bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enrichment of Nanofiber Hydrogel Composite with Fractionated Fat Promotes Regenerative Macrophage Polarization and Vascularization for Soft-Tissue Engineering
Authors: Henn Dominic , Fischer Katharina S. , Chen Kellen , Greco Autumn H. , Martin Russell A. , Sivaraj Dharshan , Trotsyuk Artem A. , Mao Hai-Quan , Reddy Sashank K. , Kneser Ulrich , Gurtner Geoffrey C. , Schmidt Volker J. , Sacks Justin M. 
Published: February 2022

Background:
Fractionated fat has been shown to promote dermal regeneration; however, the use of fat grafting for reconstruction of soft-tissue defects is limited because of volume loss over time. The authors have developed a novel approach for engineering of vascularized soft tissue using an injectable nanofiber hydrogel composite enriched with fractionated fat.

Methods:
Fractionated fat was generated by emulsification of groin fat pads from rats and mixed in a 3:1 ratio with nanofiber hydrogel composite (nanofiber hydrogel composite with fractionated fat). Nanofiber hydrogel composite with fractionated fat or nanofiber hydrogel composite alone was placed into isolation chambers together with arteriovenous loops, which were subcutaneously implanted into the groin of rats (n = 8 per group). After 21 days, animals were euthanized and systemically perfused with ink, and tissue was explanted for histologic analysis. Immunofluorescent staining and confocal laser scanning microscopy were used to quantify CD34+ progenitor cell and macrophage subpopulations.

Results:
Nanofiber hydrogel composite with fractionated fat tissue maintained its shape without shrinking and showed a significantly stronger functional vascularization compared to composite alone after 21 days of implantation (mean vessel count, 833.5 ± 206.1 versus 296.5 ± 114.1; p = 0.04). Tissue heterogeneity and cell count were greater in composite with fractionated fat (mean cell count, 49,707 ± 18,491 versus 9263 ± 3790; p = 0.005), with a significantly higher number of progenitor cells and regenerative CD163+ macrophages compared to composite alone.

Conclusions:
Fractionated fat–enriched nanofiber hydrogel composite transforms into highly vascularized soft tissue over 21 days without signs of shrinking and promotes macrophage polarization toward regenerative phenotypes. Enrichment of injectable nanofiber hydrogel composite with fractionated fat represents a promising approach for durable reconstruction of soft-tissue defects.

Clinical Relevance Statement:
The authors' approach for tissue engineering may ultimately lay the groundwork for clinically relevant applications with the goal of generating large volumes of vascularized soft tissue for defect reconstruction without donor site morbidity.
Bedaquiline Adherence Measured by Electronic Dose Monitoring Predicts Clinical Outcomes in the Treatment of Patients With Multidrug-Resistant Tuberculosis and HIV/AIDS
Authors: O'Donnell Max R. , Padayatchi Nesri , Wolf Allison , Zelnick Jennifer , Daftary Amrita , Orrell Catherine , Nimmo Camus , Baldwin Matthew , Boodhram Resha , Maharaj Bhavna , Amico K. Rivet , Naidoo Kogieleum , Friedland Gerald 
Published: February 2022

Background:
Novel regimens have revolutionized multidrug-resistant tuberculosis (MDR-TB) treatment; however, medication adherence remains challenging and poorly characterized. We hypothesized that bedaquiline adherence, measured using electronic dose monitoring, would predict MDR-TB treatment outcomes.

Setting:
This is a prospective cohort study conducted in KwaZulu-Natal, South Africa.

Methods:
Adults with MDR-TB and HIV initiating bedaquiline and on antiretroviral therapy (ART) were eligible. Separate electronic dose monitoring devices measured bedaquiline and ART adherence through 6 months, calculated as observed versus expected doses. Whole-genome sequencing was performed to identify bedaquiline resistance–associated variants.

Results:
From November 2016 through February 2018, 199 participants with MDR-TB and HIV were enrolled and followed up through treatment completion (median 17.2 months interquartile range 12.2–19.6). The median bedaquiline adherence was higher than ART adherence (97 vs. 89%, P < 0.001) but correlated (r2 = 0.68, P < 0.001). High bedaquiline adherence (≥90%) compared with lower adherence was associated with improved end of treatment successful outcome (83.4% vs. 46.3%, P < 0.001), decreased mortality (11.0% vs. 29.6% P = 0.004), and improved retention in care through end of treatment (94.5% vs. 79.6% P = 0.002). Modeling identified a highly significant but linear association between bedaquiline adherence and outcome. On multivariable analysis, bedaquiline adherence was independently associated with mortality and outcome. Bedaquiline resistance–associated variants were seen in 12% (7/57) of sequenced isolates (7% baseline, 5% emergent) with only 28.6% experiencing successful treatment outcome.

Conclusions:
Bedaquiline adherence through 6 months independently predicted end of MDR-TB treatment outcome, but a specific bedaquiline adherence threshold was not identified. Interventions to optimize bedaquiline adherence are urgently needed to improve MDR-TB HIV treatment outcomes.
“The armor phenomenon” in obese patients with penetrating thoracoabdominal injuries: A systematic review and meta-analysis
Authors: Chen Andy Ze Lin , Lee Tae Hwan , Hsu Jeremy , Pang Tony 
Published: February 2022

BACKGROUND
Obesity represents a growing global health threat, which generally portends increased morbidity and mortality in the context of traumatic injuries. We hypothesized that there may exist a protective effect related to increased weight and truncal girth provided for obese patients in penetrating torso injuries, although this may not exert a significant positive impact overall upon clinical outcomes.

METHODS
A comprehensive review of the literature was conducted across five databases up to March 2021 (Medline, Pubmed, Embase, Web of Science and the Cochrane library) to examine the effect of obesity on penetrating thoracoabdominal injuries. The primary outcome was to determine the rate of nonsignificant injury and injury patterns. Secondary outcomes examined were lengths of stay, complications, and mortality. Comparisons were drawn by meta-analysis. The study protocol was registered with PROSPERO under CRD42020216277.

RESULTS
There were 2,952 publications assessed with 12 meeting the inclusion criteria for review. Nine studies were included for quantitative analysis, including 5,013 patients sustaining penetrating thoracoabdominal injuries, of which 29.6% were obese. Obese patients that sustained stab injuries underwent more nontherapeutic operations. Obese patients that sustained gunshot injuries had longer intensive care and total hospital length of stay. Obese patients suffered more respiratory complications and were at an increased risk of death during their admission.

CONCLUSION
The “armor phenomenon” does not truly protect obese patients, a population that experiences increased morbidity and mortality following penetrating thoracoabdominal injuries.

LEVEL OF EVIDENCE
Systematic Review and Meta-Analysis; Level IV.
Mortality and pulmonary complications in emergency general surgery patients with COVID-19: A large international multicenter study
Authors:   COVIDSurg Collaborative
Published: February 2022

OBJECTIVES
The outcomes of emergency general surgery (EGS) patients with concomitant COVID-19 infection remain unknown. With a multicenter study in 361 hospitals from 52 countries, we sought to study the mortality and pulmonary complications of COVID-19 patients undergoing EGS.

METHODS
All patients 17 years or older and diagnosed preoperatively with COVID-19 between February and July 2020 were included. Emergency general surgery was defined as the urgent/emergent performance of appendectomy, cholecystectomy, or laparotomy. The main outcomes were 30-day mortality and 30-day pulmonary complications (a composite of acute respiratory distress syndrome, unexpected mechanical ventilation, or pneumonia). Planned subgroup analyses were performed based on presence of preoperative COVID-related respiratory findings (e.g., cough, dyspnea, need for oxygen therapy, chest radiology abnormality).

RESULTS
A total of 1,045 patients were included, of which 40.1% were female and 50.0% were older than 50 years; 461 (44.1%), 145 (13.9%), and 439 (42.0%) underwent appendectomy, cholecystectomy, and laparotomy, respectively. The overall mortality rate was 15.1% (158 of 1,045 patients), and the overall pulmonary complication rate was 32.9% (344 of 1,045 patients); in the subgroup of laparotomy patients, the rates were 30.6% (134 of 438 patients) and 59.2% (260 of 439 patients), respectively. Subgroup analyses found mortality and pulmonary complication risk to be especially increased in patients with preoperative respiratory findings.

CONCLUSION
COVID-19 patients undergoing EGS have significantly high rates of mortality and pulmonary complications, but the risk is most pronounced in those with preoperative respiratory findings.

LEVEL OF EVIDENCE
Prognostic and Epidemiologic; Level IV.
Development and implementation of an automated electronic health record–linked registry for emergency general surgery
Authors: Mou Zongyang , Sitapati Amy M. , Ramachandran Mokhshan , Doucet Jay J. , Liepert Amy E. 
Published: February 2022

INTRODUCTION
Despite adoption of the emergency general surgery (EGS) service by hospitals nationally, quality improvement (QI) and research for this patient population are challenging because of the lack of population-specific registries. Past efforts have been limited by difficulties in identifying EGS patients within institutions and labor-intensive approaches to data capture. Thus, we created an automated electronic health record (EHR)–linked registry for EGS.

METHODS
We built a registry within the Epic EHR at University of California San Diego for the EGS service. Existing EHR labels that identified patients seen by the EGS team were used to create our automated inclusion rules. Registry validation was performed using a retrospective cohort of EGS patients in a 30-month period and a 1-month prospective cohort. We created quality metrics that are updated and reported back to clinical teams in real time and obtained aggregate data to identify QI and research opportunities. A key metric tracked is clinic schedule rate, as we care that discontinuity postdischarge for the EGS population remains a challenge.

RESULTS
Our registry captured 1,992 patient encounters with 1,717 unique patients in the 30-month period. It had a false-positive EGS detection rate of 1.8%. In our 1-month prospective cohort, it had a false-positive EGS detection rate of 0% and sensitivity of 85%. For quality metrics analysis, we found that EGS patients who were seen as consults had significantly lower clinic schedule rates on discharge compared with those who were admitted to the EGS service (85% vs. 60.7%, p < 0.001).

CONCLUSION
An EHR-linked EGS registry can reliably conduct capture data automatically and support QI and research.

LEVEL OF EVIDENCE
Prognostic and epidemiological, level III.
Best of intent, worst of both worlds: why sequentially combining epidemiological designs does not improve signal detection in vaccine safety surveillance
Authors: Arshad Faaizah , Schuemie Martijn J. , Minty Evan P. , Alshammari Thamir M. , Lai Lana Y.H. , Duarte-Salles Talita , Fortin Stephen , Nyberg Fredrik , Ryan Patrick B. , Hripcsak George , Prieto-Alhambra Daniel , Suchard Marc A. 
Published: February 2022

AbstractBackgroundVaccine safety surveillance commonly includes a serial testing approach with a sensitive method for “signal generation” and specific method for “signal validation.” Whether serially combining epidemiological designs improves both sensitivity and specificity is unknown.MethodsWe assessed the overall performance of serial testing using three administrative claims and one electronic health record database. We compared Type I and II errors before and after empirical calibration for historical comparator, SCCS, and the serial combination of those designs against six vaccine exposure groups with 93 negative control and 279 imputed positive control outcomes.ResultsHistorical comparator mostly had lower Type II error than SCCS. SCCS had lower Type I error than the historical comparator. Before empirical calibration, serial combination increased specificity and decreased sensitivity. Type II errors mostly exceeded 50%. After empirical calibration, Type I errors returned to nominal; sensitivity was lowest when the methods were combined.ConclusionWe recommend against the serial approach in vaccine safety surveillance. While serial combination produced fewer false positive signals compared to the most specific method, it generated more false negative signals compared to the most sensitive method. Using the noisy historical comparator in front of SCCS deteriorated overall performance in evaluating safety signals.Key MessagesUsing the serial approach in vaccine safety surveillance did not improve overall performance: specificity increased but sensitivity decreased.Without empirical calibration, Type II errors exceeded 50%; after empirical calibration, Type I error rates returned to nominal with negligible change to Type II error rates.While prior research has suggested high sensitivity of the historical comparator method in distinguishing true safety signals, there were cases when self-controlled case series was more sensitive.Vaccine safety surveillance is becoming increasingly important, so monitoring systems should closely consider the utility and sequence of epidemiological designs.
Practical application of indicators for genetic diversity in CBD post-2020 Global Biodiversity Framework implementation
Authors: Thurfjell Henrik , Laikre Linda , Ekblom Robert , Hoban Sean , Sjögren-Gulve Per 
Published: February 2022

AbstractGenetic diversity is a key aspect of biological variation for the adaptability and survival of populations of species, which must be monitored to assure maintenance. We used data from the Swedish Red-List 2020 and a recent government report to apply three indicators for genetic diversity proposed for the post-2020 Global Biodiversity Framework of the Convention on Biological Diversity (CBD). We made more detailed indicator assessments for mammals and herptiles.For indicator 1, the proportion of populations with effective population size Ne>500, 33% of 22557 investigated species had a population estimate. For herptiles and mammals, 70% and 49%, respectively likely had Ne>500.For indicator 2, the proportion of populations or range remaining within species, 20% of all species evaluated for the Red-List have data. Meanwhile, 32% of the herptile and 84% of the mammal populations are maintaining their populations/range.For indicator 3, the number of species/populations in which genetic diversity is monitored using DNA-based methods, there are studies on 3% of species, and 0.3% are monitored. In contrast 68% of mammals and 29% of herptiles are studied using DNA, and 8% of mammals and 24% of herptiles are genetically monitored.We conclude that the Red List provide data suitable for evaluating the genetic indicators, but the data quality can be improved. There is a synergy in estimating the genetic indicators in parallel with the Red-Listing process. We propose that indicator values could be included in national Red-Listing as a new category - “genetically threatened”, based on the genetic indicators.
Edible formulations of chicken egg derived IgY antibodies neutralize SarsCoV2 Omicron RBD binding to human ACE2
Authors: Meher Kranti , Sivakumar S. , Kadiyala Gopi , Iyer Subramanian , Vangala Subhramanyam , Chandran Satish , Saxena Uday 
Published: February 2022

AbstractSarsCoV2 virus driven pandemic continues to surge propelled by new mutations such as seen in Omicron strain. Omicron is now rapidly becoming the dominant strain globally with more than 30 mutations in the spike protein. The mutations have resulted in Omicron strain escaping most of the neutralizing antibodies generated by the current set of approved vaccines and diluting the protection offered by the vaccines and therapeutic monoclonal antibodies.This has necessitated the need for newer strategies to prevent this strain from spreading. Towards this unmet need we have developed chicken egg derived anti-RBD IgY antibodies that neutralize the binding of Omicron RBD to human ACE2. Furthermore, we have formulated the edible IgY as flavored beverages to allow for use as oral rinse and prevent the entry of Omicron in the oropharyngeal passage, a major access and accumulation point for this strain in humans.
Age-related differences in GABA: Impact of analysis technique
Authors: Simmonite M. , Peltier S.J. , Polk T. A. 
Published: February 2022

ABSTRACTPrevious research using magnetic resonance spectroscopy (MRS) has indicated that GABA levels decline in multiple brain regions over the course of healthy aging. However, brain atrophy also occurs during healthy aging, and as a result the tissue composition of MRS voxels (i.e., the percentage of grey matter, white matter, and cerebrospinal fluid in the voxel) may also differ between age groups. Many authors therefore argue for applying a correction to GABA estimates in order to control for differences in tissue composition. Here, we use data from a large healthy aging study to investigate the influence of three tissue correction strategies on age-group differences in GABA. We also evaluate the use of different analysis packages and reference metabolites on group differences. A 3T MEGA-PRESS sequence was used to obtain spectra from seven voxels placed in the visual, auditory, and sensorimotor cortex of 58 young adults (aged 18-29 years) and 85 older adults. We obtained several different estimates of GABA concentrations from the spectra using two analysis software packages (Gannet 3.1 and LCModel), three reference metabolites (water, creatine and N-acetylaspartate) and four tissue correction strategies. Young adults consistently demonstrated significantly higher GABA concentrations in the visual, auditory, and sensorimotor cortex when we used an uncorrected GABA estimate referenced either to water or creatine. When uncorrected GABA was referenced to N-acetylaspartate, age-related differences were observed only in the right ventral visual cortex. Similarly, when any of the four tissue corrections were applied to the data, only age-related differences in the left and right ventral visual cortex voxels remained. Correlations between GABA concentration estimates obtained from different software packages were moderate, as were correlations between uncorrected GABA estimates when different baseline metabolites were used. Correlations between all tissue corrections we explored were extremely high. These results confirm that reports of age-related differences in GABA concentrations are driven, at least in part, by changes in tissue composition.
3D bioprinting of an implantable xeno-free vascularized human skin graft
Authors: Baltazar Tania , Jiang Bo , Moncayo Alejandra , Merola Jonathan , Albanna Mohammad Z. , Saltzman W. Mark , Pober Jordan S. 
Published: February 2022

ABSTRACTBioengineered tissues or organs produced using matrix proteins or components derived from xenogeneic sources pose risks of allergic responses, immune rejection, or even autoimmunity. Here, we report successful xeno-free isolation, expansion, and cryopreservation of human endothelial cells, fibroblasts, pericytes and keratinocytes from a single donor. We further demonstrate the bioprinting of a human skin substitute with a dermal layer containing xeno-free cultured human endothelial cells (EC), fibroblasts, and pericytes in a xeno-free bioink containing human collagen type I and fibronectin layered in a biocompatible polyglycolic acid (PGA) mesh and subsequently seeded with xeno-free human keratinocytes to form an epidermal layer. Following implantation of such bilayered skin grafts on the dorsum of immunodeficient mice, keratinocytes form a mature stratified epidermis with rete ridge-like structures. The ECs and pericytes form human EC-lined perfused microvessels within 2 weeks after implantation, preventing graft necrosis, and eliciting further perfusion of the graft by angiogenic host microvessels. In summary, we describe the fabrication of a bioprinted vascularized bilayered skin substitute under completely xeno-free culture conditions demonstrating feasibility of a xeno-free approach to complex tissue engineering.
Stress granules promote chemoresistance by triggering cellular quiescence
Authors: Khong Anthony , Ripin Nina , de Vasconcelos Luisa Macedo , Spencer Sabrina , Parker Roy 
Published: February 2022

SUMMARYCells respond to cellular stress by forming stress granules, molecular condensates containing non-translating messenger ribonucleoproteins. Stress granules form during chemotherapy and promote cell survival and chemoresistance, although the mechanism of this effect is not understood. We provide several lines of evidence that stress granules enhance cell survival by promoting cellular quiescence. First, we see a correlation between spontaneous stress granule formation and cell-cycle exit under non-stress conditions. Second, cells deficient in proteins required for stress granule formation (G3BP1/2) are less likely to exit the cell cycle under non-stress, stress, and chemotherapeutic conditions. Third, rescuing stress granule formation in G3BP1/2 knockout cells restores the fraction of cycling cells to wild-type levels. Finally, cells with enhanced stress granule formation (ddx6 knockout cells) show an increased propensity to exit the cell cycle. These results suggest that stress granules are important regulators of cellular quiescence, which could enable the identification of new anti-chemoresistance therapies that target stress granules.
Pivotal role of a conserved histidine in Escherichia coli ribonuclease HI as proposed by X-ray crystallography
Authors: Liao Zengwei , Oyama Takuji , Kitagawa Yumi , Katayanagi Katsuo , Morikawa Kosuke , Oda Masayuki 
Published: February 2022

The ribonuclease (RNase) H family of enzymes catalyze the specific cleavage of RNA strands of RNA/DNA hybrid duplexes and play an important role in DNA replication and repair. Since the first report of the crystal structure of RNase HI, its catalytic mechanisms, which require metal ions, have been discussed based on numerous structural and functional analyses, including X-ray crystallography. In contrast, the function of the conserved histidine residue (His124 in Escherichia coli) in the flexible loop around the active site remains poorly understood, although an important role was suggested by NMR analyses. Here, novel high-resolution X-ray crystal structures of E. coli RNase HI are described, with a particular focus on the interactions of divalent cations with His124 oriented towards the active site. The enzyme–Mg2+ complex contains two metal ions in the active site, one of which has previously been observed. The second ion lies alongside the first and binds to His124 in an octahedral coordination scheme. In the enzyme–Zn2+ complex a single metal ion was found to bind to the active site, showing a tetrahedral coordination geometry with the surrounding atoms, including His124. These results provide structural evidence that His124 plays a crucial role in the catalytic activity of RNase HI by interacting weakly and transiently with metal ions in the catalytic center.