bluuebunny/crossref_metadata_2025_split huggingface dataset:
New insights into the microbiome in kidney transplantation
Authors: Kim Joshua S. , Sze Christina , Barbar Tarek , Lee John R. 
Published: September 2021

Purpose of review
Research in the past decade has revealed important implications for the microbiome in human health. Studies have defined a distinct gut microbiota in kidney transplant recipients and have recently linked the microbiota to infectious complications, similar to the allogeneic stem cell transplant population.

Recent findings
In this review, we focus on the metabolism of immunosuppressive medications by the gut microbiota and on the urinary microbiome in the setting of infectious and immunological complications. We highlight seminal studies showing the role of specific gut microbiota in the direct metabolism of tacrolimus into a lesser effective immunosuppressant as well as the role of the gut microbiota in the metabolism of mycophenolic acid (MPA) glucuronide. We describe distinct urinary microbiota patterns in kidney transplant recipients with interstitial fibrosis tubular atrophy, chronic allograft nephropathy, tolerance, and bacterial and viral complications.

Summary
The microbiota has important implications for immunosuppressive medications and immunological outcomes in kidney transplant recipients. Further research is needed to better delineate the impact of the metabolism of tacrolimus and MPA by gut bacteria and the role of the urine microbiota in the development of immunological and infectious complications.
The Spice of Death
Authors: Steele Ryan W. , Moran Jeffery H. , Patton Amy L. , Kokes Charles P. , James Laura P. , Storm Elizabeth A. , Schexnayder Stephen M. 
Published: September 2021

Abstract
Novel psychoactive substances (NPSs), commonly referred to as “K2” or “spice,” are a relatively new toxicology challenge for pediatricians. Adolescents often incorrectly believe that these drugs are safe and can be used without major adverse effects. Although recent legislation attempts to ensure that these drugs are not commercially available, many are able to be purchased online as “not fit for human consumption” or under various misnomers such “incense.” In addition, there is a wide chemical variation among these substances, making regulation challenging. Standard urine drug screens test for tetrahydrocannabinol, which may not cross-react with synthetic substances, making NPS poisonings difficult to diagnose. We report a case of fatal cardiac arrest in a 16-year-old adolescent boy temporally associated with use of the NPS, 5F-ADB. The case illustrates the dangerous consequences that these unregulated substances pose to users, as well as the need for the consideration of comprehensive toxicological testing in patients with a history of substance use and sudden cardiac arrest, despite a negative drug screen.
Laparoscopic Versus Open Simultaneous Resection of Primary Colorectal Cancer and Associated Liver Metastases: A Comparative Retrospective Study
Authors: Sawaied Muneer , Berger Yael , Mahamid Ahmad , Abu-Zaydeh Omar , Verter Eden , Khoury Wissam , Goldberg Natalia , Sadot Eran , Haddad Riad 
Published: September 2021

Purpose:
The aim was to compare the short-term and long-term outcomes of patients with metastatic colorectal cancer (CRC) undergoing laparoscopic versus open colorectal resection with simultaneous resection for liver metastases. Currently there is a lack of studies that have investigated the oncosurgical aspects and the short and long-term outcomes from these procedures.

Materials and Methods:
A retrospective study of patients who underwent simultaneous resections for CRC and synchronous liver metastases between 2008 and 2019 in 2 university affiliated medical centers.

Results:
Sixty-three patients were identified of whom 21 had successful laparoscopic simultaneous resections. In 43% of patients, the primary tumor was located in the right colon. The 3-year overall survival and disease-free survival rates were 87% and 48%, respectively. When compared with a separate control group of 42 patients who underwent conventional open resections, the laparoscopic approach was associated with an increased operative time (286 vs. 225 min, P=0.05), but a shorter hospital stay (6 vs. 8 d, P=0.008).

Conclusions:
Simultaneous laparoscopic colorectal and parenchymal sparing liver resection for metastatic CRC is safe, feasible, and it is a preferable approach because of better short-term outcome compared with open surgery while not compromising survival and disease recurrence.
Improving Patient Recall of Planned Intervention After Surgical Counseling: The IRIS Randomized Controlled Trial
Authors: Chernyak Sofiya , Caraballo Ricardo , Chiu Stephanie , Salamon Charbel 
Published: September 2021

Objective
The aim of the study was to determine whether an easy-to-read patient education card given at the preoperative visit can increase patient recall of the planned surgery.

Methods
This was a randomized controlled trial. Patients scheduled to undergo pelvic reconstructive surgery were recruited during their preoperative visits. All participants received standard surgical counseling, whereas the intervention group also received a 4 × 6 inch card highlighting the anticipated procedure. The primary outcome was correct recall of the planned surgery as measured by a preoperative questionnaire. Secondary outcomes were correct recall of the surgery postoperatively and patient satisfaction with the information provided.

Results
One hundred twenty-eight patients were enrolled with 64 participants in each arm. One hundred twenty-seven participants were analyzed because 1 patient was lost to follow-up. No difference was found between patient demographics, including types of surgical procedures performed. There was a statistically significant improvement in preoperative recall: 30 of 63 participants (47.6%) in the intervention group answered all questions correctly versus 18 of 64 patients (28.6%) patients in the standard counseling group (P = 0.021). There was no difference in the postoperative scores between the 2 groups: 48.3% (28 of 58) and 52.5% (32 of 61) of the participants answered all questions correctly in the intervention and standard counseling only groups, respectively (P = 0.648). There was no difference in satisfaction scores, with a median score of 20 out of 20 for either group (interquartile range = 19–20).

Conclusions
A concise and easy-to-use education card enhanced patient preoperative recall of the proposed surgery. This difference was not sustained postoperatively. High satisfaction with the information provided was reported regardless of counseling method.
Thrombomodulin-mediated Inhibition of Neutrophil Extracellular Trap Formation Alleviates Hepatic Ischemia-reperfusion Injury by Blocking TLR4 in Rats Subjected to Liver Transplantation
Authors: Liu Yanyao , Lei Zilun , Chai Hao , Xiang Song , Wang Yihua , Yan Ping , Cao Zhenrui , Pu Xingyu , Wu Zhongjun 
Published: September 2021

Background.
Hepatic ischemia-reperfusion injury (IRI) is an unavoidable outcome of liver transplantation, during which neutrophil extracellular traps (NETs) may play a critical role in the IRI-induced immune response to inflammation. The purpose of this study was to identify the function of recombinant human thrombomodulin (rTM) in the remission of hepatic IRI after liver transplantation and elucidate the specific mechanism.

Methods.
NET formation (NETosis) was detected in the serum of liver transplantation patients and rats following liver transplantation. Hematoxylin–eosin staining, terminal deoxynucleotidyl transferase 2´-deoxyuridine, 5´-triphosphate nick-end labeling staining, immunohistochemistry, and immunofluorescence were used to assess the effect of rTM on NETosis in vitro and in vivo.

Results.
We found that rTM markedly inhibited neutrophil formation in NETs, reduced apoptosis in hepatocytes, alleviated rat hepatic IRI, and improved liver function. In vitro, rTM inhibited neutrophil formation in NETs, and lipopolysaccharide (a Toll-like receptor 4 agonist) reversed the inhibitory effect of rTM on NETosisN. rTM blocked a Toll-like receptor 4 and the downstream extracellular signal-regulated kinase/c-Jun NH2 terminal kinase and nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species/peptidylarginine deiminase 4 signaling pathways to protect against hepatic IRI and inhibit NETosis. In addition, we demonstrated that combined treatment with rTM and an NADPH oxidative inhibitor had a better effect than either treatment alone.

Conclusions.
NETs are a potential therapeutic target in hepatic IRI, and rTM could be used to prevent IR-induced hepatic injury. In addition, cotargeting NETosis-related signaling pathways might be a novel therapeutic strategy for hepatic IRI treatment.
Geographic and Phylodynamic Distribution of SARS-CoV-2 from Environmental Origin
Authors: Oladipo Elijah Kolawole , Dairo Emmanuel Oluwatobi , Ayeni Ayodele Eugene , Irewolede Boluwatife Ayobami , Oyewole Moyosoluwa Precious , Adetunji Charles Oluwaseun , Oloke Julius Kola 
Published: September 2021

AbstractThe coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally. Understanding the transmission dynamics of SARS-CoV-2 contamination in the environment is essential for infection control policies. This study aims to provide a phylodynamic analysis and distribution pattern of SARS-CoV-2 from the environment in terms of Source, clades, lineages, and their location. Ninety (90) retrieved whole-genome sequences of environmental sources from GISAID were investigated to determine the evolutionary process of SARS-CoV-2 and mutation in the isolated nucleotide sequences. The analysis was carried out using R, MAFFT, and MEGA X software. Out of the five countries studied, Austria has the highest distribution with sixty-five samples (72.2%), and the highest isolates of 68 (75.6%) were from raw sewage. The highest clade in circulation as obtained from the study is G with lineages B. The phylogeny of SARS-CoV-2 whole-genome sequences from Austria, the United States, China, Brazil, and Liechtenstein indicated that the SARS-CoV-2 viruses were all clustered together, irrespective of sequence geographic location. The study concluded by demonstrating a clear interconnection between the phylogeny of SARS-CoV-2 isolates from various geographic locations, all of which were locked in the same cluster regardless of their environment specimen. Thus, depicting the possibility of their origination from a common ancestor.HighlightEnvironmental sources of specimen isolated from raw sewage have the highest occurring specimen sequence, while those from breathing air, door handle, and wastewater have the lowest sequence.Environmental surveillance of SARS-CoV-2 is of great importance to control the spread of the virus. Untreated raw sewage should be of more priority for the environmental surveillance of the virus.Eighteen (18) nucleotide sequences from this study’s multiple sequence alignment shared a 90% similarity with the Wuhan-Hu-1 reference genome, indicating a common evolutionary origin.
Disparate Impacts on Online Information Access during the COVID-19 Pandemic
Authors: Suh Jina , Horvitz Eric , White Ryen W. , Althoff Tim 
Published: September 2021

The COVID-19 pandemic has stimulated a staggering increase in online information access (1, 2), but the extent to which different communities of internet users enlist digital resources to meet everyday needs varies (2-4). We analyze 55 billion everyday web search interactions across 25,150 US ZIP codes and demonstrate that there were disparate impacts of the pandemic on online information access across several information domains, including health and pandemic-relevant online resources (e.g., online learning, online food delivery). Among many findings, we show that ZIP codes associated with higher proportions of Black residents intensified their access to unemployment resources, and ZIP codes associated with lower income reduced their access to health information resources relative to their counterpart ZIP codes. Because these disparate impacts on the access to online information may result in downstream offline gaps in health, education, employment, and well-being (3), public health interventions should target potential barriers to accessing the necessary digital resources and provide adequate support to meet the intensified digital resource needs.One Sentence SummaryLarge-scale web search logs reveal disparate impacts on online health, education, unemployment, and food information access.
Stabilization of spine Synaptopodin by mGluR1 is required for mGluR-LTD
Authors: Speranza Luisa , Inglebert Yanis , De Sanctis Claudia , Wu Pei You , Kalinowska Magdalena , McKinney R. Anne , Francesconi Anna 
Published: September 2021

AbstractDendritic spines, actin-rich protrusions forming the postsynaptic sites of excitatory synapses, undergo activity-dependent molecular and structural remodeling. Activation of group 1 metabotropic glutamate receptors - mGluR1 and mGluR5 - by synaptic or pharmacological stimulation, induces LTD but whether this is accompanied with spine elimination remains unresolved. A subset of telencephalic mushroom spines contains the spine apparatus (SA), an enigmatic organelle composed of stacks of smooth endoplasmic reticulum, whose formation depends on the expression of the actin-bundling protein Synaptopodin. Allocation of Synaptopodin to spines appears governed by cell-intrinsic mechanisms as the relative frequency of spines harboring Synaptopodin is conserved in vivo and in vitro. Here we show that expression of Synaptopodin/SA in spines is required for induction of mGluR-LTD at Schaffer collateral-CA1 synapses. Post-mGluR-LTD, mushroom spines lacking Synaptopodin/SA are selectively lost whereas spines harboring it are preserved, a process dependent on activation of mGluR1 but not mGluR5. Mechanistically, we find that mGluR1 supports physical retention of Synaptopodin within excitatory spine synapses during LTD while triggering lysosome-dependent degradation of the protein residing in dendritic shafts. Together, these results reveal a cellular mechanism, dependent on mGluR1, which enables selective preservation of stronger spines containing Synaptopodin/SA while eliminating weaker ones and potentially countering spurious strengthening by de novo recruitment of Synaptopodin. Overall our results identify spines with Synaptopodin/SA as the locus of mGluR-LTD and underscore the importance of the molecular microanatomy of spines in synaptic plasticity.
ICOS costimulation is indispensable for the differentiation of T follicular regulatory cells
Authors: Panneton Vincent , Mindt Barbara C. , Bouklouch Yasser , Bouchard Antoine , Mohammaei Saba , Chang Jinsam , Witalis Mariko , Li Joanna , Stancescu Albert , Bradley John E. , Randall Troy D. , Fritz Jörg H. , Suh Woong-Kyung 
Published: September 2021

ABSTRACTICOS is a T cell costimulatory receptor critical for Tfh cell generation and function. However, the role of ICOS in Tfr cell differentiation remains unclear. Using Foxp3-Cre-mediated ICOS knockout (ICOS FC) mice, we show that ICOS deficiency in Treg-lineage cells drastically reduces the number of Tfr cells during GC reactions but has a minimal impact on conventional Treg cells. Single-cell transcriptome analysis of Foxp3+ cells at an early stage of the GC reaction suggests that ICOS normally inhibits Klf2 expression to promote follicular features including Bcl6 upregulation. Further, ICOS costimulation promotes nuclear localization of NFAT2, a known driver of CXCR5 expression. Notably, ICOS FC mice had an unaltered overall GC B cell output but showed signs of expanded autoreactive B cells along with elevated autoantibody titers. Thus, our study demonstrates that ICOS costimulation is critical for Tfr cell differentiation and highlights the importance of Tfr cells in maintaining humoral immune tolerance during GC reactions.
Updating The Accuracy of Administrative Claims for Identifying Left Ventricular Ejection Fraction Among Patients with Heart Failure
Authors: Sandhu Alexander T , Zheng Jimmy , Heidenreich Paul A 
Published: September 2021

ABSTRACTIntroductionLeft ventricular ejection fraction (EF) is an important factor for treatment decisions for heart failure. The EF is unavailable in administrative claims. We sought to evaluate the predictive accuracy of claims diagnoses for classifying heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF) with International Classification of Disease-Tenth Revision codes.MethodsWe identified HF diagnoses for VA patients between 2017-2019 and extracted the EF from clinical notes and imaging reports using a VA natural language processing algorithm. We classified sets of codes as HFrEF-related, HFpEF-related, or non-specific based on the closest EF within 180 days. We selected a random heart failure diagnosis for each patient and tested the predictive accuracy of various algorithms for identifying HFrEF using the last 1 year of heart failure diagnoses. We performed sensitivity analyses on the EF thresholds, the cohort, and the diagnoses used.ResultsBetween 2017-2019, we identified 358,172 patients and 1,671,084 diagnoses with an EF recording within 180 days. After dividing diagnoses into HFrEF-related, HFpEF-related, or non-specific, we found using the proportion of specific diagnoses classified as HFrEF-related had an AUC of 0.76 for predicting EF≤40% and 0.80 for predicting EF<50%. However, 23.3% of patients could not be classified due to only having non-specific codes. Predictive accuracy increased among patients with ≥4 HF diagnoses over the preceding year.DiscussionIn a VA cohort, administrative claims with ICD-10 codes had moderate accuracy for identifying reduced ejection fraction. This level of specificity is likely inadequate for performance measures. Administrative claims need to better align terminology with relevant clinical definitions.
The secretome of M1 and M2 microglia differently regulate proliferation, differentiation and survival of adult neural stem/progenitor cell
Authors: Jiang Xue , Yi Saini , Liu Qin , Zhang Jinqiang 
Published: September 2021

AbstractMicroglia has been reported to be able to regulate the proliferation, differentiation and survival of adult Neural stem/progenitor cells (NSPCs) by modulating the microenvironment, which results in different consequences of adult neurogenesis. However, whether the microglial activation is beneficial or harmful to NSPCs is still controversial because of the complexity and variability of microglial activation phenotypes. In this study, we detected the expression levels of M1 marker and M2 marker in IFN-γ- and IL-4-induced microglia at different time, respectively. The phenotypic markers of M1 and M2 microglia were stable for 24 h after removal of IFN-γ and IL-4 intervention, but exhibited different change patterns during the next 24 h. Then, the adult NSPCs were treated by the conditioned medium from IFN-γ- and IL-4-activated microglia. The conditioned medium from IFN-γ-activated microglia promoted apoptosis and astroglial differentiation of NSPCs, while suppressed proliferation and neuronal differentiation of NSPCs. However, the conditioned medium from IL-4-activated microglia exhibited opposite effects on these physiological processes. In addition, the direct treatment of IFN-γ or IL-4 alone did not significantly affect the proliferation, differentiation and survival of NSPCs. These results suggest that the secretome of pro-inflammatory (M1) and anti-inflammatory (M2) microglia differently regulated the proliferation, differentiation and survival of adult NSPCs. These findings will help further study the biological mechanism of microglia regulating neurogenesis, and provide a therapeutic strategy for neurological diseases by regulating microglial phenotypes to affect neurogenesis.
Nurr1 modulation mediates neuroprotective effects of statins
Authors: Willems Sabine , Kilu Whitney , Faudone Giuseppe , Heering Jan , Merk Daniel 
Published: September 2021

AbstractThe ligand-sensing transcription factor Nurr1 emerges as a promising therapeutic target for neurodegenerative pathologies but Nurr1 ligands for functional studies and therapeutic validation are lacking. Here we report pronounced Nurr1 modulation by statins for which clinically relevant neuroprotective effects have been demonstrated. Several statins directly affected Nurr1 activity in cellular and cell-free settings with low micromolar to sub-micromolar potencies. Simvastatin exhibited anti-inflammatory effects in astrocytes which were abrogated by Nurr1 knockdown. Differential gene expression analysis in native and Nurr1 silenced cells revealed strong proinflammatory effects of Nurr1 knockdown while simvastatin treatment induced several neuroprotective mechanisms via Nurr1, for example, in energy utilization and reduced apoptosis. These findings suggest Nurr1 involvement in the well-documented but mechanistically elusive neuroprotection by statins.
EXPLICIT-Kinase: a gene expression predictor for dissecting the functions of the Arabidopsis kinome
Authors: Peng Yuming , Zuo Wanzhu , Qin Yue , Ma Shisong 
Published: September 2021

ABSTRACTProtein kinases regulate virtually all cellular processes, but it remains challenging to determine the functions of all protein kinases, collectively called the kinome, in any species. We developed an approach called EXPLICIT-Kinase to predict the functions of the Arabidopsis kinome. Because the activities of many kinases can be regulated transcriptionally, their gene expression patterns provide clues to their functions. A universal gene expression predictor for Arabidopsis was constructed to predict the expression of 30,172 non-kinase genes based on the expression of 994 protein kinase genes. The model reconstituted highly accurate transcriptomes for diverse Arabidopsis samples. It identified the significant kinases as predictor kinases for predicting the expression of Arabidopsis genes and pathways. Strikingly, these predictor kinases were often known regulators of the related pathways, as exemplified by those involved in cytokinesis, tissue development, and stress responses. Comparative analyses have revealed that portions of these predictor kinases, including the novel ones, are shared and conserved between Arabidopsis and maize. The conservation between species provide additional evidence to support the novel predictor kinases as bona fide regulators of the pathways involved. Thus our approach enables the systematic dissection of the functions of the Arabidopsis kinome.