bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatocyte nuclear factor 4α in the pathogenesis of non-alcoholic fatty liver disease
Authors: Pan Xiaoli , Zhang Yanqiao 
Published: February 2022

Abstract
Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. It refers to a range of liver conditions affecting people who drink little or no alcohol. NAFLD comprises non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. NASH is featured by steatosis, lobular inflammation, hepatocyte injury, and various degrees of fibrosis. Although much progress has been made over the past decades, the pathogenic mechanism of NAFLD remains to be fully elucidated. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear hormone receptor that is highly expressed in hepatocytes. Hepatic HNF4α expression is markedly reduced in NAFLD patients and mouse models of NASH. HNF4α has been shown to regulate bile acid, lipid, glucose, and drug metabolism. In this review, we summarize the recent advances in the understanding of the pathogenesis of NAFLD with a focus on the regulation of HNF4α and the role of hepatic HNF4α in NAFLD. Several lines of evidence have shown that hepatic HNF4α plays a key role in the initiation and progression of NAFLD. Recent data suggest that hepatic HNF4α may be a promising target for treatment of NAFLD.
Accuracy and applications of sequencing and genotyping approaches for CYP2A6 and homologous genes
Authors: Langlois Alec W.R. , El-Boraie Ahmed , Fukunaga Koya , Mushiroda Taisei , Kubo Michiaki , Lerman Caryn , Knight Jo , Scherer Steven E. , Chenoweth Meghan J. , Tyndale Rachel F. 
Published: February 2022

Objectives
We evaluated multiple genotyping/sequencing approaches in a homologous region of chromosome 19, and investigated associations of two common 3’-UTR CYP2A6 variants with activity in vivo.

Methods
Individuals (n = 1704) of European and African ancestry were phenotyped for the nicotine metabolite ratio (NMR), an index of CYP2A6 activity, and genotyped/sequenced using deep amplicon exon sequencing, SNP array, genotype imputation and targeted capture sequencing. Amplicon exon sequencing was the gold standard to which other methods were compared within-individual for CYP2A6, CYP2A7, CYP2A13, and CYP2B6 exons to identify highly discordant positions. Linear regression models evaluated the association of CYP2A6*1B and rs8192733 genotypes (coded additively) with logNMR.

Results
All approaches were ≤2.6% discordant with the gold standard; discordant calls were concentrated at few positions. Fifteen positions were discordant in >10% of individuals, with 12 appearing in regions of high identity between homologous genes (e.g. CYP2A6 and CYP2A7). For six, allele frequencies in our study and online databases were discrepant, suggesting errors in online sources. In the European-ancestry group (n = 935), CYP2A6*1B and rs8192733 were associated with logNMR (P < 0.001). A combined model found main effects of both variants on increasing logNMR. Similar trends were found in those of African ancestry (n = 506).

Conclusion
Multiple genotyping/sequencing approaches used in this chromosome 19 region contain genotyping/sequencing errors, as do online databases. Gene-specific primers and SNP array probes must consider gene homology; short-read sequencing of related genes in a single reaction should be avoided. Using improved sequencing approaches, we characterized two gain-of-function 3’-UTR variants, including the relatively understudied rs8192733.
Changes in the Healthcare Environment Prompt Leaders to Think Digitally
Authors: Gannotta Richard J. 
Published: February 2022

SUMMARY
Hospitals have been facing an epic crisis, with the COVID-19 pandemic overwhelming emergency departments and forcing the implementation of surge protocols to manage care delivery and treatment. These realities have affected both inpatient care delivery and caregiver effectiveness. The need to reevaluate clinical operations is challenging the healthcare delivery structure and its leadership to think differently—digitally. Supporting care for patients in the home has played an important role in mitigating many safety and access issues, accelerating telehealth adoption and solidifying its place in the ongoing transformation of healthcare delivery. As this shift continues to unfold, it is also bringing an opportunity to improve clinical outcomes, patient satisfaction, and cost reduction efforts as well as advance access and promote diversity, equity, and inclusion in the US healthcare delivery system.
Sustainable Digital Health Demands Cybersecurity Transformation
Authors: DeFord Drexel 
Published: February 2022

SUMMARY
Technology has become a mission-critical part of healthcare business operations. The electronic health record, medical equipment, revenue cycle, enterprise resource planning, marketing, legal, planning and building new facilities… every component today is dependent on automated tools. When computer systems go offline, everyone feels the stress of conducting business and delivering care without access to all the information they need. Downtimes are especially dangerous for patients.
While there are many reasons that these systems go offline, cybersecurity breaches are primary culprits. Logically then, digital innovation becomes unsustainable in healthcare without cybersecurity transformation. What was good enough at one time is not acceptable anymore. As healthcare has accelerated toward digital dependence, particularly through the COVID-19 pandemic, cybersecurity threats have also increased. The time to transform cybersecurity is now.
The first thing for healthcare leaders to understand is this: You do not have a malware problem or a ransomware problem—you have a cybersecurity adversary problem. It is important to learn everything about the organizations attacking you, including their structure, motivation, and goals. Armed with those insights, you are more likely to be able to defend your health system. By transforming your cybersecurity program, you will build a foundation on which you can thrive as a modern healthcare operation.
Contact Lenses for Ocular Surface Disease
Authors: Wang Xueyang , Jacobs Deborah S. 
Published: February 2022

Abstract:
Ocular surface disease can be difficult to manage, causing patients discomfort and vision loss. Therapeutic contact lenses are an important treatment option that is often neglected because it is conventional wisdom that eyes that are dry or irritated are not good candidates for contact lens. In this focused review, we consider the substantial literature on the use of bandage soft contact lenses (BSCL), scleral lenses, and customized prosthetic devices in the management of ocular graft-vs-host disease. Reports on BSCLs for recurrent corneal erosion are reviewed, as is literature on scleral lenses and prosthetic replacement of the ocular surface ecosystem treatment for Stevens–Johnson syndrome. Clinical pearls for fitting BSCLs are presented, and the issue of antibiotic prophylaxis is considered.
Mechanisms Underlying Contact Lens-Related Keratitis Caused by Pseudomonas aeruginosa
Authors: Suzuki Takashi , Inoue Hidenori 
Published: February 2022

Abstract:
Infectious keratitis is a severe complication associated with contact lens (CL) wear, and can progress rapidly with suppurative infiltration, resulting in the loss of vision. Contact lens wearers with poor and improper care are susceptible to develop infectious keratitis. Gram-negative bacilli such as Pseudomonas aeruginosa, have an ability to form biofilms on CL cases and CLs. Moreover, P. aeruginosa has various virulence factors such as type III secretion system (TTSS) which is an important factor for pathogenicity in keratitis. The effector proteins of TTSS have been identified, namely ExoU, ExoS, ExoT, and ExoY. Pseudomonas aeruginosa strains with ExoU show resistance to disinfection. The strains isolated from CL-related keratitis have higher ExoU gene positivity. Expression of elastase and swarming motility of P. aeruginosa isolates significantly correlates with focus size of keratitis. In addition to education of lens care for the CL wearer, development of CL cleaning solutions targeting suppression of virulence factors are needed for prevention of CL-related keratitis in the future.
Corneal hysteresis: ready for prime time?
Authors: Jammal Alessandro A. , Medeiros Felipe A. 
Published: February 2022

Purpose of the review
This review summarizes recent findings on corneal hysteresis, a biomechanical property of the cornea. Corneal hysteresis measurements can be easily acquired clinically and may serve as surrogate markers for biomechanical properties of tissues in the back of the eye, like the lamina cribrosa and peripapillary sclera, which may be related to the susceptibility to glaucomatous damage.

Recent findings
Several studies have provided evidence of the associations between corneal hysteresis and clinically relevant outcomes in glaucoma. Corneal hysteresis has been shown to be predictive of glaucoma development in eyes suspected of having the disease. For eyes already diagnosed with glaucoma, lower corneal hysteresis has been associated with higher risk of progression and faster rates of visual field loss over time. Such associations appear to be stronger than those for corneal thickness, suggesting that corneal hysteresis may be a more important predictive factor. Recent evidence has also shown that cornealcorrected intraocular pressure measurements may present advantages compared to conventional Goldmann tonometry in predicting clinically relevant outcomes in glaucoma.

Summary
Given the evidence supporting corneal hysteresis as an important risk factor for glaucoma development and its progression, practitioners should consider measuring corneal hysteresis in all patients at risk for glaucoma, as well as in those already diagnosed with the disease.
Role of artificial intelligence in the diagnosis and management of kidney disease: applications to chronic kidney disease and acute kidney injury
Authors: Tangri Navdeep , Ferguson Thomas W. 
Published: February 2022

Purpose of review
Chronic kidney disease (CKD) and acute kidney injury (AKI) are global public health problems associated with a significant burden of morbidity, healthcare resource use, and all-cause mortality. This review explores recently published studies that take a machine learning approach to the diagnosis, management, and prognostication in patients with AKI or CKD.

Recent findings
The release of novel therapeutics for CKD has highlighted the importance of accurately identifying patients at the highest risk of progression. Many models have been constructed with reasonable predictive accuracy but have not been extensively externally validated and peer reviewed. Similarly, machine learning models have been developed for prediction of AKI and have found sufficient accuracy. There are issues to implementing these models, however, with conflicting results with respect to the relationship between prediction of an AKI outcome and improvements in the occurrence of other adverse events, and in some circumstances potential harm.

Summary
Artificial intelligence models can help guide management of CKD and AKI, but it is important to ensure that they are broadly applicable and generalizable to various settings and associated with improved clinical decision-making and outcomes.
Colonoscope “Looping” During Ileo‐Colonoscopy in Children is Significantly Different to that Observed in Adult Practice
Authors: Thomson Mike , Belsha Dalia , Nedelkopoulou Natalia , Sharma Shishu , Campbell David , Narula Priya , Rao Prithvi , Urs Arun , D'Ambrosio Angelo , Isoldi Sara 
Published: February 2022

ABSTRACTObjectives:Ileo‐colonoscopy (IC) can be technically challenging because of unpredictable colonoscope loop formation. Aims of this study were to assess the risk of loop formation and to attempt to understand which factors were likely to predispose to which subtype of loop.Methods:Prospective study conducted on children referred for an IC at Sheffield Children's Hospital. Presence and type of loop was objectively assessed using the magnetic endoscope imaging tool.Results:Three hundred procedures were prospectively evaluated. Only 9% of paediatric ICs were loop‐free. Alpha loops were the most common loop in children older than 5, whereas reverse alpha loops and a wider variety of complex and repetitive loops were observed in younger patients. Once a specific type of loop has formed, the risk of re‐looping in a different way or in a different position of the colon is reduced. Left lateral starting position was found to increase the risk of reverse alpha loops and re‐looping. Challenging loops, such as reverse alpha, were more frequent in males. Higher body mass index (BMI) was associated with an increased risk of alpha and deep transverse loops formation, while lower BMI with a higher incidence of reverse alpha and N loop. Loop formation did not prevent 100% ileal intubation.Conclusions:This study represents the first attempt to describe loop formation according to patient characteristics in a large paediatric series. Further studies are needed in order to establish if these findings could be helpful in simplifying the execution of IC procedures in children and facilitate the learning curve during endoscopy training programs.
Combined Surgical-Orthodontic Treatment of Patients With Severe Parry-Romberg Syndrome
Authors: Cui Ya , Zhao Jinglei , Hu Xiangying , Fang Bing , Mao Lixia 
Published: February 2022

Abstract:
Parry-Romberg syndrome (PRS) refers to a relatively rare dysfunction disease that is characterized by chronic progressive maxillofacial atrophy, especially one side of facial skin, subcutaneous tissue, muscle, and bone. According to the atrophy degree of skin, subcutaneous tissue, and skeleton in the area innervated by the trigeminal nerve, PRS can be classified into mild, moderate, and severe. In general, cases with different severity have specific treatment regimens. For mild and moderate cases, soft tissue augmentation techniques are the optimal strategy for aesthetic reconstruction. In this study, the authors report a 19-year-old female with severe PRS. Considering the severity of the case, a combined surgical and orthodontic treatment was performed, which was involved in alveolar bone augmentation, preoperative and postoperative orthodontic treatment in combination with orthognathic surgery, medpor filling of zygomatic and maxillary complex, free fat grafting, as well as angulus oris and lip trimming. Comprehensive treatment is recommended for severe cases with extensive atrophy of soft tissue and craniofacial bone, obvious deviation of the chin and occlusal plane.
Successful Repair of a Forehead Depression Deformation due to En Coup de Sabre Using Costal Cartilage Transplantation
Authors: Numahata Takao , Kitamura Yutaro , Okazaki Mutsumi 
Published: February 2022

Abstract:
The authors report a successful repair of a case of en coup de sabre using costal cartilage for depression deformation of the forehead. A 23-year-old woman was diagnosed with linear scleroderma at age 10 and underwent a dermal fat transplant at another hospital when she was 18. However, after surgery, the graft began to atrophy. In about 2 years, the deformation was almost the same as before surgery. Therefore, she visited our hospital for surgical intervention. The authors treated the deformity with costal cartilage transplantation. There were no postoperative complications, and the deformation did not recur during a one-year follow-up period after surgery. As far as the authors know, this is the first report of repairing a forehead deformity due to en coup de sabre using costal cartilage. The authors suggest that costal cartilage grafting is a good surgical option because costal cartilage can be easily carved and maintain its shape without absorption.
Quantitative genetic study suggests sex-specific genetic architecture for fetal testosterone in a wild mammal
Authors: Fishman Ruth , Kralj-Fišer Simona , Marglit Sivan , Koren Lee , Vortman Yoni 
Published: February 2022

AbstractTestosterone plays a critical role in mediating fitness-related traits in many species. Although it is highly responsive to environmental and social conditions, evidence from several species show a heritable component to its individual variation. Despite the known effects that in utero testosterone exposure have on adult fitness, the heritable component of individual testosterone variation in fetuses is mostly unexplored. Furthermore, testosterone has sex-differential effects on fetal development, i.e., a specific level may be beneficial for male fetuses but detrimental for females. The above mentioned may lead to a different genetic structure underlying the heritability of testosterone between the sexes. Here, we used a wild animal model, the feral nutria, quantified testosterone using hair-testing and estimated its heritability between parent and offspring from the same and opposite sex. We found that in utero accumulated hair testosterone levels were heritable between parents and offspring of the same sex. However, there was a low additive genetic covariance between the sexes, and a relatively low cross-sex genetic correlation, suggesting a potential for sex-dependent trait evolution, expressed early on, in utero.
Steering clear of the confusion effect: aerial predators target fixed points in dense prey aggregations
Authors: Brighton Caroline H. , Kloepper Laura N. , Larkman Lucy , Zusi Lillias , McGowan Kathryn , Taylor Graham K. 
Published: February 2022

SummaryCollective behaviours are widely assumed to confuse predators, but empirical support for a confusion effect is often lacking, and its importance must depend on the predator’s targeting mechanism. Here we show that raptors steer attacks on swarming bats by turning towards a fixed point in the swarm, rather than by using closed-loop pursuit of an individual. Any prey that the predator is on a collision course with will appear on a constant bearing, so target selection emerges naturally from the geometry of a collision. Our results show how predators can simplify the demands on their sensory system by decoupling steering from targeting when grabbing prey from a dense swarm. We anticipate that the same tactic will be used against flocks and schools across a wide range of taxa, in which case a confusion effect is paradoxically more likely to occur in attacks on sparse groups, for which steering and targeting cannot be decoupled.
Soluble extracts from amnion and chorion membranes improve hMSC osteogenic response in a mineralized collagen scaffold
Authors: Kolliopoulos Vasiliki , Dewey Marley J. , Polanek Maxwell , Xu Hui , Harley Brendan A.C. 
Published: February 2022

ABSTRACTCraniomaxillofacial (CMF) bone injuries present a major surgical challenge and cannot heal naturally due to their large size and complex topography. Approximately 26% of injured Iraq war veterans sustained CMF injuries in the form of blast wounds, and 0.1% of births involve CMF defects like cleft palate. We previously developed a class of mineralized collagen scaffolds designed to mimic native extracellular matrix (ECM) features of bone. These scaffolds induce in vitro human mesenchymal stem cell (hMSC) osteogenic differentiation and in vivo bone formation without the need for exogenous osteogenic supplements. Here, we seek to enhance cellular bioactivity and osteogenic activity via inclusion of placental-derived products in the scaffold architecture. The amnion and chorion membranes are distinct components of the placenta that individually have displayed anti-inflammatory, immunogenic, and osteogenic properties. They represent a potentially powerful compositional modification to the mineralized collagen scaffolds to improve bioactivity. Here we examine introduction of the placental-derived amnion and chorion membranes or soluble extracts derived from these membranes into the collagen scaffolds, comparing the potential for these modifications to improve hMSC osteogenic activity. We report structural analysis of the scaffolds via mechanical compression testing, imaging via scanning electron microscopy (SEM), and assessments of various metrics for osteogenesis including gene expression (Nanostring), protein elution (ELISA), alkaline phosphatase (ALP) activity, inductively coupled plasma mass spectrometry (ICP) for mineralization, and cell viability (AlamarBlue). Notably, a post fabrication step to incorporate soluble extracts from the amnion membrane induces the highest levels of metabolic activity and performs similarly to the conventional mineralized collagen scaffolds in regard to mineral deposition and elution of the osteoclast inhibitor osteoprotegerin (OPG). Together, these findings suggest that mineralized collagen scaffolds modified using elements derived from amnion and chorion membranes, particularly their soluble extracts, represent a promising environment conducive to craniomaxillofacial bone repair.
Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine
Authors: Goel Rishi R. , Painter Mark M. , Lundgreen Kendall A. , Apostolidis Sokratis A. , Baxter Amy E. , Giles Josephine R. , Mathew Divij , Pattekar Ajinkya , Reynaldi Arnold , Khoury David S. , Gouma Sigrid , Hicks Philip , Dysinger Sarah , Hicks Amanda , Sharma Harsh , Herring Sarah , Korte Scott , KC Wumesh , Oldridge Derek A. , Erickson Rachel I. , Weirick Madison E. , McAllister Christopher M. , Awofolaju Moses , Tanenbaum Nicole , Dougherty Jeanette , Long Sherea , D’Andrea Kurt , Hamilton Jacob T. , McLaughlin Maura , Williams Justine C. , Adamski Sharon , Kuthuru Oliva , Drapeau Elizabeth M. , Davenport Miles P. , Hensley Scott E. , Bates Paul , Greenplate Allison R. , Wherry E. John 
Published: February 2022

AbstractDespite a clear role in protective immunity, the durability and quality of antibody and memory B cell responses induced by mRNA vaccination, particularly by a 3rd dose of vaccine, remains unclear. Here, we examined antibody and memory B cell responses in a cohort of individuals sampled longitudinally for ∼9-10 months after the primary 2-dose mRNA vaccine series, as well as for ∼3 months after a 3rd mRNA vaccine dose. Notably, antibody decay slowed significantly between 6- and 9-months post-primary vaccination, essentially stabilizing at the time of the 3rd dose. Antibody quality also continued to improve for at least 9 months after primary 2-dose vaccination. Spike- and RBD-specific memory B cells were stable through 9 months post-vaccination with no evidence of decline over time, and ∼40-50% of RBD-specific memory B cells were capable of simultaneously recognizing the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells induced by the first 2 doses of mRNA vaccine were boosted significantly by a 3rd dose and the magnitude of this boosting was similar to memory B cells specific for other variants. Pre-3rd dose memory B cell frequencies correlated with the increase in neutralizing antibody titers after the 3rd dose. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit reactivation of immunological memory and constrain further antibody boosting by mRNA vaccines. These data provide a deeper understanding of how the quantity and quality of antibody and memory B cell responses change over time and number of antigen exposures. These data also provide insight into potential immune dynamics following recall responses to additional vaccine doses or post-vaccination infections.Graphical Summary