Four male and seven female, all Iranian) with established classical trigeminal neuralgia were injected with Orthokine (2 mL per injection) once a week for three consecutive weeks (total of four injections). Numeric rating scale scores for facial pain intensity and also carbamazepine daily dose were confirmed at pretreatment (T0) and at week 1 (T1), week 2 (T2), week 3 (T3), week 4 (T4), and month 2 (T5) posttreatment. Pain intensity was significantly reduced in the first 3 weeks of follow-up in comparison with baseline (T0 to T3) (8.18 ± 1.99 to 2.82 ± 2.13, p < 0.001), an effect that was retained at week 4 (T4) and month 2 (T5) follow-ups (2.82 ± 2.13 to 3.36 ± 2.69, p = 0.886). Carbamazepine consumption was significantly reduced in the first 3 weeks of follow-up in comparison with baseline (T0 to T3) (636.36 ± 307.48 to 200.00 ± 296.64, p = 0.003), an effect that was retained at week 4 and month 2 follow-ups (200.00 ± 296.64 to 200.00 ± 282.84, p = 0.802). There were no serious adverse events in participants.

Conclusion
Orthokine injection led to consistent pain relief and reduced carbamazepine dosage in patients with trigeminal neuralgia, with acceptable safety.
Hypoxic mesenchymal stem cell-derived extracellular vesicles ameliorate renal fibrosis after ischemia–reperfusion injure by restoring CPT1A mediated fatty acid oxidation
Authors: Gao Zhumei , Zhang Chuyue , Peng Fei , Chen Qianqian , Zhao Yinghua , Chen Liangmei , Wang Xu , Chen Xiangmei 
Published: May 2022

Abstract
Background
Renal fibrosis is a common pathological process of chronic kidney diseases induced by multiple factors. Hypoxic pretreatment of mesenchymal stem cells can enhance the efficacy of secreted extracellular vesicles (MSC-EVs) on various diseases, but it is not clear whether they can better improve renal fibrosis. The latest research showed that recovery of fatty acid oxidation (FAO) can reduce renal fibrosis. In this study, we aimed to examine whether hypoxic pretreatment with MSC extracellular vesicles (Hypo-EVs) can improve FAO to restore renal fibrosis and to investigate the underlying mechanism.

Methods
Hypo-EVs were isolated from hypoxia-pretreated human placenta-derived MSC (hP-MSC), and Norm-EVs were isolated from hP-MSC cultured under normal conditions. We used ischemia–reperfusion (I/R)-induced renal fibrosis model in vivo. The mice were injected with PBS, Hypo-EVs, or Norm-EVs immediately after the surgery and day 1 postsurgery. Renal function, kidney pathology, and renal fibrosis were assessed for kidney damage evaluation. For mechanistic exploration, fatty acid oxidation (FAO), mitochondrial morphological alterations, ATP production and mitochondrial mass proteins were detected in vivo. Mitochondrial membrane potential and reactive oxygen species (ROS) production were investigated in vitro.

Results
We found that Hypo-EVs confer a superior therapeutic effect on recovery of renal structure damage, restoration of renal function and reduction in renal fibrosis. Meanwhile, Hypo-EVs enhanced mitochondrial FAO in kidney by restoring the expression of a FAO key rate-limiting enzyme carnitine palmitoyl-transferase 1A (CPT1A). Mechanistically, the improvement of mitochondrial homeostasis, characterized by repaired mitochondrial structure, restoration of mitochondrial mass and ATP production, inhibition of oxidative stress, and increased mitochondrial membrane potential, partially explains the effect of Hypo-EVs on improving mitochondrial FAO and thus attenuating I/R damage.

Conclusions
Hypo-EVs suppress the renal fibrosis by restoring CPT1A-mediated mitochondrial FAO, which effects may be achieved through regulation of mitochondrial homeostasis. Our findings provide further mechanism support for development cell-free therapy of renal fibrosis.
TRPM8 deficiency attenuates liver fibrosis through S100A9-HNF4α signaling
Authors: Liu Qiang , Lei Xiaohua , Cao Zhenyu , Zhang Ju , Yan Likun , Fu Jie , Tong Qing , Qin Wei , Shao Yaoli , Liu Chun , Liu Zhiqiang , Wang Zicheng , Chu Yuan , Xu Ge , Liu Siyuan , Wen Xueyi , Yamamoto Hirofumi , Mori Masaki , Liang Xin. M. , Xu Xundi 
Published: May 2022

Abstract
Background
Liver fibrosis represent a major global health care burden. Data emerging from recent advances suggest TRPM8, a member of the transient receptor potential (TRP) family of ion channels, plays an essential role in various chronic inflammatory diseases. However, its role in liver fibrosis remains unknown. Herein, we assessed the potential effect of TRPM8 in liver fibrosis.

Methods
The effect of TRPM8 was evaluated using specimens obtained from classic murine models of liver fibrosis, namely wild-type (WT) and TRPM8−/− (KO) fibrotic mice after carbon tetrachloride (CCl4) or bile duct ligation (BDL) treatment. The role of TRPM8 was systematically evaluated using specimens obtained from the aforementioned animal models after various in vivo and in vitro experiments.

Results
Clinicopathological analysis showed that TRPM8 expression was upregulated in tissue samples from cirrhosis patients and fibrotic mice. TRPM8 deficiency not only attenuated inflammation and fibrosis progression in mice but also helped to alleviate symptoms of cholangiopathies. Moreover, reduction in S100A9 and increase in HNF4α expressions were observed in liver of CCl4- and BDL- treated TRPM8−/− mice. A strong regulatory linkage between S100A9 and HNF4α was also noticed in L02 cells that underwent siRNA-mediated S100A9 knockdown and S100A9 overexpressing plasmid transfection. Lastly, the alleviative effect of a selective TRPM8 antagonist was confirmed in vivo.

Conclusions
These findings suggest TRPM8 deficiency may exert protective effects against inflammation, cholangiopathies, and fibrosis through S100A9-HNF4α signaling. M8-B might be a promising therapeutic candidate for liver fibrosis.

Graphical Abstract
LRP4 is required for the olfactory association task in the piriform cortex
Authors: Yan Min , Xiong Mingtao , Wu Yongqiang , Lin Dong , Chen Peng , Chen Jiang , Liu Ziyang , Zhang Hang , Ren Dongyan , Fei Erkang , Lai Xinsheng , Zou Suqi , Wang Shunqi 
Published: May 2022

Abstract
Background
Low-density lipoprotein receptor-related protein 4 (LRP4) plays a critical role in the central nervous system (CNS), including hippocampal synaptic plasticity, maintenance of excitatory synaptic transmission, fear regulation, as well as long-term potentiation (LTP).

Results
In this study, we found that Lrp4 was highly expressed in layer II of the piriform cortex. Both body weight and brain weight decreased in Lrp4ECD/ECD mice without TMD (Transmembrane domain) and ICD (intracellular domain) of LRP4. However, in the piriform cortical neurons of Lrp4ECD/ECD mice, the spine density increased, and the frequency of both mEPSC (miniature excitatory postsynaptic current) and sEPSC (spontaneous excitatory postsynaptic current) was enhanced. Intriguingly, finding food in the buried food-seeking test was prolonged in both Lrp4ECD/ECD mice and Lrp4 cKO (conditional knockout of Lrp4 in the piriform cortex) mice.

Conclusions
This study indicated that the full length of LRP4 in the piriform cortex was necessary for maintaining synaptic plasticity and the integrity of olfactory function.
Power minimization for GSIC-based uplink cell-free massive MIMO-NOMA systems
Authors: Cui Tao , Liu Chengcheng , Du Peng , Song Rongfang 
Published: May 2022

AbstractNon-orthogonal multiple access (NOMA) and multiple-input multiple-output (MIMO) are considered promising techniques to satisfy the demands for high spectrum efficiency and massive connectivity in future wireless communication. In this paper, a novel framework to realize transmission in cell-free massive MIMO-NOMA system with deep integration between MIMO and NOMA is proposed. A new method is developed to divide users into different groups according to their equivalent path loss, and then “group-level successive interference cancellation” (GSIC) is used to cancel the inter-group interference when demodulating the users. Based on the new framework, a rigorous closed-form expression of the achievable sum rate in uplink cell-free massive MIMO-NOMA system is derived. In addition, a parallel iterative method is used to obtain the best power control scheme. Simulations show that the proposed scheme can effectively reduce the total power consumption and outperforms the orthogonal multiple access (OMA) transmission and traditional SIC-NOMA schemes based on user clustering.
Point prevalence study of antibiotic appropriateness and possibility of early discharge from hospital among patients treated with antibiotics in a Swiss University Hospital
Authors: Moulin Estelle , Boillat-Blanco Noémie , Zanetti Giorgio , Plüss-Suard Catherine , de Vallière Serge , Senn Laurence 
Published: May 2022

Abstract
Background
The growing threat of multidrug resistant organisms have led to increasingly promote prudent and rational use of antimicrobials as well as early hospital discharge plan. Antibiotic stewardship programs (ASP) have been developed as multifaceted approaches to improve use of current antibiotics and are now widely applied through different strategies. Proactive interventions are still limited in Switzerland and data on antimicrobial appropriateness and early discharge strategies are lacking. We aimed to describe the opportunities of antibiotics prescriptions optimization at Lausanne University Hospital, Switzerland and evaluate the suitability for early discharge among patients receiving antibiotics. The need for outpatient medical structures was also assessed.

Methods
We conducted a point prevalence survey of antibiotic prescriptions in adult medical and surgical units with exclusion of intermediate and intensive care units. All hospitalized patients receiving a systemic antibiotic on the day of evaluation were included. An infectious diseases specialist evaluated antimicrobial appropriateness and assessed suitability for discharge according to medical and nursing observations. The need of flexible additional outpatient facility for a close medical follow-up was evaluated concomitantly.

Results
A total of 564 patients’ files were reviewed. 182 (32%) patients received one or more systemic antibiotic: 62 (34%) as a prophylaxis and 120 (66%) as a treatment with or without concomitant prophylaxis. 37/62 (60%) patients receiving prophylaxis had no indication to continue the antibacterial. Regarding the patients treated with antibiotics, 69/120 (58%) presented at least one opportunity for treatment optimization, mainly interruption of treatment. A previous ID consultation was recorded for 55/120 (46%) patients, of whom 21 (38%) could have benefited from antimicrobial therapy optimization on the day of the point assessment. 9.2% patients were eligible for discharge of whom 64% could leave the hospital with a close outpatient follow-up for infectious issues.

Conclusions
This point prevalence study offers precious indicators for tailoring future antibiotic stewardship interventions that can be combined with early discharge. Any centre considering implementing ASP should conduct this type of analysis with a pragmatic approach to gain insight into local practices and needed resources.