bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peer leader perspectives from a PLTL implementation in a Hispanic-serving institution
Authors: Narayanan Madhavan , Powers Kasey , Premawardena Dhananjaya , Colby Kelly , Liou Mark Janet , Rao Nagaraj , Smyth Davida S. , Knopp-Kelly Mary 
Published: September 2023

ABSTRACT
Peer-Led Team Learning (PLTL) is a pedagogical approach that has been shown to benefit all students, especially underrepresented minority students and peer leaders in Science, Technology, Engineering, and Mathematics (STEM) disciplines. In this work, we present results from our study of the impact of PLTL on our peer leaders from a controlled implementation in general biology, general chemistry, and statistics courses at a Hispanic-serving, minority-serving institution. More specifically, we have measured our PLTL program’s impact on our peer leaders' skill development, engagement with the subject material, and sense of belonging as peer leaders. Weekly peer leader reflections analyzed using the Dreyfus model exhibited a consistent set of skills, while those analyzed using the Pazos model revealed a consistent type of student-peer leader interactions, allowing for peer leaders to be assigned to specific levels in the hierarchy of each of the models. Analysis of eight skill-based Likert-scale questions on the SALG survey showed an overall positive shift at the highest level. Independent of the skill or interaction level of the peer leader, we observed several instances of peer leaders acknowledging development in their communication skills, sincere attempts at creating an engaging classroom, and a deep investment in their student’s success. Peer leaders also reported improvements in understanding of the subjects they were teaching, wanting to persevere and solve problems independently, and feeling passionate about helping other students.
Host genetic variation at a locus near CHD1L impacts HIV sequence diversity in a South African population
Authors: Schulz Vanessa E. , Tuff Jeffrey F. , Tough Riley H. , Lewis Lara , Chimukangara Benjamin , Garrett Nigel , Abdool Karim Quarraisha , Abdool Karim Salim S. , McKinnon Lyle R. , Kharsany Ayesha B. M. , McLaren Paul J. 
Published: September 2023

ABSTRACT

There is variability in viral load (VL) among individuals with untreated human immunodeficiency virus (HIV) infection, and this variability can be partly attributed to host genetics. HIV is known to develop escape mutations to evade host immune pressure, particularly from HLA alleles and, in some cases, counteracts the protective effect of host alleles. A recent genome-wide association study (GWAS) of HIV VL in individuals of African ancestry identified a locus on chromosome 1, near the protein-coding gene chromodomain helicase DNA-binding protein 1 like (
CHD1L
), that has a novel association with control of HIV replication. However, not all individuals carrying the protective alleles maintain low VL, and the region’s impact on viral evolution has not been investigated. To address this, we conducted a host-virus regional association analysis in 147 people living with HIV (PLWH) from South Africa with both human and viral genome data available. We observed significant associations between the
CHD1L
variants rs77029719 (G) (
P
= 1.6 × 10
−2
), rs7519713 (T) (
P
= 2.3 × 10
−2
), and rs59784663 (G) and 73004025 (T) (
P
= 1.4 × 10
−2
) with codon 248 of HIV reverse transcriptase (RT) and between
CHD1L
variant rs7519713 (T) and codon 18 (
P
= 3.2 × 10
−2
) and 147 (
P
= 3.9 × 10
−2
) of HIV gag. These associations are consistent with viral escape from CHD1L pressure. In addition, we observed significant associations between
HLA B*81
(
P
= 1.5 × 10
−5
) and
HLA C*18
(
P
= 7.0 × 10
−4
) with RT codon 4 and
HLAB*58
with RT codon 196 (
P
= 9.0 × 10
−4
). This study reveals new evidence of host genetic variation impacting viral evolution in a population highly affected by HIV.

IMPORTANCE

It has been previously shown that genetic variants near
CHD1L
on chromosome 1 are associated with reduced HIV VL in African populations. However, the impact of these variants on viral diversity and how they restrict viral replication are unknown. We report on a regional association analysis in a South African population and show evidence of selective pressure by variants near
CHD1L
on HIV RT and gag. Our findings provide further insight into how genetic variability at this locus contributes to host control of HIV in a South African population.
The antihelminth drug rafoxanide reverses chromosomal-mediated colistin-resistance in
Klebsiella pneumoniae
Authors: Han Rongjia , Xing Jiabao , Sun Huarun , Guo Zeyu , Yi Kaifang , Hu Gongzheng , Zhai Yajun , Velkov Tony , Wu Hua 
Published: September 2023

ABSTRACT

The emergence and rapid spread of multi-drug-resistant (MDR) bacteria pose a serious threat to global healthcare. Although the synergistic effect of rafoxanide and colistin was reported, little is known regarding the potential mechanism of this synergy, particularly against chromosomal-mediated colistin-resistant
Klebsiella pneumoniae
. In the present study, we elucidated the synergistic effect of rafoxanide and colistin against chromosomal-mediated colistin-resistant
Klebsiella pneumoniae
isolates from human (KP-9) and swine (KP-1) infections. Treatment with 1 mg/L rafoxanide overtly reversed the MIC max to 512-fold. Time-kill assays indicated that rafoxanide acted synergistically with colistin against the growth of KP-1 and KP-9. Mechanistically, we unexpectedly found that the combination destroys the inner-membrane integrity, and ATP synthesis was also quenched, albeit, not via F
1
F
0
-ATPase; thereby also inhibiting the activity of efflux pumps. Excessive production of reactive oxygen species (ROS) was also an underlying factor contributing to the bacterial-killing effect of the combination. Transcriptomic analysis unraveled overt heterogeneous expression as treated with both administrations compared with monotherapy. Functional analysis of these differentially expressed genes (DEGs) targeted to the plasma membrane and ATP-binding corroborated phenotypic screening results. These novel findings highlight the synergistic mechanism of rafoxanide in combination with colistin which effectively eradicates chromosomal-mediated colistin-resistant
Klebsiella pneumoniae
.

IMPORTANCE

The antimicrobial resistance of
Klebsiella pneumoniae
caused by the abuse of colistin has increased the difficulty of clinical treatment. A promising combination (i.e., rafoxanide+ colistin) has successfully rescued the antibacterial effect of colistin. However, we still failed to know the potential effect of this combination on chromosome-mediated
Klebsiella pneumoniae
. Through a series of
in vitro
experiments, as well as transcriptomic profiling, we confirmed that the MIC of colistin was reduced by rafoxanide by destroying the inner-membrane integrity, quenching ATP synthesis, inhibiting the activity of the efflux pump, and increasing the production of reactive oxygen species. In turn, the expression of relevant colistin resistance genes was down-regulated. Collectively, our study revealed rafoxanide as a promising colistin adjuvant against chromosome-mediated
Klebsiella pneumoniae
.
Reconstitution of a minimal ESX-5 type VII secretion system suggests a role for PPE proteins in the outer membrane transport of proteins
Authors: Bunduc C. M. , Ding Y. , Kuijl C. , Marlovits T. C. , Bitter W. , Houben E. N. G. 
Published: September 2023

ABSTRACT

Mycobacteria utilize type VII secretion systems (T7SSs) to secrete proteins across their highly hydrophobic and diderm cell envelope. Pathogenic mycobacteria have up to five different T7SSs, called ESX-1 to ESX-5, which are crucial for growth and virulence. Here, we use a functionally reconstituted ESX-5 system in the avirulent species
Mycobacterium smegmatis
that lacks ESX-5, to define the role of each
esx-5
gene in system functionality. By creating an array of gene deletions and assessing protein levels of components and membrane complex assembly, we observed that only the five components of the inner membrane complex are required for its assembly. However, in addition to these five core components, active secretion also depends on both the Esx and PE/PPE substrates. Tagging the PPE substrates followed by subcellular fractionation, surface labeling and membrane extraction showed that these proteins localize to the mycobacterial outer membrane. This indicates that they could play a role in secretion across this enigmatic outer barrier. These results provide the first full overview of the role of each
esx-5
gene in T7SS functionality.

IMPORTANCE

Pathogenic mycobacteria, such as the notorious
Mycobacterium tuberculosis
, are highly successful as pathogens, in part due to their specific and diderm cell envelope, with a mycolic acid-containing outer membrane. The architecture of this highly impermeable membrane is little understood and the proteins that populate it even less so. To transport proteins across their cell envelope, mycobacteria employ a specialized transport pathway called type VII secretion. While recent studies have elucidated the type VII secretion membrane channel that mediates transport across the inner membrane, the identity of the outer membrane channel remains a black box. Here, we show evidence that specific substrates of the type VII pathway could form these channels. Elucidating the pathway and mechanism of protein secretion through the mycobacterial outer membrane will allow its exploitation for the development of novel mycobacterial therapeutics.
Expanding success in the isolation of abundant marine bacteria after reduction in grazing and viral pressure and increase in nutrient availability
Authors: Rey-Velasco Xavier , Deulofeu-Capo Ona , Sanz-Sáez Isabel , Cardelús Clara , Ferrera Isabel , Gasol Josep M. , Sánchez Olga 
Published: September 2023

ABSTRACT

Isolation of microorganisms is a useful approach to gathering knowledge about their genomic properties, physiology, and ecology, in addition to allowing the characterization of novel taxa. We performed an extensive isolation effort on samples from seawater manipulation experiments that were carried out during the four astronomical seasons in a coastal site of the northwest Mediterranean to evaluate the impact of grazing, viral mortality, resource competition reduction, and light presence/absence on bacterioplankton growth. Isolates were retrieved using two growth media, and their full 16S rRNA gene was sequenced to assess their identity and calculate their culturability across seasons and experimental conditions. A total of 1,643 isolates were obtained, mainly affiliated to the classes
Gammaproteobacteria
(44%),
Alphaproteobacteria
(26%), and
Bacteroidia
(17%). Isolates pertaining to class
Gammaproteobacteria
were the most abundant in all experiments, while
Bacteroidia
were preferentially enriched in the treatments with reduced grazing. Sixty-one isolates had a similarity below 97% to cultured taxa and are thus putatively novel. Comparison of isolate sequences with 16S rRNA gene amplicon sequences from the same samples showed that the percentage of reads corresponding to isolates was 21.4% within the whole data set, with dramatic increases in the summer virus-reduced (71%) and diluted (47%) treatments. In fact, we were able to isolate the top 10 abundant taxa in several experiments and from the whole data set. We also show that top-down and bottom-up controls differentially affect taxa in terms of culturability. Our results indicate that culturing marine bacteria using agar plates can be successful in certain ecological situations.

IMPORTANCE
Bottom-up and top-down controls greatly influence marine microbial community composition and dynamics, which in turn have effects on their culturability. We isolated a high amount of heterotrophic bacterial strains from experiments where seawater environmental conditions had been manipulated and found that decreasing grazing and viral pressure as well as rising nutrient availability are key factors increasing the success in culturing marine bacteria. Our data hint at factors influencing culturability and underpin bacterial cultures as a powerful way to discover new taxa.
Leukoaraiosis and stroke severity scores in post-rtPA intracerebral haemorrhage
Authors: Boonrod Arunnit , Tangsakul Prompan , Kasemsap Narongrit , Vorasoot Nisa , Tiamkao Somsak , Sawanyawisuth Kittisak , Kongbunkiat Kannikar 
Published: September 2023

IntroductionPost thrombolytic symptomatic intracerebral haemorrhage (sICH) is a major concern in patients who had acute ischaemic stroke. Leukoaraiosis (LA) is reported to be related with sICH after intravenous thrombolytic treatment. However, the influence of LA and stroke neurological and imaging severity scores is still debated.ObjectiveTo evaluate if LA or severity scores are related with sICH in patients who had acute ischaemic stroke who received thrombolytic therapy. And, predictors for sICH were also studied with adjustment of baseline severity scores.MethodsThis was a retrospective, analytical study. The inclusion criteria were adult patients diagnosed as acute ischaemic stroke who received the recombinant tissue plasminogen activator (rtPA) treatment within 4.5 hours. The study period was between May 2007 and November 2016. Predictors for sICH were determined using logistic regression analysis.ResultsDuring the study period, there were 504 eligible patients. Of those, 45 patients (8.92%) had sICH. Among nine factors in the final model for predicting sICH, there were four independent factors including previous antiplatelet therapy, previous anticoagulant therapy, presence of LA and hyperdense artery sign. The highest adjusted OR was previous anticoagulant therapy (5.08 with 95% CI of 1.18 to 11.83), while the LA factor had adjusted OR (95% CI) of 2.52 (1.01 to 6.30).ConclusionsLA, hyperdense artery sign, previous antiplatelet therapy and previous anticoagulant therapy were associated with post-rtPA sICH. Further studies are required to confirm the results of this study.
COVID-19 pandemic impact on screening and diagnosis of prostate cancer: a systematic review
Authors: Mostafavi Zadeh Seyed Mostafa , Tajik Fatemeh , Gheytanchi Elmira , Kiani Jafar , Ghods Roya , Madjd Zahra 
Published: September 2023

IntroductionThe healthcare level has been greatly affected by the COVID-19 pandemic compared with before the outbreak. This study aimed to review the impact of COVID-19 on the screening and diagnosis of prostate cancer (PCa).MethodThe current study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The keywords used to perform the search strategy were COVID-19 and prostate neoplasms. The four primary electronic databases comprising PubMed/MEDLINE, Web of Science, Scopus and Embase were searched until 1 September 2022. After screening and selecting studies through the EndNote software, data were extracted from each included study by two independent authors. All studies were evaluated according to Newcastle–Ottawa Scale quality assessment tool.ResultsAs a result, 40 studies were included, categorised into two subjects. The majority of studies indicated a significant decrease in screening prostate-specific antibody tests during the COVID-19 pandemic compared with the pre-pandemic period, leading to delays in cancer diagnosis. The decrease in the number of diagnosed cases with low/intermediate stages to some extent was more than those with advanced stages. The PCa screening and diagnosis reduction ranged from nearly 0% to 78% and from 4.1% to 71.7%, respectively.ConclusionOur findings showed that during the COVID-19 lockdown, delays in PCa screening tests and diagnoses led to the negative health effects on patients with PCa. Thus, it is highly recommended performing regular cancer screening to reduce the impact of the COVID-19 lockdown.PROSPERO registration numberCRD42021291656.
The non-nutritive sweetener sucralose increases β-arrestin signaling at the constitutively active orphan G protein-coupled receptor GPR52
Authors: Power Madeline E. , Fernandez Nicholas R. , Oni Olaiya Peter , Kalia Aditaya , Rourke Jillian L. 
Published: September 2023

Non-nutritive sweeteners are popular food additives owing to their low caloric density and powerful sweetness relative to natural sugars. Their lack of metabolism contributes to evidence proclaiming their safety, yet several studies contradict this, demonstrating that sweeteners activate sweet taste G protein-coupled receptors (GPCRs) and elicit deleterious metabolic functions through unknown mechanisms. We hypothesize that activation of GPCRs, particularly orphan receptors due to their abundance in metabolically active tissues, contributes to the biological activity of sweeteners. We quantified the response of 64 orphans to the sweeteners saccharin and sucralose using a high-throughput β-arrestin-2 recruitment assay (PRESTO-Tango). GPR52 was the sole receptor that significantly responded to a mixture of sucralose and saccharin. Subsequent experiments revealed sucralose as the activating sweetener. Activation of GPR52 was concentration-dependent, with an EC50 of 0.23 mmol/L and an Emax of 3.43 ± 0.24 fold change at 4 mmol/L. GPR52 constitutively activates CRE pathways; however, we show that sucralose-induced activation of GPR52 does not further activate this pathway. Identification of this novel sucralose–GPCR interaction supports the notion that sucralose elicits off-target signaling through the activation of GPR52, calling into question sucralose's assumed lack of bioactivity.
MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C. 
Published: September 2023

Abstract
Despite the initial benefit from tyrosine kinase inhibitors (TKI) targeting oncogenic ALK and ROS1 gene fusions in non–small cell lung cancer, complete responses are rare and resistance ultimately emerges from residual tumor cells. Although several acquired resistance mechanisms have been reported at the time of disease progression, adaptative resistance mechanisms that contribute to residual diseases before the outgrowth of tumor cells with acquired resistance are less clear. For the patients who have progressed after TKI treatments, but do not demonstrate ALK/ROS1 kinase mutations, there is a lack of biomarkers to guide effective treatments. Herein, we found that phosphorylation of MIG6, encoded by the ERRFI1 gene, was downregulated by ALK/ROS1 inhibitors as were mRNA levels, thus potentiating EGFR activity to support cell survival as an adaptive resistance mechanism. MIG6 downregulation was sustained following chronic exposure to ALK/ROS1 inhibitors to support the establishment of acquired resistance. A higher ratio of EGFR to MIG6 expression was found in ALK TKI-treated and ALK TKI-resistant tumors and correlated with the poor responsiveness to ALK/ROS1 inhibition in patient-derived cell lines. Furthermore, we identified and validated a MIG6 EGFR-binding domain truncation mutation in mediating resistance to ROS1 inhibitors but sensitivity to EGFR inhibitors. A MIG6 deletion was also found in a patient after progressing to ROS1 inhibition. Collectively, this study identifies MIG6 as a novel regulator for EGFR-mediated adaptive and acquired resistance to ALK/ROS1 inhibitors and suggests EGFR to MIG6 ratios and MIG6-damaging alterations as biomarkers to predict responsiveness to ALK/ROS1 and EGFR inhibitors.
Early Metabolic Alteration Predicts Outcome With Middle Cerebral Artery Occlusion Treated by Mechanical Thrombectomy
Authors: Herpe Guillaume , Giraud Clément , Thomas Clément , Neau Jean‐Philippe , Velasco Stéphane , Dumas Victor , Pellerin Luc , Guillevin Carole , Guillevin Rémy 
Published: September 2023

Background

Predicting clinical outcome based on either the postprocedural recanalization score (modified treatment in cerebral infarction) or the initial National Institute of Health Stroke Scale (NIHSS) clinical score performed immediately after the acute phase remains controversial. The
gold standard
to predict clinical outcome is the NIHSS score with diffusion weighted imaging. However, magnetic resonance spectroscopy could provide useful metabolic informations. Our study aimed to determine early metabolic factors predictive of long‐term clinical outcome after acute ischemic stroke in patients with middle cerebral artery occlusion successfully treated by mechanical thrombectomy.

Methods
Patients with proximal middle cerebral artery occlusion, an NIHSS score greater than 6 and successfully treated by mechanical thrombectomy with or without intravenous therapy were included. All patients underwent within 24 hours after mechanical thrombectomy, brain magnetic resonance imaging examination with multivoxel proton‐phosphorus‐magnetic resonance spectroscopy. Functional disability at 90 days with reference to pre‐stroke activities was categorized using the modified Rankin scale. Metabolite ratios were measured and confronted to modified Rankin scale.

Results

A total of 49 patients were included with initial mean NIHSS of 15.19±5.48. Time delay between: onset‐thrombectomy was 6.77 hours±3.22, thrombectomy‐magnetic resonance imaging was 29.83 hours±15.01. Results in the lesion compared with the contralateral area show an increase of Lac/Cr (0.88 versus 0.21;
P
<10
−10
) and a decrease of PhosphoMonoEster/PhosphoDiEster (0.80 versus 0.83;
P
=0.00165). Lac/Cr in the lesion was significantly higher in the poor outcome group than in the favorable outcome group (1.03±0.41 and 0.75±0.42;
P
=0.01). Our model built with NIHSS+proton‐magnetic resonance spectroscopy compared with the
gold standard model
(NIHSS+diffusion weighted imaging) is better (85.29% versus 77.55%) to predict clinical outcome.

Conclusion
Our study shows that early Lac/Cr alteration visible 24 hours after stroke is a strong predictor of 90 days clinical outcome for middle cerebral artery occlusion patients successfully treated by mechanical thrombectomy. Our NIHSS+proton‐magnetic resonance spectroscopy model is the first to predict patients’ long‐term functional outcome with an accuracy of 85.3%, superior to existing models including diffusion weighted imaging.