bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world efficacy of second-line therapies for Helicobacter pylori: a population-based study
Authors: Guo Chuan-Guo , Jiang Fang , Li Yueyue , Chen Yijun , Wu Jialin , Zhang Shutian , Leung Wai K
Published: July 2024

Background

With the increasing prevalence of antibiotic resistance, real-world data on the optimal empirical second-line therapy for Helicobacter pylori are still limited.

Objectives

To evaluate the real-world efficacy of various second-line therapies for H. pylori.

Patients and methods

This was a retrospective population-based cohort study of all H. pylori-infected patients who had received the second-line treatment after the failure of primary clarithromycin triple therapy in Hong Kong between 2003 and 2018. The retreatment success rates of different second-line therapies were evaluated.

Results

A total of 7591 patients who received second-line treatment were included. Notably, the most commonly prescribed regimen was still clarithromycin triple therapy, but the frequency of use had decreased from 59.5% in 2003–06 to 28.7% in 2015–18. Concomitant non-bismuth quadruple therapy had emerged as the commonest regimen (from 3.3% to 43.9%). In a validation analysis, the sensitivity and specificity of retreatment-inferred second-line treatment failure were 88.3% and 97.1%, respectively. The overall success rate of second-line therapies was 73.6%. Bismuth quadruple therapy had the highest success rate of 85.6%, while clarithromycin triple therapy had the lowest success rate of 63.5%. Specifically, bismuth/metronidazole/tetracycline quadruple, metronidazole/tetracycline triple, levofloxacin/metronidazole/tetracycline quadruple, rifabutin/amoxicillin triple and amoxicillin/levofloxacin triple therapies had relatively higher success rates over 80%. Age, treatment duration, baseline conditions and first-line treatment used were associated with success rate.

Conclusions

Bismuth quadruple therapy was the most effective second-line regimen for H. pylori in this real-world study. Despite a very low success rate, clarithromycin-containing triple therapies were still commonly used as second-line regimens.
Clinicomicrobiological risk factors for infective endocarditis in viridans group streptococci bacteraemia
Authors: Bae Jiyeon , Park Jae Hyeon , Lee Minkyeong , Jo Hyeon Jae , Lee Chan Mi , Kang Chang Kyung , Choe Pyoeng Gyun , Park Wan Beom , Kim Nam Joong , Kim Inho , Oh Myoung-don
Published: July 2024

Background

When to perform echocardiography to rule out infective endocarditis (IE) in patients with viridans group streptococci (VGS) bloodstream infections (BSIs) is unclear.

Objectives

We aimed to identify independent risk factors for IE in patients with VGS BSI.

Methods

This retrospective study conducted at Seoul National University Hospital from January 2013 to December 2022 involved patients with VGS and nutritionally variant streptococcal BSI, excluding single positive blood cultures and polymicrobial BSI cases. Independent risk factors were identified by multivariate logistic regression and sensitivity analyses according to echocardiography results, VGS species or the inclusion of possible IE cases.

Results

Of 845 VGS BSI cases, 349 were analysed and 86 IE cases were identified (24.6%). In the multivariate analysis, heart valve disease [adjusted odds ratio (aOR), 14.14, 95% CI, 6.14–32.58; P < 0.001], persistent bacteraemia (aOR, 5.12, 95% CI, 2.03–12.94; P = 0.001), age (per year, aOR, 0.98; 95% CI, 0.96–1.00; P = 0.015), solid cancer (aOR, 0.26; 95% CI, 0.13–0.53; P < 0.001) and haematologic malignancy (aOR, 0.04; 95% CI, 0.01–0.41; P = 0.006) were independently associated with IE. Sensitivity analyses yielded consistent results; also, infection by a member of the mitis group was independent risk factor for IE (aOR, 6.50; 95% CI, 2.87–14.68; P < 0.001).

Conclusions

Younger age, heart valve disease, persistent bacteraemia, absence of underlying malignancy and BSI by a member of the mitis group were independent risk factors for IE in patients with VGS BSI. Echocardiographic evaluation could be prudently considered based on these clinicomicrobiological risk factors.
Machine learning classification of new firearm injury encounters in the St Louis region: 2010-2020
Authors: Ancona Rachel M , Cooper Benjamin P , Foraker Randi , Kaser Taylor , Adeoye Opeolu , Mueller Kristen L
Published: July 2024

Objectives

To improve firearm injury encounter classification (new vs follow-up) using machine learning (ML) and compare our ML model to other common approaches.

Materials and Methods

This retrospective study used data from the St Louis region-wide hospital-based violence intervention program data repository (2010-2020). We randomly selected 500 patients with a firearm injury diagnosis for inclusion, with 808 total firearm injury encounters split (70/30) for training and testing. We trained a least absolute shrinkage and selection operator (LASSO) regression model with the following predictors: admission type, time between firearm injury visits, number of prior firearm injury emergency department (ED) visits, encounter type (ED or other), and diagnostic codes. Our gold standard for new firearm injury encounter classification was manual chart review. We then used our test data to compare the performance of our ML model to other commonly used approaches (proxy measures of ED visits and time between firearm injury encounters, and diagnostic code encounter type designation [initial vs subsequent or sequela]). Performance metrics included area under the curve (AUC), sensitivity, and specificity with 95% confidence intervals (CIs).

Results

The ML model had excellent discrimination (0.92, 0.88-0.96) with high sensitivity (0.95, 0.90-0.98) and specificity (0.89, 0.81-0.95). AUC was significantly higher than time-based outcomes, sensitivity was slightly (but not significantly) lower than other approaches, and specificity was higher than all other methods.

Discussion

ML successfully delineated new firearm injury encounters, outperforming other approaches in ruling out encounters for follow-up.

Conclusion

ML can be used to identify new firearm injury encounters and may be particularly useful in studies assessing re-injuries.
Receptor tyrosine kinase-like orphan receptor serves as a potential target in cancer immunotherapy
Authors: Wang Jiaqi , Li Zhoufang , Zhao Qi
Published: July 2024

Receptor tyrosine kinase-like orphan receptor (ROR), consisting of ROR1 and ROR2, is a conserved family of receptor tyrosine kinase superfamily that plays crucial roles during embryonic development with limited expression in adult normal tissues. However, it is overexpressed in a range of hematological malignancies and solid tumors and functions in cellular processes including cell survival, polarity, and migration, serving as a potential target in cancer immunotherapy. This review summarizes the expression and structure of ROR in developmental morphogenesis and its function in cancers associated with Wnt5a signaling and highlights the cancer immunotherapy strategies targeting ROR.
Personalized starting age of gastric cancer screening based on individuals’ risk profiles: a population-based, prospective study
Authors: He Siyi , Zhang Zhiyi , Song Guohui , Wang Zhenhai , Li He , Cao Maomao , Yang Fan , Sun Dianqin , Yan Xinxin , Zhang Shaoli , Teng Yi , Li Qianru , Xia Changfa , Chen Wanqing
Published: July 2024

Background

The current recommended starting age for gastric cancer screening lacks unified guideline and individualized criteria. We aimed to determine the risk-stratified starting age for gastric cancer screening in China based on individuals’ risk profiles and to develop an online calculator for clinical application.

Methods

In this multicenter, population-based, prospective study, we allocated participants enrolled between 2015 and 2017 (N = 59 771, aged 40-69 years) to screened and unscreened groups and observed them for primary endpoints: gastric cancer occurrence as well as all-cause and gastric cancer–specific death. Median follow-up was 6.07 years. To determine the reference starting age, the effectiveness of gastric cancer screening was assessed by age group after propensity score matching. Further, we categorized the calculated individual risk scores (using well-established risk factors) by quantile. Subsequently, we used age-specific, 10-year cumulative risk curves to estimate the risk-stratified starting age—that is, when the individual’s risk level matches the reference starting age risk threshold.

Results

During follow-up, 475 gastric cancer case patients, 182 gastric cancer–related deaths, and 1860 all-cause deaths occurred. All-cause and gastric cancer–specific mortality decreased among screened individuals 45 years of age and older and 50 to 59 years of age, respectively. Thus, the average population (referent) starting age was set as 50 years. The 10-year cumulative risk of gastric cancer in the average population aged 50 years was 1.147%. We stratified the starting age using 8 risk factors and categorized participants as low-risk, medium-risk, and high-risk individuals whose risk-stratified starting age was 58, 50, and 46 years, respectively.

Conclusion

Although high-risk individuals warrant starting gastric cancer screening 3 to 5 years earlier than for the average population (aged 50 years), low-risk individuals can tolerate delayed screening. Our online, personalized starting age calculator will help with risk-adapted gastric cancer screening (https://web.consultech.com.cn/gastric/#/).
Serialism in regressive voicing assimilation: The case of heterorganic obstruent clusters in Modern Hebrew
Authors: Alqahtani Mufleh Salem M
Published: July 2024

This paper examines serialism (i.e. serial derivations) in regressive voicing assimilation (RVA) within the framework of harmonic serialism in coping with heterorganic obstruent clusters in Modern Hebrew. The study depends primarily on data gathered from literature, including books, articles, and theses. The findings show that RVA in Modern Hebrew operates through two derivational steps in a feeding order (i.e. transparent rule interaction): the first step involves delinking the [voice] feature of the target consonant feeds and spreading the [voice] feature of the trigger consonant. Heterorganic obstruent clusters are created by attaching the hitpa'el prefix /hit-/ to the root initial [z] and require RVA and metathesis. RVA occurs before metathesis in a counterbleeding order, constituting an opaque rule interaction. In other words, this opaque phonological derivation embodies RVA and metathesis where RVA counterbleeds metathesis. This research shows that harmonic serialism, in contrast to parallel optimality theory (P-OT), effectively expresses the generalization about RVA in Modern Hebrew.
Comparative histology of abscission zones reveals the extent of convergence and divergence in seed shattering in weedy and cultivated rice
Authors: Li Xiang , Lowey Daniel , Lessard Jessica , Caicedo Ana L
Published: July 2024

The modification of seed shattering has been a recurring theme in rice evolution. The wild ancestor of cultivated rice disperses its seeds, but reduced shattering was selected during multiple domestication events to facilitate harvesting. Conversely, selection for increased shattering occurred during the evolution of weedy rice, a weed invading cultivated rice fields that has originated multiple times from domesticated ancestors. Shattering requires formation of a tissue known as the abscission zone (AZ), but how the AZ has been modified throughout rice evolution is unclear. We quantitatively characterized the AZ characteristics of relative length, discontinuity, and intensity in 86 cultivated and weedy rice accessions. We reconstructed AZ evolutionary trajectories and determined the degree of convergence among different cultivated varieties and among independent weedy rice populations. AZ relative length emerged as the best feature to distinguish high and low shattering rice. Cultivated varieties differed in average AZ morphology, revealing lack of convergence in how shattering reduction was achieved during domestication. In contrast, weedy rice populations typically converged on complete AZs, irrespective of origin. By examining AZ population-level morphology, our study reveals its evolutionary plasticity, and suggests that the genetic potential to modify the ecologically and agronomically important trait of shattering is plentiful in rice lineages.
Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma
Authors: Kim Hyery , Yoon Hee Mang , Kim Eun Key , Ra Young Shin , Kim Hyo-Won , Yum Mi-Sun , Kim Min-Jee , Baek Jae Suk , Sung Yu Sub , Lee Sang Min , Lim Hyeong-Seok , Lee Byung Joo , Lim Hyun Taek , Kim Dohyung , Yoon Jihee , Bae Hyunwoo , Hwang Soojin , Choi Yun-Ha , Kim Kyung Ah , Choi In Hee , Lee Seung Won , Park Su-Jung , Lee Beom Hee
Published: July 2024

Background

The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1 manifestations (eg, neurocognitive function, growth reduction, and café-au-lait spots) are unknown.

Methods

This open-label, phase II trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hours for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated.

Results

Fifty-nine children and 30 adults (median age, 16 years; range, 3–47) received an average of 22 ± 5 (4–26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%–92.2%), and 81 (91%) patients showed partial response (≥20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P < .05). Prepubertal patients showed increases in height score and growth velocity (P < .05). Café-au-lait spot intensity decreased significantly (P < .05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation.

Conclusions

Selumetinib decreases PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in nonmalignant diverse NF1 manifestations.

Trial Registration

Cris.nih.go.kr Identifier (KCT0003700).
The H1/H5 domain contributes to OsTRBF2 phase separation and gene repression during rice development
Authors: Xuan Hua , Li Yanzhuo , Liu Yue , Zhao Jingze , Chen Jianhao , Shi Nan , Zhou Yulu , Pi Limin , Li Shaoqing , Xu Guoyong , Yang Hongchun
Published: July 2024

Transcription factors (TFs) tightly control plant development by regulating gene expression. The phase separation of TFs plays a vital role in gene regulation. Many plant TFs have the potential to form phase-separated protein condensates; however, little is known about which TFs are regulated by phase separation and how it affects their roles in plant development. Here, we report that the rice (Oryza sativa) single Myb TF TELOMERE REPEAT-BINDING FACTOR 2 (TRBF2) is highly expressed in fast-growing tissues at the seedling stage. TRBF2 is a transcriptional repressor that binds to the transcriptional start site of thousands of genes. Mutation of TRBF2 leads to pleiotropic developmental defects and misexpression of many genes. TRBF2 displays characteristics consistent with phase separation in vivo and forms phase-separated condensates in vitro. The H1/H5 domain of TRBF2 plays a crucial role in phase separation, chromatin targeting, and gene repression. Replacing the H1/H5 domain by a phase-separated intrinsically disordered region from Arabidopsis (Arabidopsis thaliana) AtSERRATE partially recovers the function of TRBF2 in gene repression in vitro and in transgenic plants. We also found that TRBF2 is required for trimethylation of histone H3 Lys27 (H3K27me3) deposition at specific genes and genome wide. Our findings reveal that phase separation of TRBF2 facilitates gene repression in rice development.
GLUTAMYL-tRNA SYNTHETASE 1 deficiency confers thermosensitive male sterility in rice by affecting reactive oxygen species homeostasis
Authors: Liu Huixin , You Hanli , Liu Changzhen , Zhao Yangzi , Chen Jiawei , Chen Zhuoran , Li Yafei , Tang Ding , Shen Yi , Cheng Zhukuan
Published: July 2024

Temperature is one of the key environmental factors influencing crop fertility and yield. Understanding how plants sense and respond to temperature changes is, therefore, crucial for improving agricultural production. In this study, we characterized a temperature-sensitive male sterile mutant in rice (Oryza sativa), glutamyl-tRNA synthetase 1-2 (ers1-2), that shows reduced fertility at high temperatures and restored fertility at low temperatures. Mutation of ERS1 resulted in severely delayed pollen development and meiotic progression at high temperatures, eventually leading to male sterility. Moreover, meiosis-specific events, including synapsis and crossover formation, were also delayed in ers1-2 compared with the wild type. However, these defects were all mitigated by growing ers1-2 at low temperatures. Transcriptome analysis and measurement of ascorbate, glutathione, and hydrogen peroxide (H2O2) contents revealed that the delayed meiotic progression and male sterility in ers1-2 were strongly associated with changes in reactive oxygen species (ROS) homeostasis. At high temperatures, ers1-2 exhibited decreased accumulation of ROS scavengers and overaccumulation of ROS. In contrast, at low temperatures, the antioxidant system of ROS was more active, and ROS contents were lower. These data suggest that ROS homeostasis in ers1-2 is disrupted at high temperatures but restored at low temperatures. We speculate that ERS1 dysfunction leads to changes in ROS homeostasis under different conditions, resulting in delayed or rescued meiotic progression and thermosensitive male fertility. ers1-2 may hold great potential as a thermosensitive material for crop heterosis breeding.
Light-responsive transcription factors VvHYH and VvGATA24 mediate wax terpenoid biosynthesis in Vitis vinifera
Authors: Yang Mingyi , Xiang Yizhou , Luo Zisheng , Gao Yizhou , Wang Lei , Hu Qiannan , Dong Yingying , Qi Ming , Li Dong , Liu Lingling , Kačániová Miroslava , Ban Zhaojun , Li Li
Published: July 2024

The cuticular wax that covers the surfaces of plants is the first barrier against environmental stresses and increasingly accumulates with light exposure. However, the molecular basis of light-responsive wax biosynthesis remains elusive. In grape (Vitis vinifera), light exposure resulted in higher wax terpenoid content and lower decay and abscission rates than controls kept in darkness. Assay for transposase-accessible chromatin with high-throughput sequencing and RNA-seq data were integrated to draw the chromatin accessibility and cis-elements regulatory map to identify the potential action sites. Terpenoid synthase 12 (VvTPS12) and 3-hydroxy-3-methylglutaryl-CoA reductase 2 (VvHMGR2) were identified as grape wax biosynthesis targets, while VvHYH and VvGATA24 were identified as terpenoid biosynthesis activators, as more abundant wax crystals and higher wax terpenoid content were observed in transiently overexpressed grape berries and Nicotiana benthamiana leaves. The interaction between VvHYH and the open chromatin of VvTPS12 was confirmed qualitatively using a dual luciferase assay and quantitatively using surface plasma resonance, with an equilibrium dissociation constant of 2.81 nm identified via the latter approach. Molecular docking simulation implied the structural nature of this interaction, indicating that 24 amino acid residues of VvHYH, including Arg106A, could bind to the VvTPS12 G-box cis-element. VvGATA24 directly bound to the open chromatin of VvHMGR2, with an equilibrium dissociation constant of 8.59 nm. Twelve amino acid residues of VvGATA24, including Pro218B, interacted with the VvHMGR2 GATA-box cis-element. Our work characterizes the mechanism underlying light-mediated wax terpenoid biosynthesis and provides gene targets for future molecular breeding.
Law enforcement training on child trafficking: Engaging all stakeholders
Authors: Harmon-Darrow Caroline , Aggarwal Nikita , Finigan-Carr Nadine
Published: July 2024

Since the passage of the Victims of Trafficking and Violence Protection Act in 2000, there have been rapid changes in the criminal justice and juvenile justice systems’ ability to identify, investigate, and prosecute cases of human trafficking and work effectively with survivors. Law enforcement officers are often the first to encounter victims, and their training in this area is critical. While trainings have expanded, they are still missing in many jurisdictions and are understudied. The impact of a 2-day, interdisciplinary, skill-based, and victim-centred child trafficking in-service training is evaluated via regression analysis of pre–post surveys with 187 participants. Results indicate that the training significantly improved both perceived trafficking-related knowledge and self-efficacy. Implications for policing and research include expanding and deepening skill-focussed interdisciplinary child sex trafficking training for law enforcement personnel that engages multiple stakeholders, including trafficking survivors.
CT features associated with contralateral recurrence of spontaneous pneumothorax
Authors: Burn L A , Wetscherek M T , Pharoah P D , Marciniak S J
Published: July 2024

Introduction

Spontaneous pneumothorax recurs in 30–54% of patients without surgery. Identifying individuals likely to suffer a recurrence, who might benefit from pre-emptive surgery, is challenging. Previous meta-analysis suggested a relationship between contralateral recurrence and specific CT findings.

Methods

We analysed CT images and recurrence rates of 243 patients seen by our tertiary referral pneumothorax service.

Results

We validated the meta-analysis observation that contralateral lung cysts are associated with a higher risk of contralateral recurrence in younger individuals. Furthermore, we observed that the size of contralateral cysts to be associated with increased contralateral recurrence in younger patients.

Conclusion

The detection of contralateral lung cysts might therefore help identify younger patients more likely to benefit from pre-emptive surgery.
The limits of co-production: linking regulatory capacity to co-production of authoritative knowledge for environmental policy
Authors: Large Daniel
Published: July 2024

This paper introduces a novel perspective on co-production of authoritative knowledge in environmental policy, shifting focus from perceived flaws in knowledge production to structural and governance challenges impeding knowledge uptake. It argues that these challenges, including diminishing support for public authority and widespread enthusiasm for collaboration, contribute to regulatory capacity deficits, which undermine knowledge claims’ authority. This account is tested through case study analysis of policy stakeholders in Colorado, USA, who sought to co-produce a scientific assessment for biodiversity offsetting. Despite repeated efforts, industry stakeholders disengaged twice, leading to abandonment of the policy initiative. Analysis demonstrates regulatory capacity’s crucial role in fostering co-production and integration of authoritative scientific knowledge in policymaking. By analyzing the failure to sustain stakeholder engagement in terms of interplay between regulatory capacity and co-production, this study contributes a critique of mainstream co-production and demonstrates the value of analyzing how institutional arrangements shape knowledge and policy integration.
Italy: The updated provisions on the taxation of income distributions from foreign trusts and similar entities residing in ‘privileged tax jurisdictions’
Authors: Maisto Guglielmo
Published: July 2024

The article provides an in-depth analysis of Italy’s updated provisions, effective late 2019, on the taxation of income distributions from foreign trusts and similar entities residing in ‘privileged tax jurisdictions’. It highlights the Italian Revenue Agency’s efforts to clarify the tax treatment of these distributions, as well as the challenges posed by the deemed-income-characterization provision whereby any distribution made by such trusts and entities is presumed to be income unless the recipient may document the contrary (ie the characterisation as capital). The article provides a thorough overview of the regulatory landscape, highlighting critical areas and addressing interpretative challenges.
Estimation of phloem conductance at tree level in young, middle-aged and old-aged Scots pine trees growing in different climatic conditions in boreal forests
Authors: Tarelkina Tatiana V , Serkova Aleksandra A , Galibina Natalia A , Novichonok Elena V , Moshnikov Sergei A , Ivanova Diana S , Semenova Ludmila I
Published: July 2024

In forests, a significant proportion of the carbon fixed by trees during photosynthesis is transported belowground along the conducting phloem, so variations in phloem anatomy can lead to variations in transport capacity. Phloem conductance at tree level (Ktree) is also affected by tree height. Both the phloem anatomy and the tree size change during ontogeny, and also differ under different environmental conditions. The goal of our work was to identify the main drivers of variation in Ktree in Scots pine trees growing in natural boreal forests. We conducted a phloem anatomical study and calculated Ktree in trees of three age groups growing in different climatic conditions along a latitudinal gradient from south to north. We found that Ktree was maintained at the same level in actively growing pine trees (25–80-years-old) but increased in old-aged trees (180–190-years-old), possibly reflecting the shift in source-sink relationships of aboveground and belowground parts of trees. Trees of the same age group growing in different climatic conditions demonstrated similar values of Ktree due to coordinated changes in the phloem anatomy and the tree height. In general, the negative influence of tree height on Ktree is offset by the positive influence of phloem width (or trunk diameter) and sieve cell diameter. The exception was young trees growing in the transition zone of the northern taiga subzone to the tundra, where Ktree was the highest in its age group and even exceeded Ktree of middle-aged trees.
Microbial Community Analysis Offers Insight into the Complex Origins of Plant Disease in a Smallholder Farm Context
Authors: Alford Betsy A. , Bekele Dagnachew , Yimer Sultan M. , Fayyaz Amna , Carrasquilla-Garcia Noelia , Chang Peter L. , Badger Calen , Surendrarao Anandkumar , von Wettberg Eric J. B. , Munis M. Farooq H. , Tesfaye Kassahun , Fikre Asnake , Cook Douglas R.
Published: July 2024

Classical approaches to plant disease diagnosis assume a single pathogen/single disease paradigm. Here, we revisit the presumed role of Fusarium oxysporum as the causal agent of wilting and yellowing of chickpea plants on smallholder farms in Ethiopia. Contrary to expectations, detection of Fusarium DNA using conserved PCR primers failed to associate the pathogen with symptomatic plants. Instead, culture-independent sequencing of microbial communities nominated unexpected pathogens and revealed patchiness in the assembly of common microbial consortia. Surprisingly, tests of differential enrichment identified Phytophthora as the most common disease-associated taxon. More generally, across all field sites, multilevel pattern analysis identified indicator taxa whose patterns of co-occurrence demarcate discrete microbial communities and are consistent with a range of specific interactions, including mutualism and antagonism. Taken together, these data indicate that soilborne chickpea disease in Ethiopia has heterogeneous origins and that despite decades of emphasis and disease resistance breeding, the role of Fusarium as the frequent agent of chickpea disease in Ethiopia remains enigmatic.
The multifaceted role of beta‐blockers in overcoming cancer progression and drug resistance: Extending beyond cardiovascular disorders
Authors: Cavalu Simona , Saber Sameh , Amer Ahmed E. , Hamad Rabab S. , Abdel‐Reheim Mustafa Ahmed , Elmorsy Elsayed A. , Abdelhamid Amir Mohamed
Published: July 2024

Beta‐blockers are commonly used medications that antagonize β‐adrenoceptors, reducing sympathetic nervous system activity. Emerging evidence suggests that beta‐blockers may also have anticancer effects and help overcome drug resistance in cancer treatment. This review summarizes the contribution of different isoforms of beta‐adrenoceptors in cancer progression, the current preclinical and clinical data on associations between beta‐blockers use and cancer outcomes, as well as their ability to enhance responses to chemotherapy and other standard therapies. We discuss proposed mechanisms, including effects on angiogenesis, metastasis, cancer stem cells, and apoptotic pathways. Overall, results from epidemiological studies and small clinical trials largely indicate the beneficial effects of beta‐blockers on cancer progression and drug resistance. However, larger randomized controlled trials are needed to firmly establish their clinical efficacy and optimal utilization as adjuvant agents in cancer therapy.
Assessing Practice Variation of Anesthetic Management for Endovascular Thrombectomy in Acute Ischemic Stroke: A Comprehensive Multicenter Survey
Authors: Sharma Sonal , Dube Surya Kumar , Esmail Tariq , Hoefnagel Amie L. , Jangra Kiran , Mejia-Mantilla Jorge , Shiferaw Ananya Abate , De Sloovere Veerle , Wright David , Lele Abhijit Vijay , Blacker Samuel Neal
Published: July 2024

Objective:

This study explored the current global landscape of periprocedural care of acute ischemic stroke patients undergoing endovascular thrombectomy (EVT).

Methods:

An anonymous, 54-question electronic survey was sent to 354 recipients in hospitals worldwide. The responses were stratified by World Bank country income level into high-income (HICs) and low/middle-income (LMICs) countries.

Results:

A total of 354 survey invitations were issued. Two hundred twenty-three respondents started the survey, and 87 fully completed surveys were obtained from centers in which anesthesiologists were routinely involved in EVT care (38 in HICs; 49 in LMICs). Respondents from 35 (92.1%) HICs and 14 (28.6%) LMICs reported that their centers performed >50 EVTs annually. Respondents from both HICs and LMICs reported low rates of anesthesiologist involvement in pre-EVT care, though a communication system was in place in 100% of HIC centers and 85.7% of LMIC centers to inform anesthesiologists about potential EVTs. Respondents from 71.1% of HIC centers and 51% of LMIC centers reported following a published guideline during EVT management, though the use of cognitive aids was low in both (28.9% and 24.5% in HICs and LMICs, respectively). Variability in multiple areas of practice, including choice of anesthetic techniques, monitoring and management of physiological variables during EVT, and monitoring during intrahospital transport, were reported. Quality metrics were rarely tracked or reported to the anesthesiology teams.

Conclusions:

This study demonstrated variability in anesthesiology involvement and in clinical care during and after EVT. Centers may consider routinely involving anesthesiologists in pre-EVT care, using evidence-based recommendations for EVT management, and tracking adherence to published guidelines and other quality metrics.
A review and critical analysis of the history of intramedullary nailing
Authors: Kanakamedala Ajay C. , Schoof Lauren H. , Schultz Blake J. , Kyriakides Peter W. , Ganta Abhishek , Konda Sanjit R.
Published: July 2024

Although intramedullary nailing (IMN) rapidly grew during the 1980s and 1990s to become the standard of care for most diaphyseal femur and tibial fractures as well as peri-trochanteric hip fractures, its history dates back over a century. While IMN has gone through multiple generations, its evolution has been cyclical, several techniques being introduced, abandoned, and subsequently re-introduced. While knowledge of the evolution of intramedullary nailing can help guide future advancements in IMN, it is also important for practicing surgeons to understand the principles and foundations of IMN as its indications expand to other areas such as humeral and fibular fractures. This review presents a review and critical analysis of the history of IMN from its origins to future directions, including how various surgeons’ experiences with IMN shaped its evolution from Küntscher’s original marrow nail to the current generation of intramedullary nails.
Molecular and therapeutic landscape of ferroptosis in skin diseases
Authors: Le Jiayuan , Meng Yu , Wang Ying , Li Daishi , Zeng Furong , Xiong Yixiao , Chen Xiang , Deng Guangtong
Published: July 2024

Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features of iron accumulation, lipid peroxidation, and involvement of various inhibitory antioxidant systems. In recent years, an expanding body of research has solidly linked ferroptosis to the emergence of skin disorders. Therefore, understanding the mechanisms underlying ferroptosis in skin diseases is crucial for advancing therapy and prevention strategies. This review commences with a succinct elucidation of the mechanisms that underpin ferroptosis, embarks on a thorough exploration of ferroptosis’s role across a spectrum of skin conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, and dermatological ailments precipitated by ultraviolet (UV) exposure, and scrutinizes the potential therapeutic benefits of pharmacological interventions aimed at modulating ferroptosis for the amelioration of skin diseases.
Leukocyte immunoglobulin-like receptor B4 (LILRB4) in acute myeloid leukemia: From prognostic biomarker to immunotherapeutic target
Authors: Li Muzi , Zhao Xiangyu
Published: July 2024

Leukocyte immunoglobulin-like receptor (LILR) B4 (also known as ILT3/CD85k) is an immune checkpoint protein that is highly expressed in solid tumors and hematological malignancies and plays a significant role in the pathophysiology of cancer. LILRB4 is highly expressed in acute myeloid leukemia (AML), and this phenotype is associated with adverse patient outcomes. Its differential expression in tumors compared to normal tissues, its presence in tumor stem cells, and its multifaceted roles in tumorigenesis position it as a promising therapeutic target in AML. Currently, several immunotherapies targeting LILRB4 are undergoing clinical trials. This review summarizes advancements made in the study of LILRB4 in AML, focusing on its structure, ligands, expression, and significance in normal tissues and AML; its protumorigenic effects and mechanisms in AML; and the application of LILRB4-targeted therapies in AML. These insights highlight the potential advantages of LILRB4 as an immunotherapeutic target in the context of AML.
Salbutamol, a Short Acting Beta-2 Agonist, Reduces Risk and Improves Prognosis of Prostate Cancer
Authors: Lehrer Steven , Rheinstein Peter H.
Published: July 2024

Objectives:

Beta-blockers, a class of drugs commonly used to manage blood pressure, have been the subject of research regarding their relationship to prostate cancer (PC) risk, prognosis, and treatment. Beta-blockers reduce risk and improve the prognosis of PC. Perioperative use of a nonselective beta-blocker improves outcomes after radical prostatectomy. However, a related class of drugs, beta-2 adrenergic agonists, has received little attention in PC.

Methods:

We studied the relationship of the beta-2 adrenergic agonist salbutamol to PC risk and survival. We analyzed Food and Drug Administration MedWatch data to determine whether salbutamol could influence the risk of PC. We used UK Biobank data to assess the effect of salbutamol on PC survival.

Results:

Salbutamol significantly reduces PC risk, proportional reporting ratio, and 95% CI (lower bound; upper bound): 0.131 (0.11; 0.155) and improves prognosis. Mean survival was 7.35 years for subjects not taking salbutamol, and 10.5 years for subjects taking salbutamol (P = 0.041, log-rank test. To adjust for the effect of age, we performed proportional hazards regression, survival time-dependent variable, age, and salbutamol use independent variables. Salbutamol use was significantly related to survival time (P = 0.016) and independent of the significant effect of age (P < 0.001).

Conclusions:

We found a lower proportion of PCs in salbutamol-treated people, but we have not demonstrated that PC risk is reduced (there is no proof of causality). There is no causality relationship between salbutamol and the survival of patients with PC treated with salbutamol versus those not treated with the drug. Yet, there is a trend in favor of salbutamol-treated patient survival. Therefore, salbutamol and other beta-adrenergic agonists might represent a new class of drugs for the treatment of PC.
Cardiovascular Outcomes of Sodium–Glucose Cotransporter 2 Inhibitors Across Body Mass Index Spectrum in Patients With Heart Failure: An Updated Systematic Review and Meta-Analysis
Authors: Zhou Lingyan , Huang Zijia , Zeng Ya , Zhang Ying
Published: July 2024

Sodium–glucose cotransporter 2 (SGLT-2) inhibitors have shown efficacy in improving cardiovascular outcomes in patients with chronic heart failure (HF). However, their impact on HF patients with varying body mass index (BMI) levels remains uncertain. To explore potential interactions between baseline BMI and the cardiovascular benefits of SGLT-2 inhibitors, we conducted a systematic review of studies from PubMed, Scopus, and the Cochrane Library database spanning from inception to March 2024. Eligible studies reported cardiovascular outcomes according to baseline BMI in HF patients treated with SGLT-2 inhibitors. Ultimately, our analysis included 4 studies encompassing 20,723 patients. We conducted separate random-effects meta-analyses for the composite outcome of first hospitalization for HF (HHF) or cardiovascular death (CVD), total HHF, CVD, and all-cause mortality. Compared with placebo, SGLT-2 inhibitors significantly reduced the risk of the composite outcome of first HHF or CVD (hazard ratio = 0.78, 95% confidence interval: 0.72–0.83) and total HHF (hazard ratio = 0.73, 95% confidence interval: 0.61–0.83), with consistent effects observed across different BMI categories (test for subgroup differences: P = 0.63 and P = 0.56, respectively). Furthermore, no statistical heterogeneity was found in the effects of SGLT-2 inhibitors on CVD (P = 0.84, I2 = 0%) and all-cause mortality (P = 0.52, I2 = 0%) across each baseline BMI subgroup in patients with HF. No significant difference in safety was found between the placebo and SGLT-2 inhibitor arms. In conclusion, our findings suggest that the cardiovascular benefits of SGLT-2 inhibitors seem to be independent of baseline BMI in patients with HF.
Involvement of D1 dopamine receptor in the nucleus of the solitary tract of rats in stress-induced hypertension and exercise
Authors: Yamanaka Ko , Suzuki Makoto , Pham Linh Thuy , Tomita Keisuke , Van Nguyen Thu , Takagishi Miwa , Tsukioka Kei , Gouraud Sabine , Waki Hidefumi
Published: July 2024

Objective:

Chronic stress can cause hypertension, whereas daily exercise promotes healthy well being through destressing. Although the nucleus of the solitary tract (NTS) is involved in the development of hypertension, the molecular and physiological mechanisms of stress and exercise remain unclear. In this study, we tested whether gene expression in the NTS is altered by stress and daily exercise and whether this is involved in cardiovascular regulation.

Methods:

We have performed RT2 Profiler PCR arrays targeting a panel of neurotransmitter receptor genes in the NTS of Wistar rats subjected to chronic restraint stress (1 h a day over 3 weeks) with or without voluntary wheel exercise. We also performed immunohistochemistry to determine whether the identified molecules were expressed at the protein level. Additionally, microinjection studies in anesthetized rats were performed to examine whether validated molecules exhibit physiological roles in cardiovascular regulation of the NTS.

Results:

We observed that blood pressure was significantly increased by stress and the increase was suppressed by exercise. Using PCR analysis, we determined that the expression levels of four genes in the NTS, including the dopamine receptor D1 gene (Drd1), were significantly affected by stress and suppressed by exercise. We also examined dopamine D1 receptor (D1R) expression in NTS neurons and found significantly greater expression in the stressed than nonstressed animals. Furthermore, the microinjection of a D1R agonist into the NTS in anesthetized rats induced hypotensive effects.

Conclusion:

These results suggest that NTS D1R plays a role in the counteracting processes of stress-induced hypertension.
Development of a Nuclear Safety and Security Integration Assessment Tool for Research Reactors and Associated Facilities
Authors: Thomas Theodore , Harris Jason
Published: July 2024

Nuclear safety and security are essential elements of radiation protection. Integration of nuclear safety and security provides a means to identify conflict and synergy points. Research has not been performed to enable integrated practices at the facility level. A tool was developed through research to help staff and regulators assess the level of integration practiced within a research reactor. This tool aims to improve the identification of synergistic and conflict points. Eight criteria of nuclear safety and security integration were used to create the integration assessment tool: access control, transportation, emergency response, proper disposal of materials, testing and maintenance, defense in depth, training and education, and culture. The tool’s final score can range from 0.0375 to 1, with a score of 1 indicating complete integration. The tool was used by research reactor staff to assess practiced integrative techniques. The testing and maintenance criterion scored the highest level of integration (0.84). Training and education and culture scored the lowest levels of integration (0.50). The areas with the highest scores identified points of actively practiced integration. In contrast, those areas with lower scores indicated a lack of integrative practices. The total integration score was 0.69. This tool determined that the facility practiced an adequate level of integration. By analyzing integration levels with this tool, a measurable standard of integrative practices can be employed to achieve improved radiation protection.
Landolt Ring-Shaped Epithelial Keratopathy: A Novel Corneal Disease in a Non-Japanese White Patient
Authors: Elsharawi Radwa , Pegany Roma B. , Redd Travis K. , Huang David , Stutzman Richard D. , Chamberlain Winston D. , Nanji Afshan A.
Published: July 2024

Purpose:

Landolt ring-shaped epithelial keratopathy is a corneal disease that has only been reported in 11 Japanese patients in 2014.
1
We describe the first case of Landolt ring-shaped epithelial keratopathy in the United States in a patient of European background.

Methods:

This is a single case report with longitudinal care.

Results:

A 35-year-old White patient presented with a history of ocular burning, photophobia, and decreased vision. Corneal examination showed bilateral and asymmetric microcystic lesions in a unique Landolt ring (or the letter “C”) shape, distributed randomly in the epithelium. Confocal microscopy revealed cellular ballooning and hyperreflective opacities in the basal layer of the corneal epithelium. The patient has had multiple recurrences of her symptoms year-round, each lasting 4 to 8 days. Topical treatment with cyclosporine, steroids, and lubrication resolved her symptoms but without complete resolution of signs on examination.

Conclusions:

Our patient's clinical signs and symptoms are similar to those described previously in 11 Japanese patients. However, unlike those patients, our patient demonstrates symptomatic response to topical treatment, no seasonal association to her condition, and to date, incomplete resolution of her disease after more than 2 years. This case highlights that Landolt ring-shaped epithelial keratopathy, a novel corneal disease of unclear origin, has relevance outside of the Japanese population.
AI-Powered Patient-Centered Care: A Call to Action for Innovation
Authors: Rothlisberger Paige N.
Published: July 2024

The influential report Crossing the Quality Chasm: A New Health System for the 21st Century established six core objectives to enhance healthcare quality. It highlighted the necessity for healthcare to encompass safety, effectiveness, a patient-centered approach, timeliness, efficiency, and equity. This essay focuses on one of these six core objectives: a patient-centered approach. Healthcare leaders actively seek solutions to improve and ensure the delivery of high-quality care. The imperative to provide quality healthcare underscores the need for artificial intelligence (AI) to become an essential component in a patient-centered approach rather than merely an optional advantage. Despite the expansion of AI, there is a lack of understanding of how AI can improve patient-centered care. This essay examines the fundamental aspects of patient-centered care, as outlined by the Picker Institute, while also exploring the prospective role of AI in advancing the core principles of patient-centered care and proposing frameworks for applying AI in healthcare.
Fall Risk Screening in Older Adult Patients on Chronic Opioid Therapy: A Quality Improvement Project
Authors: Greenberg Johanna , Curtin Andrew , Taylor Eliza , Fortenberry Katherine
Published: July 2024

Many older adults prescribed opioid pain medications may be at increased risk of falls. As a quality improvement (QI) initiative, the University of Utah Sugar House clinic initiated a 9-month fall risk screening pilot for older adult patients on chronic opioids. This QI project sought to determine the feasibility of adding screening to a busy clinical practice, examine risk of falls in this patient cohort, and examine whether there were significant clinical and demographic differences between the patients who did or did not receive screening. We observed whether conventionally understood fall risk factors, including higher opioid doses, concurrent benzodiazepine prescription, and age, correlate with high fall risk. After the screening initiative, we determined that it was possible to significantly increase fall risk screening rates with prompts in Electronic Health Record (EHR). This cohort's fall risk screening increased from 18% to 33%. In the patients who were screened, 43% were found to be at high risk of falls. We did not see a correlation with high fall risk and patients taking higher doses of opioids or concurrent benzodiazepine prescriptions. These findings emphasize the need for consistent screening in primary care because review of the medication list alone is not a reliable predictor of fall risk.