bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple sclerosis and the microbiota
Authors: Engelenburg Hendrik J , Lucassen Paul J , Sarafian Joshua T , Parker William , Laman Jon D 
Published: June 2022

AbstractMultiple sclerosis (MS), a neurological autoimmune disorder, has recently been linked to neuro-inflammatory influences from the gut. In this review, we address the idea that evolutionary mismatches could affect the pathogenesis of MS via the gut microbiota. The evolution of symbiosis as well as the recent introduction of evolutionary mismatches is considered, and evidence regarding the impact of diet on the MS-associated microbiota is evaluated. Distinctive microbial community compositions associated with the gut microbiota of MS patients are difficult to identify, and substantial study-to-study variation and even larger variations between individual profiles of MS patients are observed. Furthermore, although some dietary changes impact the progression of MS, MS-associated features of microbiota were found to be not necessarily associated with diet per se. In addition, immune function in MS patients potentially drives changes in microbial composition directly, in at least some individuals. Finally, assessment of evolutionary histories of animals with their gut symbionts suggests that the impact of evolutionary mismatch on the microbiota is less concerning than mismatches affecting helminths and protists. These observations suggest that the benefits of an anti-inflammatory diet for patients with MS may not be mediated by the microbiota per se. Furthermore, any alteration of the microbiota found in association with MS may be an effect rather than a cause. This conclusion is consistent with other studies indicating that a loss of complex eukaryotic symbionts, including helminths and protists, is a pivotal evolutionary mismatch that potentiates the increased prevalence of autoimmunity within a population.
Projected winter warming unlikely to affect germination success of balsam fir regeneration in Atlantic Canada
Authors: Vaughn William Robert , Taylor Anthony R 
Published: June 2022

AbstractClimate warming has the potential to influence forest composition and species recruitment over the course of the 21st century. Although many of these impacts are expected to occur during the growing season, important life history events, like seed dormancy release, may be affected during the winter. For seeds of balsam fir (Abies balsamea (L.) Mill.) to germinate, they require a lengthy cold stratification period to break seed dormancy, which may not be experienced under warmer winters. Moreover, within Atlantic Canada, balsam fir populations experience very different climates. Dissimilarities among the genetics of these balsam fir populations and adaptations to their local environments may engender variations in population response to winter warming. In this study, we selected three balsam fir seedlots each from four different seed origin zones within Atlantic Canada and subjected them to simulated winter warming in outdoor seed plots that were heated to ≈ 6°C above the ambient temperature from December to April. Contrary to our hypotheses, germination success of the heated balsam fir seeds did not significantly decrease relative to the controls, and there was no interaction between warming and seed origin zone. Seedlots of some seed origin zones exhibited variable responses to warming, suggesting that dormancy levels substantially differ among populations from similar climates. This diversity in phenotype expression within balsam fir populations may improve this species resilience under future climate change.
Pharmacokinetic modelling of caspofungin to develop an extended dosing regimen in paediatric patients
Authors: Gastine Silke , Hempel Georg , Neely Michael N , Walsh Thomas J , Groll Andreas H 
Published: June 2022

Abstract

Background
Echinocandins are commonly used in treatment and prophylaxis of invasive fungal diseases. Intravenous daily dosing for prophylaxis in the outpatient setting can however become a hurdle for adequate compliance in the paediatric population.

Objectives
Simulations were performed to assess extended twice-weekly dosing for antifungal prophylaxis using caspofungin.

Methods
A population pharmacokinetic model was developed based on previously published data from children aged 3 months to 17 years. Using the final model, Monte Carlo simulations were performed to assess the dose needed for adequate exposure in a twice-weekly setting. Mean weekly AUC0–24 h/MIC together with reported AUC0–24 h from previously reported paediatric trials were used to guide adequate exposure.

Results and Conclusions
A two-compartment model with linear elimination and allometric scaling using fixed exponents was found most adequate to describe the given paediatric populations. Simulations showed that a 200 mg/m2 twice-weekly regimen with maximal 200 mg total dose should result in exposures matching registered daily dosing as well as commonly used pharmacokinetic/pharmacodynamic targets.
The transcription factor SlWRKY37 positively regulates jasmonic acid- and dark-induced leaf senescence in tomato
Authors: Wang Zhirong , Gao Ming , Li Yafei , Zhang Jialong , Su Hui , Cao Meng , Liu Ziji , Zhang Xichun , Zhao Bing , Guo Yang-Dong , Zhang Na 
Published: June 2022

Abstract
Initiation and progression of leaf senescence are triggered by various environmental stressors and phytohormones. Jasmonic acid (JA) and darkness accelerate leaf senescence in plants. However, the mechanisms that integrate these two factors to initiate and regulate leaf senescence have not been identified. Here, we report a transcriptional regulatory module centred on a novel tomato WRKY transcription factor, SlWRKY37, responsible for both JA- and dark-induced leaf senescence. The expression of SlWRKY37, together with SlMYC2, encoding a master transcription factor in JA signalling, was significantly induced by both methyl jasmonate (MeJA) and dark treatments. SlMYC2 binds directly to the promoter of SlWRKY37 to activate its expression. Knock out of SlWRKY37 inhibited JA- and dark-induced leaf senescence. Transcriptome analysis and biochemical experiments revealed SlWRKY53 and SlSGR1 (S. lycopersicum senescence-inducible chloroplast stay-green protein 1) as direct transcriptional targets of SlWRKY37 to control leaf senescence. Moreover, SlWRKY37 interacted with a VQ motif-containing protein SlVQ7, and the interaction improved the stability of SlWRKY37 and the transcriptional activation of downstream target genes. Our results reveal the physiological and molecular functions of SlWRKY37 in leaf senescence, and offer a target gene to retard leaf yellowing by reducing sensitivity to external senescence signals, such as JA and darkness.
On the time evolution of the Md−M⋆ and Ṁ–M⋆ correlations for protoplanetary discs: the viscous time-scale increases with stellar mass
Authors: Somigliana Alice , Toci Claudia , Rosotti Giovanni , Lodato Giuseppe , Tazzari Marco , Manara Carlo F , Testi Leonardo , Lepri Federico 
Published: June 2022

ABSTRACT
Large surveys of star-forming regions have unveiled power-law correlations between the stellar mass and the disc parameters, such as the disc mass $M_{\mathrm{d}} \!-\! {M_{\star }}$ and the accretion rate $\dot{M} \!-\! {M_{\star }}$. The observed slopes appear to be increasing with time, but the reason behind the establishment of these correlations and their subsequent evolution is still uncertain. We conduct a theoretical analysis of the impact of viscous evolution on power-law initial conditions for a population of protoplanetary discs. We find that, for evolved populations, viscous evolution enforces the two correlations to have the same slope, λm = λacc, and that this limit is uniquely determined by the initial slopes λm, 0 and λacc, 0. We recover the increasing trend claimed from the observations when the difference in the initial values, δ0 = λm, 0−λacc, 0, is larger than 1/2; moreover, we find that this increasing trend is a consequence of a positive correlation between the viscous time-scale and the stellar mass. We also present the results of disc population synthesis numerical simulations, that allow us to introduce a spread and analyse the effect of sampling, which show a good agreement with our analytical predictions. Finally, we perform a preliminary comparison of our numerical results with observational data, which allows us to constrain the parameter space of the initial conditions to λm, 0 ∈ [1.2, 2.1], λacc, 0 ∈ [0.7, 1.5].
TWIST1 methylation by SETD6 selectively antagonizes LINC-PINT expression in glioma
Authors: Admoni-Elisha Lee , Elbaz Tzofit , Chopra Anand , Shapira Guy , Bedford Mark T , Fry Christopher J , Shomron Noam , Biggar Kyle , Feldman Michal , Levy Dan 
Published: June 2022

Abstract
Gliomas are one of the most common and lethal brain tumors among adults. One process that contributes to glioma progression and recurrence is the epithelial to mesenchymal transition (EMT). EMT is regulated by a set of defined transcription factors which tightly regulate this process, among them is the basic helix-loop-helix family member, TWIST1. Here we show that TWIST1 is methylated on lysine-33 at chromatin by SETD6, a methyltransferase with expression levels correlating with poor survival in glioma patients. RNA-seq analysis in U251 glioma cells suggested that both SETD6 and TWIST1 regulate cell adhesion and migration processes. We further show that TWIST1 methylation attenuates the expression of the long-non-coding RNA, LINC-PINT, thereby promoting EMT in glioma. Mechanistically, TWIST1 methylation represses the transcription of LINC-PINT by increasing the occupancy of EZH2 and the catalysis of the repressive H3K27me3 mark at the LINC-PINT locus. Under un-methylated conditions, TWIST1 dissociates from the LINC-PINT locus, allowing the expression of LINC-PINT which leads to increased cell adhesion and decreased cell migration. Together, our findings unravel a new mechanistic dimension for selective expression of LINC-PINT mediated by TWIST1 methylation.
LTBK-03. Targeted mass spectrometry of serial CSF and serum specimens from children with diffuse intrinsic pontine glioma treated with intracranial B7-H3 CAR T cells
Authors: Vitanza Nicholas , Wilson Ashley , Huang Wenjun , Whiteaker Jeffrey , Gust Juliane , Orentas Rimas , Gardner Rebecca , Park Julie , Jensen Michael , Paulovich Amanda 
Published: June 2022

Abstract
Considering the high expression of B7-H3 (CD276) on diffuse intrinsic pontine glioma (DIPG) and preliminary evidence that repeated locoregional delivery of CAR T cells to patients with CNS tumors was feasible and tolerable, we open the phase 1 trial BrainChild-03 (NCT04185038). Children with DIPG in Dose Regimen 1 received 40 intraventricular B7H3CAR doses, with the two patients enrolling post-progression surviving &gt;400 days from initial CAR T infusion. To evaluate for immune and tumor responses that may correlate with clinical and radiographic evaluations, we performed targeted proteomic analysis on serial CSF and serum biospecimens.
MRM-MS is a targeted mass spectrometry that provides sensitive measurement of proteins in cancer tissues and fluids. In 2 patients with longitudinal biospecimens, we identified 50 CSF and 59 serum proteins above level of detection. In general, there were fewer serum fluctuations compared to the CSF, supporting that intracranial delivery provides local immune activation. Sharp fluctuations of several immunoregulatory peptides were measured in the CSF at pre and post infusion timepoints, including BCL10, CXCL13, TIM-3, ICOSLG, and PD-L2. Notably, several analytes tracked consistently in the CSF of both patients, including markers of macrophage maturation and immune cell recruitment, including CD14, CD163, CD44, CSF-1, CXCL13 and VCAM-1. B7-H3 was detected in the CSF and serum of both patients. S005, who progressed on protocol therapy, had a sharp increase in B7-H3 in the CSF during Course 2, while S008, who had clinical improvement on protocol therapy, had consistently lower B7-H3 present. Notably, serum B7-H3 steadily declined in both patients over time, with the exception of a transient increase in S005 between Courses 4 and 5. Future work for all enrolled patients with DIPG will explore the correlation of these targeted proteomic measurements with clinical end points for potential use as markers of efficacy of therapy or adverse events.
Borrelia miyamotoi Meningoencephalitis in an Immunocompetent Patient
Authors: Gandhi Shiv , Narasimhan Sukanya , Workineh Aster , Mamula Mark , Yoon Jennifer , Krause Peter J , Farhadian Shelli F 
Published: June 2022

Abstract
Borrelia miyamotoi is an underdiagnosed cause of tick-borne illness in endemic regions and, in rare cases, causes neurological disease in immunocompetent patients. Here, we present a case of serologically confirmed Borrelia miyamotoi meningoencephalitis in an otherwise healthy patient who rapidly improved following initiation of antibiotic therapy.
Half-century trends in alpha and beta diversity of phytoplankton summer communities in the Helsinki Archipelago, the Baltic Sea
Authors: Olli Kalle , Nyman Emil , Tamminen Timo 
Published: June 2022

Abstract
We analyzed phytoplankton biodiversity trends in a 52 year (1967–2018) monitoring time-series from the archipelago of Helsinki, Gulf of Finland, the Baltic Sea. The community ordination revealed strong ordering of samples along the time axis (generalized additive model—gam fit: R2 = 0.9). Species richness increased in time and was the most influential alpha diversity descriptor related to the community structure (gam fit: R2 = 0.56–0.70). Changes in species richness accounted for 35–36% of the mean between-sample beta diversity. The remaining 64–65% was due to species turnover—the dominant component of the biodiversity trend. The temporal beta diversity trend reflected the eutrophication history of the geographically confined region, with a turning point in mid-1990s demarking the adaptation and recovery phases of the phytoplankton community. Trends in spatial beta diversity revealed homogenization of the communities in the outer archipelago zone, but not in the inner bays. The temporal decay of community similarity revealed high turnover rate, with 23.6 years halving time in the outer archipelago and 11.3 years in the inner bays, revealing the differences in eutrophication strength. The observed phytoplankton trends manifest the regional eutrophication history, and dispersal of new species to the unsaturated brackish species pool.
The transcription factor OsMYBc and an E3 ligase regulate expression of a K+ transporter during salt stress
Authors: Xiao Longyun , Shi Yiyuan , Wang Rong , Feng Yu , Wang Lesheng , Zhang Hongsheng , Shi Xingyu , Jing Guangqin , Deng Ping , Song Tengzhao , Jing Wen , Zhang Wenhua 
Published: June 2022

Abstract
Sodium (Na+) and potassium (K+) homeostasis is essential for plant survival in saline soils. A member of the High-Affinity K+ Transporter (HKT) family in rice (Oryza sativa), OsHKT1;1, is a vital regulator of Na+ exclusion from shoots and is bound by a MYB transcription factor (OsMYBc). Here, we generated transgenic rice lines in the oshkt1;1 mutant background for genetic complementation using genomic OsHKT1;1 containing a native (Com) or mutated (mCom) promoter that cannot be bound by OsMYBc. In contrast to wild-type (WT) or Com lines, the mCom lines were not able to recover the salt-sensitive phenotype of oshkt1;1. The OsMYBc-overexpressing plants were more tolerant to salt stress than WT plants. A yeast two-hybrid screen using the OsMYBc N-terminus as bait identified a rice MYBc stress-related RING finger protein (OsMSRFP). OsMSRFP is an active E3 ligase that ubiquitinated OsMYBc in vitro and mediated 26S proteasome-mediated degradation of OsMYBc under semi-in vitro and in vivo conditions. OsMSRFP attenuated OsMYBc-mediated OsHKT1;1 expression, and knockout of OsMSRFP led to rice salt tolerance. These findings uncover a regulatory mechanism of salt response that fine-tunes OsHKT1;1 transcription by ubiquitination of OsMYBc.
Switching charge states in quasi-2D molecular conductors
Authors: Huang Yulong , Mitchell Travis , Zheng Yixiong , Hu Yong , Benedict Jason B , Seo Jung-Hun , Ren Shenqiang 
Published: June 2022

Abstract
2D molecular entities build next-generation electronic devices, where abundant elements of organic molecules are attractive due to the modern synthetic and stimuli control through chemical, conformational, and electronic modifications in electronics. Despite its promising potential, the insufficient control over charge states and electronic stabilities must be overcome in molecular electronic devices. Here, we show the reversible switching of modulated charge states in an exfoliatable 2D-layered molecular conductor based on bis(ethylenedithio)tetrathiafulvalene molecular dimers. The multiple stimuli application of cooling rate, current, voltage, and laser irradiation in a concurrent manner facilitates the controllable manipulation of charge crystal, glass, liquid, and metal phases. The four orders of magnitude switching of electric resistance are triggered by stimuli-responsive charge distribution among molecular dimers. The tunable charge transport in 2D molecular conductors reveals the kinetic process of charge configurations under stimuli, promising to add electric functions in molecular circuitry.
Does latentToxoplasmainfection have a protective effect against developing multiple sclerosis? Evidence from an updated meta-analysis
Authors: Rostami Ali , Riahi Seyed Mohammad , Mollalo Abolfazl , Razavian Iman , Akbari Nahid , Marhoommirzabak Elika , Mahjour Sanaz , Sartip Behnam , Arshadi Mahdi , Razavian Elnaz , Ardekani Ali 
Published: June 2022

AbstractPrevious epidemiologic evidence suggests a protective effect of Toxoplasma gondii infection against multiple sclerosis (MS) development; however, inconsistent findings have been reported in this regard. Therefore, we performed an updated meta-analysis of observational studies to investigate the association of To. gondii infection with MS development. We searched all articles published in PubMed, Scopus, Embase and Web of Science databases as of 20 December 2021. A random effects meta-analysis model was used to generate the pooled OR at 95% CIs. The heterogeneity between studies was assessed using I2 and Cochran's Q statistics. Moreover, the likelihood of publication bias was determined by Egger's regression test. A total of 11 studies were eligible for meta-analysis, including 1172 MS cases and 1802 controls. Our findings indicated that 29.8% (95% CI 22.8 to 37.2%) of MS patients were seropositive for To. gondii infection, compared with 34.2% (95% CI 21.9 to 47.6%) of control subjects. The estimated pooled OR was 0.79 (95% CI 0.49 to 1.26), suggesting a non-significant negative association between To. gondii infection and MS development (p&gt;0.05). The current study does not support the significant protective role of To. gondii infection on MS development. Our findings imply that further well-designed epidemiological and mechanistic studies are warranted to ascertain the possible association between To. gondii infection and MS and to exclude the potential confounders.
Evaluating the Effect of Duloxetine Premedication on Postoperative Analgesic Requirement in Patients Undergoing Laparoscopic Cholecystectomies
Authors: Nath Shivika , Saha Ambhrin , Srivastava Aarti 
Published: June 2022

Objective:
The aim was to evaluate the effect of oral administration of preoperative duloxetine on postoperative pain and total analgesic requirement in the postoperative period as the primary objective. The secondary objective was to evaluate the perioperative hemodynamic parameters, sedation scores, demographic data, and incidence of side effects (if any) in patients undergoing laparoscopic cholecystectomy.

Materials and Methods:
This was a prospective, randomized, double-blind, placebo-controlled study conducted in a tertiary level medical college on 60 patients of either sex posted for laparoscopic cholecystectomies with American Society of Anesthesiologists (ASA) I and II. The patients were divided into 2 groups (n=30), the patients were given duloxetine 60 mg capsules and placebo capsules (Becosules) 2 hours before surgery.

Results:
The total requirement for both first and second rescue analgesics was higher in placebo as compared with duloxetine and was found to be significant (P<0.05). The difference in mean visual analog scale score was significantly (P<0.001) higher in placebo as compared with duloxetine at all-time intervals postoperatively 0 minute (7.6±0.7 vs. 4.6±0.8); 15 minutes (5.9±0.8 vs. 4.2±1.0); 30 minutes (4.4±0.5 vs. 3.6±0.9); 4 hours (6.6±0.06 vs. 5.3±1.3); 8 hours (5.2±1.2 vs. 3.9±1.0); and 12 hours (5.1±1.3 vs. 2.3±0.7). The mean arterial blood pressure and heart rate were significantly higher in placebo compared with duloxetine in most of the time intervals in the perioperative period. There was no significant difference in the sedation score between the groups except the 30 minutes and 8 hours postoperative.

Discussion:
Preoperative oral duloxetine during laparoscopic cholecystectomy could reduce postoperative pain, postoperative analgesic requirements, and better optimization of hemodynamics without causing major side effects.
Perioperative Myomectomy Outcomes Based on the Current Coding Rules
Authors: Andrews Brooke , Siewertsz van Reesema Lauren , Gaughan Thomas , Hoffman Mark , Movilla Peter 
Published: June 2022

OBJECTIVE:
To assess postoperative outcomes based on surgical approach for myomectomies with increasing leiomyoma burden.

METHODS:
We conducted a retrospective analysis using the American College of Surgeons National Surgical Quality Improvement Program database from 2014 to 2019 of benign myomectomy procedures. These cases were categorized into “smaller” and “larger” procedures based on leiomyoma burden. Smaller myomectomies included leiomyomas weighing less than 250 g or with one–four leiomyomas (Current Procedural Terminology [CPT] codes 58545 and 58140); larger myomectomies included leiomyomas weighing 250 g or more or with five or more leiomyomas (CPT codes 58546 and 58146). Postoperative complications estimated using the Clavien-Dindo classification system were compared based on surgical approach.

RESULTS:
Of 8,363 total myomectomy procedures, 3,117 (37.3%) were performed using minimally invasive surgery (MIS) and 5,246 (62.7%) were performed using laparotomy. Among MIS cases, 2,080 (66.7%) were categorized as smaller myomectomies and 1,037 (33.3%) cases as larger myomectomies. Among laparotomy cases, 2,587 (49.3%) were smaller myomectomies, and 2,659 (50.7%) were larger myomectomies. Regardless of myomectomy size, MIS was associated with a lower perioperative blood transfusion rate than laparotomy (1.63% vs 8.93%, respectively, P<.01). Laparotomy was associated with an increased rate of minor complications (adjusted odds ratio [aOR] 2.86 (95% CI 2.24–3.67) for smaller leiomyoma burden (11.91% vs 4.28%) and for larger leiomyoma burden (21.59% vs 6.75%, aOR 3.43, 95% CI 2.64–4.47) cases. Laparotomy demonstrated an increased cumulative major complication rate (3.31% vs 1.25%) (aOR 2.45, 95% CI 1.35–4.45) for larger myomectomies.

CONCLUSION:
A minimally invasive surgical approach for both smaller and larger myomectomies was associated with fewer minor complications compared with laparotomy. Minimally invasive surgery for larger myomectomies was associated with fewer cumulative major complications compared with laparotomy.