bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic code degeneracy is established by the decoding center of the ribosome
Authors: Ye Shixin , Lehmann Jean 
Published: March 2022

Abstract
The degeneracy of the genetic code confers a wide array of properties to coding sequences. Yet, its origin is still unclear. A structural analysis has shown that the stability of the Watson–Crick base pair at the second position of the anticodon–codon interaction is a critical parameter controlling the extent of non-specific pairings accepted at the third position by the ribosome, a flexibility at the root of degeneracy. Based on recent cryo-EM analyses, the present work shows that residue A1493 of the decoding center provides a significant contribution to the stability of this base pair, revealing that the ribosome is directly involved in the establishment of degeneracy. Building on existing evolutionary models, we show the evidence that the early appearance of A1493 and A1492 established the basis of degeneracy when an elementary kinetic scheme of translation was prevailing. Logical considerations on the expansion of this kinetic scheme indicate that the acquisition of the peptidyl transferase center was the next major evolutionary step, while the induced-fit mechanism, that enables a sharp selection of the tRNAs, necessarily arose later when G530 was acquired by the decoding center.
ChIP-Atlas 2021 update: a data-mining suite for exploring epigenomic landscapes by fully integrating ChIP-seq, ATAC-seq and Bisulfite-seq data
Authors: Zou Zhaonan , Ohta Tazro , Miura Fumihito , Oki Shinya 
Published: March 2022

Abstract
ChIP-Atlas (https://chip-atlas.org) is a web service providing both GUI- and API-based data-mining tools to reveal the architecture of the transcription regulatory landscape. ChIP-Atlas is powered by comprehensively integrating all data sets from high-throughput ChIP-seq and DNase-seq, a method for profiling chromatin regions accessible to DNase. In this update, we further collected all the ATAC-seq and whole-genome bisulfite-seq data for six model organisms (human, mouse, rat, fruit fly, nematode, and budding yeast) with the latest genome assemblies. These together with ChIP-seq data can be visualized with the Peak Browser tool and a genome browser to explore the epigenomic landscape of a query genomic locus, such as its chromatin accessibility, DNA methylation status, and protein–genome interactions. This epigenomic landscape can also be characterized for multiple genes and genomic loci by querying with the Enrichment Analysis tool, which, for example, revealed that inflammatory bowel disease-associated SNPs are the most significantly hypo-methylated in neutrophils. Therefore, ChIP-Atlas provides a panoramic view of the whole epigenomic landscape. All datasets are free to download via either a simple button on the web page or an API.
Mechanisms of myostatin and activin A accumulation in chronic kidney disease
Authors: Bataille Stanislas , Dou Laetitia , Bartoli Marc , Sallée Marion , Aniort Julien , Ferkak Borhane , Chermiti Rania , McKay Nathalie , Da Silva Nathalie , Burtey Stéphane , Poitevin Stéphane 
Published: March 2022

ABSTRACT

Background
Myostatin and activin A induce muscle wasting by activating the ubiquitin proteasome system and inhibiting the Akt/mammalian target of rapamycin pathway. In chronic kidney disease (CKD), myostatin and activin A plasma concentrations are increased, but it is unclear if there is increased production or decreased renal clearance.

Methods
We measured myostatin and activin A concentrations in 232 CKD patients and studied their correlation with estimated glomerular filtration rate (eGFR). We analyzed the myostatin gene (MSTN) expression in muscle biopsies of hemodialysis (HD) patients. We then measured circulating myostatin and activin A in plasma and the Mstn and Inhba expression in muscles, kidney, liver and heart of two CKD mice models (adenine and 5/6 nephrectomy models). Finally, we analyzed whether the uremic toxin indoxyl sulfate (IS) increased Mstn expression in mice and cultured muscle cells.

Results
In patients, myostatin and activin A were inversely correlated with eGFR. MSTN expression was lower in HD patients’ muscles (vastus lateralis) than in controls. In mice with CKD, myostatin and activin A blood concentrations were increased. Mstn was not upregulated in CKD mice tissues. Inha was upregulated in kidney and heart. Exposure to IS did not induce Mstn upregulation in mouse muscles and in cultured myoblasts and myocytes.

Conclusion
During CKD, myostatin and activin A blood concentrations are increased. Myostatin is not overproduced, suggesting only an impaired renal clearance, but activin A is overproduced in the kidney and heart. We propose to add myostatin and activin A to the list of uremic toxins.
TERT promoter C228T mutation in neural progenitors confers growth advantage following telomere shortening in vivo
Authors: Miki Shunichiro , Koga Tomoyuki , Mckinney Andrew M , Parisian Alison D , Tadokoro Takahiro , Vadla Raghavendra , Marsala Martin , Hevner Robert F , Costello Joseph F , Furnari Frank 
Published: March 2022

Abstract

Background
Heterozygous TERT (telomerase reverse transcriptase) promoter mutations (TPMs) facilitate TERT expression and are the most frequent mutation in glioblastoma (GBM). A recent analysis revealed this mutation is one of the earliest events in gliomagenesis. However, no appropriate human models have been engineered to study the role of this mutation in the initiation of these tumors.

Method
We established GBM models by introducing the heterozygous TPM in human induced pluripotent stem cells (hiPSCs) using a two-step targeting approach in the context of GBM genetic alterations, CDKN2A/B and PTEN deletion, and EGFRvIII overexpression. The impact of the mutation was evaluated through the in vivo passage and in vitro experiment and analysis.

Results
Orthotopic injection of neuronal precursor cells (NPCs) derived from hiPSCs with the TPM into immunodeficient mice did not enhance tumorigenesis compared to TERT promoter wild type NPCs at initial in vivo passage presumably due to relatively long telomeres. However, the mutation recruited GA-Binding Protein and engendered low-level TERT expression resulting in enhanced tumorigenesis and maintenance of short telomeres upon secondary passage as observed in human GBM. These results provide the first insights regarding increased tumorigenesis upon introducing a TPM compared to isogenic controls without TPMs.

Conclusion
Our novel GBM models presented the growth advantage of heterozygous TPMs for the first time in the context of GBM driver mutations relative to isogenic controls, thereby allowing for the identification and validation of TERT promoter-specific vulnerabilities in a genetically accurate background.
Zombies at Large? Corporate Debt Overhang and the Macroeconomy
Authors: Jordà Òscar , Kornejew Martin , Schularick Moritz , Taylor Alan M 
Published: March 2022

Abstract
Debt overhang is associated with higher financial fragility and slower recovery from recession. However, while household credit booms have been extensively documented to have this property, we find that corporate debt does not fit the same pattern. Newly collected data on nonfinancial business liabilities for 18 advanced economies over the past 150 years shows that, in the aggregate, greater frictions in corporate debt resolution make for slower recoveries, with weak investment and more persistent “zombie firms” and that this is an important factor in explaining the difference in outcomes relative to household credit booms.
Clinical and laboratory characteristics of dengue and COVID-19 coinfected patients in Dhaka, Bangladesh
Authors: Hannan Tabiha Binte , Hossain Zazeba , Hasan Md Nazmul , Khan Abed Hussain , Alam Md Rafiqul , Rahman Md Mujibur , Arafat Shohael Mahmud , Chowdhury Fazle Rabbi 
Published: March 2022

Abstract

Background
Dengue–COVID-19 coinfection is one of the greatest emerging challenges in dengue-endemic areas during the continuing pandemic. With coinciding clinical and laboratory pictures, early diagnosis becomes burdensome, with management discrepancy.

Methods
A descriptive study was performed on dengue–COVID-19 coinfected patients during July–August 2021 for an overview of disease progression, severity and outcome. A total of 11 patients who were positive for dengue NS1 and/or antidengue IgM were included in this study.

Results
In total, 45.5% patients developed severe COVID-19 disease, 45.5% patients developed group B dengue fever and 9% patients developed group C dengue fever. Concurrent severity of both diseases was seen to be rare, except for in one patient.

Conclusion
Early diagnosis and compatible management still stand as basic principles to prevent fatality and morbidity.
The observed relationship between the degree of parasite aggregation and the prevalence of infection within human host populations for soil-transmitted helminth and schistosome infections
Authors: Kura Klodeta , Truscott James E , Collyer Benjamin S , Phillips Anna , Garba Amadou , Anderson Roy M 
Published: March 2022

AbstractBackgroundSoil-transmitted helminths (STH) and schistosome parasites are highly aggregated within the human population. The probability distribution of worms per person is described well by the negative binomial probability distribution with aggregation parameter, k, which varies inversely with parasite clustering. The relationship between k and prevalence in defined populations subject to mass drug administration is not well understood.Methods and ResultsWe use statistical methods to estimate k using two large independent datasets for STH and schistosome infections from India and Niger, respectively, both of which demonstrate increased aggregation of parasites in a few hosts, as the prevalence of infections declines across the dataset.ConclusionsA greater attention needs to be given in monitoring and evaluation programmes to find and treat the remaining aggregates of parasites.
Factors Related to Passive Social Withdrawal and Active Social Avoidance in Schizophrenia
Authors: Farina Emily A. , Assaf Michal , Corbera Silvia , Chen Chi-Ming 
Published: March 2022

Abstract
Social withdrawal in schizophrenia may be a result of “passive” motivation (reduced drive to engage) or “active” motivation (increased drive to avoid). We conducted a cross-sectional, between-subjects study using self-report measures and social cognition tasks to evaluate the relationships between motivational subtypes, social abilities, and social functioning in schizophrenia spectrum (n = 52, ages 19–34). Regression models showed significant differences in passive and active withdrawal. Passive, but not active, motivation predicted social functioning as measured by a clinical interview. This suggests that motivation, especially passive type, plays an important role in social withdrawal in schizophrenia. However, on a self-report measure of social functioning, neither passive nor active motivation predicted outcomes, suggesting a potential disconnect between observer versus self-report measures when assessing social motivation. Furthermore, performance on tasks of social abilities did not predict motivation, which supports the idea that motivation is distinct from social ability and should be specifically addressed in treatment.
Protein Phosphatase PPM1B Inhibits Gastric Cancer Progression and Serves as a Favorable Prognostic Biomarker
Authors: Li Riheng , Dou Jian , Bai Tianliang , Cai Bindan , Liu Yabin 
Published: March 2022

Background:
Protein phosphatase PPM1B, also named as PP2Cβ, is a member of serine/threonine phosphatase family. Dysregulated expression of PPM1B has been reported in several malignancies; nevertheless, its role in gastric cancer remains unknown. Here, we aimed to initially investigate the expression and function of PPM1B in gastric adenocarcinoma.

Methods:
We firstly evaluated the protein expression of PPM1B in our enrolled retrospective cohort (n=161) via immunohistochemistry staining. Univariate and multivariate analyses were conducted to assess its prognostic value. Cellular experiments and xenografts in mice model were also performed to validate the role of PPM1B in gastric adenocarcinoma progression.

Results:
The advanced tumor stage was characterized with a lower PPM1B level. Lower PPM1B was associated with poor prognosis in both The Cancer Genome Atlas (TCGA) dataset and our cohort (P<0.05). Furthermore, Cox regression analysis demonstrated that PPM1B was a novel independent prognostic factor for gastric adenocarcinoma patients (hazard ratio=0.35, P=0.001). Finally, cellular and xenografts data confirmed that overexpressing PPM1B can remarkably attenuated gastric adenocarcinoma growth.

Conclusion:
Low expression of PPM1B may be a potential molecular marker for poor prognosis in gastric adenocarcinoma.
Association Between Subjective-Objective Discrepancy of Sleeping Time and Health-Related Quality of Life: A Community-Based Polysomnographic Study
Authors: Cho Seo-Eun , Kang Jae Myeong , Ko Kwang-Pil , Lim Weon-Jeong , Redline Susan , Winkelman John W. , Kang Seung-Gul 
Published: March 2022

ABSTRACT

Objective
This study aimed to investigate the existence of a difference in quality of life (QOL) between individuals with and without significant subjective-objective discrepancy (SOD) in total sleep time (TST).

Methods
From the Sleep Heart Health Study 2, 2540 individuals who had completed polysomnography, a morning sleep survey, and the 36-item Short-Form Health Survey (SF-36) were included in the analyses. The participants were classified as normoestimators (estimation of TST <±60 minutes), underestimators (underestimation of TST ≥60 minutes), or overestimators (overestimation of TST ≥60 minutes). The standardized SF-36 QOL scores were compared among the three groups. An adjusted partial correlation analysis was conducted between SOD and QOL.

Results
Of the 2540 participants, 1617 (63.7%), 433 (17.0%), and 490 (19.3%) were assigned to the normoestimator, underestimator, and overestimator groups, respectively. The bodily pain and social functioning components of the SF-36 score were significantly lower in the underestimators than in the normoestimators, whereas the physical functioning component was significantly lower in the overestimators than in the normoestimators. The absolute value of SOD in the TST showed a significant negative correlation with the physical and mental components of the SF-36.

Conclusions
QOL was significantly better in the normoestimator than in the other groups and linearly correlated with the absolute value of SOD. This study suggests that a high prevalence of positive and negative sleep misperception in a community population can be a potential factor associated with poor QOL and potential comorbidities.
Impact of an Enhanced Patient Care Intervention on Viral Suppression Among Patients Living With HIV in Kenya
Authors: Wachira Juddy , Genberg Becky , Mwangi Ann , Chemutai Diana , Braitstein Paula , Galarraga Omar , Siika Abraham , Wilson Ira 
Published: March 2022

Background:
Effective patient-centered interventions are needed to promote patient engagement in HIV care. We assessed the impact of a patient-centered intervention referred to as enhanced patient care (EPC) on viral suppression among unsuppressed patients living with HIV in Kenya.

Setting:
Two rural HIV clinics within the Academic Model Providing Access to Health care.

Methods:
This was a 6-month pilot randomized control trial. The EPC intervention incorporated continuity of clinician–patient relationships, enhanced treatment dialog, and improved patients' clinic appointment scheduling. Provider–patient communication training was offered to all clinicians in the intervention site. We targeted 360 virally unsuppressed patients: (1) 240 in the intervention site with 120 randomly assigned to provider–patient communication (PPC) training + EPC and 120 to PPC training + standard of care (SOC) and (2) 120 in the control site receiving SOC. Logistic regression analysis was applied using R (version 3.6.3).

Results:
A total of 328 patients were enrolled: 110 (92%) PPC training + EPC, 110 (92%) PPC training + SOC, and 108 (90%) SOC. Participants' mean age at baseline was 48 years (SD: 12.05 years). Viral suppression 6 months postintervention was 84.4% among those in PPC training + EPC, 83.7% in PPC training + SOC, and 64.4% in SOC (P ≤ 0.001). Compared with participants in PPC training + EPC, those in SOC had lower odds of being virally suppressed 6 months postintervention (odds ratio = 0.36, 95% confidence interval: 0.18 to 0.72).

Conclusions:
PPC training may have had the greatest impact on patient viral suppression. Hence, adequate training and effective PPC implementation strategies are needed.
Traumatic brain injury patients with platelet inhibition receiving platelet transfusion demonstrate decreased need for neurosurgical intervention and decreased mortality
Authors: Miles M. Victoria P. , Hicks R. Chace , Parmer Hunter , Brown Caroline , Edwards Abigail , Stewart Kathryn , Gao Lani , Maxwell Robert 
Published: March 2022

BACKGROUND
Platelet dysfunction is known to occur in patients with traumatic brain injury (TBI), and the correction of platelet dysfunction may prevent hemorrhagic progression in TBI. Thromboelastography with platelet mapping (TEG-PM; Haemonetics) evaluates the degree of platelet function inhibition through the adenosine diphosphate (ADP) and arachidonic acid (AA) pathways. We hypothesized that ADP and AA inhibition would improve with the transfusion of platelets in patients with TBI.

METHODS
A retrospective review was conducted at a Level I trauma center of all patients presenting with TBI from December 2019 to December 2020. Per a practice management guideline, a platelet mapping assay was obtained on all patients with TBI upon admission. If ADP or AA was found to be inhibited (>60%), the patient was transfused 1 unit of platelets and a repeat platelet mapping assay was ordered. Demographic data, laboratory values, and outcomes were analyzed.

RESULTS
Over the 13-month study period, 453 patients with TBI underwent TEG-PM with a protocol adherence rate of 66.5% resulting in a total of 147 patients who received platelets for ADP and/or AA inhibition; of those, 107 underwent repeat TEG-PM after platelets were administered. With the administration of platelets, ADP (p < 0.0001), AA (p < 0.0001), and MA (p = 0.0002) all significantly improved. Of 330 patients with TBI not taking antiplatelet medications, 50.9% showed inhibition in ADP and/or AA. If AA or ADP inhibition was noted on admission, mortality was increased (p = 0.0108). If ADP improved with platelet administration, the need for neurosurgical intervention was noted to decrease (p = 0.0182).

CONCLUSION
Patients with TBI and platelet inhibition may benefit from the administration of platelets to correct platelet dysfunction. Thromboelastography with platelet mapping may be implemented in the initial workup of patients presenting with TBI to assess platelet dysfunction and provide prognostic information, which may guide treatment.

LEVEL OF EVIDENCE
Therapeutic / Care Management, level III.
Effects of antifibrinolytics on systemic and cerebral inflammation after traumatic brain injury
Authors: Wallen Taylor E. , Singer Kathleen E. , Baucom Matthew R. , England Lisa G. , Schuster Rebecca M. , Pritts Timothy A. , Goodman Michael D. 
Published: March 2022

BACKGROUND
Administration of antifibrinolytic medications, including tranexamic acid (TXA), may reduce head injury–related mortality. The effect of these medications on post–traumatic brain injury (TBI) inflammatory response is unknown. The goal of this study was to investigate the role of available antifibrinolytic medications on both systemic and cerebral inflammation after TBI.

METHODS
An established murine weight drop model was used to induce a moderate TBI. Mice were administered 1, 10, or 100 mg/kg of TXA, 400 mg/kg of aminocaproic acid (Amicar, Hospira, Lake Forest, IL), 100 kIU/kg of aprotonin, or equivalent volume of normal saline (NS) 10 minutes after recovery. Mice were euthanized at 1, 6, or 24 hours. Serum and cerebral tissue were analyzed for neuron-specific enolase and inflammatory cytokines. Hippocampal histology was evaluated at 30 days for phosphorylated tau accumulation.

RESULTS
One hour after TBI, mice given TXA displayed decreased cerebral cytokine concentrations of tumor necrosis factor α (TNF-α) and, by 24 hours, displayed decreased concentrations of cerebral TNF-α, interleukin (IL)-6, and monocyte chemoattractant protein 1 compared with TBI-NS. However, serum concentrations of TNF-α and macrophage inflammatory protein 1α (MIP-1α) were significantly elevated from 1 to 24 hours in TBI-TXA groups compared with TBI-NS. The concentration of phosphorylated tau was significantly decreased in a dose-dependent manner in TBI-TXA groups compared with TBI-NS. By contrast, Amicar administration increased cerebral cytokine levels of IL-6 1 hour after TBI, with serum elevations noted in TNF-α, MIP-1α, and monocyte chemoattractant protein 1 at 24 hours compared with TBI-NS. Aprotonin administration increased serum TNF-α, IL-6, and MIP-1α from 1 to 24 hours without differences in cerebral cytokines compared with TBI-NS.

CONCLUSION
Tranexamic acid administration may provide acute neuroinflammatory protection in a dose-dependent manner. Amicar administration may be detrimental after TBI with increased cerebral and systemic inflammatory effects. Aprotonin administration may increase systemic inflammation without significant contributions to neuroinflammation. While no antifibrinolytic medication improved systemic inflammation, these data suggest that TXA may provide the most beneficial inflammatory modulation after TBI.
A Comorbidity Index and Pretransplant Physical Status Predict Survival in Older Kidney Transplant Recipients: A National Prospective Study
Authors: Tsarpali Vasiliki , Midtvedt Karsten , Lønning Kjersti , Bernklev Tomm , Åsberg Anders , Fawad Haris , von der Lippe Nanna , Reisæter Anna Varberg , Røysland Kjetil , Heldal Kristian 
Published: March 2022

Background.
Kidney transplantation (KT) is considered the best treatment for end-stage kidney disease (ESKD). In the increasing elderly ESKD population, KT should be reserved for carefully selected candidates who are expected to experience favorable outcomes. We aimed to prospectively evaluate pretransplant recipient factors that may predict patient survival and can eventually guide therapeutic decisions in elderly with ESKD.

Methods.
Recipient factors were evaluated in KT candidates aged ≥65 y. Comorbidity was assessed at waitlisting according to the Liu comorbidity index (LCI). Health-related quality of life outcomes were measured using the Kidney Disease Quality of Life Short Form, version 1.3. The Cox proportional hazard regression was used to evaluate predictors of patient survival.

Results.
We included 192 recipients, with a mean age of 72.1 (4.1) y, who were transplanted with kidneys from deceased brain-dead donors. During a median observation period of 4.6 (3.2–6.3) y, 66 recipients died. Elevated LCI consistently predicted poor patient survival. In recipients with LCI ≥4, dialysis >2 y comprised a 2.5-fold increase in mortality risk compared with recipients on dialysis ≤2 y. Self-reported pretransplant physical function was also proven to be a significant positive predictor of survival.

Conclusion.
The implementation of LCI and a physical function score during the evaluation of older kidney transplant candidates may improve the selection and thereby optimize posttransplant outcomes.