bluuebunny/crossref_metadata_2025 huggingface dataset:
Dancing in the purple rain: color affinity and oviposition choices in Aedes sierrensis (Diptera: Culicidae)
Authors: Bibbs Christopher S , Casci Kai , Widmer Thomas D , Dewsnup M Andrew , Jay Kaia , Meredith Kirsten D , Faraji Ary , Vickers Neil J
Published: January 2024

The western tree hole mosquito, Aedes sierrensis (Ludlow) (Diptera: Clucidae), is a pestiferous mosquito with a range extending over the entire pacific seaboard and into portions of the intermountain west. As a peridomestic heartworm vector, it demands at least some level of surveillance to understand its abundance. However, the species is refractory to a majority of conventional vector surveillance approaches for tracking mosquitoes. To find more options for Aedes sierrensis surveillance, a variety of oviposition attractants were evaluated in arena-style choice assays using colony reared adults. A range of infusion treatments (e.g., alfalfa, oak, and beetroot) were examined and then combined with investigations of liquid color as well as ovicup color and entryway position. These studies revealed that Ae. sierrensis have an affinity for purple coloration, plain water, and larger entryway sizes for oviposition cups. A prototype ovicup was 3D-printed using purple filament and multiple types of entryways, and used to re-test infusion waters. No particular attraction differences were detected after normalizing for purple color. Comparisons to black 3D-printed cups yielded surprising observations that male mosquitoes also aggregated on purple cups while females sheltered, but not necessarily oviposited, in black cups. Although this was only a laboratory-based assessment, these studies provide useful information for future field trials of potential oviposition traps for surveillance of Ae. sierrensis.
Relapse and failure rates between CAD/CAM and conventional fixed retainers: a 2-year follow-up of a randomized controlled clinical trial
Authors: Tran Giau , Rucker Ryan , Foley Patrick , Bankhead Brent , Adel Samar M , Kim Ki Beom
Published: January 2024

Background

Retention has been always considered a major challenge in orthodontics. Recently computer-aided design/computer-aided manufacturing (CAD/CAM) fixed retainers (FRs) have been introduced as a marked development in retainer technology, offering potential advantages.

Objective

The objective of this study was to compare the differences in relapse and failure rates in patients treated with FRs using CAD/CAM technology, lab-based technique, and chairside method.

Trial design

A double-blinded, prospective, randomized controlled clinical trial was conducted over a 2-year period at a single centre.

Methods

Participants

Initially, 81 patients were recruited, but only 43 patients who came back for a 2-year retention were included in the study.

Interventions

These patients were divided into three groups: CAD/CAM group with multistranded Stainless Steel wires (CAD/CAM, n = 14), lab group with the same multistranded wires (lab, n = 15), and a chairside group with Stainless Steel Ortho-FlexTech wires (chairside, n = 14).

Outcomes

Inter-canine width (ICW) and Little’s irregularity index were digitally measured from scans at the orthodontic debonding (T1), 6-month retention (T2), 1-year retention (T3), and 2-year retention (T4) visits. All forms of failure were documented and analyzed.

Randomization

Participants were randomly assigned to the three groups using online randomization software (randomization.com) by a statistician who was not involved in the study.

Blinding

Patients were blinded in terms of the FR group to which they were each randomly assigned. The principal investigator was blinded upon data analysis since patients’ records were coded to minimize observer and measurement bias.

Results

Initially 81 patients were assessed for eligibility. Seventy-five patients were randomly allocated into the three study groups. After 2-year follow-up, 43 patients came back for the follow-up and were analyzed. The CAD/CAM group showed significantly less reduction in ICW compared to the chairside group at all time intervals (P < .05) and compared to the lab group at 6 months (P = .038). In terms of LII, the CAD/CAM group exhibited significantly less change than the chairside and lab groups at all time intervals (P < .05). The CAD/CAM group had the lowest failure rate (21.4%), followed by chairside group (28.6%) and then lab group (33.3%), however the differences were insignificant. No harms were observed in the current study.

Conclusion

Within 2 years of fixed retention, CAD/CAM FRs showed significantly less relapse than lab-based and chairside FRs. However, there was no significant difference in failure rates among the groups.

Trial registration

NCT05915273
The relationship between third molar agenesis and craniofacial morphology: a systematic review and meta-analysis
Authors: Le Yushi , Li Mingjuan , Li Feng , Wu Shuxuan , Zhu Chongjie , Wan Qilong
Published: January 2024

Background

Agenesis of third molar agenesis has a higher incidence than other tooth development anomalies. Previous research identified a potential correlation between third molar agenesis and specific craniofacial morphology; however, no systematic review and meta-analysis on this topic currently exists.

Objective

The objective of this systematic review and meta-analysis was to evaluate the association between third molar agenesis and craniofacial sagittal and vertical morphology.

Search methods

An electronic search was conducted on PubMed, Embase, Web of Science, and the Cochrane Library without restrictions on publication year or language; this was supplemented by the manual retrieval of relevant literature.

Selection criteria

Cross-sectional studies that compared craniofacial morphology using angular and linear measurements obtained from lateral cephalography between patients with third molar agenesis and those without were included.

Data collection and analysis

The quality assessment of the enrolled articles was evaluated by the Joanna Briggs Institute critical appraisal tool. Meta-analysis and sensitivity analysis were performed by Review Manager software (The Cochrane Collaborative, version 5.4, Cochrane IMS).

Results

A total of seven studies were included. Meta-analysis demonstrated that the ANB (mean differences (MD) = –0.75, 95% CI: –1.31 to –0.19, P < 0.01), palate length (ANS–PNS, MD = –1.68, 95% CI: –2.24 to –1.11, P < 0.01), and mandibular length (Go-Pog, MD = –0.36, 95% CI: –0.59 to –0.13, P < 0.01) were smaller in patients with third molar agenesis. With regard to vertical craniofacial morphology, the mandibular plane angle (MP-FH; MD = –1.88, 95% CI: –3.45 to –0.31, P = 0.02), gonial angle (gonial angle; MD = –1.73, 95% CI: –2.69 to –0.77, P < 0.01) and lower face height (lower face heigh angle; MD = –1.36, 95% CI: –1.94 to –0.77, P < 0.01) were smaller in patients with third molar agenesis, indicating a flatter or brachyfacial skeletal pattern.

Conclusions

The results of this study suggest that third molar agenesis maybe associated with a reduced maxillary length and a flatter mandible. However, these findings need to be interpreted with caution due to inconsistencies in the certainty of evidence.

Clinical Trial Registration

PROSPERO (CRD42023448226).
‘Real National Work’: The Politics of Nazi Race Science in Upper Silesia, 1934–1942
Authors: Evans Andrew D
Published: January 2024

This article analyses the political and scientific controversy surrounding a race science project undertaken by the anthropologist Egon Freiherr von Eickstedt under National Socialism. Beginning in 1934, Eickstedt and his team of assistants conducted a series of racial studies on the population of Upper Silesia, a contested borderland in East Prussia. Motivated by a nationalist desire to counter the work of Polish anthropologists in the region, Eickstedt argued that the population of Upper Silesia belonged predominantly to the so-called ‘Nordic race’ and that the territory was thus fundamentally German. Nazi officials, however, viewed the Silesian studies with alarm, since the results also appeared to show that people in the area were a racial mixture and that the ‘Nordic race’ made up less than 40 per cent of the population in some locales. They worried that Eickstedt’s studies could undermine Germany’s territorial claims in the region and threaten national unity. The ensuing controversy presents a case in which the anthropological concept of ‘race’, rather than serving its usual role in Nazi thinking as the biological underpinning of the Volk (or people), threatened to undermine its coherence. The reaction to Eickstedt’s Silesian studies demonstrates a lack of consensus on race within the Nazi system, suggesting that understandings of race in Nazi Germany were neither as coherent nor as uniform as the paradigm of the ‘racial state’ has assumed.
Trademark Protection Versus Parodic Use in Commerce: A Comparative Analysis of the US Approach Post Jack Daniel’s Properties v. VIP Products and the German Likelihood of Confusion Analysis
Authors: Chiampi Ohly Diana D
Published: January 2024

In June 2023, the US Supreme Court delivered its highly anticipated verdict in Jack Daniel’s Properties v. VIP Products. The case involves a parodic use of the famous Jack Daniel’s Tennessee whiskey trade dress, name, logo and appearance by VIP Products, which sells dog toys called ‘Silly Squeakers.’ The disputed toy, named ‘Bad Spaniels,’ resembles the whiskey bottle in shape and design but with humorous alterations.

Jack Daniel’s argued that this use could confuse consumers and harm the company’s reputation. VIP Products, on the other hand, claimed it was exercising its First Amendment right to free speech through parody. Jack Daniel’s requested VIP Products to stop advertising and selling the toy.

The central issue is the balance between brand protection under US Trademark Law and the right to a parodic use in a commercial context when a mark is used as a mark with a source-identifying purpose. Additionally, the impact of consumer surveys for determining the likelihood of confusion in case of an infringement action is emphasized. Overall, the case raises critical questions about trademark protection and freedom of speech, with potential implications for future parodic uses of famous marks in commercial contexts.

The distinction between actions for infringement and dilution by tarnishment lies in their respective purposes. Dilution actions aim to safeguard the reputation of a famous mark’s owner, while infringement actions seek to prevent confusion among consumers. These fundamental principles hold true in both US and German trademark law. The forthcoming analysis will delve into the implications and consequences of the US Supreme Court’s ruling, comparing it with pertinent German case law concerning freedom of speech and artistic expression. Particular focus will be given to the potential authorization of parodic use of a mark resembling another’s trademark for commercial purposes. Notably, a relevant case involving canines, referred to as the ‘Leaping Poodle,’ will be central to this contemplation.
Older Adults With Inflammatory Bowel Disease Are at Higher Risk of Developing Antibodies to Infliximab
Authors: Faye Adam S , Lee Kate E , Hudesman David , Dervieux Thierry
Published: January 2024

Lay Summary

Although older age is thought to confer immunosenescence, we found that older adults with inflammatory bowel disease are independently at higher risk to develop antibodies to infliximab. Additionally, older adults are less likely to receive escalated doses of infliximab.
Infliximab Monotherapy vs Combination Therapy for Pediatric Crohn’s Disease Exhibit Similar Pharmacokinetics
Authors: Colman Ruben J , Vuijk Stephanie A , Mathôt Ron A A , Van Limbergen Johan , Jongsma Maria M E , Schreurs Marco W J , Minar Phillip , de Ridder Lissy , D’Haens Geert R A M
Published: January 2024

Background

The use of concomitant azathioprine may improve efficacy and pharmacokinetic (PK) properties of infliximab (IFX) but is also associated with an increased risk of adverse events. Proactive therapeutic drug monitoring (pTDM) of IFX monotherapy is an alternative strategy to improve PK. The aim of this study was to evaluate whether IFX with an immunomodulator (combo) has PK benefits over IFX-pTDM (mono) in pediatric Crohn’s disease (CD).

Methods

This PK analysis included pediatric CD patients who started either IFX combo (TISKids study) or IFX mono with pTDM (REFINE cohort). Combo and mono IFX trough levels (TLs) and antibodies-to-infliximab were assessed at infusion 3, 4, and 5. A population PK model was built to compare IFX PK outcomes (clearance [CL], TLs and cumulative exposure) between combo and mono groups at infusion 4 and 5. Clinical response and steroid-free clinical remission (SFCR) was assessed at infusion 4 and 5.

Results

This study included 128 pediatric CD patients (66 mono and 62 combo). At infusion 5, there was no significant difference between mono and combo median TLs 4.1 µg/mL (2.1, 7.8) vs 5.9 µg/mL (3.2, 9.4; P = .14) or median CL 0.26 L/d (0.21, 0.32) vs 0.26 L/d (0.21, 0.33; P = .81). Mono patients had a lower SFCR rate at infusion 5 (53% [31 of 59] vs 80% [32 of 40]; P = .01). Clinical response rates were significantly higher among combo than mono patients at both infusion 4 and 5.

Conclusions

This study suggests that there are no PK differences (TLs and CL) between combo and mono therapy in pediatric CD patients who started IFX.
Moving Lexicographical Mountains for the Community: A Comparison of Print and Online Resources of Mountaineering English
Authors: Leuckert Sven
Published: January 2024

The specialised community of (Anglophone) mountaineers began producing their own systematic lexicographical output in the second half of the 19th century. Since then, digitalisation has led to more and more online resources of ‘Mountaineering English’ (MountE) being created. In this contribution, a major print dictionary by Samet (2011) is compared to four online resources of MountE in terms of their micro-structure and their macro-structure. The study shows that, with few exceptions, the online resources make little use of digital affordances; the print dictionary is the most comprehensive and the most complex in almost all aspects. However, there are important differences between all five resources as far as their micro- and macro-structures are concerned. Overall, the paper highlights that, while the lexicographical efforts of the community are laudable, more work needs to be done.
Political Turmoil and Attitude Change Among the Diaspora. The Impact of the 2016 Attempted Military Coup on Homeland Orientation Among Recent Turkish Immigrants in the Netherlands
Authors: Lubbers Marcel , Fleischmann Fenella , Geurts Nella , Gijsberts Mérove
Published: January 2024

This study underscores the significance of home-country events in shaping connections between diaspora and their country of origin. Focusing on immigrants from Turkey who migrated to the Netherlands in 2012/2013, our panel-study sheds light on post-migration developments concerning interest in Turkish politics and sense of identification with Turkey. Leveraging the 2016 failed military coup as a natural experiment, we apply also rally effect theory. Our findings reveal that political interest increased in the aftermath of the coup attempt and stronger so among immigrants who supported the AK-party. Conversely, identification with Turkey declined, while remaining stable among migrants identifying as Turkish majority members. This research demonstrates the importance of examining responses to home-country events, elucidating on variations observed across subgroups.
Is Science for the Rich and Powerful? Investigating the Relation Between Income and Trust in Science Across 145 Countries
Authors: Fuglsang Simon
Published: January 2024

Prior research indicates that income relates to trust in science. However, no prior studies exclusively focus on this relationship, leaving questions on the characteristics and universality of the relationship unanswered. This study enriches our understanding of the relationship between individual-level income and trust in science on 3 fronts. First, this study explicates income into the dimensions of relative income (objective economic status) and subjective income (perceived economic hardship and satisfaction). Second, it provides a global overview by assessing the aforementioned relationship across 145 countries, investigating whether the relationship is universal or contingent on country-level characteristics. Third, the study investigates moderators at country and individual-level. Results indicate that subjective income is more strongly related to trust in science than relative income and that it is strongest in previously studied populations. The relationship is moderated by institutional quality (which increases the relationship) and economic climate (GDP per capita increasing the relationship) at the country-level, and science efficacy (increasing the relationship) and trust in government (decreasing the relationship) at the individual-level.
Partisan Risk Tolerance for In-Person Voting During the Pandemic: Survey Evidence from the U.S. 2020 Election
Authors: Whitt Sam , Yanus Alixandra B , McDonald Brian , Kifer Martin
Published: January 2024

To what extent will people turn out to vote under high-risk, high-cost circumstances? We examine the impact of risk tolerance on willingness to vote in person in the U.S. 2020 election during the coronavirus disease-2019 (COVID-19) pandemic. Our results are based on pre- and postelection surveys that indicated partisan Republicans were more willing to vote in person than Democrats or Independents, who preferred voting by mail. Using behavioral measures of risk-taking, we find that Republican in-person voting is predicted by greater generalized and pandemic-related risk tolerance compared with Democrats and nonpartisans. To explain risk tolerance, we employ prospect theory to illustrate how Republicans’ fear of electoral loss, alongside conservative elite and media efforts to downplay COVID-19 severity, likely influenced Republican readiness to assume risks of in-person voting during the pandemic. We urge scholars to consider the implications of risk tolerance for models of electoral behavior under high-risk and high-cost voting conditions.
Formality in the Deligne-Langlands Correspondence
Authors: Antor Jonas
Published: January 2024

The Deligne-Langlands correspondence parametrizes irreducible representations of the affine Hecke algebra $\mathcal{H}^{\operatorname{aff}}$ by certain perverse sheaves. We show that this can be lifted to an equivalence of triangulated categories. More precisely, we construct for each central character $\chi $ of $\mathcal{H}^{\operatorname{aff}}$ an equivalence of triangulated categories between a perfect derived category of dg-modules $D_{\operatorname{perf}}(\mathcal{H}^{\operatorname{aff}}/(\ker (\chi )) - \operatorname{dgMod})$ and the triangulated category generated by the corresponding perverse sheaves. The main step in this construction is a formality result that we prove for a wide range of ‘Springer sheaves’.
Downregulation of TCF7 and LEF1 is a key determinant of tumor-infiltrating regulatory T-cell function
Authors: Kidani Yujiro , Kitagawa Yohko , Hagiwara Masaki , Kawashima Atsunari , Kanazawa Takayuki , Wada Hisashi , Uemura Motohide , Nonomura Norio , Motooka Daisuke , Nakamura Shota , Ohkura Naganari , Sakaguchi Shimon
Published: January 2024

Forkhead box P3 (Foxp3)-expressing regulatory T (Treg) cells play essential roles in immune homeostasis but also contribute to establish a favorable environment for tumor growth by suppressing anti-tumor immune responses. It is thus necessary to specifically target tumor-infiltrating Treg cells to minimize effects on immune homeostasis in cancer immunotherapy. However, molecular features that distinguish tumor-infiltrating Treg cells from those in secondary lymphoid organs remain unknown. Here we characterize distinct features of tumor-infiltrating Treg cells by global analyses of the transcriptome and chromatin landscape. They exhibited activated phenotypes with enhanced Foxp3-dependent transcriptional regulation, yet being distinct from activated Treg cells in secondary lymphoid organs. Such differences may be attributed to the extensive clonal expansion of tumor-infiltrating Treg cells. Moreover, we found that TCF7 and LEF1 were specifically downregulated in tumor-infiltrating Treg cells both in mice and humans. These factors and Foxp3 co-occupied Treg suppressive function-related gene loci in secondary lymphoid organ Treg cells, whereas the absence of TCF7 and LEF1 accompanied altered gene expression and chromatin status at these gene loci in tumor-infiltrating Treg cells. Functionally, overexpression of TCF7 and LEF1 in Treg cells inhibited the enhancement of Treg suppressive function upon activation. Our results thus show the downregulation of TCF7 and LEF1 as markers of highly suppressive Treg cells in tumors and suggest that their absence controls the augmentation of Treg suppressive function in tumors. These molecules may be potential targets for novel cancer immunotherapy with minimum effects on immune homeostasis.
P03 Amikacin drug levels and efficacy—a 3 month remissive study
Authors: Coutinho Ana
Published: January 2024

Background

The therapeutic drug monitoring (TDM) of toxic drugs is a routine practice in our 200-bed hospital. Amikacin is not often used except in MDR bacteria. TDM is based on trough and peak levels of aminoglycosides, although AUC TDM may be the way forward, as discussed in the conclusions. According to the literature, measurement of serum amikacin levels is indicated in cases when prolonged aminoglycoside therapy is expected or in patients with compromised renal function and is not recommended for aminoglycoside use for less than 5–7 days or for treatment of mild infections in patients with no risk factors for drug toxicity.

Objectives

This study delivers some controversy on not to recommend monitoring for aminoglycoside use for less than 5–7 days, or for treatment of mild infections in patients with no risk factors for drug toxicity.

Methods

A retrospective study was conducted in our hospital between May and June 2023. Five patients aged 62–82 years on amikacin therapy for 5 to 10 days were included, all with Klebsiella pneumoniae OXA-48 UTI. At least two peak and trough samples were collected, and data were submitted to the Precise PK© software for precision dosing. The software is designed to predict population-based levels and patient-based levels. Interpretation of these values by pharmacists delivers optimized/viable amikacin intervals and dose individualized recommendations.

Results

Results are shown in Table 1.

Conclusions

Serum amikacin monitoring should guide therapy to ensure adequate levels, especially in Gram-negative resistant bacterial infections. According to these results, with Gram-negative resistant bacteria, it is worth monitoring even the short treatments—as seen in Patient 3. AUC TDM instead of peak TDM might be the way forward— this obviates distribution phase underdosing and delivers more accurate correlation to efficacy after changing intervals.
Diagnostic Test Utilization Management Strategies as an Opportunity for Equitable Access to Molecularly Informed Clinical Care
Authors: Hou Helen X , Li Annie , Thierauf Julia C , Lennerz Jochen K
Published: January 2024

Background

Companion diagnostics are an essential component of oncology. Timing, cost, and adaptability to new drug/biomarker approvals represent challenges in assuring value-based care. Overcoming these challenges requires strategies for equitable access and efficient integration.

Methods

Based on prior laboratory improvements and payor policy implementations, we define equitable access in laboratory testing and conceptualized a framework for initiatives that optimize diagnostic performance.

Results

We define equitable access as an imperative goal seeking to remove disparities that may arise due to financial hardships, geographical isolation, cultural differences, or other social determinants of health. We distinguish (a) utilization, as the practice pattern of ordered tests, (b) utilization management, as the evidence-based guidance of the utilization decisions, and (c) utilization management strategies, defined as the tools and techniques used to influence decision-making. These 3 dimensions establish a standardized vocabulary to clarify equitable alignment of strategies in specific care pathways. Alignment of logistic, administrative, and financial incentive structures is paramount when creating sustainable personalized care pathway programs.

Conclusions

Strategies to accomplish equitable and meaningful use of diagnostic tests can help enhance access to timely and accurate diagnoses, ultimately leading to improved patient outcomes.
Interrogating Pharmacogenetics Using Next-Generation Sequencing
Authors: Ji Yuan , Shaaban Sherin
Published: January 2024

Background

Pharmacogenetics or pharmacogenomics (PGx) is the study of the role of inherited or acquired sequence change in drug response. With the rapid evolution of molecular techniques, bioinformatic tools, and increased throughput of functional genomic studies, the discovery of PGx associations and clinical implementation of PGx test results have now moved beyond a handful variants in single pharmacogenes and multi-gene panels that interrogate a few pharmacogenes to whole-exome and whole-genome scales. Although some laboratories have adopted next-generation sequencing (NGS) as a testing platform for PGx and other molecular tests, most clinical laboratories that offer PGx tests still use targeted genotyping approaches.

Content

This article discusses primarily the technical considerations for clinical laboratories to develop NGS-based PGx tests including whole-genome and whole-exome sequencing analyses and highlights the challenges and opportunities in test design, content selection, bioinformatic pipeline for PGx allele and diplotype assignment, rare variant classification, reporting, and briefly touches a few additional areas that are important for successful clinical implementation of PGx results.

The accelerated speed of technology development associated with continuous cost reduction and enhanced ability to interrogate complex genome regions makes it inevitable for most, if not all, clinical laboratories to transition PGx testing to an NGS-based platform in the near future. It is important for laboratories and relevant professional societies to recognize both the potential and limitations of NGS-based PGx profiling, and to work together to develop a standard and consistent practice to maximize the variant or allele detection rate and utility of PGx testing.
Benefits of Implementing Reflex Genomic Analysis for Nonsmall Cell Lung Cancer
Authors: Smith Benjamin F , Hampel Ken J , Sidiropoulos Nikoletta
Published: January 2024

Background

Molecular biomarker analysis is standard of care in advanced nonsmall cell lung cancer (NSCLC). Pathologist-driven reflex testing protocols are one approach to initiating this analysis. Two years after insourcing genomic analysis at our institution, a reflex testing protocol for advanced NSCLC was initiated.

Methods

A retrospective review of the records of 578 NSCLC biopsies was performed to assess the impact of 3 genomic testing workflows (send-out, in-house clinician-ordered, and in-house reflex) on time to initiation of molecular testing [initiation time (IT)], reporting time (RT), proportion of test failures, and test ordering practices. The proportion of test failures by test methodology was also assessed.

Results

IT was lowest for reflex protocol orders (mean weekdays: 30.0 send-out, 27.4 in-house clinician-ordered, 0.95 reflex). Test failure was highest for send-out testing (31.7% vs. 10% each for in-house clinician-ordered and reflex). RT remained consistent across the 3 workflows (mean weekdays: 11.1 send-out, 11.9 in-house clinician-ordered, and 11.4 reflex). Guideline-congruent molecular testing increased upon insourcing genomic analysis and again upon implementing reflex testing with a reduction in nonbiomarker informed care (58.8% send-out, 19.5% in-house clinician-ordered, 11.5% reflex).

Conclusions

Implementation of reflex in-house genomic analysis for advanced NSCLC ensured consistency in RT and significantly decreased IT and proportion of test failures. Insourcing genomic analysis and thoughtful care pathway design improve equitable access to molecular biomarker analysis and mitigate nonbiomarker informed cancer care in NSCLC.
Establishing Population Values for Chlorine Exposure in the United States (2015–2016) Using 2 Chlorine Biomarkers, 3-Chlorotyrosine and 3,5-Dichlorotyrosine
Authors: Boles Stephanie L , Pantazides Brooke G , Perez Jonas W , Sternberg Maya R , Crow Brian S , Blake Thomas A
Published: January 2024

Background

In the United States, 12 million short tons of chlorine are manufactured and transported each year. Due to the volume of this volatile chemical, large- and small-scale chemical exposures occur frequently. To diagnose and treat potentially exposed individuals, reference range values for confirmatory biomarkers are required to differentiate between normal and abnormal exposure levels.

Methods

Serum surplus samples (n = 1780) from the National Health and Nutrition Examination Survey (NHANES) 2015–2016 were measured for 2 chlorine biomarkers, 3-chlorotyrosine (Cl-Tyr) and 3,5-dichlorotyrosine (Cl2-Tyr), by liquid chromatography coupled to a triple quadrupole mass spectrometer. We evaluated demographic factors associated with elevated biomarker levels.

Results

Participant samples were analyzed for the chlorine biomarkers Cl-Tyr and Cl2-Tyr. In the unweighted analysis of these samples, 1349 (75.8%) were under the limit of detection (< LOD) of 2.50 ng/mL for Cl-Tyr and 1773 (99.6%) were < LOD for Cl2-Tyr. Samples within the method reportable range were 2.50 to 35.6 ng/mL for Cl-Tyr and 2.69 to 11.2 ng/mL for Cl2-Tyr. Since only 7 of the 1780 participants had detectable Cl2-Tyr, statistical analysis was limited to Cl-Tyr. Of the demographic characteristics examined, age, body mass index (BMI), estimated glomerular filtration rate (eGFR), and sex exhibited statistically significant differences in the weighted prevalence of detectable Cl-Tyr.

Conclusions

This is the first reported set of Cl-Tyr and Cl2-Tyr population values for the United States. This population range coupled with NHANES demographic information could help healthcare professionals distinguish between normal and abnormal chlorine biomarker levels in an emergency. With this information, an inference could be made when determining acute chlorine exposure in individuals.
Perturbed collagen metabolism underlies lymphatic recanalization failure in Gata2 heterozygous deficient mice
Authors: Watanabe-Asaka Tomomi , Hayashi Moyuru , Harada Takuya , Uemura Satoshi , Takai Jun , Nakamura Yasuhiro , Moriguchi Takashi , Kawai Yoshiko
Published: January 2024

Lymphedema has become a global health issue following the growing number of cancer surgeries. Curative or supportive therapeutics have long been awaited for this refractory condition. Transcription factor GATA2 is crucial in lymphatic development and maintenance, as GATA2 haploinsufficient disease often manifests as lymphedema. We recently demonstrated that Gata2 heterozygous deficient mice displayed delayed lymphatic recanalization upon lymph node resection. However, whether GATA2 contributes to lymphatic regeneration by functioning in the damaged lymph vessels' microenvironment remains explored. In this study, our integrated analysis demonstrated that dermal collagen fibers were more densely accumulated in the Gata2 heterozygous deficient mice. The collagen metabolism-related transcriptome was perturbed, and collagen matrix contractile activity was aberrantly increased in Gata2 heterozygous embryonic fibroblasts. Notably, soluble collagen placement ameliorated delayed lymphatic recanalization, presumably by modulating the stiffness of the extracellular matrix around the resection site of Gata2 heterozygous deficient mice. Our results provide valuable insights into mechanisms underlying GATA2-haploinsufficiency-mediated lymphedema and shed light on potential therapeutic avenues for this intractable disease.
Point-of-care neutrophil and monocyte surface markers differentiate bacterial from viral infections at the emergency department within 30 min
Authors: Jukema Bernard N , de Hond Titus A P , Kroon Martijn , Maranus Anna E , Koenderman Leo , Kaasjager Karin A H
Published: January 2024

Rapid discrimination between viral and bacterial infections in a point-of-care setting will improve clinical outcome. Expression of CD64 on neutrophils (neuCD64) increases during bacterial infections, whereas expression of CD169 on classical monocytes (cmCD169) increases during viral infections. The diagnostic value of automated point-of-care neuCD64 and cmCD169 analysis was assessed for detecting bacterial and viral infections at the emergency department. Additionally, their value as input for machine learning models was studied. A prospective observational cohort study in patients suspected of infection was performed at an emergency department. A fully automated point-of-care flow cytometer measured neuCD64, cmCD169, and additional leukocyte surface markers. Flow cytometry data were gated using the FlowSOM algorithm. Bacterial and viral infections were assessed in standardized clinical care. The sole and combined diagnostic value of the markers was investigated. Clustering based on unsupervised machine learning identified unique patient clusters. Eighty-six patients were included. Thirty-five had a bacterial infection, 30 had a viral infection, and 21 had no infection. neuCD64 was increased in bacterial infections (P < 0.001), with an area under the receiver operating characteristic curve (AUROC) of 0.73. cmCD169 was higher in virally infected patients (P < 0.001; AUROC 0.79). Multivariate analyses incorporating additional markers increased the AUROC for bacterial and viral infections to 0.86 and 0.93, respectively. The additional clustering identified 4 distinctive patient clusters based on infection type and outcome. Automated neuCD64 and cmCD169 determination can discriminate between bacterial and viral infections. These markers can be determined within 30 min, allowing fast infection diagnostics in the acute clinical setting.
The jet composition of GRB 230307A: Poynting-flux-dominated outflow?
Authors: Du Zhao-Wei , Lü HouJun , Liu Xiaoxuan , Liang EnWei
Published: January 2024

The jet composition of GRB plays an important role in understanding the energy dissipation and radiation mechanisms in GRB physics, but it is poorly constrained from the observational data. Recently, an interesting long-duration GRB 230307A with redshift z = 0.065 has attracted great attention. The lack of detected thermal emission and mini-structure of prompt emission light curve of this burst suggest that the outflow is Poynting-flux-dominated and point towards the ICMART model. In this paper, we invoke two independent methods to investigate the jet composition of GRB 230307A. The high magnetization parameter (σ > 7 or ever large) for R0 = 1010 cm that is used to suppress thermal component, strongly suggests that a significant fraction of the outflow energy is likely in a Poynting flux entrained with the baryonic matter. Moreover, it is found that the radiation efficiency of this burst for typical values ϵe = 0.1 and ϵB = 0.01 can reach as high as $~50{{\ \rm per\ cent}}$ which disfavours the internal shock model, but is consistent with ICMART model. Finally, a possible unified picture to produce GRB 230307A originated from a compact star merger is also discussed.
Risk factor analysis for a rapid progression of chronic kidney disease
Authors: Vestergaard Anne H S , Jensen Simon K , Heide-Jørgensen Uffe , Frederiksen Line E , Birn Henrik , Jarbøl Dorte E , Søndergaard Jens , Persson Frederik , Thomsen Reimar W , Christiansen Christian F
Published: January 2024

Background

Chronic kidney disease (CKD) is a growing global health concern. Identifying individuals in routine clinical care with new-onset CKD at high risk of rapid progression of the disease is imperative to guide allocation of prophylactic interventions, but community-based data are limited. We aimed to examine the risk of rapid progression, kidney failure, hospitalization and death among adults with incident CKD stage G3 and to clarify the association between predefined risk markers and rapid CKD progression.

Methods

Using plasma creatinine measurements for the entire Danish population from both hospitals and primary care, we conducted a nationwide, population-based cohort study, including adults in Denmark with incident CKD stage G3 in 2017–2020. We estimated 3-year risks of rapid progression (defined by a confirmed decline in estimated glomerular filtration rate of ≥5 mL/min/1.73 m2/year), kidney failure, all-cause hospitalization and death. To examine risk markers, we constructed a heat map showing the risk of rapid progression based on predefined markers: albuminuria, sex, diabetes and hypertension/cardiovascular disease.

Results

Among 133 443 individuals with incident CKD stage G3, the 3-year risk of rapid progression was 14.6% [95% confidence interval (CI) 14.4–14.8]. The 3-year risks of kidney failure, hospitalization and death were 0.3% (95% CI 0.3–0.4), 53.3% (95% CI 53.0–53.6) and 18.1% (95% CI 17.9–18.4), respectively. In the heat map, the 3-year risk of rapid progression ranged from 7% in females without albuminuria, hypertension/cardiovascular disease or diabetes, to 46%–47% in males and females with severe albuminuria, diabetes and hypertension/cardiovascular disease.

Conclusion

This population-based study shows that CKD stage G3 is associated with considerable morbidity in a community-based setting and underscores the need for optimized prophylactic interventions among such patients. Moreover, our data highlight the potential of using easily accessible markers in routine clinical care to identify individuals who are at high risk of rapid progression.
Bioinspired polysaccharide-based nanocomposite membranes with robust wet mechanical properties for guided bone regeneration
Authors: Xiao Jian-Hong , Zhang Zhen-Bang , Li JiaHao , Chen Si-Ming , Gao Huai-Ling , Liao YinXiu , Chen Lu , Wang ZiShuo , Lu YiFan , Hou YuanZhen , Wu HengAn , Zou DuoHong , Yu Shu-Hong
Published: January 2024

Polysaccharide-based membranes with excellent mechanical properties are highly desired. However, severe mechanical deterioration under wet conditions limits their biomedical applications. Here, inspired by the structural heterogeneity of strong yet hydrated biological materials, we propose a strategy based on heterogeneous crosslink-and-hydration (HCH) of a molecule/nano dual-scale network to fabricate polysaccharide-based nanocomposites with robust wet mechanical properties. The heterogeneity lies in that the crosslink-and-hydration occurs in the molecule-network while the stress-bearing nanofiber-network remains unaffected. As one demonstration, a membrane assembled by bacterial cellulose nanofiber-network and Ca2+-crosslinked and hydrated sodium alginate molecule-network is designed. Studies show that the crosslinked-and-hydrated molecule-network restricts water invasion and boosts stress transfer of the nanofiber-network by serving as interfibrous bridge. Overall, the molecule-network makes the membrane hydrated and flexible; the nanofiber-network as stress-bearing component provides strength and toughness. The HCH dual-scale network featuring a cooperative effect stimulates the design of advanced biomaterials applied under wet conditions such as guided bone regeneration membranes.
Early Prediction of Poststroke Rehabilitation Outcomes Using Wearable Sensors
Authors: O’Brien Megan K , Lanotte Francesco , Khazanchi Rushmin , Shin Sung Yul , Lieber Richard L , Ghaffari Roozbeh , Rogers John A , Jayaraman Arun
Published: January 2024

Objective

Inpatient rehabilitation represents a critical setting for stroke treatment, providing intensive, targeted therapy and task-specific practice to minimize a patient’s functional deficits and facilitate their reintegration into the community. However, impairment and recovery vary greatly after stroke, making it difficult to predict a patient’s future outcomes or response to treatment. In this study, the authors examined the value of early-stage wearable sensor data to predict 3 functional outcomes (ambulation, independence, and risk of falling) at rehabilitation discharge.

Methods

Fifty-five individuals undergoing inpatient stroke rehabilitation participated in this study. Supervised machine learning classifiers were retrospectively trained to predict discharge outcomes using data collected at hospital admission, including patient information, functional assessment scores, and inertial sensor data from the lower limbs during gait and/or balance tasks. Model performance was compared across different data combinations and was benchmarked against a traditional model trained without sensor data.

Results

For patients who were ambulatory at admission, sensor data improved the predictions of ambulation and risk of falling (with weighted F1 scores increasing by 19.6% and 23.4%, respectively) and maintained similar performance for predictions of independence, compared to a benchmark model without sensor data. The best-performing sensor-based models predicted discharge ambulation (community vs household), independence (high vs low), and risk of falling (normal vs high) with accuracies of 84.4%, 68.8%, and 65.9%, respectively. Most misclassifications occurred with admission or discharge scores near the classification boundary. For patients who were nonambulatory at admission, sensor data recorded during simple balance tasks did not offer predictive value over the benchmark models.

Conclusion

These findings support the continued investigation of wearable sensors as an accessible, easy-to-use tool to predict the functional recovery after stroke.

Impact

Accurate, early prediction of poststroke rehabilitation outcomes from wearable sensors would improve our ability to deliver personalized, effective care and discharge planning in the inpatient setting and beyond.
Early monitoring of anti-infliximab antibodies by drug-tolerant assay predicts later immunogenicity and drug survival in rheumatic diseases
Authors: Martínez-Feito Ana , Novella-Navarro Marta , Hernández-Breijo Borja , Nozal Pilar , Peiteado Diana , Villalba Alejandro , Nuño Laura , Monjo Irene , Pascual-Salcedo Dora , Balsa Alejandro , Plasencia-Rodríguez Chamaida
Published: January 2024

Objectives

To investigate the appearance of anti-drug antibodies (ADA) against infliximab (IFX) determined by drug-sensitive and drug-tolerant assays and their relationship with drug levels and drug survival.

Methods

This longitudinal observational study included 45 patients with RA and 61 with SpA. Serum samples were obtained at weeks 2, 6, 12, 24 and 52. Serum IFX levels were measured by a capture ELISA and ADA by an in-house drug-sensitive two-site (bridging) ELISA (bELISA) and a commercially available drug-tolerant ELISA (IDK, Immundiagnostik, Germany).

Results

ADA were detected earlier by IDK than by bELISA. Once ADA appeared, positivity persisted throughout the study period. Patients who were bELISA ADA+ had higher IDK ADA levels (than bELISA ADA– patients). Circulating IFX levels were detected in all patients except those found to be bELISA ADA+. Serum IFX levels were lower in IDK ADA+ than in IDK ADA– patients. Most patients (64%) discontinued due to inefficacy. The early onset of immunogenicity was related to IFX survival. In both RA and SpA, the median survival (years) was shorter in patients with earlier development of ADA (IDK+ before or at week 24) than those who became IDK+ later (after week 24) or never developed ADA.

Conclusion

A drug-tolerant assay detects ADA during IFX therapy earlier and more frequently than a drug-sensitive assay. The onset of immunogenicity detected by drug-tolerant assays is related to the subsequent detection of ADA by drug-sensitive assays and drug survival.
Comparative Analysis of the Avirulence Effectors Produced by the Fungal Stem Rust Pathogen of Wheat
Authors: Lubega Jibril , Figueroa Melania , Dodds Peter N. , Kanyuka Kostya
Published: January 2024

Crops are constantly exposed to pathogenic microbes. Rust fungi are examples of these harmful microorganisms, which have a major economic impact on wheat production. To protect themselves from pathogens like rust fungi, plants employ a multilayered immune system that includes immunoreceptors encoded by resistance genes. Significant efforts have led to the isolation of numerous resistance genes against rust fungi in cereals, especially in wheat. However, the evolution of virulence of rust fungi hinders the durability of resistance genes as a strategy for crop protection. Rust fungi, like other biotrophic pathogens, secrete an arsenal of effectors to facilitate infection, and these are the molecules that plant immunoreceptors target for pathogen recognition and mounting defense responses. When recognized, these effector proteins are referred to as avirulence (Avr) effectors. Despite the many predicted effectors in wheat rust fungi, only five Avr genes have been identified, all from wheat stem rust. Knowledge of the Avr genes and their variation in the fungal population will inform deployment of the most appropriate wheat disease-resistance genes for breeding and farming. The review provides an overview of methodologies as well as the validation techniques that have been used to characterize Avr effectors from wheat stem rust.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Identification and validation of genes associated with aging‐related cardiovascular disease
Authors: Li Jing , Jiang Shengping , Huang Chengyun , Lu Baihui , Yang Xiaolong
Published: January 2024

Aging is acknowledged as the most significant risk factor for cardiovascular disease (CVD). This study sought to identify and validate potential aging‐related genes associated with CVD by using bioinformatics. The confluence of the limma test, weighted correlation network analysis (WGCNA), and 2129 aging and senescence‐associated genes led to the identification of aging‐related differential expression genes (ARDEGs). By using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), potential biological roles and pathways of ARDEGs were identified. To find the significantly different functions between CVD and non‐cardiovascular disease (nCVD) and to reckon the processes score, enrichment analysis of all genes was carried out using gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). By using GO and KEGG, potential biological roles and pathways of ARDEGs were identified. To evaluate the immune cell composition of the immune microenvironment, we performed an immune infiltration analysis on the dataset from the training group. We were able to acquire four ARDEGs (PTGS2, MMP9, HBEGF, and FN1). Aging, cellular senescence, and nitric oxide signal transduction were selected for biological function analysis. The diagnostic value of the four ARDEGs in distinguishing CVD from nCVD samples was deemed to be favorable. This research identified four ARDEGs that are associated with CVD. This study provides insight into prospective novel biomarkers for aging‐related CVD diagnosis and progression monitoring.