bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candidate Biomarkers for Sepsis-Associated Acute Kidney Injury Mechanistic Studies
Authors: Odum James D. , Standage Steve , Alder Matthew , Zingarelli Basilia , Devarajan Prasad , Wong Hector R. 
Published: March 2022

ABSTRACT

Introduction:
Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication of sepsis, yet the pathophysiologic mechanisms of SA-AKI are incompletely understood. PERSEVERE is a clinically validated serum biomarker panel with high sensitivity in predicting mortality from sepsis, and recent evidence suggests it can also predict severe, persistent SA-AKI at day 3 of hospitalization among septic children. We developed a murine model of PERSEVERE (mPERSEVERE) to further interrogate the sepsis-related biological underpinnings of SA-AKI using candidate biomarkers within mPERSEVERE.

Methods:
Eight-week-old C57BL/6 male mice underwent induction of sepsis by cecal ligation and puncture (CLP). mPERSEVERE biomarkers were collected at 8-hours and kidneys were harvested at 24-hours post-CLP Classification and regression tree analysis (CART) was used to generate a SA-AKI predictive model. Kidney gene expression levels of candidate biomarkers were quantified using real time polymerase chain reaction.

Results:
Thirty- five mice underwent CLP Among mice identified by mPERSEVERE as high-risk for mortality, 70% developed SA-AKI at 24-hours compared to 22% of low-risk mice. CART analysis identified two mPERSEVERE biomarkers—C-C motif chemokine ligand 3 (CCL3) and keratinocyte-derived chemokine (KC)—as most predictive for SA-AKI with an area under the receiver operating curve of 0.90. In mice that developed SA-AKI, renal expression of KC was significantly increased compared to mice without SA-AKI (p
= 0.013), whereas no difference was seen in renal expression of CCL3 in mice with SA-AKI vs. no SA-AKI. KC and CCL3 localized to renal tubule epithelial cells as opposed to infiltrating immune cells by immunohistochemistry.

Conclusions:
The combination of plasma CCL3+KC can predict SA-AKI development in mice at 24-hours following CLP Of these two biomarkers, only renal expression of KC is increased in mice with SA-AKI. Further studies are required to determine if KC directly contributes to the underlying pathobiology of SA-AKI.
Targeted Regional Optimization in Action: Dose-dependent End-organ Ischemic Injury with Partial Aortic Occlusion in the Setting of Ongoing Liver Hemorrhage
Authors: Ronaldi Alley E. , Lauria Alexis L. , Paterson Jeanette E. , Kersey Alexander J. , Leung Lai Yee , Burmeister David M. , Baer David G. , White Paul W. , Rasmussen Todd E. , White Joseph M. 
Published: March 2022

ABSTRACT

Introduction:
Targeted regional optimization (TRO) describes partial resuscitative endovascular balloon occlusion of the aorta strategy that allows for controlled distal perfusion to balance hemostasis and tissue perfusion. This study characterized hemodynamics at specific targeted distal flow rates in a swine model of uncontrolled hemorrhage to determine if precise TRO by volume was possible.

Methods:
Anesthetized swine were subjected to liver laceration and randomized into TRO at distal flows of 300 mL/min (n = 8), 500 mL/min (n = 8), or 700 mL/min (n = 8). After 90 min, the animals received damage control packing and were monitored for 6 h. Hemodynamic parameters were measured continuously, and hematology and serologic labs obtained at predetermined intervals.

Results:
During TRO, the average percent deviation from the targeted flow was lower than 15.9% for all cohorts. Average renal flow rates were significantly different across all cohorts during TRO phase (P < 0.0001; TRO300 = 63.1 ± 1.2; TRO500 = 133.70 ± 1.93; TRO700 = 109.3 ± 2.0), with the TRO700 cohort having less renal flow than TRO500. The TRO500 and TRO700 average renal flow rates inverted during the intensive care unit phase (P < 0.0001; TRO300 = 86.20 ± 0.40; TRO500 = 148.50 ± 1.45; TRO700 = 181.1 ± 0.70). There was higher blood urea nitrogen, creatinine, and potassium in the TRO300 cohort at the end of the experiment, but no difference in lactate or pH between cohorts.

Conclusion:
This study demonstrated technical feasibility of TRO as a strategy to improve outcomes after prolonged periods of aortic occlusion and resuscitation in the setting of ongoing solid organ hemorrhage. A dose-dependent ischemic end-organ injury occurs beginning with partial aortic occlusion that progresses through the critical care phase, with exaggerated effect on renal function.
Evaluation of Postgraduate Educational Environment of Doctors Training in Psychiatry: a mixed method study
Authors: Elzain Musaab , Moran Lisa , McCarthy Geraldine , Hyde Sarah , McFarland John 
Published: March 2022

AbstractIntroductionEducational Environment (EE) is of paramount importance in Medical Education, but can be intangible and hard to clearly determine. Professional satisfaction and patient care improve in a pleasant learning environment; where postgraduate physicians are encouraged, suitably supervised, and fostered. A negative learning environment can be detrimental to trainees’ and teams’ morale and can jeopardize the multidisciplinary working relationship.ObjectivesThe objective of this study was to measure the Educational Environment (EE) of Psychiatry postgraduate training in the Midwest of Ireland training Deanery; what aspects of training are working well and what areas are seen as not optimal.MethodsThis study took place between April and June 2021. A mixed methods approach was adopted, using the Postgraduate Hospital Educational Environment Measure (PHEEM) and semi-structured one-to-one interviews.ResultsResponse rate was 88% (n=22). The total PHEEM score was 105.64±23.52, indicating a postgraduate EE with more positive than negative aspects, but with room for improvement. There were no differences in overall PHEEM and subscale scores between trainees’ gender, training grades or years of working experience. Three themes were identified that contribute to trainees’ perception of EE: the commitment of the trainees’ supervisors to the role they play in trainees’ overall development, the clinical workload of the trainee, and the day-to-day working conditions of the trainee. Definite disparities between work placements were evident in the collected data across these three themes.ConclusionsAlthough the training program had an overall positive EE, specific answers and interview themes indicated some areas of weakness that may contribute to trainee dissatisfaction and possible burnout. Planned interventions targeting these areas and tracking changes in EE and burnout rates over time may be useful measures going forward.Declaration of InterestNone
Rapid review of government issued documents relevant to mitigation of COVID-19 in the US food manufacturing and processing industry
Authors: Chen Ziqian , Bulut Ece , Trmčić Aljoša , Ivanek Renata 
Published: March 2022

ABSTRACTWe surveyed publicly available records published by the United States (US) government between the start of the Coronavirus Disease 2019 (COVID-19) pandemic and September 30th, 2021, to identify documents containing resources or guidelines about COVID-19 mitigation relevant to the US food manufacturing and processing industry (hereafter referred to as “the food processing industry”). Among 36 documents identified and reviewed (including 35 from government agencies and one from a relevant professional association), we extracted 19 categories of mitigation strategies covering the themes of employee biosafety, surveillance, vaccination, social distancing, and worker education. We concluded that the priority of COVID-19 mitigation in the food processing industry was to protect the health and safety of industry workers while maintaining food supply chain resilience to minimize disturbance in the food market and avoid food crisis. A collated list of the identified documents and their comprehensive review will (i) aid researchers and public health workers in interpreting the potential impacts of the recommended mitigations on the epidemiology of the disease among workers in the food processing industry and (ii) help the food processing industry sort out the most essential strategies to take in face of a pandemic.
Macrophage depletion blocks congenital SARM1-dependent neuropathy
Authors: Dingwall Caitlin B. , Strickland Amy , Yum Sabrina W. , Yim Aldrin K. , Zhu Jian , Wang Peter L. , Yamada Yurie , Schmidt Robert E. , Sasaki Yo , Bloom A. Joseph , DiAntonio Aaron , Milbrandt Jeffrey 
Published: March 2022

ABSTRACTAxon loss contributes to many common neurodegenerative disorders. In healthy axons, the axon survival factor NMNAT2 inhibits SARM1, the central executioner of programmed axon degeneration. We identified two rare NMNAT2 missense variants in two brothers afflicted with a progressive neuropathy syndrome. The polymorphisms result in amino acid substitutions, V98M and R232Q, which reduce NMNAT2 NAD+-synthetase activity. We generated a mouse model of the human syndrome and found that Nmnat2V98M/Nmnat2R232Q compound-heterozygous CRISPR mice survive to adulthood but develop progressive motor dysfunction, peripheral axon loss, and macrophage infiltration. These disease phenotypes are all SARM1-dependent. Remarkably, macrophage depletion therapy blocks and reverses neuropathic phenotypes in Nmnat2V98M/R232Q mice, identifying a SARM1-dependent neuroimmune mechanism as a key driver of disease pathogenesis. These findings demonstrate that SARM1 induces an inflammatory neuropathy and highlight the potential of immune therapy to treat this rare syndrome and other neurodegenerative conditions associated with NMNAT2 loss and SARM1 activation.
CLE42 Delays Leaf Senescence by Antagonizing Ethylene Pathway in Arabidopsis
Authors: Zhang Yi , Tan Shuya , Gao Yuhan , Kan Chengcheng , Wang Hou-Ling , Yang Qi , Xia Xinli , Ishida Takashi , Sawa Shinichiro , Guo Hongwei , Li Zhonghai 
Published: March 2022

SummaryLeaf senescence is the final stage of leaf development and is influenced by numerous internal and environmental factors. CLE family peptides are plant-specific peptide hormones that regulate various developmental processes. However, the role of CLE in regulating leaf senescence remains unclear. Here, we found that CLE42 is a negative regulator of leaf senescence by using a CRISPR/Cas9-produced CLE mutant collection. The cle42 mutant displayed earlier senescence phenotypes, while overexpression of CLE42 delayed age-dependent and dark-induced leaf senescence. Moreover, application of the synthesized 12-aa peptide (CLE42p) also delayed leaf senescence under natural and dark conditions. CLE42 and CLE41/44 displayed functional redundancy in leaf senescence, and the cle41 cle42 cle44 triple mutant displayed more pronounced earlier senescence phenotypes than any single mutant. Analysis of differentially expressed genes obtained by RNA-Seq methodology revealed that ethylene pathway was suppressed by overexpressing CLE42. Moreover, CLE42 suppressed ethylene biosynthesis and thus promoted the protein accumulation of EBF, which in turn decreased the function of EIN3. Accordingly, mutation of EIN3/EIL1 or overexpression of EBF1 suppressed the earlier senescence phenotypes of the cle42 mutant. Together, our results reveal that the CLE peptide hormone regulates leaf senescence by communicating with ethylene pathway.
Fine-mapping and identification of candidate causal genes for tail length in the Merinolandschaf breed
Authors: Lagler Dominik Karl , Hannemann Elisabeth , Eck Kim , Klawatsch Jürgen , Seichter Doris , Russ Ingolf , Mendel Christian , Lühken Gesine , Krebs Stefan , Blum Helmut , Upadhyay Maulik , Međugorac Ivica 
Published: March 2022

AbstractBackgroundDocking the tails of young lambs in long-tailed sheep breeds is a common practice worldwide. This practice is associated with pain, suffering and damage to the affected animals. Breeding for a shorter tail in long-tailed sheep breeds could offer one of the alternatives. This study aimed to analyze the natural tail length variation in the most common German Merino variety, and to identify possible causal alleles for the short tail phenotype segregating within a typical long-tailed breed.ResultsHaplotype-based mapping in 362 genotyped (Illumina OvineSNP50) and phenotyped Merinolandschaf lambs resulted in a genome-wide significant mapping at position 37,111,462 bp on sheep chromosome 11 and on chromosome 2 at position 94,538,115 bp (Oar_v4.0). Targeted capture sequencing of these regions in 48 selected sheep and comparative analyses of WGS data of various long and short-tailed sheep breeds as well as wild sheep subspecies identified a SNP and a SINE element as the promising candidates. The PCR genotyping of these candidates revealed complete linkage of both the candidate variants. The SINE element is located in the promotor region of HOXB13, while the SNP was located in the first exon of HOXB13 and predicted to result in a nonsynonymous mutation.ConclusionsOur approach successfully identified HOXB13 as candidate genes and the likely causal variants for tail length segregating within a typical long-tailed Merino breed. This would enable more precise breeding towards shorter tails, improve animal welfare by amplification of ancestral alleles and contribute to a better understanding of differential embryonic development.
Social cues of safety can override differences in threat level
Authors: Ferreira Clara H , Heinemans Mirjam , Farias Matheus , Gonçalves Rui , Moita Marta A 
Published: March 2022

AbstractAnimals in groups integrate social information with that directly-gathered about the environment to guide decisions regarding reproduction, foraging and defense against predatory threats. In the context of predation, usage of social information has acute fitness benefits, aiding the detection of predators, the mounting of concerted defensive responses, or allowing the inference of safety, permitting other beneficial behaviors such as foraging for food. Individual and group defense responses to predatory threats can vary in modality and vigor depending on the perceived threat level. Moreover, predation level has been shown to modulate the use of social cues about foraging sites. Whether and how different threat levels affect the use of social cues to guide defense responses, is currently unknown. We previously showed that Drosophila melanogaster display a graded decrease in freezing behavior, triggered by an inescapable visual threat, with increasing group sizes. Crucially, we identified the movement of others as a cue of safety and its cessation a cue of threat and found the group responses to be primarily guided by the safety cues, resulting in a net social buffering effect. Here, we investigated how threat level impacts the use of social cues by exposing flies individually and in groups to two threat imminences using looms of different speeds. We show that freezing responses are stronger to the faster looms regardless of social condition. However, social buffering was stronger for groups exposed to the fast looms, such that the increase in freezing caused by the higher threat was less prominent in flies tested in groups than those tested individually. Through artificial control of behavior, we created different group compositions, titrating the motion cues that were maintained across threat levels. We, found that the same level of safety motion cues had a bigger weight on the flies’ decisions when these were exposed to the higher threat, thus overriding differences in perceived threat levels. These findings shed light on the ‘safety in numbers’ effect, revealing the modulation of the saliency of social safety cues across threat intensities, a possible mechanism to regulate costly defensive responses.
Stable nebulization and muco-trapping properties of Regdanvimab/IN-006 supports its development as a potent, dose-saving inhaled therapy for COVID-19
Authors: McSweeney Morgan , Stewart Ian , Richardson Zach , Kang Hyunah , Park Yoona , Kim Cheolmin , Tiruthani Karthik , Wolf Whitney , Schaefer Alison , Kumar Priya , Aurora Harendra , Hutchins Jeff , Cho Jong Moon , Hickey Anthony J. , Lee Soo Young , Lai Samuel 
Published: March 2022

AbstractThe respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries around the world, can effectively trap SARS-CoV-2 virus-like-particles in fresh human airway mucus. IN-006, a reformulation of Regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-CoV-2 and other respiratory pathologies.
Increased reliability of visually-evoked activity in area V1 of the MECP2-duplication mouse model of autism
Authors: Ash Ryan T. , Palagina Ganna , Park Jiyoung , Fernandez-Leon Jose A. , Seilheimer Rob , Lee Sangkyun , Sabharwal Jasdeep , Reyes Fredy , Wang Jing , Lu Dylan , Wu Sam , Smirnakis Stelios M. 
Published: March 2022

ABSTRACTAtypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in layer 2/3 neurons of adult primary visual cortex in the MECP2-duplication syndrome animal model of autism. Increased response reliability was due in part to decreased response amplitude, decreased fluctuations in endogenous activity, and decreased neuronal coupling to endogenous activity. Similarly to what was observed neuronally, the optokinetic reflex occurred more reliably at low contrasts in mutant mice compared to controls. Retinal responses did not explain our observations. These data suggest that the circuit mechanisms for convolution of sensory-evoked and endogenous signal and noise may be altered in this form of syndromic autism.
More persistent bacterial than fungal associations in the microbiota of a pest
Authors: Gurung Kiran , Vink Stefanie Nicoline , Salles Joana Falcão , Wertheim Bregje 
Published: March 2022

AbstractThe invasive fly Drosophila suzukii is a pest that can infest a diverse range of intact, ripening fruits, using its serrated ovipositor. This constitutes a different niche compared to the rotting fruits its ancestors use, especially because these intact fruits have limited quantities of microbes and soluble nutrients for the developing larvae. To investigate the potential role of microbial associations in the niche expansion of this invasive fly, we characterized the bacterial and fungal communities of D. suzukii and various wild fruits from which they developed. To assess cross-generational microbial associations, we also lab-reared fly populations and characterized their microbial communities. Diversity metrics of microbial communities differed significantly between flies and fruits. Different fruit types varied substantially in microbial composition, while flies showed relatively uniform bacterial communities, irrespective of the fruit source they developed on. After lab-rearing, bacterial communities still showed considerable overlap with those of wild flies. Fungal communities of flies and fruits showed larger resemblance, with a substantial overlap between wild flies and the corresponding fruits on which they had developed. Our study thus reports that the fungal community structure in these pests largely reflects those on the breeding substrates, while these flies might have formed more persistent associations with bacteria and transmit these across generations rather than obtaining them from their food source.
Combinatorial engineering for photoautotrophic production of recombinant products from the green microalga Chlamydomonas reinhardtii
Authors: Abdallah Malak N. , Wellman Gordon B. , Overmans Sebastian , Lauersen Kyle J. 
Published: March 2022

AbstractChlamydomonas reinhardtii has emerged as a powerful green cell factory for metabolic engineering of sustainable products created from the photosynthetic lifestyle of this microalga. Advances in nuclear genome and transgene expression engineering are allowing robust engineering strategies to be demonstrated in this host. However, commonly used lab strains are not equipped with features to enable their broader implementation in non-sterile conditions and high-cell density concepts. Here, we use combinatorial chloroplast and nuclear genome engineering to complement the C. reinhardtii strain UVM4 with publicly available genetic tools to enable the use of inorganic phosphite and nitrate as a sole the source phosphorous and nitrogen, respectively. We present recipes to create phosphite-buffered media solutions that enable high cell density algal cultivation. We then combine previously reported engineering strategies to produce the heterologous sesquiterpenoid patchoulol to high titers from our engineered green cell factories and show these products are possible to produce in under non-sterile conditions. Our work presents a straightforward means to generate C. reinhardtii strains for broader application in bio-processes for the sustainable generation of products.