bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-intensity ultrasound restores long-term potentiation and memory in senescent mice through pleiotropic mechanisms including NMDAR signaling
Authors: Blackmore Daniel G. , Turpin Fabrice , Palliyaguru Tishila , Evans Harrison T. , Chicoteau Antony , Lee Wendy , Pelekanos Matthew , Nguyen Nghia , Song Jae , Sullivan Robert K. P. , Sah Pankaj , Bartlett Perry F. , Götz Jürgen 
Published: May 2021

AbstractAdvanced physiological aging is associated with impaired cognitive performance and the inability to induce long-term potentiation (LTP), an electrophysiological correlate of memory. Here, we demonstrate in the physiologically aged, senescent mouse brain that scanning ultrasound combined with microbubbles (SUS+MB), by transiently opening the blood–brain barrier, fully restores LTP induction in the dentate gyrus of the hippocampus. Intriguingly, SUS treatment without microbubbles (SUSonly), i.e., without the uptake of blood-borne factors, proved even more effective, not only restoring LTP, but also ameliorating the spatial learning deficits of the aged mice. This functional improvement is accompanied by an altered milieu of the aged hippocampus, including a lower density of perineuronal nets, increased neurogenesis, and synaptic signaling, which collectively results in improved spatial learning. We therefore conclude that therapeutic ultrasound is a non-invasive, pleiotropic modality that may enhance cognition in elderly humans.
Whole-exome sequencing in eccrine porocarcinoma indicates promising therapeutic strategies
Authors: Denisova Evgeniya , Westphal Dana , Surowy Harald M. , Meier Friedegund , Hutter Barbara , Reifenberger Julia , Rütten Arno , Schulz Alexander , Sergon Mildred , Ziemer Mirjana , Brors Benedikt , Betz Regina C. , Redler Silke 
Published: May 2021

AbstractMalignant sweat gland tumours are rare, with the most common form being Eccrine porocarcinoma (EP). To investigate the mutational landscape of EP, we performed whole-exome sequencing (WES) on 14 formalin-fixed paraffin-embedded samples of matched primary EP and healthy surrounding tissue. Mutational profiling revealed a high overall median mutation rate. This was attributed to signatures of mutational processes related to ultraviolet (UV) exposure, APOBEC enzyme dysregulation, and defective homologous double-strand break repair. All of these processes cause genomic instability and are implicated in carcinogenesis. Recurrent driving somatic alterations were detected in the EP candidate drivers TP53, FAT2, CACNA1S, and KMT2D. The analyses also identified copy number alterations and recurrent gains and losses in several chromosomal regions including that containing BRCA2, as well as deleterious alterations in multiple HRR components. In accordance with this reduced or even a complete loss of BRCA2 protein expression was detected in 50% of the investigated EP tumours. Our results implicate crucial oncogenic driver pathways and suggest that defective homologous double-strand break repair and the p53 pathway are involved in EP aetiology. Targeting of the p53 axis and PARP inhibition, and/or immunotherapy may represent promising treatment strategies.
Retinoic acid signaling is critical during the totipotency window in early mammalian development
Authors: Iturbide Ane , Ruiz Tejada Segura Mayra L. , Noll Camille , Schorpp Kenji , Rothenaigner Ina , Ruiz-Morales Elias R. , Lubatti Gabriele , Agami Ahmed , Hadian Kamyar , Scialdone Antonio , Torres-Padilla Maria-Elena 
Published: May 2021

AbstractTotipotent cells hold enormous potential for regenerative medicine. Thus, the development of cellular models recapitulating totipotent-like features is of paramount importance. Cells resembling the totipotent cells of early embryos arise spontaneously in mouse embryonic stem (ES) cell cultures. Such ‘2-cell-like-cells’ (2CLCs) recapitulate 2-cell-stage features and display expanded cell potential. Here, we used 2CLCs to perform a small-molecule screen to identify new pathways regulating the 2-cell-stage program. We identified retinoids as robust inducers of 2CLCs and the retinoic acid (RA)-signaling pathway as a key component of the regulatory circuitry of totipotent cells in embryos. Using single-cell RNA-seq, we reveal the transcriptional dynamics of 2CLC reprogramming and show that ES cells undergo distinct cellular trajectories in response to RA. Importantly, endogenous RA activity in early embryos is essential for zygotic genome activation and developmental progression. Overall, our data shed light on the gene regulatory networks controlling cellular plasticity and the totipotency program.
Passive sampling and benchmarking to rank HOC levels in the aquatic environment
Authors: Allan Ian John , Vrana Branislav , de Weert Jasperien , Kringstad Alfhild , Ruus Anders , Christensen Guttorm , Terentjev Petr , Green Norman Whitaker 
Published: May 2021

AbstractThe identification and prioritisation of water bodies presenting elevated levels of anthropogenic chemicals is a key aspect of environmental monitoring programmes. Albeit this is challenging owing to geographical scales, choice of indicator aquatic species used for chemical monitoring, and inherent need for an understanding of contaminant fate and distribution in the environment. Here, we propose an innovative methodology for identifying and ranking water bodies according to their levels of hydrophobic organic contaminants (HOCs) in water. This is based on a unique passive sampling dataset acquired over a 10-year period with silicone rubber exposures in surface water bodies across Europe. We show with these data that, far from point sources of contamination, levels of hexachlorobenzene (HCB) and pentachlorobenzene (PeCB) in water approach equilibrium with atmospheric concentrations near the air/water surface. This results in a relatively constant ratio of their concentrations in the water phase. This, in turn, allows us to (i) identify sites of contamination with either of the two chemicals when the HCB/PeCB ratio deviates from theory and (ii) define benchmark levels of other HOCs in surface water against those of HCB and/or PeCB. For two polychlorinated biphenyls (congener 28 and 52) used as model chemicals, differences in contamination levels between the more contaminated and pristine sites are wider than differences in HCB and PeCB concentrations endorsing the benchmarking procedure.
Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes
Authors: Baratchian Mehdi , McManus Jeffrey M. , Berk Mike P. , Nakamura Fumihiko , Mukhopadhyay Sanjay , Xu Weiling , Erzurum Serpil , Drazba Judy , Peterson John , Klein Eric A. , Gaston Benjamin , Sharifi Nima 
Published: May 2021

AbstractThe sex discordance in COVID-19 outcomes has been widely recognized, with males generally faring worse than females and a potential link to sex steroids. A plausible mechanism is androgen-induced expression of TMPRSS2 and/or ACE2 in pulmonary tissues that may increase susceptibility or severity in males. This hypothesis is the subject of several clinical trials of anti-androgen therapies around the world. Here, we investigated the sex-associated TMPRSS2 and ACE2 expression in human and mouse lungs and interrogated the possibility of pharmacologic modification of their expression with anti-androgens. We found no evidence for increased TMPRSS2 expression in the lungs of males compared to females in humans or mice. Furthermore, in male mice, treatment with the androgen receptor antagonist enzalutamide did not decrease pulmonary TMPRSS2. On the other hand, ACE2 and AR expression was sexually dimorphic and higher in males than females. ACE2 was moderately suppressible with enzalutamide administration. Our work suggests that sex differences in COVID-19 outcomes attributable to viral entry are independent of TMPRSS2. Modest changes in ACE2 could account for some of the sex discordance.
Identification of mucin degraders of the human gut microbiota
Authors: Raimondi Stefano , Musmeci Eliana , Candeliere Francesco , Amaretti Alberto , Rossi Maddalena 
Published: May 2021

AbstractMucins are large glycoproteins consisting of approximately 80% of hetero-oligosaccharides. Gut mucin degraders of healthy subjects were investigated, through a culture dependent and independent approach. The faeces of five healthy adults were subjected to three steps of anaerobic enrichment in a medium with sole mucins as carbon and nitrogen sources. The bacterial community was compared before and after the enrichment by 16S rRNA gene profiling. Bacteria capable of fermenting sugars, such as Anaerotruncus, Holdemania, and Enterococcaceae likely took advantage of the carbohydrate chains. Escherichia coli and Enterobacteriaceae, Peptococcales, the Coriobacteriale Eggerthella, and a variety of Clostridia such as Oscillospiraceae, Anaerotruncus, and Lachnoclostridium, significantly increased and likely participated to the degradation of the protein backbone of mucin. The affinity of E. coli and Enterobacteriaceae for mucin may facilitate the access to the gut mucosa, promoting gut barrier damage and triggering systemic inflammatory responses. Only three species of strict anaerobes able to grow on mucin were isolated from the enrichments of five different microbiota: Clostridium disporicum, Clostridium tertium, and Paraclostridium benzoelyticum. The limited number of species isolated confirms that in the gut the degradation of these glycoproteins results from cooperation and cross-feeding among several species exhibiting different metabolic capabilities.
A plant endophyte Staphylococcus hominis strain MBL_AB63 produces a novel lantibiotic, homicorcin and a position one variant
Authors: Aftab Uddin M. , Akter Shammi , Ferdous Mahbuba , Haidar Badrul , Amin Al , Shofiul Islam Molla A. H. M. , Khan Haseena , Islam Mohammad Riazul 
Published: May 2021

AbstractHere we report a jute endophyte Staphylococcus hominis strain MBL_AB63 isolated from jute seeds which showed promising antimicrobial activity against Staphylococcus aureus SG511 when screening for antimicrobial substances. The whole genome sequence of this strain, annotated using BAGEL4 and antiSMASH 5.0 to predict the gene clusters for antimicrobial substances identified a novel antimicrobial peptide cluster that belongs to the class I lantibiotic group. The predicted lantibiotic (homicorcin) was found to be 82% similar to a reported peptide epicidin 280 having a difference of seven amino acids at several positions of the core peptide. Two distinct peaks obtained at close retention times from a RP-HPLC purified fraction have comparable antimicrobial activities and LC–MS revealed the molecular mass of these peaks to be 3046.5 and 3043.2 Da. The presence of an oxidoreductase (homO) similar to that of epicidin 280- associated eciO or epilancin 15X- associated elxO in the homicorcin gene cluster is predicted to be responsible for the reduction of the first dehydrated residue dehydroalanine (Dha) to 2-hydroxypropionate that causes an increase of 3 Da mass of homicorcin 1. Trypsin digestion of the core peptide and its variant followed by ESI–MS analysis suggests the presence of three ring structures, one in the N-terminal and other two interlocking rings at the C-terminal region that remain undigested. Homicorcin exerts bactericidal activity against susceptible cells by disrupting the integrity of the cytoplasmic membrane through pore formation as observed under FE-SEM.
LncRNA AWPPH as a prognostic predictor in human cancers in Chinese population: evidence from meta-analysis
Authors: Li Yongfeng , Rui Xinmiao , Chen Daobao , Xuan Haojun , Yang Hongjian , Meng Xuli 
Published: May 2021

Abstract
Background: Long non-coding RNA associated with poor prognosis of hepatocellular carcinoma (AWPPH) is dysregulated in a variety of human cancers. However, the prognostic value of AWPPH in various cancers remains unclear.
Methods: Comprehensive literature search was performed in PubMed, Web of Science, CNKI and Wangfang databases, and eligible studies were obtained according to the inclusion and exclusion criteria. The pooled hazard ratios (HRs) and odds ratios (ORs) were applied to assess the clinical value of AWPPH expression for overall survival (OS) and clinicopathological features.
Results: A total of 19 articles including 1699 cancer patients were included in the study. The pooled results demonstrated that evaluated AWPPH expression was positively related to a poorer overall survival of patients with cancers (HR = 1.79, 95%CI: 1.44–2.14, P&lt;0.001). Subgroup analysis revealed that tumor type and sample size affect the predictive value of AWPPH on OS, whereas cut-off value and HR estimation method have no impact on it. In addition, the pooled data also showed that AWPPH was positively linked to advanced TNM stage (OR = 2.50, 95%CI: 1.94–3.22, P&lt;0.001), bigger tumor size (OR = 2.64, 95%CI: 1.47–4.73, P=0.001), macro-vascular invasion (OR = 2.08, 95%CI: 1.04–4.16, P=0.04) and lymph node metastasis (OR = 2.68, 95%CI: 1.82–3.96, P&lt;0.001). Moreover, the results of the trim and fill analysis confirmed the reliability of our finding.
Conclusions: Up-regulation of AWPPH was associated with advanced TNM stage, bigger tumor size, worse lymph node metastasis, macro-vascular invasion and shorter overall survival, suggesting that AWPPH may serve as a biomarker for prognosis and clinicopathological characteristics in human cancers among the Chinese population.
Implementation and results of a gastrointestinal cancer screening program in an Amazon rainforest village: A descriptive study
Authors: Averbach Pedro , Ferrari Angelo Paulo , Toscano Cristiana M , Borges José Luiz , Averbach Marcelo 
Published: May 2021

Abstract
Background and study aims Gastrointestinal cancer is an important cause of death worldwide. Remote populations are especially vulnerable to these conditions due to reduced access to screening and adequate treatment. In this context, the Belterra project was designed as a pilot taskforce to deliver gastrointestinal screening to an underserved Amazonian population and to spread knowledge and practice to local health workers. This study aimed to describe the implementation and present the results of the Belterra Project.
Patients and methods The project took place between October 2014 and December 2017 in Belterra, Pará, Brazil. Public-private partnerships were obtained and were essential for funding. The project required complex logistic solutions to provide gastrointestinal screening to every inhabitant between 50 and 70 years of age, including medical equipment and personal transportation to a remote area. Subjects were asked about their medical history, and received a physical examination, endoscopic examinations, and stool tests.
Results Over the course of 19 expeditions, we screened 2,022 inhabitants of Belterra, aged 50 to 70 years. Five colorectal and six gastric adenocarcinomas were diagnosed, as were several lower-stage lesions. Overall, 26 % of the participants undergoing colonoscopy showed some type of colonic lesion.
Conclusions Notwithstanding the geographical, cultural, and financial barriers, this study suggests that the implementation of a gastrointestinal cancer screening program for remote Brazilian populations is feasible, reaching high adherence. Although logistics is very demanding, such campaigns may be a good strategy to provide mass gastrointestinal cancer screening for underserved populations.
Evaluation of post-ERCP pancreatitis after biliary stenting with self-expandable metal stents vs. plastic stents in benign and malignant obstructions
Authors: Martinez Nichol S. , Inamdar Sumant , Firoozan Sheila N. , Izard Stephanie , Lee Calvin , Benias Petros C. , Trindade Arvind J. , Sejpal Divyesh V. 
Published: May 2021

Abstract
Background and study aims There are conflicting data regarding the risk of post-ERCP pancreatitis (PEP) with self-expandable metallic stents (SEMS) compared to polyethylene stents (PS) in malignant biliary obstructions and limited data related to benign obstructions.
Patients and methods A retrospective cohort study was performed of 1136 patients who underwent ERCP for biliary obstruction and received SEMS or PS at a tertiary-care medical center between January 2011 and October 2016. We evaluated the association between stent type (SEMS vs PS) and PEP in malignant and benign biliary obstructions.
Results Among the 1136 patients included in our study, 399 had SEMS placed and 737 had PS placed. Patients with PS were more likely to have pancreatic duct cannulation, pancreatic duct stent placement, double guidewire technique, sphincterotomy and sphincteroplasty as compared to the SEMS group. On multivariate analysis, PEP rates were higher in the SEMS group (8.0 %) versus the PS group (4.8 %) (OR 2.27 [CI, 1.22, 4.24]) for all obstructions. For malignant obstructions, PEP rates were 7.8 % and 6.6 % for SEMS and plastic stents, respectively (OR 1.54 [CI, 0.72, 3.30]). For benign obstructions the PEP rate was higher in the SEMS group (8.8 %) compared to the PS group (4.2 %) (OR 3.67 [CI, 1.50, 8.97]). No significant differences between PEP severity were identified based on stent type when stratified based on benign and malignant.
Conclusions PEP rates were higher when SEMS were used for benign obstruction as compared to PS. For malignant obstruction, no difference was identified in PEP rates with use of SEMS vs PS.
Management of intra-abdominal hypertension during ECMO: Total water-assisted colonoscopy as a step-up minimally invasive treatment, and a literature review
Authors: Martucci Gennaro , Amata Michele , di Francesco Fabrizio , Traina Mario , Arcadipane Antonio , Lorusso Roberto , Granata Antonino 
Published: May 2021

Abstract
Background and study aims During extracorporeal membrane oxygenation (ECMO), intra-abdominal hypertension (IAH) can impair ECMO venous drainage, reducing its ability to provide an adequate oxygenated blood flow. When medical therapy is ineffective in managing IAH, guidelines recommend a decompressive laparotomy (DL), though the procedure is associated with several complications and poor outcomes.
Patients and methods This was a case series of IAH in patients affected with acute respiratory distress syndrome (ARDS) on veno-venous (V-V) ECMO, in whom we performed total water-assisted colonoscopy (t-WAC) to treat IAH.
Results In three patients who underwent t-WAC, we report a real-time intra-procedural reduction of IAH, normalization of ECMO blood flow, and a reduction of vasopressors and lactates. t-WAC was performed in the context of evident abdominal compartment syndrome with multiorgan failure, and in one case was performed because of IAH and ECMO impairment. One patient was discharged alive, while the other two died of multiorgan failure, although the cause of death was apparently not secondary to IAH.
Conclusions During ECMO, in select cases,T-WAC may represent a first-line non-invasive approach.
CYP2C19 genotype variability in patients with refractory gastroesophageal reflux after per-oral endoscopic myotomy (POEM)
Authors: Perbtani Yaseen B. , Westerveld Donevan R. , Yang Dennis J. , Draganov Peter V. 
Published: May 2021

Abstract
Background and study aims Symptomatic gastroesophageal reflux is a recognized potential adverse event following peroral endoscopic myotomy (POEM). Proton pump inhibitors (PPIs) are an effective first-line therapy; although their efficacy can be affected by genotype cytochrome P450 2C19 (CYP2C19) variability leading to enhanced clearance of PPIs. The aim of our study was to evaluate the incidence of CYP2C19 genotype variability in POEM patients with refractory gastroesophageal reflux symptoms.
Patients and methods This was a single-center, prospective, cohort study of consecutive POEM cases during a 7-year study period (2013–2020). Reflux symptoms were assessed with the validated gastroesophageal reflux disease questionnaire (GerdQ) and objective pH testing after POEM. CYP2C19 genotype testing was obtained in all patients with refractory gastroesophageal reflux disease (GERD) symptoms, defined as an abnormal pH study and GerdQ score ≥ 8 while on PPIs twice daily.
Results POEM was performed in 325 consecutive patients (48.3 % female; mean age 57 years) during the study period. Twenty patients (6.8 %) had PPI-refractory, post-POEM gastroesophageal reflux based on their GerdQ score (median 9, range 8–11) and abnormal pH studies. CYP2C19 genotype testing identified 55 % (11/20) of these patients as being rapid metabolizers. Out of these, 9 (82 %) had improvement in clinical GERD symptoms after changing to a PPI less affected by CYP2C19 pharmacogenetics.
Conclusions Post-POEM, PPI-refractory GERD is rare. As shown in this study, rapid metabolizers commonly respond by changing to a PPI less affected by CYP2C19 pharmacogenetics, thereby reducing the risk of long-term consequences from GERD and unnecessary anti-reflux surgery.
VACStent: Combining the benefits of endoscopic vacuum therapy and covered stents for upper gastrointestinal tract leakage
Authors: Lange Jonas , Dormann Arno , Bulian Dirk Rolf , Hügle Ulrich , Eisenberger Claus Ferdinand , Heiss Markus Maria 
Published: May 2021

Abstract
Background and study aims Endoscopic treatment has markedly improved the high morbidity and mortality in patients with upper gastrointestinal tract leakage. Most procedures employ either covered self-expanding metal stents (SEMS) or endoscopic vacuum therapy (EVT), both with good clinical success but also with concomitant significant shortcomings inherent in each technique. A newly developed device, the VACStent, combines the fully covered SEMS with a polyurethane sponge cylinder anchored on the outside. This allows endoluminal EVT while keeping the intestinal lumen patent. The benefit is prevention of stent migration because the suction force of the sponge-cylinder immobilizes the VACStent on the intestinal wall, while at the same time, the attached external vacuum pump suctions off any secretions and improves healing with negative-pressure wound treatment (NPWT).
Patients and methods In this pilot study, the first patients to receive the VACStent were assessed. Outcomes included the applicability and stability of the VACStent system together with the clinical course.
Results Three patients with different clinical courses were managed with the VACStent. The first patient suffered anastomotic leakage following subtotal esophagectomy and was successfully treated with two postoperative VACStents for 12 days. The second patient received a covered SEMS for 14 days for acute Boerhaave syndrome. Due to persistent leakage, management was converted to EVT. Seven days, later a VACStent was inserted to allow oral nutrition while the leak finally closed. In the third patient, a LINX Reflux Management System had to be removed for erosion, leaving the gastroesophageal junction (GEJ) with a full-thickness gap. After VACstent insertion, successful closure was achieved within 4 days.
Conclusions These clinical cases demonstrate the applicability and efficacy of the VACstent in management of esophageal and anastomotic leakage. With its vacuum sponge, the stent fosters wound healing while the covered SEMS keeps the passage patent for nutrition.