bluuebunny/crossref_metadata_2025_split huggingface dataset:
Underrepresentation of Racial and Ethnic Minorities in Metastatic Colorectal Carcinoma Clinical Trials within the United States
Authors: Pu Tracey , Gustafson Alexandra , Luberice Kenneth , Akmal Sarfraz R. , Li Wei , Hernandez Jonathan M. , Blakely Andrew M. , Snyder Rebecca A. , Eng Oliver S. 
Published: August 2024

Objective:
To investigate if underrepresentation of racial and ethnic minorities exists in metastatic colorectal carcinoma (CRC) clinical trials.

Summary Background Data:
Representation of vulnerable subpopulations is essential for generalizability of clinical trials. Limited studies to date have investigated racial and ethnic representation of patients enrolled in clinical trials for metastatic CRC.

Methods:
ClinicalTrials.gov was queried for metastatic CRC clinical trials in the United States from 2000-2020. Incidence data were extracted from the SEER Database. Enrollment fraction (EF) was defined as number of trial participants divided by U.S. incidence of metastatic CRC in each race, ethnicity, and gender. Representation Quotient (RQ) was defined as the proportion of trial participants divided by proportion of U.S. metastatic CRC incidence for each subgroup.

Results:
8084 patients from 135 clinical trials were analyzed. 49.6% of clinical trials reported race data and 34.8% reported ethnicity data. Compared to 2000-2009, 2010-2019 had increased representation data reporting for race (61.2% vs. 38.8%) and ethnicity (64.6% vs. 35.4%). Of trials with race data, White patients represented 77.0%, Black patients 6.6%, Asian/Pacific Islander (API) patients 16.1%, American Indian/Alaska Native (AIAN) patients 0.2%, and Hispanic patients 6.8%. Black patients (median RQ 0.54), API patients (median RQ 0.19), AIAN patients (median RQ 0.00), and Hispanic patients (median RQ 0.26) were underrepresented. Black patients had a higher degree of underrepresentation in clinical trials with serum creatinine inclusion criteria (RQ 0.40 vs. 0.86, P=0.034).

Conclusions:
Strategies are needed to increase minority enrollment in clinical trials for metastatic CRC. Identification of systemic barriers is integral in public policy advocacy to increase representation.
Neuro-Ophthalmic Manifestations of Adult Polyglucosan Body Disease
Authors: Dugue Andrew G. , Abreu Nicolas J. , Pillai Cinthi , Galetta Steven L. , Grossman Scott N. 
Published: August 2024

Background:
Adult polyglucosan body disease (APBD) is caused by a deficiency in glycogen branching enzyme that leads to polyglucosan accumulation in multiple organs. It has a progressive clinical course with prominent neurologic manifestations. We aim to describe the neuro-ophthalmic manifestations of APBD.

Methods:
This is a case series of 3 individuals with genetically proven APBD. Written informed consent was provided by the brothers. We also performed a literature review on the current state of knowledge on APBD through PubMed.

Results:
Brother 1 developed gait imbalance and length-dependent polyneuropathy in his 40s followed by progressive urinary symptoms in his 50s. He reported diplopia and blurry vision in his 60s. Neuro-ophthalmic assessment revealed bilateral optic neuropathy, convergence insufficiency, and a right fourth nerve palsy. Genetic testing showed a homozygous pathogenic variant in GBE1 c.986A>C p.Tyr329Ser. Brother 2 developed progressive urinary symptoms in his 40s that were followed by cognitive deficits, length-dependent polyneuropathy, and lower extremity weakness in his 50s and 60s. He reported blurred vision, and neuro-ophthalmic evaluation revealed bilateral optic neuropathy. Genetic testing revealed the same variant as Brother 1, GBE1 c.986A>C p.Tyr329Ser. Brother 3 developed progressive urinary urgency and lower extremity weakness in his 50s followed by a length-dependent polyneuropathy in his 60s. He reported diplopia and blurry vision in his 70s. Neuro-ophthalmic assessment revealed bilateral optic neuropathy and convergence insufficiency. Genetic testing revealed the same variant as Brothers 1 and 2, GBE1 c.986A>C p.Tyr329Ser.

Conclusions:
There is an array of afferent and efferent neuro-ophthalmic manifestations in APBD. Neuro-ophthalmic evaluation is crucial in evaluating and treating patients with APBD, particularly in those with visual dysfunction.
Evaluating the Therapeutic Effects of Amino Acid Treatment on Vaso-Occlusive Pain in Sickle Cell Disease: A Systematic Review and Meta-Analysis Protocol
Authors: Zhang Bohan , Bubb Ciaran , Yao Sophie , Dong Vivian , Patel Priyal , Shahani Aanya , Lobner Katie , Badaki-Makun Oluwakemi 
Published: August 2024

2AbstractIntroductionSickle Cell Disease (SCD) affects over 100,000 individuals in the United States and 20 million globally, causing acute and chronic pain. The disease is characterized by misshapen red blood cells caused by mutations in beta-hemoglobin genes. SCD leads to multiorgan damage, chronic anemia, and severe pain crises, with a median life expectancy of 43 years. Current treatments involve opioids, blood transfusions, and hydroxyurea. Amino acids, especially L-Glutamine, have shown promise in managing SCD pain. This systematic review aims to comprehensively analyze the effects of amino acid treatments on vaso-occlusive pain crises in SCD patients.MethodsFollowing the Cochrane Handbook and PRISMA-P guidelines, this systematic review will include studies comparing amino acid treatment to placebo or standard care for SCD pain crises. Eligible studies of all age ranges, settings, and amino acid types will be considered. A comprehensive search strategy will be employed in PubMed, Embase, and Scopus databases. Studies will be assessed for risk of bias using Cochrane’s RoB2 tool. Primary outcomes include a reduction in pain, measured quantitatively through pain scales. Secondary outcomes encompass quality of life, hospital length of stay, and opioid equivalents used.DiscussionExisting literature underscores the therapeutic potential of amino acids, yet there still lacks a systematic review comparing the overall effects of different amino acid treatments for vaso-occlusive crises in patients with SCD. This review aims to serve as a valuable resource for clinicians, offering insights into amino acid interventions as alternatives or supplements to opioid treatments. Additionally, it seeks to encourage further randomized clinical trials, contributing to an informed clinical use of amino acids for pain management in SCD. Ultimately, the findings aim to enhance the understanding of the therapeutic effects of essential amino acids on pediatric patients with SCD, facilitating evidence-based clinical decisions.
Phylogenetic proximity drives temporal succession of marine giant viruses in a five-year metagenomic time-series
Authors: Laperriere Sarah M. , Minch Benjamin , Weissman JL , Hou Shengwei , Yeh Yi-Chun , Cesar Ignacio-Espinoza J. , Ahlgren Nathan A. , Moniruzzaman Mohammad , Fuhrman Jed A. 
Published: August 2024

AbstractNucleocytoplasmic Large DNA Viruses (NCLDVs, also called giant viruses) are widespread in marine systems and infect a broad range of microbial eukaryotes (protists). Recent biogeographic work has provided global snapshots of NCLDV diversity and community composition across the world’s oceans, yet little information exists about the guiding ‘rules’ underpinning their community dynamics over time. We leveraged a five-year monthly metagenomic time-series to quantify the community composition of NCLDVs off the coast of Southern California and characterize these populations’ temporal dynamics. NCLDVs were dominated by Algavirales (Phycodnaviruses, 59%) and Imitervirales (Mimiviruses, 36%). We identified clusters of NCLDVs with distinct classes of seasonal and non-seasonal temporal dynamics. Overall, NCLDV population abundances were often highly dynamic with a strong seasonal signal. The Imitervirales group had highest relative abundance in the more oligotrophic late summer and fall, while Algavirales did so in winter. Generally, closely related strains had similar temporal dynamics, suggesting that evolutionary history is a key driver of the temporal niche of marine NCLDVs. However, a few closely-related strains had drastically different seasonal dynamics, suggesting that while phylogenetic proximity often indicates ecological similarity, occasionally phenology can shift rapidly, possibly due to host-switching. Finally, we identified distinct functional content and possible host interactions of two major NCLDV orders-including connections of Imitervirales with primary producers like the diatomChaetocerosand widespread marine grazers likeParaphysomonasand Spirotrichea ciliates. Together, our results reveal key insights on season-specific effect of phylogenetically distinct giant virus communities on marine protist metabolism, biogeochemical fluxes and carbon cycling.
Torsional Twist of the SARS-CoV and SARS-CoV-2 SUD-N and SUD-M domains
Authors: Rosas-Lemus Monica , Minasov George , Brunzelle Joseph S. , Taha Taha Y. , Lemak Sofia , Yin Shaohui , Shuvalova Ludmilla , Rosecrans Julia , Khanna Kanika , Seifert H Steven , Savchenko Alexei , Stogios Peter J. , Ott Melanie , Satchell Karla J. F. 
Published: August 2024

ABSTRACTCoronavirus non-structural protein 3 (nsp3) forms hexameric crowns of pores in the double membrane vacuole that houses the replication-transcription complex. Nsp3 in SARS-like viruses has three unique domains absent in other coronavirus nsp3 proteins. Two of these, SUD-N (Macrodomain 2) and SUD-M (Macrodomain 3), form two lobes connected by a peptide linker and an interdomain disulfide bridge. We resolve the first complete x-ray structure of SARS-CoV SUD-N/M as well as a mutant variant of SARS-CoV-2 SUD-N/M modified to restore cysteines for interdomain disulfide bond naturally lost by evolution. Comparative analysis of all structures revealed SUD-N and SUD-M are not rigidly associated, but rather, have significant rotational flexibility. Phylogenetic analysis supports that the disulfide bond cysteines are also absent in pangolin-SARS and closely related viruses, consistent with pangolins being the presumed intermediate host in the emergence of SARS-CoV-2. The absence of these cysteines does not impact viral replication or protein translation.
Bibacillin 1: A two-component lantibiotic fromBacillus thuringiensis
Authors: Moreira Ryan , Yang Yi , Luo Youran , Gilmore Michael S. , van der Donk Wilfred 
Published: August 2024

AbstractHere we describe bibacillin 1 – a two-component lantibiotic fromBacillus thuringiensis. The peptides that comprise bibacillin 1 are modified by a class II lanthipeptide synthetase Bib1M producing two peptides with non-overlapping ring patterns that are reminiscent of cerecidin and the short component of the enterococcal cytolysin (CylLS”), a virulence factor associated with human disease. Stereochemical analysis demonstrated that each component contains LL-methyllanthionine and DL-lanthionine. The mature bibacillin 1 peptides showed cooperative bactericidal activity against Gram-positive bacteria, including members of ESKAPE pathogens, and weak hemolytic activity. Optimal ratio studies suggest that bibacillin 1 works best when the components are present in a 1:1 ratio, but near optimal activity was observed at ratios strongly favouring one component over the other, suggesting that the two peptides may have different but complementary targets. Mechanism of action studies suggest a lipid II-independent killing action distinguishing bibacillin 1 from two other two-component lantibiotics haloduracin and lacticin 3147. One of the two components of bibacillin 1 showed cross reactivity with the cytolysin regulatory system. These result support the involvement of bibacillin 1 in quorum sensing and raise questions about the impact of CylLS”-like natural products on lanthipeptide expression in diverse bacterial communities.
Alzheimer’s disease protective allele ofClusterinmodulates neuronal excitability through lipid-droplet-mediated neuron-glia communication
Authors: Zhao Xiaojie , Li Yan , Zhang Siwei , Sudwarts Ari , Zhang Hanwen , Kozlova Alena , Moulton Matthew J. , Goodman Lindsey D. , Pang Zhiping P. , Sanders Alan R. , Bellen Hugo J. , Thinakaran Gopal , Duan Jubao 
Published: August 2024

SummaryGenome-wide association studies (GWAS) of Alzheimer’s disease (AD) have identified a plethora of risk loci. However, the disease variants/genes and the underlying mechanisms remain largely unknown. For a strong AD-associated locus nearClusterin(CLU), we tied an AD protective allele to a role of neuronal CLU in promoting neuron excitability through lipid-mediated neuron-glia communication. We identified a putative causal SNP ofCLUthat impacts neuron-specific chromatin accessibility to transcription-factor(s), with the AD protective allele upregulating neuronalCLUand promoting neuron excitability. Transcriptomic analysis and functional studies in induced pluripotent stem cell (iPSC)-derived neurons co-cultured with mouse astrocytes show that neuronal CLU facilitates neuron-to-glia lipid transfer and astrocytic lipid droplet formation coupled with reactive oxygen species (ROS) accumulation. These changes cause astrocytes to uptake less glutamate thereby altering neuron excitability. Our study provides insights into how CLU confers resilience to AD through neuron-glia interactions.
Conserved role of the SERK–BIR module in development and immunity across land plants
Authors: Yan Yijia , Mellüh Jaqueline , Mecchia Martin A. , Jeon Hyung-Woo , Melkonian Katharina , Holzberger Clemens , Harzen Anne , Stolze Sara Christina , Franzen Rainer , Hirakawa Yuki , Delgado Ana I. Caño , Nakagami Hirofumi 
Published: August 2024

SummarySOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASES (SERKs), which are subfamily II of leucine-rich repeat receptor-like kinases (LRR-RLKs), play diverse roles in development and immunity in the angiospermArabidopsis thaliana. AtSERKs act as co-receptors for many LRR-RLKs, including BRASSINOSTEROID INSENSITIVE 1 (BRI1) and FLAGELLIN SENSITIVE 2 (FLS2).1–4The conserved tyrosine (Y) residue in AtSERK3 is crucial for signaling specificity in differentiating BRI1- and FLS2-mediated pathways.5BRI1-ASSOCIATED RECEPTOR KINASE 1 (BAK1)-INTERACTING RECEPTOR-LIKE KINASES (BIRs) interact with SERKs under resting conditions, negatively regulating SERK-mediated pathways.6,7SERK and BIR are highly conserved in land plants, whereas BRI1 and FLS2 homologs are absent or poorly conserved in bryophyte lineages.8,9The biological functions of SERK homologs in non-flowering plants are largely unknown. The genome of the liverwortMarchantia polymorphaencodes single homologs for SERK and BIR, namely MpSERK and MpBIR.9We here show that Mpserkdisruptants display growth and developmental defects with no observable sexual or vegetative reproduction. Complementation analysis revealed a contribution of the conserved Y residue of MpSERK to growth. Proximity labelling-based interactomics identified MpBIR as a MpSERK interactor. Mpbirdisruptants displayed defects in reproductive organ development. Patterns of development- and immunity-related gene expression in Mpserkand Mpbirwere antagonistic, suggesting that MpBIR functions as a MpSERK repressor. The pathogenic bacteriumPseudomonas syringaepv.tomatoDC3000 grew poorly on Mpbir, indicating a significant role of the MpSERK1MpBIR module in immunity. Taken together, we propose that the SERK–BIR functional module was already regulating both development and immunity in the last common ancestor of land plants.
Machine learning reveals genes impacting oxidative stress resistance across yeasts
Authors: Aranguiz Katarina , Horianopoulos Linda C. , Elkin Logan , Abá Kenia Segura , Wrobel Russell L. , Shiu Shin-Han , Rokas Antonis , Hittinger Chris Todd 
Published: August 2024

AbstractReactive oxygen species (ROS) are highly reactive molecules encountered by yeasts during routine metabolism and during interactions with other organisms, including host infection. Here, we characterized the variation in resistance to ROS across the ancient yeast subphylum Saccharomycotina and used machine learning (ML) to identify gene families whose sizes were predictive of ROS resistance. The most predictive features were enriched in gene families related to cell wall organization and included two reductase gene families. We estimated the quantitative contributions of features to each species’ classification to guide experimental validation and showed that overexpression of the old yellow enzyme (OYE) reductase increased ROS resistance inKluyveromyces lactis, whileSaccharomyces cerevisiaemutants lacking multiple mannosyltransferase-encoding genes were hypersensitive to ROS. Altogether, this work provides a framework for how ML can uncover genetic mechanisms underlying trait variation across diverse species and inform trait manipulation for clinical and biotechnological applications.
MoEDAL Search in the CMS Beam Pipe for Magnetic Monopoles Produced via the Schwinger Effect
Authors: Acharya B. , Alexandre J. , Behera S. C. , Benes P. , Bergmann B. , Bertolucci S. , Bevan A. , Brancaccio R. , Branzas H. , Burian P. , Campbell M. , Cecchini S. , Cho Y. M. , de Montigny M. , De Roeck A. , Ellis J. R. , Fairbairn M. , Felea D. , Frank M. , Gould O. , Hays J. , Hirt A. M. , Ho D. L.-J. , Hung P. Q. , Janecek J. , Kalliokoski M. , Lacarrère D. H. , Leroy C. , Levi G. , Margiotta A. , Maselek R. , Maulik A. , Mauri N. , Mavromatos N. E. , Millward L. , Mitsou V. A. , Musumeci E. , Ostrovskiy I. , Ouimet P.-P. , Papavassiliou J. , Patrizii L. , Păvălaş G. E. , Pinfold J. L. , Popa L. A. , Popa V. , Pozzato M. , Pospisil S. , Rajantie A. , Ruiz de Austri R. , Sahnoun Z. , Sakellariadou M. , Sakurai K. , Sarkar S. , Semenoff G. , Shaa A. , Sirri G. , Sliwa K. , Soluk R. , Spurio M. , Staelens M. , Suk M. , Tenti M. , Togo V. , Tuszyński J. A. , Upreti A. , Vento V. , Vives O. 
Published: August 2024

We report on a search for magnetic monopoles (MMs) produced in ultraperipheral Pb-Pb collisions during Run 1 of the LHC. The beam pipe surrounding the interaction region of the CMS experiment was exposed to 184.07  μb−1 of Pb-Pb collisions at 2.76 TeV center-of-mass energy per collision in December 2011, before being removed in 2013. It was scanned by the MoEDAL experiment using a SQUID magnetometer to search for trapped MMs. No MM signal was observed. The two distinctive features of this search are the use of a trapping volume very close to the collision point and ultrahigh magnetic fields generated during the heavy-ion run that could produce MMs via the Schwinger effect. These two advantages allowed setting the first reliable, world-leading mass limits on MMs with high magnetic charge. In particular, the established limits are the strongest available in the range between 2 and 45 Dirac units, excluding MMs with masses of up to 80 GeV at a 95% confidence level.

Published by the American Physical Society
2024
Unveiling the dynamics of revisit intention and word-of-mouth: an attribution theory approach to Halal-friendly hotel attributes and service encounter evaluation
Authors: Patwary Ataul Karim , Alam Mirza Mohammad Didarul , Zainol Noor Azimin , Ashraf Muhammad Umair , Alam Mohammad Nurul , Hayat Naeem , khreis Sawsan Haider Abdullah 
Published: August 2024

PurposeThis study examined the revisit intention of tourists in Muslim-friendly hotels in nexus with Halal-friendly hotel attributes (social environment, facilities, food and beverage, locals and staff, and services), corporate image, customer engagement, perceived value, and service encounter evaluation. It further examined the mediating role of corporate image, customer engagement and perceived value between Halal-friendly hotel attributes and service encounter evaluation.Design/methodology/approachUsing a structured survey instrument, 390 valid responses were gathered from international tourists who visited Malaysia. The collected data were analyzed using Partial Least Squares – Structural Equation Modeling (PLS-SEM) to test the assumed relationships.FindingsThe research shows that corporate image (CI), customer engagement (CE), and perceived value (PV) are directly influenced by Halal-friendly hotel attributes (HFHA) and exert influence on service encounter evaluation (SEE). Findings also suggest the mediating effect of CI, CE, and PV between HFHA and SEE. SEE further positively and significantly enhances the revisit intention and positive word-of-mouth.Practical implicationsThe findings of this study stipulate that hotel owners should ensure the presence of HFHA in their offers to retain their existing guests and ensure their positive communication towards potential visitors through developing a fascinating image, engagement, and lucrative value.Originality/valueGrounded on the attribution theory, this study contributes to the Halal tourism literature by exploring the role of Halal-friendly hotel attributes in enhancing the hotel’s image, customer engagement, and perceived value to enhance positive service encounter evaluation and revisiting intention for the hotel.
Drain amylase values for clinically relevant post‐operative pancreatic fistulae
Authors: Burasakarn Pipit , Hongjinda Sermsak , Thienhiran Anuparp , Fuengfoo Pusit 
Published: August 2024

AbstractAimThis study aims to identify the cut‐off drain amylase (DA) values on the first, third, and fifth post‐operative days (POD1‐DA, POD3‐DA, and POD5‐DA) that are correlated with clinically relevant post‐operative pancreatic fistula (CR‐POPF).Patients and MethodsAll data were retrospectively collected from patients who underwent pancreatectomy at the Department of Surgery, Phramongkutklao Hospital, from January 2015 to December 2023. A total of 195 patients were included in the study.ResultsA total of 195 patients were analysed, including 35 patients with CR‐POPF, with a mean age of 60.84 years. There were no statistically significant differences in demographic data between patients with CR‐POPF and those without. In addition, no statistical differences were observed in pancreatic duct diameter (3 mm vs 2 mm), operative time (468.9 min vs 500.29 min), or blood loss (600 mL vs 600 mL) between the CR‐POPF and no CR‐POPF groups. Length of hospital stays was longer in the CR‐POPF group compared with the no CR‐POPF group (33 days vs 11 days, P = .001). In addition, the CR‐POPF group had significantly higher rates of post‐operative pancreatic haemorrhage (20% vs 2.5%), bile leakage (5.71% vs 0%), delayed gastric emptying (45.71% vs 3.13%), wound complications (34.29% vs 5%), and mortality (17.14% vs 1.88%) compared with the no CR‐POPF group. The optimal cut‐off values for CR‐POPF were 1313 U/L on day 1 (D1; area under the curve [AUC] 0.72, 95% confidence interval [CI] 0.65–0.84, sensitivity 91%, specificity 52%), 492 U/L on D3 (AUC 0.77, 95% CI 0.70–0.83, sensitivity 91%, specificity 64%), and 360 U/L on D5 (AUC 0.65, 95% CI 0.52–0.75, sensitivity 69%, specificity 61%). There were no significant perioperative factors associated with CR‐POPF in our study.ConclusionDA levels of 1313, 492, and 360 U/L on post‐operative D1, D3, and D5, respectively, were associated with CR‐POPF. Drain removal can be safely performed without the risk of CR‐POPF when these levels are met.