bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation and Conclusion
Authors: Hayward Benjamin
Published: September 2024

This chapter discusses the implementation of a (modified) Art 4 Rome Convention rule for arbitral conflicts through the reform of arbitration rules and the reform of arbitral laws. It argues that, on the current state of arbitral law and practice, there are significant difficulties with the regulatory status quo concerning conflicts of laws in international commercial arbitration. Nevertheless, these difficulties may give way to a test properly adapted to party expectation, party intention, and the appropriate prioritization of substantive certainty over procedural flexibility in arbitral conflicts of laws—should this book’s recommendations be adopted through reform to arbitration rules, the reform of arbitral laws, or through some other appropriate implementation methodology.
Synergistic effect of split DNA activators of Cas12a with exon-unwinding and induced targeting effect
Authors: Huang Shen , Lou Yongliang , Zheng Laibao
Published: September 2024

CRISPR-Cas12a, an RNA-guided nuclease, has been repurposed for genome editing and molecular diagnostics due to its capability of cis-cleavage on target DNA and trans-cleavage on non-target single-strand DNA (ssDNA). However, the mechanisms underlying the activation of trans-cleavage activity of Cas12a, particularly in the context of split DNA activators, remain poorly understood. We elucidate the synergistic effect of these activators and introduce the concepts of induced targeting effect and exon-unwinding to describe the phenomenon. We demonstrate that upon binding of split DNA activators adjacent to the Protospacer Adjacent Motif (PAM) to the Cas12a ribonucleoprotein (Cas12a–RNP), a ternary complex form that can capture and interact with distal split DNA activators to achieve synergistic effects. Notably, if the distal activator is double-strand DNA (dsDNA), the complex initiates exon-unwinding, facilitating the RNA-guide sequence's access. Our findings provide a mechanistic insight into action of Cas12a and propose a model that could significantly advance our understanding of its function.
DNA double-strand break movement in heterochromatin depends on the histone acetyltransferase dGcn5
Authors: Kendek Apfrida , Sandron Arianna , Lambooij Jan-Paul , Colmenares Serafin U , Pociunaite Severina M , Gooijers Iris , de Groot Lars , Karpen Gary H , Janssen Aniek
Published: September 2024

Cells employ diverse strategies to repair double-strand breaks (DSBs), a dangerous form of DNA damage that threatens genome integrity. Eukaryotic nuclei consist of different chromatin environments, each displaying distinct molecular and biophysical properties that can significantly influence the DSB-repair process. DSBs arising in the compact and silenced heterochromatin domains have been found to move to the heterochromatin periphery in mouse and Drosophila to prevent aberrant recombination events. However, it is poorly understood how chromatin components, such as histone post-translational modifications, contribute to these DSB movements within heterochromatin. Using irradiation as well as locus-specific DSB induction in Drosophila tissues and cultured cells, we find enrichment of histone H3 lysine 9 acetylation (H3K9ac) at DSBs in heterochromatin but not euchromatin. We find this increase is mediated by the histone acetyltransferase dGcn5, which rapidly localizes to heterochromatic DSBs. Moreover, we demonstrate that in the absence of dGcn5, heterochromatic DSBs display impaired recruitment of the SUMO E3 ligase Nse2/Qjt and fail to relocate to the heterochromatin periphery to complete repair. In summary, our results reveal a previously unidentified role for dGcn5 and H3K9ac in heterochromatic DSB repair and underscore the importance of differential chromatin responses at heterochromatic and euchromatic DSBs to promote safe repair.
The rice R2R3 MYB transcription factor FOUR LIPS connects brassinosteroid signaling to lignin deposition and leaf angle
Authors: Liu Huichao , Zhang Jie , Wang Junxue , Fan Zhibin , Qu Xiaoxiao , Yan Min , Zhang Chunxia , Yang Kezhen , Zou Junjie , Le Jie
Published: September 2024

Leaf angle is an important agronomic trait for crop architecture and yield. In rice (Oryza sativa), the lamina joint is a unique structure connecting the leaf blade and sheath that determines leaf angle. Brassinosteroid (BR) signaling involving GLYCOGEN SYNTHASE KINASE-3 (GSK3)/SHAGGY-like kinases and BRASSINAZOLE-RESISTANT1 (BZR1) has a central role in regulating leaf angle in rice. In this study, we identified the atypical R2R3-MYB transcription factor FOUR LIPS (OsFLP), the rice homolog of Arabidopsis (Arabidopsis thaliana) AtFLP, as a participant in BR-regulated leaf angle formation. The spatiotemporal specificity of OsFLP expression in the lamina joint was closely associated with lignin deposition in vascular bundles and sclerenchyma cells. OsFLP mutation caused loose plant architecture with droopy flag leaves and hypersensitivity to BRs. OsBZR1 directly targeted OsFLP, and OsFLP transduced BR signals to lignin deposition in the lamina joint. Moreover, OsFLP promoted the transcription of the phenylalanine ammonia-lyase family genes OsPAL4 and OsPAL6. Intriguingly, OsFLP feedback regulated OsGSK1 transcription and OsBZR1 phosphorylation status. In addition, an Ala-to-Thr substitution within the OsFLP R3 helix-turn-helix domain, an equivalent mutation to that in Osflp-1, affected the DNA-binding ability and transcriptional activity of OsFLP. Our results reveal that OsFLP functions with OsGSK1 and OsBZR1 in BR signaling to maintain optimal leaf angle by modulating the lignin deposition in mechanical tissues of the lamina joint.
How coat proteins shape autophagy in plant cells
Authors: Chung Taijoon , Choi Ye Eun , Song Kyoungjun , Jung Hyera
Published: September 2024

Autophagy is a membrane trafficking pathway through which eukaryotic cells target their own cytoplasmic constituents for degradation in the lytic compartment. Proper biogenesis of autophagic organelles requires a conserved set of autophagy-related (ATG) proteins and their interacting factors, such as signalling phospholipid phosphatidylinositol 3-phosphate (PI3P) and coat complex II (COPII). The COPII machinery, which was originally identified as a membrane coat involved in the formation of vesicles budding from the endoplasmic reticulum, contributes to the initiation of autophagic membrane formation in yeast, metazoan, and plant cells; however, the exact mechanisms remain elusive. Recent studies using the plant model species Arabidopsis thaliana have revealed that plant-specific PI3P effectors are involved in autophagy. The PI3P effector FYVE2 interacts with the conserved PI3P effector ATG18 and with COPII components, indicating an additional role for the COPII machinery in the later stages of autophagosome biogenesis. In this Update, we examined recent research on plant autophagosome biogenesis and proposed working models on the functions of the COPII machinery in autophagy, including its potential roles in stabilizing membrane curvature and sealing the phagophore.
VvbHLH036, a basic helix-loop-helix transcription factor regulates the cold tolerance of grapevine
Authors: Hou Yujun , Wong Darren Chern Jan , Sun Xiaoming , Li Qingyun , Zhou Huimin , Meng Lin , Liao Xiaoli , Liang Zhenchang , Aryal Rishi , Wang Qingfeng , Xin Haiping
Published: September 2024

Cold stress is an adverse environmental factor that limits the growth and productivity of horticulture crops such as grapes (Vitis vinifera). In this study, we identified a grapevine cold-induced basic helix-loop-helix (bHLH) transcription factor (VvbHLH036). Overexpression and CRISPR/Cas9-mediated knockout (KO) of VvbHLH036 enhanced and decreased cold tolerance in grapevine roots, respectively. Transcriptome analysis of VvbHLH036-overexpressed roots identified threonine synthase (VvThrC1) as a potential downstream target of VvbHLH036. We confirmed that VvbHLH036 could bind the VvThrC1 promoter and activate its expression. Both the transcripts of VvThrC1 and the content of threonine were significantly induced in the leaves and roots of grapevine under cold treatment compared to controls. Conversely, these dynamics were significantly suppressed in the roots of CRISPR/Cas9-induced KO of VvbHLH036. These observations support the regulation of threonine accumulation by VvbHLH036 through VvThrC1 during cold stress in grapevine. Furthermore, overexpression and CRISPR/Cas9-mediated KO of VvThrC1 also confirmed its role in regulating threonine content and cold tolerance in transgenic roots at low temperature. Exogenous threonine treatment increased cold tolerance and reduced the accumulation of superoxide anions and hydrogen peroxide in grapevine leaves. Together, these findings point to the pivotal role of VvbHLH036 and VvThrC1 in the cold stress response in grapes by regulating threonine biosynthesis.
Metrological Uncertainties in the Integrated Luminosity Measurement with the Updated Design of a Detector at CEPC
Authors: Smiljanić Ivan , Božović Ivanka , Kačarević Goran
Published: September 2024

In order to measure integrated luminosity with the required precision of $10^{-4}$ at the $Z^0$ pole, the proposed CEPC $e^{+}e^{-}$ collider requires a luminometer, a specially designed calorimeter placed in the very forward region to identify Bhabha scattering at low polar angles. Usually, such a device is placed at the outgoing beams, to keep the spatial symmetries of the head-on collisions at accelerators with a nonzero crossing angle. At CEPC it is currently proposed to place the luminometer on the z-axis. We review the feasibility of measurement of the integrated luminosity at the $Z^{0}$ pole with the required precision, focusing on the luminometer centered around the z-axis and the post-CDR beam properties.
Firms and Labor in Times of Violence: Evidence from the Mexican Drug War
Authors: Utar Hale
Published: September 2024

This paper examines the impact of violence resulting from drug trafficking on manufacturing firms in an emerging economy. By utilizing comprehensive longitudinal data spanning all of Mexico from 2005 to 2010, and employing an instrumental variable strategy that leverages plausibly exogenous spatiotemporal variations in the homicide rate during the outbreak of drug violence, the analysis reveals a significant negative effect of violence on plant output, employment, product scope, and capacity utilization. The negative effect on employment is entirely driven by blue-collar employment and concentrated among low-wage, female-intensive firms. Further, consistent with a violent-environment-induced blue-collar labor-supply shock, the results show positive effects on blue-collar wages and negative effects on white-collar wages at the firm level. Output resilience to violence is also shown to be lower among labor-intensive, domestically selling and sourcing, less diversified firms. These findings show the rise of drug violence has a significant negative effect on development of domestic industrial capability in Mexico and shed light on the characteristics of the most affected firms and the channels through which they are affected.
Copper Efficacy Field Trials for Control of Pseudomonas syringae pv. tabaci in Nicotiana tabacum Production
Authors: Webb A. B. , Bailey W. A.
Published: September 2024

Since 2015, Pseudomonas syringae pv. tabaci tox− has become the most significant foliar disease in the dark tobacco growing regions of Kentucky and Tennessee. Streptomycin sulfate, the main control mechanism that growers utilize to combat this bacterial disease, has evidence of resistance at 200 ppm. Field trials were established to evaluate the efficacy of copper-based products for control of angular leaf spot compared with streptomycin sulfate. Field trials were conducted from 2020 to 2022 at the West Farm of Murray State University in Murray, KY, to evaluate the efficacy of streptomycin sulfate, cuprous oxide, copper sulfate pentahydrate, and copper octanoate. In all years, the moderately susceptible dark tobacco variety KT D8LC was planted and inoculated with a streptomycin-sensitive isolate of P. syringae pv. tabaci. Tobacco treated with five applications of copper octanoate had a lower area under the disease progress curve (AUDPC) than tobacco treated with streptomycin sulfate in 2020 and 2022. Data analysis showed that in one of the three years, tobacco treated with cuprous oxide had a higher yield compared with tobacco treated with streptomycin sulfate. Tobacco treated with cuprous oxide had a higher quality grade index compared with streptomycin sulfate in 2020. Although no treatment eliminated this bacterial disease, copper products, particularly cuprous oxide and copper octanoate, are suitable alternatives to streptomycin sulfate for management of angular leaf spot.
The role of neutrophil extracellular traps in inflammatory rheumatic diseases
Authors: Hanata Norio , Kaplan Mariana J.
Published: September 2024

Purpose of review

Dysregulation in neutrophil extracellular trap (NET) formation and degradation has been reported in several inflammatory rheumatic diseases. This review summarizes the recent advances in the understanding the role of NETs in the context of inflammatory rheumatic diseases.

Recent findings

NET formation is enhanced in peripheral blood of patients with large vessel vasculitis and polymyalgia rheumatica. NETs are detected in affected organs in autoimmune conditions, and they might play pathological roles in tissues. Several understudied medications and supplements suppress NET formation and ameliorate animal models of inflammatory rheumatic diseases. NETs and anti-NET antibodies have potential utility as disease biomarkers.

Growing evidence has suggested the contribution of NET dysregulation to the pathogenesis of several inflammatory rheumatic diseases. Further research is warranted in regard to clinical impact of modulating aberrant NET formation and clearance in inflammatory rheumatic diseases.
Enhanced Disease-Specific Survival Among Individuals With Malignant Adnexal Tumors of the Skin Treated With Mohs Surgery: A National Database Study
Authors: Taylor Mitchell A. , Swedek Michelle , Halloran Peter , Georgesen Corey , Voss Vanessa B. , Wysong Ashley
Published: September 2024

BACKGROUND

Malignant adnexal tumors of the skin are a rare group of tumors that can be locally aggressive and require surgical excision with strict margin control to achieve clearance. Given the rarity of these tumors, there is a limited understanding within the medical community regarding optimal treatment approaches.

OBJECTIVE

To examine surgical management trends and outcomes for patients diagnosed with cutaneous adnexal tumors from 2000 to 2020.

MATERIALS AND METHODS

The Surveillance, Epidemiology, and End Results database was queried to identify biopsy-proven cases of cutaneous adnexal tumors between 2000 and 2020. Clinical and disease characteristics were examined, and disease-specific survivals were compared between surgical approaches using Kaplan–Meier curves and Cox proportional hazards models.

RESULTS

Mohs surgery demonstrated a significant increase in utilization from 2000 to 2020 (+447.1%) and improvements in disease-specific survival (mean 231.7 months; p < .001) compared with no surgery; wide local excision exhibited no improved disease-specific survival (227.7 months; p = .070). Multivariable Cox regression further highlighted that only Mohs surgery exhibited a reduced disease-specific mortality risk compared with no surgery (adjusted HR 0.49; p = .011).

CONCLUSION

Given the enhanced disease-specific survival coupled with tissue preservation strategies, Mohs surgery emerges as a promising surgical approach for the treatment of malignant adnexal tumors of the skin.
Exploring the bioactive substances and mechanisms of Chuanxiong Rhizoma treating acute lung injury based on combined network pharmacological, phytochemical, and pharmacological investigations
Authors: Xu Lintao , Cheng Xinping , Hu Qingwen , Peng Guangcheng , Qi Xinyu , Zhao Yu , Wang Xiaoning , Xu Zhenpeng , Shen Tao
Published: September 2024

Background:

Acute lung injury (ALI) is a high-fatality respiratory disease, and the development of new therapeutic agents is ongoing. Chuanxiong Rhizoma has been prescribed for the therapy of ALI in traditional Chinese medicine.

Objective:

The purpose of this article is to explore the effective ingredients, targets, and mechanisms in the treatment of Chuanxiong Rhizoma on ALI.

Methods:

The active ingredients of Chuanxiong Rhizoma were obtained in the TCMSP, and their potential targets and ALI targets were predicted in TCMSP, Swiss target prediction, and Genecards database. A PPI network was constructed in the string online platform, and KEGG and GO enrichment analysis were conducted in the metascape online platform. Phytochemical investigation of Chuanxiong Rhizoma was performed with chemical separation methods and structural elucidation techniques, and their pharmacological effects were evaluated using LPS-induced mouse ALI model and cell-based assays.

Results:

Network pharmacology analyses indicated that the treatment of Chuanxiong Rhizoma on ALI was associated with its anti-inflammatory effect. The key genes mainly include TNF, STAT3, EGFR, AKT1, BCL2, CASP3, and SRC, and the active compounds are its signature component, phthalides. Phytochemical investigation led to the elucidation of 23 phthalides, which demonstrated an anti-inflammatory effect in vitro and in vivo. Of which, chuanxiongdiolide A, levistilide A, butylphthalide, and senkyunolide A were indeed effective in mitigating ALI in an LPS-induced mouse model.

Conclusions:

The combined network pharmacological, phytochemical, and pharmacological investigations revealed that the therapeutical effect of Chuanxiong Rhizoma against ALI was associated with inhibition of the inflammatory response by phthalides.
Deep learning aided measurement of outer retinal layer metrics as biomarkers for inherited retinal degenerations: opportunities and challenges
Authors: Pennesi Mark E. , Wang Yi-Zhong , Birch David G.
Published: September 2024

Purpose of review

The purpose of this review was to provide a summary of currently available retinal imaging and visual function testing methods for assessing inherited retinal degenerations (IRDs), with the emphasis on the application of deep learning (DL) approaches to assist the determination of structural biomarkers for IRDs.

Recent findings

(clinical trials for IRDs; discover effective biomarkers as endpoints; DL applications in processing retinal images to detect disease-related structural changes)

Assessing photoreceptor loss is a direct way to evaluate IRDs. Outer retinal layer structures, including outer nuclear layer, ellipsoid zone, photoreceptor outer segment, RPE, are potential structural biomarkers for IRDs. More work may be needed on structure and function relationship.
Artificial intelligence applications in cataract and refractive surgeries
Authors: Rampat Radhika , Debellemanière Guillaume , Gatinel Damien , Ting Darren S.J.
Published: September 2024

Purpose of review

This review highlights the recent advancements in the applications of artificial intelligence within the field of cataract and refractive surgeries. Given the rapid evolution of artificial intelligence technologies, it is essential to provide an updated overview of the significant strides and emerging trends in this field.

Recent findings

Key themes include artificial intelligence-assisted diagnostics and intraoperative support, image analysis for anterior segment surgeries, development of artificial intelligence-based diagnostic scores and calculators for early disease detection and treatment planning, and integration of generative artificial intelligence for patient education and postoperative monitoring.

The impact of artificial intelligence on cataract and refractive surgeries is becoming increasingly evident through improved diagnostic accuracy, enhanced patient education, and streamlined clinical workflows. These advancements hold significant implications for clinical practice, promising more personalized patient care and facilitating early disease detection and intervention. Equally, the review also highlights the fact that only some of this work reaches the clinical stage, successful integration of which may benefit from our focus.
Effectiveness of cascade screening for elevated lipoprotein(a), an underdiagnosed family disorder
Authors: Annink Maxim E. , Janssen Emma S. , Reeskamp Laurens F.
Published: September 2024

Purpose of review

Elevated lipoprotein(a) [Lp(a)] is a prevalent, independent, genetic risk factor for cardiovascular disease. Though crucial for adequate risk assessment, detection of individuals at increased risk because of elevated Lp(a) is severely lacking in practice. In this light, several consensus statements have recommended familial cascade screening strategies to increase detection of elevated Lp(a). This review aims to synthesize findings from recent research into the effectiveness of cascade screening for elevated Lp(a).

Recent findings

Cascade screening is an effective method for identifying individuals with elevated Lp(a) and is superior to opportunistic screening. Cascade screening identifies approximately one new case of elevated Lp(a) ≥ 125 nmol/L for every two first-degree relatives screened. The number needed to screen (NNS) ranged from 1.3 to 2.9, depending on Lp(a) threshold values and selected population.

Cascade screening appears to be a promising strategy for identifying individuals with elevated Lp(a). However, several challenges persist regarding the implementation of this strategy in clinical practice. Deciding on threshold values for initiating cascade screening, considering the implications of ethnicity-related variability of Lp(a) levels, and further research into the clinical relevance of cascade screening are crucial steps. Understanding these factors will be essential for optimizing cascade screening protocols and enhancing its effectiveness in clinical practice.
Cost-effectiveness of Operative Intervention for Mucinous Cystic Neoplasm
Authors: Smith Savannah R. , Sarmiento Juan M.
Published: September 2024

Objectives

Small mucinous cystic neoplasms (MCNs) of the pancreas are managed with operative resection in otherwise healthy patients; however, postoperative diabetes development is not considered in recommendations for resection.

Materials and Methods

Via probabilistic microsimulation Markov modeling, we assessed clinical and economic implications of laparoscopic distal pancreatectomy (LDP) versus surveillance for non-diabetes mellitus (DM) patients with suspected MCN of 2 cm without high-risk or worrisome features. Primary outcomes included quality-adjusted life years (QALYs), medical costs (2021 USD), and incremental cost-effectiveness ratios. We conducted sensitivity analyses to evaluate the robustness of our model to changes in input parameters. All analyses were repeated for a population with pre-DM.

Results

Surveillance resulted in 6.52 QALYs and $61,200, while LDP accumulated 6.12 QALYs and $63,700. Almost 20% of the LDP cohort developed DM over the first 10 years, compared with 11% of the surveillance cohort. In a pre-DM cohort, LDP remained dominated in the base case, with over 40% developing DM postoperatively. In sensitivity analyses, surveillance remained the preferred strategy in most iterations for both cohorts.

Conclusions

Surveillance for small suspected MCNs without high-risk features is the preferred strategy from a clinical and economic standpoint. Consensus guidelines should consider the long-term implications of postoperative diabetes development after LDP.
Nurse-Led Interventions in Managing Cancer-Related Fatigue
Authors: Mazlan Ain Noor Farieha , Tuan Rusli Nabila Afiqah , Wee Lei Hum , Ahmad Mahadir , Chan Caryn Mei Hsien
Published: September 2024

Background

Cancer-related fatigue (CRF) is common among patients with cancer. Various interventions have been reported to reduce fatigue, and some evidence suggests that nurse-led interventions may be effective in the management of CRF. A systematic review was conducted to assess the effectiveness of nurse-led interventions for CRF in patients with cancer and survivors.

Objective

The aim of this study was to review and appraise the evidence for the effectiveness of different types of nurse-led interventions on fatigue in patients with cancer and survivors.

Methods

Electronic databases such as PubMed, Scopus, Cochrane Library, Web of Science, and ScienceDirect were searched to identify studies published from January 2013 to October 2023. The studies that described nurse-led interventions in patients with cancer or survivors regardless of treatment duration, modes of intervention delivery, and any based intervention were included. The studies were excluded if no fatigue was an outcome measure.

Results

Twelve studies from 2013 to 2023 were included and eligible for the review. Nine studies obtained a Jadad score of 3 or more, indicating high quality for the quality assessment. Eleven of the included studies reported a significant effect of the nurse-led interventions in reducing fatigue in patients with cancer or survivors.

Conclusions

Nurse-led interventions that focus on multidisciplinary, exercise, psychological, and behavioral approaches appear promising in the management of CRF. More research is needed in order to determine the most acceptable forms of intervention.

Implications for Practice

The development of evidence-based interventions for managing CRF is significant to nursing practice.
Effects of immunosuppression after limb fracture in mice on nociceptive, cognitive, and anxiety-related outcomes
Authors: Sahbaie Peyman , Guo Tian-Zhi , Shi Xiao-you , Kingery Wade S. , Clark J. David
Published: September 2024

Introduction:

Chronic pain is a common and problematic consequence of injuries with few proven methods for prevention or treatment. In addition to pain, functional limitations and neuropsychiatric changes such as cognitive impairment and anxiety worsen outcomes.

Objectives:

To determine whether inhibiting activation of the adaptive immune response after limb fracture would reduce pain, functional loss, memory changes, and anxiety.

Methods:

These experiments used a murine tibial fracture/cast immobilization model that develops these adverse outcomes. Adaptive immunity was blocked using the immunosuppressant FK506 beginning at the time of fracture.

Results:

The administration of FK506 reduced mechanical allodynia and hind limb unweighting for weeks after cast removal as well as nonevoked pain measures. Fracture was associated with working memory loss in the Y-maze assay in vehicle- but not FK506-treated mice. Object recognition memory was not improved with FK506 after fracture. Also, vehicle- but not FK506-treated mice developed an anxiety phenotype. Impaired running wheel performance after cast removal over the following 2 weeks was not improved with FK506 administration. In addition, FK506 treatment blocked Immunoglobulin M (IgM) accumulation in the skin of the fractured limbs, and hippocampal enhancement of matrix metalloproteinase-8 expression, a metalloproteinase associated with neuroplastic changes after injuries, was completely blocked.

Conclusion:

Taken together, our results show that blocking the adaptive immune response after limb trauma reduces the severity of nociceptive and biological changes. The same treatment may reduce the adverse consequences of anxiety and memory deficits using some measures, but other measures of memory are not affected, and activity is not enhanced.
CXCR4-Targeted PET Imaging in Hematologic Malignancies
Authors: Chavoshi Mohammadreza , Mirshahvalad Seyed Ali , Kohan Andres , Ortega Claudia , Metser Ur , Farag Adam , Kridel Robert , Hodgson David , Bhella Sita , Kukreti Vishal , Veit-Haibach Patrick
Published: September 2024

Purpose

The aims of this study were to perform a comprehensive review and meta-analyses and to report pooled diagnostic results on CXCR4-targeted PET, particularly considering detection, visualization, and prognostication.

Patients and Methods

This study followed PRISMA-DTA. A systematic search was conducted on major medical literature databases up to March 1, 2024. The search strategy was designed to include CXCR4 PET studies in hematologic malignancies. A random-effects model combined sensitivity values derived from 2-by-2 contingency tables. Pooled means for SUVmax were computed. Analyses were performed by R software.

Results

The initial search resulted in a total of 1428 studies. Ultimately, 18 were eligible for systematic review and meta-analytic calculations. Twelve studies (320 patients) included B-cell lymphoma. The pooled detection rate of CXCR4 PET was 99.4% (95% confidence interval [CI]: 88.3%–100%). Marginal zone lymphoma was investigated in 5 studies (209 patients), with a pooled sensitivity of 97.6% (95% CI: 79.7%–99.8%). In studies on central nervous system lymphoma, CXCR4 PET demonstrated 100% accuracy at both patient and lesion levels. Also, it demonstrated a significantly higher tumor-to-background ratio than 18F-FDG PET. For multiple myeloma, 5 studies (116 patients) showed a patient-level pooled sensitivity of 77.8% (95% CI: 64.4%–87.2%), whereas 18F-FDG PET had 65.0% (95% CI: 55.2%–73.7%). The pooled SUVmax for CXCR4 PET was 13.6 (95% CI: 9.3–17.8) versus 9.0 (95% CI: 6.3–11.7) for 18F-FDG PET. Additionally, CXCR4 PET-derived parameters were significant predictors of survival in multiple myeloma.

Conclusions

CXCR4 PET can be a helpful imaging tool for evaluating hematologic malignancies, particularly in B-cell lymphoma and multiple myeloma patients. In specific clinical scenarios, it appears to be superior compared with the current standard-of-care imaging.
A Real-World Experience of Rituximab: A Panacea in Therapy of Multiple Sclerosis in Low- and Middle-Income Settings
Authors: Raja Pritam , Dhamija Kamakshi , Samim M.M. , Saini Jitender , Manjappaiah Mandara Ganganakudige , Kandavel Thennarasu , M Netravathi
Published: September 2024

Background

Anti-CD20 monoclonal antibodies have received increasing attention in the past few years in the treatment of multiple sclerosis (MS).

Objectives

This study describes the (i) efficacy and safety of rituximab in people living with MS and (ii) assesses clinical and imaging outcomes following rituximab in MS

Method

This is a chart review from the MS registry maintained at the institute from a University Hospital in South India.

Result

Eighty-three (M:F, 26:57) people living with MS received rituximab as immunomodulation between 2007 and 2022 with a median follow-up duration of 18 months. Fifty-nine (71%) were classified as relapsing-remitting MS, 16 (19%) were secondary progressive MS, and 8 (10%) were primary progressive MS. Seventy-two (87%) MS patients did not experience any relapse after receiving rituximab. In relapsing-remitting MS patients, the mean annualized recurrence rate dropped from 1.24 ± 1.19 to 0.16 ± 0.37. Infusion-related reaction occurred in 5 (6% of adverse events), urinary infections in 7 (8.4%), systemic infections in 3 (3%), Pneumocystis carinii pneumonia occurred in 1 (1%), and herpes zoster infection in 1 (1%) patient. Mortality was observed in 3 (3.5%) patients. While being on rituximab, 18 (22%) patients had mild COVID-19 illness and they all made complete recovery without any sequalae.

Conclusions

Rituximab is a safe, well-tolerated, easily accessible, inexpensive, and effective therapeutic option for people with MS. Rituximab showed both clinical and radiological improvement after a median follow-up of 1.5 years. None of our patients showed any severe COVID infection nor side effects after receiving COVID vaccination.
Genetic association of SLC6A3 (dopamine transporter) gene polymorphisms with personality disorders and substance abuse disorders: a systematic review and meta-analysis
Authors: Vogiatzoglou Angeliki V. , Kontou Panagiota I. , Bagos Pantelis G. , Braliou Georgia G.
Published: September 2024

Introduction

Personality disorders (PD) are characterized by socially dysfunctional behavioral patterns that affect patients and show higher incidence rates within families. Substance abuse disorders (SAD) are exemplified by extensive and prolonged use of substances, including alcohol, nicotine, or illegal drugs. Genetic predisposition for both PD and SAD has been reported to involve gene variants regulating dopaminergic pathways. Yet, discrepancy among reported results necessitates further elucidation of potential hereditary-related risk factors. Because both disorders impose a societal burden, knowledge on the impact of certain genetic backgrounds on these diseases could help develop evidence-based strategies for efficacious treatment approaches.

Materials and methods

In the present study a systematic review was performed, and the association between dopamine transporter gene polymorphism (SLC6A3), particularly rs28363170 entailing a 40-bp variable number tandem repeat, and PD as well as SAD was investigated recruiting meta-analysis approach.

Results

Initial literature search for PD yielded 1577, from which nine fulfilled eligibility criteria to be used in a meta-analysis including 729 cases and 2113 controls. From the 934 studies retrieved for SAD, only 29 articles with 5221 cases and 4822 controls were used for meta-analysis. A statistically significant association was seen between rs28363170 (for the 9-repeat allele) and PD in European populations according to the co-dominant mode of inheritance. For SAD no statistically significant correlation under any mode of inheritance was observed. There was no indication of time-trend phenomena.

Conclusion

Our findings demonstrate the association of SLC6A3 gene polymorphism with PD, thus underling the need to understand neurobiological mechanisms inherent to the above disorders to guide treatment strategies under the perspective of personalized medicine.
A millimetre-scale capacitive biosensing and biophysical stimulation system for emerging bioelectronic bone implants
Authors: Pires Diogo G. , Silva Nuno M. , de Sousa Bárbara M. , Marques João L. , Ramos António , Ferreira Jorge A. F. , Morais Raul , Vieira Sandra I. , Soares dos Santos Marco P.
Published: September 2024

Bioelectronic bone implants are being widely recognized as a promising technology for highly personalized bone/implant interface sensing and biophysical therapeutic stimulation. Such bioelectronic devices are based on an innovative concept with the ability to be applied to a wide range of implants, including in fixation and prosthetic systems. Recently, biointerface sensing using capacitive patterns was proposed to overcome the limitations of standard imaging technologies and other non-imaging technologies; moreover, electric stimulation using capacitive patterns was proposed to overcome the limitations of non-instrumented implants. We here provide an innovative low-power miniaturized electronic system with ability to provide both therapeutic stimulation and bone/implant interface monitoring using network-architectured capacitive interdigitated patterns. It comprises five modules: sensing, electric stimulation, processing, communication and power management. This technology was validated using
in vitro
tests: concerning the sensing system, its ability to detect biointerface changes ranging from tiny to severe bone-implant interface changes in target regions was validated; concerning the stimulation system, its ability to significantly enhance bone cells’ full differentiation, including matrix maturation and mineralization, was also confirmed. This work provides an impactful contribution and paves the way for the development of the new generation of orthopaedic biodevices.
A novel, scenario-based approach to comparing non-pharmaceutical intervention strategies across nations
Authors: Calabrese Justin M. , Schüler Lennart , Fu Xiaoming , Gawel Erik , Zozmann Heinrich , Bumberger Jan , Quaas Martin , Wolf Gerome , Attinger Sabine
Published: September 2024

Comparing COVID-19 response strategies across nations is a key step in preparing for future pandemics. Conventional comparisons, which rank individual non-pharmaceutical intervention (NPI) effects, are limited by: (i) a focus on epidemiological outcomes; (ii) NPIs typically being applied as packages of interventions; and (iii) different political, economic and social conditions among nations. Here, we develop a coupled epidemiological–behavioural–macroeconomic model that can transfer NPI effects from a reference nation to a focal nation. This approach quantifies epidemiological, behavioural and economic outcomes while accounting for both packaged NPIs and differing conditions among nations. As a first proof of concept, we take Germany as our focal nation during Spring 2020, and New Zealand and Switzerland as reference nations with contrasting NPI strategies. Our results suggest that, while New Zealand’s more aggressive strategy would have yielded modest epidemiological gains in Germany, it would have resulted in substantially higher economic costs while dramatically reducing social contacts. In contrast, Switzerland’s more lenient strategy would have prolonged the first wave in Germany, but would also have increased relative costs. More generally, these findings indicate that our approach can provide novel, multifaceted insights on the efficacy of pandemic response strategies, and therefore merits further exploration and development.
The causal relationship between cathepsins and multiple sclerosis : a mendelian randomization study
Authors: Lin Haining , Shi Yuqing , Xiong Huazhong , Wang Dongyi , Wang Shilei , Kang Hailan , Wang ZiXu , Wang Zeyu , Ren Jixiang
Published: September 2024

Background

Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease. Although some evidence indicates the potential involvement of cathepsins in the MS process, the precise nature of this involvement remains uncertain. The objective of this study was to ascertain whether there is a causal relationship between cathepsins and MS.

Methods

This study aimed to examine the relationship between nine cathepsins and MS, incorporating heterogeneity and sensitivity analyses into the study design. The MR study was reported according to the STROBE-MR checklist.

Results

The MR analysis revealed a causal relationship between cathepsin H and MS (IVW: P=0.036, OR=1.095, 95% CI=1.006-1.192); and an inverse causal relationship between cathepsin E and MS (IVW: P=0.031, OR=1.043, 95% CI=1.004-1.083).

Conclusion

Genetically predicted risk of developing MS was associated with increased cathepsin H, whereas elevated cathepsin E was associated with developing MS, and their causal relationships were both unidirectional.
Natural weed seed predators reduce crop yield loss due to weeds by 20% in cereal fields
Authors: Muneret Lucile , Carbonne Benjamin , Chauvel Bruno , Dosset Alexandre , Ducourtieux Chantal , Henon Nicolas , Felten Emeline , Laurent Emilien , Matejicek Annick , Petit Sandrine
Published: September 2024

While many herbicide active substances have been banned and weed infestation is a major threat to crop productivity, it is still unknown to what extent natural weed control provided by seed predators can help farmers manage weed communities. We aim to quantify the contribution of seed predators to crop productivity through weed control and to evaluate whether the magnitude of their influence depends on farming systems such as conservation agriculture. We set up 112 seed predator-exclusion cages in 28 cereal fields in France (14 pairs of conservation and conventional agriculture fields), surveyed weed emergence and biomass, measured crop yield and sampled the main seed predators: carabid beetles and rodents. We found that seed predators’ activity reduces the yield loss due to weeds by 20%. By extrapolation, it represents an economic gain of 285€/ha. However, the yield loss remains at 60% below the maximum crop yield potential reached in the absence of weeds. Moreover, conservation agriculture enhances weed control, but this does not translate into increased crop yield. This study demonstrates the tangible importance of considering seed predators for weed control but highlights the need to combine this approach with weed control practices or to substantially redesign cropping systems to enhance the beneficial effects of biodiversity on crop productivity.

Significance statement

Although weed biomass is the main driver of decreasing the crop productivity worldwide and the use of herbicides is massively disparaged, we have not yet quantified the role played by on-farm biodiversity to control weeds. Using an experimental design set up in 28 commercial cereal fields in France, we showed that weed seed predators reduce crop yield loss due to weeds by 20%. By extrapolation, it represents an economic gain of 285€/ha. However, in the absence of any other weed control practices, the yield loss remains at 60% below the maximum crop yield potential reached in the absence of weeds. This study demonstrates the quantitative importance of considering seed predators to design pesticide-free systems.
Sustainable integration of a vertical voluntary medical male circumcision program into routine health services in Zimbabwe: A mixed methods evaluation of a participatory change intervention
Authors: Chung Amanda Marr , Murungu Joseph , Chitapi Precious , Chikodzore Rudo , Case Peter , Gosling Jonathan , Gosling Roly , Xaba Sinokuthemba , Ncube Getrude , Mugurungi Owen , Kunaka Patience , Bertozzi Stefano M. , Feldacker Caryl
Published: September 2024

The global health community has recognized the importance of integrating and sustaining health programs and forming equitable partnerships. Corresponding with these objectives, international aid donors are embracing the principle of localization. The Voluntary Medical Male Circumcision (VMMC) in Zimbabwe is a large vertical HIV prevention program primarily funded through development assistance for health. Program stakeholders want to sustainably integrate VMMC into routine health services so that the program will continue to be a cost-effective HIV prevention strategy through 2030. The purpose of this paper is to describe a bottom-up process of sustainably integrating the program into routine health services through an approach that empowers local stakeholders. At the district level, we facilitated changes to accelerate integration and sustainability. To evaluate our intervention, we used a mixed methods design comprising analysis of district-level work plans with qualitative and quantitative indicators, combined with a survey assessing sustainability capacity of the program, administered at midline and endline to district teams. In all five pilot districts we facilitated the transition of VMMC into the government’s district administration, resulting in a locally owned and managed program, while also strengthening individual and team capacity. We observed improvements across all World Health Organization health system building blocks, suggesting that the intervention strengthened the overall health system. The sustainability survey showed a reduction in funding stability but a significant increase in communications, program adaptation, and organizational capacity. Compared to traditional top-down change initiatives, the participatory approach to integration was an effective way of addressing specific VMMC challenges at the district level whilst maintaining management and oversight at provincial and national levels. Other health programs in low- and middle-income countries seeking to integrate and sustain health services at subnational levels should consider this diagonal, bottom-up model to promote local leadership development and health system strengthening.
Riemannian Geometry for the classification of brain states with fNIRS
Authors: Näher Tim , Bastian Lisa , Vorreuther Anna , Fries Pascal , Goebel Rainer , Sorger Bettina
Published: September 2024

Background

Functional near-infrared spectroscopy (fNIRS) has recently gained momentum as a reliable and accurate tool for assessing brain states. This increase in popularity is due to its robustness to movement, non-invasive nature, portability, and user-friendly application. However, compared to functional magnetic resonance imaging (fMRI), fNIRS is less sensitive to deeper brain activity and offers less coverage. Additionally, due to fewer advancements in method development, the performance of fNIRS-based brain-state classification still lags behind more prevalent methods like fMRI.

Methods

We introduce a novel classification approach grounded in Riemannian geometry for the classification of kernel matrices, leveraging the temporal and spatial channel relationships and inherent duality of fNIRS signals—more specifically, oxygenated and deoxygenated hemoglobin. For the Riemannian geometry-based models, we compared different kernel matrix estimators and two classifiers: Riemannian Support Vector Classifier and Tangent Space Logistic Regression. These were benchmarked against four models employing traditional feature extraction methods. Our approach was tested in two brain-state classification scenarios based on the same fNIRS dataset: an 8-choice classification, which includes seven established plus an individually selected imagery task, and a 2-choice classification of all possible 28 2-task combinations.

Results

The novel approach achieved a mean 8-choice classification accuracy of 65%, significantly surpassing the mean accuracy of 42% obtained with traditional methods. Additionally, the best-performing model achieved an average accuracy of 96% for 2-choice classification across all possible 28 task combinations, compared to 78% with traditional models.

Conclusion

To our knowledge, we are the first to demonstrate that the proposed Riemannian geometry-based classification approach is both powerful and viable for fNIRS data, considerably increasing the accuracy in binary and multi-class classification of brain activation patterns.
xCell 2.0: Robust Algorithm for cell type Proportion Estimation Predicts Response to Immune Checkpoint Blockade
Authors: Angel Almog , Naom Loai , Nabet-Levy Shir , Aran Dvir
Published: September 2024

Background: Accurate estimation of cell type proportions from bulk gene expression data is essential for understanding the cellular heterogeneity underlying complex tissues and diseases. Here, we introduce xCell 2.0, an advanced version of the xCell algorithm, featuring a training function that permits the utilization of any reference dataset. xCell 2.0 generates cell type gene signatures using an improved methodology, including automated handling of cell type dependencies and more robust signature generation. Methods: We benchmarked xCell 2.0 against ten popular deconvolution methods using nine human and mouse reference sets and 26 validation datasets, encompassing 1,749 samples and 67 cell types. Additionally, we validated xCell 2.0 using the independent Deconvolution DREAM Challenge dataset. As an applicative test case, we curated pan-cancer data of 2,007 patients pre-treated with immune checkpoint blockade (ICB). Features of the tumor microenvironment (TME) were generated using xCell 2.0 and other methods and fed into a LightGBM model using nested cross-validation to obtain robust predictions of ICB response. Results: Benchmarking results showed that xCell 2.0 outperformed all other tested methods across distinct reference datasets, demonstrating superior accuracy and consistency across diverse biological contexts. xCell 2.0 also showed the best performance in minimizing spillover effects between related cell types. In the ICB response prediction task, xCell 2.0-derived TME features significantly improved prediction accuracy compared to models using only cancer type and treatment information, and outperformed other deconvolution methods and established ICB prediction scores. Conclusions: xCell 2.0 is a versatile and robust tool for cell type deconvolution that maintains high performance across various reference types and biological contexts. It is available both via a web application and as a Bioconductor-compatible package, equipped with a large collection of pre-trained cell type signatures for human and mouse research. The improved prediction of ICB responses highlights the potential of xCell 2.0 to advance precision medicine in cancer and other diseases.