bluuebunny/crossref_metadata_2025_split huggingface dataset:
A plea for personalization of the hemodynamic management of septic shock
Authors: De Backer Daniel , Cecconi Maurizio , Chew Michelle S. , Hajjar Ludhmila , Monnet Xavier , Ospina-Tascón Gustavo A. , Ostermann Marlies , Pinsky Michael R. , Vincent Jean-Louis 
Published: December 2022

AbstractAlthough guidelines provide excellent expert guidance for managing patients with septic shock, they leave room for personalization according to patients’ condition. Hemodynamic monitoring depends on the evolution phase: salvage, optimization, stabilization, and de-escalation. Initially during the salvage phase, monitoring to identify shock etiology and severity should include arterial pressure and lactate measurements together with clinical examination, particularly skin mottling and capillary refill time. Low diastolic blood pressure may trigger vasopressor initiation. At this stage, echocardiography may be useful to identify significant cardiac dysfunction. During the optimization phase, echocardiographic monitoring should be pursued and completed by the assessment of tissue perfusion through central or mixed-venous oxygen saturation, lactate, and carbon dioxide veno-arterial gradient. Transpulmonary thermodilution and the pulmonary artery catheter should be considered in the most severe patients. Fluid therapy also depends on shock phases. While administered liberally during the resuscitation phase, fluid responsiveness should be assessed during the optimization phase. During stabilization, fluid infusion should be minimized. In the de-escalation phase, safe fluid withdrawal could be achieved by ensuring tissue perfusion is preserved. Norepinephrine is recommended as first-line vasopressor therapy, while vasopressin may be preferred in some patients. Essential questions remain regarding optimal vasopressor selection, combination therapy, and the most effective and safest escalation. Serum renin and the angiotensin I/II ratio may identify patients who benefit most from angiotensin II. The optimal therapeutic strategy for shock requiring high-dose vasopressors is scant. In all cases, vasopressor therapy should be individualized, based on clinical evaluation and blood flow measurements to avoid excessive vasoconstriction. Inotropes should be considered in patients with decreased cardiac contractility associated with impaired tissue perfusion. Based on pharmacologic properties, we suggest as the first test a limited dose of dobutamine, to add enoximone or milrinone in the second line and substitute or add levosimendan if inefficient. Regarding adjunctive therapies, while hydrocortisone is nowadays advised in patients receiving high doses of vasopressors, patients responding to corticosteroids may be identified in the future by the analysis of selected cytokines or specific transcriptomic endotypes. To conclude, although some general rules apply for shock management, a personalized approach should be considered for hemodynamic monitoring and support.
Silver-coated versus uncoated locking plates in subjects with fractures of the distal tibia: a randomized, subject and observer-blinded, multi-center non-inferiority study
Authors: Schoder S. , Lafuente M. , Alt V. 
Published: December 2022

Abstract
Background
Antimicrobial coatings of implants are of interest to reduce infection rate in orthopedic surgery. Demonstration of clinical effectiveness of such coated implants to obtain market approval is challenging. The objective of this article is to define a design for a randomized controlled trial to evaluate the clinical performance of a silver-coating for locking plates for fracture treatment.

Methods
The study design has to respect different criteria, such as feasibility, focus on overall complications, such as functional impairment, fracture healing, and particularly on infection rates. Distal tibia fractures were chosen due to the high prevalence of infections in this type of injuries, which warrants a particular benefit of antimicrobial prophylaxis and thus might allow to see a statistical trend in favor of the coated product. The study design was defined as a randomized, controlled, subject and observer-blinded, multi-center study in subjects with fractures of the distal tibia with a total of 226 patients. A number of 113 patients are planned for each of the two treatment arms with treatment of the fracture with a silver-coated device (first arm) or with an uncoated device (second arm). Inclusion criteria are closed fractures of the distal tibia according to the Tscherne-Oestern classification or open fractures of the distal tibia according to the Gustilo-Anderson classification in subjects older than 18 years. Primary outcome parameter is the Anticipated Adverse Device Effects (AADE) including all typical complications of this type of injury, such as functional impairment of the affected limb, non-union, and infections based on a non-inferiority study design. Also, silver-typical complications, such as argyria, are included. Secondary parameters are infection rates and fracture healing. Follow-up of patients includes five visits with clinical and X-ray evaluations with a follow-up time of 12 months.

Discussion
Demonstration of clinical effectiveness of antimicrobial coatings of fracture fixation devices remains a challenge. Definition of a prospective randomized pre-market trial design and recruitment of clinical sites for such a study is possible. A confirmative proof of the expected clinical benefit in terms of reduction of device-related infections will be addressed with a prospective post-market clinical follow-up study in a second step due to the large sample size required.

Trial registration
ClinicalTrials.gov NCT05260463. Registered on 02 March 2022.
Fractal correlation properties of HRV as a noninvasive biomarker to assess the physiological status of triathletes during simulated warm-up sessions at low exercise intensity: a pilot study
Authors: Schaffarczyk Marcelle , Rogers Bruce , Reer Rüdiger , Gronwald Thomas 
Published: December 2022

Abstract
Background
The non-linear index alpha 1 of Detrended Fluctuation Analysis (DFA a1) of heart rate variability, has been shown to be a marker of fatigue during endurance exercise. This report aims to explore its ability to assess the physiological status as a surrogate metric for “readiness to train” while performing simulated warm-up sessions the day after two different exercise sessions.

Methods
11 triathletes were recruited to determine the first ventilatory threshold (VT1) during a baseline assessment and to perform 10-min of cycling at 90% of VT1 (simulating a warm-up bout) before (PRE) and within 36 h after (POST) light and heavy running exercise. RR intervals were recorded for DFA a1 analysis along with neuromuscular testing to verify the effects of the performed exercise sessions. In addition to common statistical methods, magnitude-based inferences (MBI) were applied to assess the changes in true score and thus also the practical relevance of the magnitude.

Results
Rating of perceived exertion for the heavy exercise session showed a significant higher rating as opposed to the light exercise session (p < 0.001, d = 0.89). In regard of MBIs, PRE versus POST comparisons revealed a significant reduced DFA a1 with large effect size after the heavy exercise session (p = 0.001, d = − 1.44) and a 99% chance that this negative change was clinically relevant.

Conclusions
Despite inter-individual differences, DFA a1 offers potential to assess physiological status and guide athletes in their training as an easy-to-apply monitoring procedure during a standardized warm-up. A regular assessment including individual data history and statistical references for identification of response is recommended. Further data are necessary to confirm the results in a larger and more homogeneous population.
Incorporation of DNA methylation quantitative trait loci (mQTLs) in epigenome-wide association analysis: application to birthweight effects in neonatal whole blood
Authors: Li Shaobo , Mancuso Nicholas , Metayer Catherine , Ma Xiaomei , de Smith Adam J. , Wiemels Joseph L. 
Published: December 2022

Abstract
Background
Epigenome-wide association studies (EWAS) have helped to define the associations between DNA methylation and many clinicopathologic and developmental traits. Since DNA methylation is affected by genetic variation at certain loci, EWAS associations may be potentially influenced by genetic effects. However, a formal assessment of the value of incorporating genetic variation in EWAS evaluations is lacking especially for multiethnic populations.

Methods
Using single nucleotide polymorphism (SNP) from Illumina Omni Express or Affymetrix PMDA arrays and DNA methylation data from the Illumina 450 K or EPIC array from 1638 newborns of diverse genetic ancestries, we generated DNA methylation quantitative trait loci (mQTL) databases for both array types. We then investigated associations between neonatal DNA methylation and birthweight (incorporating gestational age) using EWAS modeling, and reported how EWAS results were influenced by controlling for mQTLs.

Results
For CpGs on the 450 K array, an average of 15.4% CpGs were assigned as mQTLs, while on the EPIC array, 23.0% CpGs were matched to mQTLs (adjusted P value < 0.05). The CpGs associated with SNPs were enriched in the CpG island shore regions. Correcting for mQTLs in the EWAS model for birthweight helped to increase significance levels for top hits. For CpGs overlapping genes associated with birthweight-related pathways (nutrition metabolism, biosynthesis, for example), accounting for mQTLs changed their regression coefficients more dramatically (> 20%) than for other random CpGs.

Conclusion
DNA methylation levels at circa 20% CpGs in the genome were affected by common SNP genotypes. EWAS model fit significantly improved when taking these genetic effects into consideration. Genetic effects were stronger on CpGs overlapping genetic elements associated with control of gene expression.
PGCLCs of human 45,XO reveal pathogenetic pathways of neurocognitive and psychosocial disorders
Authors: Shang Dantong , Lan Tian , Wang Yue , Li Xuanyu , Liu Quanyi , Dong Huimin , Xu Bo , Cheng Hanhua , Zhou Rongjia 
Published: December 2022

Abstract
Background
Neurocognitive disorders and psychosocial difficulties are common in patients with Turner syndrome and multiple neurodegenerative diseases, yet there is no effective cure. Human primordial germ cells (hPGCs) are pluripotent germline stem cells in early embryo, which pass genetic information from one generation to the next, whereas all somatic cells will die along with the end of life. However, it is not known whether patient hPGCs with Turner syndrome contain information of neurocognitive and psychosocial illness.

Results
In this report, we used a high-density of culture system of embryoids derived from iPSCs of a patient with Turner syndrome to ask how pathogenetic pathways are associated with onset of neurocognitive and psychosocial disorders. The hPGC-Like Cells (hPGCLCs) were in vitro specified from iPSCs of 45,XO, 46,XX and 46,XY by the high-density induction of embryoids. Amazingly, we found that the specification process of the hPGCLCs in 45,XO, compared to those in 46,XX and 46,XY, enriched several common pathogenetic pathways regulating neurocognitive and psychosocial disorders, that shared among multiple neurodegenerative diseases and Turner syndrome. The downregulated chemical synaptic transmission pathways, including glutamatergic, GABAergic, and nicotine cholinergic synapses, indicated synaptic dysfunctions, while upregulated pathways that were associated with imbalance of mitochondrial respiratory chain complexes and apoptosis, may contribute to neuronal dysfunctions. Notably, downregulation of three types of ubiquitin ligases E1-E2-E3 and lysosome-associated sulfatases and RAB9A, owing to haploinsufficiency and parental preference of the X chromosome expression, indicated that two pathways of cellular degradation, lysosome and ubiquitin–proteasome, were impaired in the specification process of 45,XO hPGCLCs. This would lead to accumulation of undesired proteins and aggregates, which is a typically pathological hallmark in neurodegenerative diseases.

Conclusions
Our data suggest that the specification process of the hPGCLCs in 45,XO, compared to those in 46,XX and 46,XY, enriched pathogenetic pathways that are associated with the onset of neurocognitive and psychosocial disorders.
Mitochondrial fragmentation and ROS signaling in wound response and repair
Authors: Xu Shiqi , Li Shiyao , Bjorklund Mikael , Xu Suhong 
Published: December 2022

AbstractMitochondria are organelles that serve numerous critical cellular functions, including energy production, Ca2+ homeostasis, redox signaling, and metabolism. These functions are intimately linked to mitochondrial morphology, which is highly dynamic and capable of rapid and transient changes to alter cellular functions in response to environmental cues and cellular demands. Mitochondrial morphology and activity are critical for various physiological processes, including wound healing. In mammals, wound healing is a complex process that requires coordinated function of multiple cell types and progresses in partially overlapping but distinct stages: hemostasis and inflammation, cell proliferation and migration, and tissue remodeling. The repair process at the single-cell level forms the basis for wound healing and regeneration in tissues. Recent findings reveal that mitochondria fulfill the intensive energy demand for wound repair and aid wound closure by cytoskeleton remodeling via morphological changes and mitochondrial reactive oxygen species (mtROS) signaling. In this review, we will mainly elucidate how wounding induces changes in mitochondrial morphology and activity and how these changes, in turn, contribute to cellular wound response and repair.
Implementation of medicines pricing policies in sub-Saharan Africa: systematic review
Authors: Koduah Augustina , Baatiema Leonard , de Chavez Anna Cronin , Danso-Appiah Anthony , Kretchy Irene A. , Agyepong Irene Akua , King Natalie , Ensor Timothy , Mirzoev Tolib 
Published: December 2022

Abstract
Background
High medicine prices contribute to increasing cost of healthcare worldwide. Many patients with limited resources in sub-Saharan Africa (SSA) are confronted with out-of-pocket charges, constraining their access to medicines. Different medicine pricing policies are implemented to improve affordability and availability; however, evidence on the experiences of implementations of these policies in SSA settings appears limited. Therefore, to bridge this knowledge gap, we reviewed published evidence and answered the question: what are the key determinants of implementation of medicines pricing policies in SSA countries?

Methods
We identified policies and examined implementation processes, key actors involved, contextual influences on and impact of these policies. We searched five databases and grey literature; screening was done in two stages following clear inclusion criteria. A structured template guided the data extraction, and data analysis followed thematic narrative synthesis. The review followed best practices and reported using PRISMA guidelines.

Results
Of the 5595 studies identified, 31 met the inclusion criteria. The results showed thirteen pricing policies were implemented across SSA between 2003 and 2020. These were in four domains: targeted public subsides, regulatory frameworks and direct price control, generic medicine policies and purchasing policies. Main actors involved were government, wholesalers, manufacturers, retailers, professional bodies, community members and private and public health facilities. Key contextual barriers to implementation were limited awareness about policies, lack of regulatory capacity and lack of price transparency in external reference pricing process. Key facilitators were favourable policy environment on essential medicines, strong political will and international support. Evidence on effectiveness of these policies on reducing prices of, and improving access to, medicines was mixed. Reductions in prices were reported occasionally, and implementation of medicine pricing policy sometimes led to improved availability and affordability to essential medicines.

Conclusions
Implementation of medicine pricing policies in SSA shows some mixed evidence of improved availability and affordability to essential medicines. It is important to understand country-specific experiences, diversity of policy actors and contextual barriers and facilitators to policy implementation. Our study suggests three policy implications, for SSA and potentially other low-resource settings: avoiding a ‘one-size-fits-all’ approach, engaging both private and public sector policy actors in policy implementation and continuously monitoring implementation and effects of policies.

Systematic review registration
PROSPERO CRD42020178166
Experimental Seismic Structural Performance Evaluations of RC Columns Strengthened by Stiff-Type Polyurea
Authors: Lee Tae-Hee , Choi Seung-Jai , Yang Dal-Hun , Kim Jang-Ho Jay 
Published: December 2022

AbstractRecently, strong earthquakes are continuously occurring all over the world regarding, repair and strengthening of non-seismically designed structures. Presently, fiber-reinforced polymer (FRP) surface-bonding method is used as a quick and easy way to retrofit and strengthen damaged columns and walls. However, the inherent problems of the FRP surface-bonding method of bond degradation are adhesive interfaces and FRP sheet aging during service-life still. In order to overcome these problems, it is necessary to develop new materials and techniques that can induce monolithic behavior between the structural member and retrofit material by eliminating the bonding interface. One solution is to use repair and strengthening using stiff-type polyurea (STPU) developed as a seismic retrofitting material which can be applied by spraying method. In order to investigate the retrofitting effect of STPU, pseudo-dynamic push–pull test and dynamic shaking table tests are performed. The novelty of the study is that the RC columns strengthened with a newly developed STPU are tested for pseudo-dynamic (i.e., also represents the static behavior) and dynamic behavior. From the test results, overall strengthening effect of the STPU for both static and dynamic loading conditions can be understood, which can be used for retrofitting of concrete structures all over the world. The study results are discussed in detail in the paper.
Phenotypic findings and pregnancy outcomes of fetal rare autosomal aneuploidies detected using chromosomal microarray analysis
Authors: Hu Rong , Huang Weiwei , Zhou Weining , Luo Xiaohui , Ren Congmian , Huang Huajie , Hou Yaping , Guo Li , He Wei , Lu Jian 
Published: December 2022

Abstract
Background
Aneuploidies are the most common chromosomal abnormality and the main genetic cause of adverse pregnancy outcomes. Since numerous studies have focused on common trisomies, relatively little is known about the association between phenotypic findings and rare autosomal aneuploidies (RAAs). We conducted a retrospective study of 48,904 cases for chromosomal microarray analysis in a large tertiary referral center and reported the overall frequencies, clinical manifestations, and outcomes of prenatal RAAs.

Results
A total of 90 RAAs were detected, of which 83 cases were mosaic trisomies and 7 were non-mosaic trisomies. Chromosomes 16, 22, and 9 were identified as the major chromosomes involving RAAs. The four predominant indications for prenatal diagnosis in our RAA cases were RAA-positive in noninvasive prenatal screening, advanced maternal age, ultrasound abnormalities, and high-risk for serum prenatal screening. Cardiovascular defects were the most frequently observed structural abnormalities, followed by musculoskeletal anomalies. Increased nuchal translucency and persistent left superior vena cava, the major soft marker abnormalities involved, were also observed in our RAA cases. Clinical outcomes were available for all RAAs, with 63 induced abortions and 27 live births recorded.

Conclusions
Variable phenotypes and outcomes were observed, which were highly heterogeneous in cases of prenatal RAAs. Thus, a cautious and comprehensive strategy should be implemented during prenatal counseling for RAAs.
The psychological impact, risk factors and coping strategies to COVID-19 pandemic on healthcare workers in the sub-Saharan Africa: a narrative review of existing literature
Authors: Oyat Freddy Wathum Drinkwater , Oloya Johnson Nyeko , Atim Pamela , Ikoona Eric Nzirakaindi , Aloyo Judith , Kitara David Lagoro 
Published: December 2022

Abstract
Background
The ongoing COVID-19 pandemic has significantly impacted the physical and mental health of the general population worldwide, with healthcare workers at particular risk. The pandemic's effect on healthcare workers' mental well-being has been characterized by depression, anxiety, work-related stress, sleep disturbances, and post-traumatic stress disorder. Hence, protecting the mental well-being of healthcare workers (HCWs) is a considerable priority. This review aimed to determine risk factors for adverse mental health outcomes and protective or coping measures to mitigate the harmful effects of the COVID-19 crisis among HCWs in sub-Saharan Africa.

Methods
We performed a literature search using PubMed, Google Scholar, Cochrane Library, and Embase for relevant materials. We obtained all articles published between March 2020 and April 2022 relevant to the subject of review and met pre-defined eligibility criteria. We selected 23 articles for initial screening and included 12 in the final review.

Result
A total of 5,323 participants in twelve studies, predominantly from Ethiopia (eight studies), one from Uganda, Cameroon, Mali, and Togo, fulfilled the eligibility criteria. Investigators found 16.3–71.9% of HCWs with depressive symptoms, 21.9–73.5% with anxiety symptoms, 15.5–63.7% experienced work-related stress symptoms, 12.4–77% experienced sleep disturbances, and 51.6–56.8% reported PTSD symptoms. Healthcare workers, working in emergency, intensive care units, pharmacies, and laboratories were at higher risk of adverse mental health impacts. HCWs had deep fear, anxious and stressed with the high transmission rate of the virus, high death rates, and lived in fear of infecting themselves and families. Other sources of fear and work-related stress were the lack of PPEs, availability of treatment and vaccines to protect themselves against the virus. HCWs faced stigma, abuse, financial problems, and lack of support from employers and communities.

Conclusion
The prevalence of depression, anxiety, insomnia, and PTSD in HCWs in sub-Saharan Africa during the COVID-19 pandemic has been high. Several organizational, community, and work-related challenges and interventions were identified, including improvement of workplace infrastructures, adoption of correct and shared infection control measures, provision of PPEs, social support, and implementation of resilience training programs. Setting up permanent multidisciplinary mental health teams at regional and national levels to deal with mental health and providing psychological support to HCWs, supported with long-term surveillance, are recommended.