bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restoration of the immune function as a complementary strategy to treat Chronic Lymphocytic Leukemia effectively
Authors: Moreno Carol , Muñoz Cecilia , Terol María José , Hernández-Rivas José-Ángel , Villanueva Miguel 
Published: October 2021

AbstractChronic Lymphocytic Leukemia (CLL) is a hematological malignancy characterized by uncontrolled proliferation of B-cells and severe immune dysfunction. Chemo(immuno)therapies (CIT) have traditionally aimed to reduce tumor burden without fully understanding their effects on the immune system. As a consequence, CIT are usually associated with higher risk of infections, secondary neoplasms and autoimmune disorders. A better understanding of the biology of the disease has led to the development of therapeutic strategies which not only act against malignant B-cells but also reactivate and enhance the patient’s own anti-tumor immune response. Here, we review the current understanding of the underlying interplay between the malignant cells and non-malignant immune cells that may promote tumor survival and proliferation. In addition, we review the available evidence on how different treatment options for CLL including CIT regimens, small molecular inhibitors (i.e, BTK inhibitors, PI3K inhibitors, BCL-2 inhibitors) and T-cell therapies, affect the immune system and their clinical consequences. Finally, we propose that a dual therapeutic approach, acting directly against malignant B-cells and restoring the immune function is clinically relevant and should be considered when developing future strategies to treat patients with CLL.
Timing of antibiotic therapy in the ICU
Authors: Kollef Marin H. , Shorr Andrew F. , Bassetti Matteo , Timsit Jean-Francois , Micek Scott T. , Michelson Andrew P. , Garnacho-Montero Jose 
Published: October 2021

AbstractSevere or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic therapy for serious infections can have a doubling or more in their mortality. Additionally, the timing of an appropriate antibiotic regimen, one that is active against the offending pathogens based on in vitro susceptibility, also influences survival. Thus not only is early empiric antibiotic administration important but the selection of those agents is crucial as well. The duration of antibiotic infusions, especially for β-lactams, can also influence antibiotic efficacy by increasing antimicrobial drug exposure for the offending pathogen. However, due to mounting antibiotic resistance, aggressive antimicrobial de-escalation based on microbiology results is necessary to counterbalance the pressures of early broad-spectrum antibiotic therapy. In this review, we examine time related variables impacting antibiotic optimization as it relates to the treatment of life threatening infections in the ICU. In addition to highlighting the importance of antibiotic timing in the ICU we hope to provide an approach to antimicrobials that also minimizes the unnecessary use of these agents. Such approaches will increasingly be linked to advances in molecular microbiology testing and artificial intelligence/machine learning. Such advances should help identify patients needing empiric antibiotic therapy at an earlier time point as well as the specific antibiotics required in order to avoid unnecessary administration of broad-spectrum antibiotics.
Gut bacterial metabolites modulate endoplasmic reticulum stress
Authors: Ke Xiaobo , You Kwontae , Pichaud Matthieu , Haiser Henry J. , Graham Daniel B. , Vlamakis Hera , Porter Jeffrey A. , Xavier Ramnik J. 
Published: October 2021

AbstractBackgroundThe endoplasmic reticulum (ER) is a membranous organelle that maintains proteostasis and cellular homeostasis, controlling the fine balance between health and disease. Dysregulation of the ER stress response has been implicated in intestinal inflammation associated with inflammatory bowel disease (IBD), a chronic condition characterized by changes to the mucosa and alteration of the gut microbiota. While the microbiota and microbially derived metabolites have also been implicated in ER stress, examples of this connection remain limited to a few observations from pathogenic bacteria. Furthermore, the mechanisms underlying the effects of bacterial metabolites on ER stress signaling have not been well established.ResultsUtilizing an XBP1s-GFP knock-in reporter colorectal epithelial cell line, we screened 399 microbiome-related metabolites for ER stress pathway modulation. We find both ER stress response inducers (acylated dipeptide aldehydes and bisindole methane derivatives) and suppressors (soraphen A) and characterize their activities on ER stress gene transcription and translation. We further demonstrate that these molecules modulate the ER stress pathway through protease inhibition or lipid metabolism interference.ConclusionsOur study identified novel links between classes of gut microbe-derived metabolites and the ER stress response, suggesting the potential for these metabolites to contribute to gut ER homeostasis and providing insight into the molecular mechanisms by which gut microbes impact intestinal epithelial cell homeostasis.
The effect evaluation of Individual Placement and Support (IPS) for patients with substance use disorders: study protocol for a randomized controlled trial of IPS versus enhanced self-help
Authors: Rognli Eline Borger , Aas Erlend Marius , Drake Robert E. , Marsden John , Anders Paul , Bond Gary R. , Lystad June Ullevoldsæter , Reme Silje Endresen , Arnevik Espen Ajo 
Published: October 2021

Abstract
Background
Employment is associated with better outcomes of substance use treatment and protects against relapse after treatment completion. Unemployment rates are high for people with substance use disorders (SUD) who undergo treatment, with Norwegian estimates ranging from 81 to 91%. Evidence-based vocational models are lacking for patients in SUD treatment but exist for patients with psychosis in terms of Individual Placement and Support (IPS). The aim of the IPS for substance use disorders (IPS-SUD) trial is to investigate the effect of IPS in a SUD population.

Methods/design
The IPS-SUD trial is a randomized controlled trial (RCT) comparing IPS to an enhanced control intervention. The study is a seven-site, two-arm, pragmatic, parallel-group, superiority RCT. Participants are randomly assigned (1:1) to receive either IPS plus treatment as usual (TAU) or to receive a self-help guide book and 12-h workshop plus 1-h individual vocational guidance plus TAU. Aiming to recruit 200 participants, we will be able to detect a 20% difference in the main outcome of employment with 90% power. We will make assessments at inclusion and at 6- and 12-month follow-ups and obtain outcome data on employment from national mandatory registries. The primary outcome will be at least 1 day of competitive employment during the 18-month follow-up period. Secondary employment outcomes will capture the pattern and extent of employment in terms of total time worked (days/hours), time to first employment, number of different jobs, duration of the longest employment, and sustained employment. Secondary non-employment outcomes will be substance use, mental distress, and quality of life measured by validated instruments at 6, 12, and 18 months follow-up assessments. To be eligible, participants must be between 18 and 65 years, currently unemployed and in treatment for SUD.

Discussion
The IPS-SUD trial will provide evidence for the use of IPS in a SUD population. Findings from the study will have implications for service delivery.

Trial registration
ClinicalTrials.gov NCT04289415. Registered on February 28, 2020
Multiomic study of skin, peripheral blood, and serum: is serum proteome a reflection of disease process at the end-organ level in systemic sclerosis?
Authors: Farutin Victor , Kurtagic Elma , Pradines Joël R. , Capila Ishan , Mayes Maureen D. , Wu Minghua , Manning Anthony M. , Assassi Shervin 
Published: October 2021

AbstractBackgroundSerum proteins can be readily assessed during routine clinical care. However, it is unclear to what extent serum proteins reflect the molecular dysregulations of peripheral blood cells (PBCs) or affected end-organs in systemic sclerosis (SSc). We conducted a multiomic comparative analysis of SSc serum profile, PBC, and skin gene expression in concurrently collected samples.MethodsGlobal gene expression profiling was carried out in skin and PBC samples obtained from 49 SSc patients enrolled in the GENISOS observational cohort and 25 unaffected controls. Levels of 911 proteins were determined by Olink Proximity Extension Assay in concurrently collected serum samples.ResultsBoth SSc PBC and skin transcriptomes showed a prominent type I interferon signature. The examination of SSc serum profile revealed an upregulation of proteins involved in pro-fibrotic homing and extravasation, as well as extracellular matrix components/modulators. Notably, several soluble receptor proteins such as EGFR, ERBB2, ERBB3, VEGFR2, TGFBR3, and PDGF-Rα were downregulated. Thirty-nine proteins correlated with severity of SSc skin disease. The differential expression of serum protein in SSc vs. control comparison significantly correlated with the differential expression of corresponding transcripts in skin but not in PBCs. Moreover, the differentially expressed serum proteins were significantly more connected to the Well-Associated-Proteins in the skin than PBC gene expression dataset. The assessment of the concordance of between-sample similarities revealed that the molecular profile of serum proteins and skin gene expression data were significantly concordant in patients with SSc but not in healthy controls.ConclusionsSSc serum protein profile shows an upregulation of profibrotic cytokines and a downregulation of soluble EGF and other key receptors. Our multilevel comparative analysis indicates that the serum protein profile in SSc correlates more closely with molecular dysregulations of skin than PBCs and might serve as a reflection of disease severity at the end-organ level.
Predicting the nature of pleural effusion in patients with lung adenocarcinoma based on 18F-FDG PET/CT
Authors: Li Yi , Mu Wei , Li Yuan , Song Xiao , Huang Yan , Jiang Lei 
Published: October 2021

Abstract
Background
This study aims to establish a predictive model on the basis of 18F-FDG PET/CT for diagnosing the nature of pleural effusion (PE) in patients with lung adenocarcinoma.

Methods
Lung adenocarcinoma patients with PE who underwent 18F-FDG PET/CT were collected and divided into training and test cohorts. PET/CT parameters and clinical information in the training cohort were collected to estimate the independent predictive factors of malignant pleural effusion (MPE) and to establish a predictive model. This model was then applied to the test cohort to evaluate the diagnostic efficacy.

Results
A total of 413 lung adenocarcinoma patients with PE were enrolled in this study, including 245 patients with MPE and 168 patients with benign PE (BPE). The patients were divided into training (289 patients) and test (124 patients) cohorts. CEA, SUVmax of tumor and attachment to the pleura, obstructive atelectasis or pneumonia, SUVmax of pleura, and SUVmax of PE were identified as independent significant factors of MPE and were used to construct a predictive model, which was graphically represented as a nomogram. This predictive model showed good discrimination with the area under the curve (AUC) of 0.970 (95% CI 0.954–0.986) and good calibration. Application of the nomogram in the test cohort still gave good discrimination with AUC of 0.979 (95% CI 0.961–0.998) and good calibration. Decision curve analysis demonstrated that this nomogram was clinically useful.

Conclusions
Our predictive model based on 18F-FDG PET/CT showed good diagnostic performance for PE, which was helpful to differentiate MPE from BPE in patients with lung adenocarcinoma.
Evidence on respectful maternity care for adolescents: a systematic review protocol
Authors: Habib Helen H. , Mwaisaka Jefferson , Torpey Kwasi , Maya Ernest Tei , Ankomah Augustine 
Published: October 2021

Abstract
Background
Intrapartum mistreatment of women is an ubiquitous public health and human rights challenge. The issue reportedly has severe maternal and neonatal outcomes including mortality, and generally leads to a decreased satisfaction with maternity care. Intrapartum mistreatment, despite being ubiquitous, indicates higher incidence amongst adolescent parturients who are simultaneously at a higher risk of maternal morbidity and mortality. Studies have suggested that Respectful Maternity Care interventions reduce intrapartum mistreatment and improve clinical outcomes for women and neonates in general. However, evidence on the effect of RMC on adolescents is unclear. Hence, the specific aim of this study is to synthesise the available evidence relating to the provision of RMC for adolescents during childbirth.

Methods
The methodology of the proposed systematic review follows the procedural guideline depicted in the preferred reporting items for systematic review protocol. The review will include published studies and gray literature from January 1, 1990, to June 30, 2021. Electronic databases including MEDLINE, PubMed, ScienceDirect, Cochrane, CINAHL, PsycINFO, Scopus, Google Scholar and Web of Science will be searched to retrieve available studies using the appropriate search strings. Studies included in the review will be appraised for quality using tools tailored to each study design. If appropriate, we will conduct random effects meta-analysis of data to summarise the pooled estimates of respectful maternity care prevalence and outcomes. The selection of relevant studies, data extraction and quality assessment of individual studies will be carried out by two independent authors.

Results
Summaries of the findings will be compiled and synthesised in a narrative summary. In addition to the narrative synthesis, where sufficient data are available, a random-effects meta-analysis will be conducted to obtain a pooled estimate value for respectful maternity care prevalence and outcomes.

Discussion
Respectful Maternity Care for adolescents holds great promise for improved maternal and neonatal care. However, there is a gap in knowledge on the interventions that work and the extent of their effectiveness. Findings from this study will be beneficial in improving Adolescents Sexual and Reproductive Health and Rights and reducing maternal mortality, especially for adolescents.

Systematic review registration
PROSPERO CRD42020183440
An inverse problem of reconstructing the time-dependent coefficient in a one-dimensional hyperbolic equation
Authors: Huntul M. J. , Abbas Muhammad , Baleanu Dumitru 
Published: October 2021

AbstractIn this paper, for the first time the inverse problem of reconstructing the time-dependent potential (TDP) and displacement distribution in the hyperbolic problem with periodic boundary conditions (BCs) and nonlocal initial supplemented by over-determination measurement is numerically investigated. Though the inverse problem under consideration is ill-posed by being unstable to noise in the input data, it has a unique solution. The Crank–Nicolson-finite difference method (CN-FDM) along with the Tikhonov regularization (TR) is applied for calculating an accurate and stable numerical solution. The programming language MATLAB built-in lsqnonlin is used to solve the obtained nonlinear minimization problem. The simulated noisy input data can be inverted by both analytical and numerically simulated. The obtained results show that they are accurate and stable. The stability analysis is performed by using Fourier series.
An inertial parallel algorithm for a finite family of G-nonexpansive mappings with application to the diffusion problem
Authors: Charoensawan Phakdi , Yambangwai Damrongsak , Cholamjiak Watcharaporn , Suparatulatorn Raweerote 
Published: October 2021

AbstractFor finding a common fixed point of a finite family of G-nonexpansive mappings, we implement a new parallel algorithm based on the Ishikawa iteration process with the inertial technique. We obtain the weak convergence theorem of this algorithm in Hilbert spaces endowed with a directed graph by assuming certain control conditions. Furthermore, numerical experiments on the diffusion problem demonstrate that the proposed approach outperforms well-known approaches.
COVID-19 vaccination program in the mainland of China: a subnational descriptive analysis on target population size and current progress
Authors: Zheng Wen , Yan Xuemei , Zhao Zeyao , Yang Juan , Yu Hongjie 
Published: October 2021

Abstract
Background
China is facing substantial risks of imported coronavirus disease 2019 (COVID-19) cases and a domestic resurgence in the long run, and COVID-19 vaccination is expected to be the long-lasting solution to end the pandemic. We aim to estimate the size of the target population for COVID-19 vaccination at the provincial level in the mainland of China, and summarize the current progress of vaccination programs, which could support local governments in the timely determination and adjustment of vaccination policies and promotional measures.

Methods
We conducted a descriptive study of the entire population in the mainland of China, between December 2020 and August 2021. By extracting provincial-stratified data from publicly available sources, we estimated the size of priority target groups for vaccination programs, and further characterized the ongoing vaccination program at the provincial level, including the total doses administered, the coverage rate, and the vaccination capacity needed to achieve the target coverage of 80% by the end of 2021. We used R (version 4.1.0) to complete the descriptive statistics.

Results
The size of the target population shows large differences among provinces, ranging from 3.4 million to 108.4 million. As of 31 August, 2021, the speed of vaccine roll-out differs considerably as well, with the highest coverage occurring in Beijing and Shanghai, where 88.5% and 79.1% of the population has been fully vaccinated, respectively. In 22 of 31 provincial-level administrative divisions (PLADs), more than 70% of the population was administered at least one dose by August. With the current vaccination capacity, the target of 80% coverage could be achieved by 2021 in 28 PLADs.

Conclusions
Disparities exist in the target population size and vaccination progress across provinces in the mainland of China. China has made great strides in the vaccination speed since roll-out, and could basically achieve the targeted vaccine coverage.

Graphic Abstract
Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation
Authors: Gama Sosa Miguel A. , De Gasperi Rita , Pryor Dylan , Perez Garcia Georgina S. , Perez Gissel M. , Abutarboush Rania , Kawoos Usmah , Hogg Seth , Ache Benjamin , Janssen William G. , Sowa Allison , Tetreault Timothy , Cook David G. , Tappan Susan J. , Gandy Sam , Hof Patrick R. , Ahlers Stephen T. , Elder Gregory A. 
Published: October 2021

AbstractCerebral vascular injury as a consequence of blast-induced traumatic brain injury is primarily the result of blast wave-induced mechanical disruptions within the neurovascular unit. In rodent models of blast-induced traumatic brain injury, chronic vascular degenerative processes are associated with the development of an age-dependent post-traumatic stress disorder-like phenotype. To investigate the evolution of blast-induced chronic vascular degenerative changes, Long-Evans rats were blast-exposed (3 × 74.5 kPa) and their brains analyzed at different times post-exposure by X-ray microcomputed tomography, immunohistochemistry and electron microscopy. On microcomputed tomography scans, regional cerebral vascular attenuation or occlusion was observed as early as 48 h post-blast, and cerebral vascular disorganization was visible at 6 weeks and more accentuated at 13 months post-blast. Progression of the late-onset pathology was characterized by detachment of the endothelial and smooth muscle cellular elements from the neuropil due to degeneration and loss of arteriolar perivascular astrocytes. Development of this pathology was associated with vascular remodeling and neuroinflammation as increased levels of matrix metalloproteinases (MMP-2 and MMP-9), collagen type IV loss, and microglial activation were observed in the affected vasculature. Blast-induced chronic alterations within the neurovascular unit should affect cerebral blood circulation, glymphatic flow and intramural periarterial drainage, all of which may contribute to development of the blast-induced behavioral phenotype. Our results also identify astrocytic degeneration as a potential target for the development of therapies to treat blast-induced brain injury.
Variations of chlorophyll-a and particulate organic carbon in the Yellow-Bohai Sea: in response to the Typhoon Lekima event
Authors: Wang Xiaowen , Wang Xiujun , You Zai-Jin 
Published: October 2021

AbstractTyphoon events have large impacts on marginal seas’ environmental conditions with implications for biological processes and carbon cycling. However, little is known about the responses of phytoplankton and particulate organic carbon (POC) to typhoon events in the Yellow-Bohai Sea (YBS). In this study, we utilized satellite-derived datasets of chlorophyll-a (Chl-a) and POC, together with key physical parameters, to analyze their responses to the Typhoon Lekima event induced heavy rainfall and strong winds. Overall, there were enhanced upwelling, strengthened currents, and increased terrestrial runoff during weakened Typhoon Lekima in the YBS. The basin-scale response of Chl-a showed large differences post the Typhoon Lekima event, with a decrease in the Bohai Sea (BS, 0.34 ± 3.0 mg m−3) but an increase in Yellow Sea (YS, 0.23 ± 1.7 mg m−3 in the south YS and 0.54 ± 0.8 mg m−3 in the north YS). The increase of Chl-a in the YS was attributed to increased nutrients, whereas the reduction of Chl-a in the BS was caused by dilution and water exchange with the North Yellow Sea. However, there was an overall increase in POC post-Typhoon Lekima in both BS and YS. The increase of POC in the majority of BS resulted largely from enhanced sediment resuspension and terrigenous input. The increase of POC in the nearshore waters of YS was attributable to enhanced biological production, sediment resuspension, and terrigenous input of POC, whereas the increase of POC in the central YS was partly due to transportation of high-POC waters from nearshore to offshore via strengthened current. Our study highlights the complex impacts of typhoon events on the carbon cycle in marginal seas.