bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the effect of body mass index on perioperative outcomes and short-term recurrence after paraesophageal hernia repair
Authors: Han Shiwei , Qaraqe Taha , Hillenbrand Charles , Du Simo , Jenq Wesley , Kuppusamy MadhanKumar , Sternbach Joel , Hubka Michal , Low Donald E
Published: September 2024

Previous assessments suggest that surgical results of paraesophageal hernia (PEH) repair were negatively impacted by increasing levels of obesity. A better understanding of the association of obesity on outcomes of PEH repair will support surgeons making evidence-based decisions on the surgical candidacy of individual patients. This single institution retrospective cohort study included 884 consecutive patients with giant PEH undergoing surgical repair between 1 January 2000 and 30 June 2020. Preoperative body mass index (BMI) was documented at the time of surgery. Main outcomes included perioperative blood loss, length of hospital stay, major complications, early hernia recurrence, and mortality. The mean (standard deviation [SD]) age at surgery was 68.4 (11.1), and 645 (73.0%) were women. Among the 884 patients, 875 had a documented immediate preoperative BMI and were included in the analysis. Mean (SD) BMI was 29.24 (4.91) kg/m2. Increasing BMI was not associated with increased perioperative blood loss (coefficient, 0.01; 95% confidence interval [CI], −0.01 to 0.02), prolonged length of stay (coefficient, −0.01; 95% CI, −0.02 to 0.01), increased incidence of recurrent hernia (odds ratio [OR], 1.03; 95% CI, 0.95–1.10), or increased major complications (OR, 0.93; 95% CI, 0.82–1.05). The 90-day mortality rate was 0.3%. Furthermore, when compared with the normal weight group, overweight and all levels of obesity were not related to unfavorable outcomes. No association was found between BMI and perioperative outcomes or short-term recurrence in patients undergoing PEH repair. Although preoperative weight loss is advisable, a higher BMI should not preclude or delay surgical management of giant PEH.
Determining the learning curve of minimally invasive antireflux surgery: systematic review, meta-analysis, and meta-regression
Authors: Sivakumar Jonathan , Chen Qianyu , Bull Nicholas , Hii Michael W , Al-Habbal Yahya , Duong Cuong Phu
Published: September 2024

The rapid uptake of minimally invasive antireflux surgery has led to interest in learning curves for this procedure. This study ascertains the learning curve in laparoscopic and robotic-assisted antireflux surgery. A systematic review of the literature pertaining to learning curves in minimally invasive fundoplication with or without hiatal hernia repair was performed using PubMed, Medline, Embase, Web of Science, and Cochrane Library databases. A meta-regression analysis was undertaken to identify the number of cases to achieve surgical proficiency, and a meta-analysis was performed to compare outcomes between cases that were undertaken during a surgeon’s learning phase and experienced phase. Twenty-five studies met the eligibility criteria. A meta-regression analysis was performed to quantitatively investigate the trend of number of cases required to achieve surgical proficiency from 1996 to present day. Using a mixed-effects negative binomial regression model, the predicted learning curve for laparoscopic and robotic-assisted antireflux surgery was found to be 24.7 and 31.1 cases, respectively. The meta-analysis determined that surgeons in their learning phase may experience a moderately increased rate of conversion to open procedure (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.28, 4.64), as well as a slightly increased rate of intraoperative complications (OR 1.60; 95% CI 1.08, 2.38), postoperative complications (OR 1.98; 95% CI 1.36, 2.87), and needing reintervention (OR 1.64; 95% CI 1.16, 2.34). This study provides an insight into the expected caseload to be competent in performing antireflux surgery. The discrepancy between outcomes during and after the learning curve for antireflux surgery suggests a need for close proctorship for learning surgeons.
Long-term efficacy of drug-coated balloon only angioplasty for IgG4-related coronary artery disease: a case report
Authors: Yamada Mayu , Ueno Katsumi , Kojima Yoshinobu , Watanabe Mitsuru , Morita Norihiko
Published: September 2024

Background

Although coronary artery involvement in patients with IgG4-related disease (IgG4-RD) is rare, emergency revascularization is recommended for managing acute coronary syndrome. However, coronary aneurysm formation and stent migration after sirolimus-eluting stent implantation have been reported for this disease. Thus, new treatment modalities are warranted for the management of coronary artery disease in this vasculitis.

Case summary

A 70-year-old male who experienced progressive chest discomfort for 1 month underwent cardiac examination. Coronary computed tomography angiography (CCTA) revealed right coronary artery hypoplasia, coronary artery aneurysm with severely calcified stenosis in the proximal left anterior descending artery (LAD), and subtotal obstruction in the mid-LAD. The left circumflex artery (LCX) also had stenosis and dilated lesions. Additionally, diffuse perivascular soft tissue thickening was observed in the mid-LCX. The percutaneous coronary intervention was performed for the proximal- and mid-LAD lesions. Rotational atherectomy with low-pressure drug-coated balloon (DCB) dilation was considered for these lesions owing to suspicion of vasculitis. The patient was later diagnosed with Sjögren’s syndrome and IgG4-RD overlap syndrome. Oral steroids and immunosuppressive drugs were initiated. In a follow-up at 7 and 26 months, late lumen enlargement was observed in the treated area of the LAD, without enlargement of the adjacent aneurysm. CCTA performed after 26 months revealed resolution of the diffuse perivascular soft tissue thickening in the mid-LCX.

Discussion

To our knowledge, this is the first case report demonstrating favourable outcomes for treatment of a coronary artery lesion attributed to IgG4-RD with DCB, leaving nothing implanted in the coronary artery tree.
Management of aortic disease in children with FBN1-related Marfan syndrome
Authors: Muiño-Mosquera Laura , Cervi Elena , De Groote Katya , Dewals Wendy , Fejzic Zina , Kazamia Kalliopi , Mathur Sujeev , Milleron Olivier , Mir Thomas S , Nielsen Dorte G , Odermarsky Michal , Sabate-Rotes Anna , van der Hulst Annelies , Valenzuela Irene , Jondeau Guillaume
Published: September 2024

Marfan syndrome (MFS) is a hereditary connective tissue disorder with an estimated prevalence of 1:5000–1:10 000 individuals. It is a pleiotropic disease characterized by specific ocular, cardiovascular, and skeletal features. The most common cardiovascular complication is aortic root dilatation which untreated can lead to life-threatening aortic root dissection, mainly occurring in adult patients. Prompt diagnosis, appropriate follow-up, and timely treatment can prevent aortic events. Currently there are no specific recommendations for treatment of children with MFS, and management is greatly based on adult guidelines. Furthermore, due to the scarcity of studies including children, there is a lack of uniform treatment across different centres. This consensus document aims at bridging these gaps of knowledge. This work is a joint collaboration between the paediatric subgroup of the European Network of Vascular Diseases (VASCERN, Heritable Thoracic Aortic Disease Working Group) and the Association for European Paediatric and Congenital Cardiology (AEPC). A group of experts from 12 different centres and 8 different countries participated in this effort. This document reviews four main subjects, namely, (i) imaging of the aorta at diagnosis and follow-up, (ii) recommendations on medical treatment, (iii) recommendations on surgical treatment, and (iv) recommendations on sport participation.
Web of venom: exploration of big data resources in animal toxin research
Authors: Zancolli Giulia , von Reumont Björn Marcus , Anderluh Gregor , Caliskan Figen , Chiusano Maria Luisa , Fröhlich Jacob , Hapeshi Evroula , Hempel Benjamin-Florian , Ikonomopoulou Maria P , Jungo Florence , Marchot Pascale , de Farias Tarcisio Mendes , Modica Maria Vittoria , Moran Yehu , Nalbantsoy Ayse , Procházka Jan , Tarallo Andrea , Tonello Fiorella , Vitorino Rui , Zammit Mark Lawrence , Antunes Agostinho
Published: September 2024

Research on animal venoms and their components spans multiple disciplines, including biology, biochemistry, bioinformatics, pharmacology, medicine, and more. Manipulating and analyzing the diverse array of data required for venom research can be challenging, and relevant tools and resources are often dispersed across different online platforms, making them less accessible to nonexperts. In this article, we address the multifaceted needs of the scientific community involved in venom and toxin-related research by identifying and discussing web resources, databases, and tools commonly used in this field. We have compiled these resources into a comprehensive table available on the VenomZone website (https://venomzone.expasy.org/10897). Furthermore, we highlight the challenges currently faced by researchers in accessing and using these resources and emphasize the importance of community-driven interdisciplinary approaches. We conclude by underscoring the significance of enhancing standards, promoting interoperability, and encouraging data and method sharing within the venom research community.
Copyright as an Access Right: Concretizing Positive Obligations for Rightholders to Ensure the Exercise of User Rights
Authors: Geiger Christophe , Jütte Bernd Justin
Published: September 2024

The legal frameworks that govern access to information are essential for safeguarding a sustainable, creative ecosystem. Institutions, such as libraries, research organizations, educational and other cultural heritage institutions, are gateways to diverse collections of scientific production, media and other cultural artefacts. Enabling access to creative works requires careful balancing of the interest of creators, producers of information, publishers and users of that information. While copyright law has traditionally recognized that rightholders enjoy exclusive rights, courts have only recently emphasized that users of works must also enjoy rights, which better reflects that copyright is based on a social contract with reciprocal obligations. This study explores what positive obligations must be imposed on rightholders as a consequence of the rights users enjoy under copyright law. Although specific access-enabling mechanisms already exist in EU copyright law, they are often not properly implemented or lack efficient enforcement tools. For that purpose, certain exceptions and limitations must be made mandatory, prohibitions on contractual override must apply horizontally, privileged institutions should enjoy enforceable rights to obtain copies on reasonable terms, and the existing ‘lending’ right must become a ‘right to lend’. Supporting these substantive changes is the proposal for a new governance structure for the EU copyright framework through the establishment of an independent EU regulatory body. It is only through a blend of changes that copyright can serve society and that a sound ecosystem for creators and creativity is set up making the EU fit for the knowledge economy.
Exploring genetic diversity, population structure, and subgenome differences in the allopolyploid Camelina sativa: implications for future breeding and research studies
Authors: Brock Jordan R , Bird Kevin A , Platts Adrian E , Gomez-Cano Fabio , Gupta Suresh Kumar , Palos Kyle , Railey Caylyn E , Teresi Scott J , Lee Yun Sun , Magallanes-Lundback Maria , Pawlowski Emily G , Nelson Andrew D L , Grotewold Erich , Edger Patrick P
Published: September 2024

Camelina (Camelina sativa), an allohexaploid species, is an emerging aviation biofuel crop that has been the focus of resurgent interest in recent decades. To guide future breeding and crop improvement efforts, the community requires a deeper comprehension of subgenome dominance, often noted in allopolyploid species, “alongside an understanding of the genetic diversity” and population structure of material present within breeding programs. We conducted population genetic analyses of a C. sativa diversity panel, leveraging a new genome, to estimate nucleotide diversity and population structure, and analyzed for patterns of subgenome expression dominance among different organs. Our analyses confirm that C. sativa has relatively low genetic diversity and show that the SG3 subgenome has substantially lower genetic diversity compared to the other two subgenomes. Despite the low genetic diversity, our analyses identified 13 distinct subpopulations including two distinct wild populations and others putatively representing founders in existing breeding populations. When analyzing for subgenome composition of long non-coding RNAs, which are known to play important roles in (a)biotic stress tolerance, we found that the SG3 subgenome contained significantly more lincRNAs compared to other subgenomes. Similarly, transcriptome analyses revealed that expression dominance of SG3 is not as strong as previously reported and may not be universal across all organ types. From a global analysis, SG3 “was only significant higher expressed” in flower, flower bud, and fruit organs, which is an important discovery given that the crop yield is associated with these organs. Collectively, these results will be valuable for guiding future breeding efforts in camelina.
Populism and foreign policy: India's refugee policy towards the Rohingya
Authors: Barthwal-Datta Monika , Singh Shweta
Published: September 2024

In this article, we investigate how India's refugee policy towards the Rohingya is implicated in the (re)production of the Bharatiya Janata Party's (BJP) populist project. We enhance an innovative contextual intersectional framework, drawing on Ernesto Laclau's conceptualization of populism as a political logic and build on Shweta Singh and Élise Féron's understanding of this populist logic as discursively co-constituted and based on varying intersecting identity constellations including race/ethnicity, religion, caste, class or gender/sexual orientation. Using this framework, we investigate how India's refugee policy towards Rohingya refugees in particular has evolved under successive populist governments led by the BJP. Analysing three key dimensions of India's refugee policy—legal framework, admission and status, and protection and security—we demonstrate significant shifts along these dimensions in India's refugee policy towards the Rohingya, and explicate the populist logic that is reinscribed through these changes at the site of ‘foreign policy’. Our analysis reveals these shifts as co-constituted in and through the populist logic of the BJP-led governments and relying on identity assemblages that emphasized the Rohingya's ethnicity/religion (Rohingya ‘Muslims’), gender/ sexual orientation (Rohingya ‘men’) and class (Rohingya in need of resources/ privileges). Our study opens up grounds for further research on how refugee policy, as a mode of foreign policy, becomes a site where populist governments reinscribe differences between the ‘people’ and dangerous enemy ‘others’ to (re)produce their populist political projects.
Role of HLA-B*58:01–Restricted CD8+ T Cells in HIV-1 Subtype AE Infection
Authors: Nguyen Hung The , Chikata Takayuki , Zhang Yu , Van Tran Giang , Gatanaga Hiroyuki , Oka Shinichi , Takiguchi Masafumi
Published: September 2024

HLA-B*58:01 and HLA-B*57 are protective alleles against human immunodeficiency virus type 1 (HIV-1) subtype B or C infection, whereas these HLA alleles have not been reported as protective in HIV-1 subtype AE infection. Although HLA-B*58:01–restricted and HLA-B*57–restricted HIV-1–specific CD8+ T cells have been thoroughly analyzed in subtype B or C infection, they have been only partially analyzed in subtype AE infection. We identified 6 HLA-B*58:01–restricted subtype AE epitopes in Vietnamese individuals infected with subtype AE. HLA-B*58:01–restricted T-cell responses to Gag epitopes, which may control disease progression in HLA-B*58:01+ and HLA-B*57+ individuals infected with subtype B or C, were not protective in subtype AE infection. These findings suggest that the loss of HLA-B*58:01–restricted T cells specific for some Gag epitopes and/or their reduced ability may account for the lack of protective effects conferred by HLA-B*58:01 in subtype AE infection.
Modeling long-term, stage-structured dynamics of Tribolium castaneum (Coleoptera: Tenebrionidae) at food facilities with and without two types of long-lasting insecticide-incorporated netting
Authors: Ranabhat Sabita , Gerken Alison R , Scheff Deanna S , Zhu Kun Yan , Morrison William R
Published: September 2024

The red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), is a cosmopolitan and destructive external-infesting pest at many food facilities. The use of deltamethrin- and α-cypermethrin-incorporated long-lasting insecticide-incorporated netting (LLIN) has shown incredible promise for the management of stored product insects. However, it is unknown how LLIN deployed within food facilities may affect the long-term population dynamics of T. castaneum compared to populations where no LLIN is present. Exposure to LLIN has been shown to affect mortality in the current generation and decrease progeny production in the subsequent generation. Thus, we modeled the long-term population dynamics of T. castaneum at food facilities over 15 generations by incorporating realistic estimates for mortality and progeny reduction after contact with LLIN compared to baseline growth by the species. We parameterized the model with estimates from the literature and used a four-stage structured population (eggs, larvae, pupae, and adults). The model was implemented using the package popbio in R. Our models suggest that deploying LLIN led to significant population reductions based on the estimates of mortality and progeny reduction from prior work, whereas the baseline model exhibited exponential population growth. In addition, there were differences in the frequencies of each life stage under each scenario modeled. As a result, it appears deploying LLIN may contribute to the local extirpation of T. castaneum within as few as 15 generations. Our work contributes to a growing literature about the effectiveness of incorporating LLIN into existing pest management programs for managing stored product insects in food facilities.
Reference genome of the kidnapper ant, Polyergus mexicanus
Authors: Cash Elizabeth I , Escalona Merly , Ward Philip S , Sahasrabudhe Ruta , Miller Courtney , Toffelmier Erin , Fairbairn Colin , Seligmann William , Shaffer H Bradley , Tsutsui Neil D
Published: September 2024

Polyergus kidnapper ants are widely distributed, but relatively uncommon, throughout the Holarctic, spanning an elevational range from sea level to over 3,000 m. These species are well known for their obligate social parasitism with various Formica ant species, which they kidnap in dramatic, highly coordinated raids. Kidnapped Formica larvae and pupae become integrated into the Polyergus colony where they develop into adults and perform nearly all of the necessary colony tasks for the benefit of their captors. In California, Polyergus mexicanus is the most widely distributed Polyergus, but recent evidence has identified substantial genetic polymorphism within this species, including genetically divergent lineages associated with the use of different Formica host species. Given its unique behavior and genetic diversity, P. mexicanus plays a critical role in maintaining ecosystem balance by influencing the population dynamics and genetic diversity of its host ant species, Formica, highlighting its conservation value and importance in the context of biodiversity preservation. Here, we present a high-quality genome assembly of P. mexicanus from a sample collected in Plumas County, CA, United States, in the foothills of the central Sierra Nevada. This genome assembly consists of 364 scaffolds spanning 252.31 Mb, with contig N50 of 481,250 kb, scaffold N50 of 10.36 Mb, and Benchmarking Universal Single-Copy Orthologs (BUSCO) completeness of 95.4%. We also assembled the genome of the Wolbachia endosymbiont of P. mexicanus—a single, circular contig spanning 1.23 Mb. These genome sequences provide essential resources for future studies of conservation genetics, population genetics, speciation, and behavioral ecology in this charismatic social insect.
Strolling to Nothingness: Japanese tea gardens and the initiation of Bildung
Authors: Kenklies Karsten
Published: September 2024

Although the alienating journey into the unknown as the fundamental element of transformative education may have gained a paradigmatic expression in the German concept of Bildungsreise, it is neither a solely German or even European concept, nor is it a child of the 18th century: the transformative power of travelling has been acknowledged at least since antiquity in Europe, and comparable reflections and practices have evolved in other parts of the world. This article will introduce one of those examples that may, only on first view though, look quite distinct from what is suggested as Bildungsreise: the strolling on the roji (露地), the path through the tea garden, before entering the chashitsu (茶室), the tea room, to participate in chanoyu (茶の湯), the tea ceremony, as it found its classic form in 16th-century Japan. Discussing this Japanese practice will not only support an intercultural perspective on the educative nature of travel and the relevance of space for the theory and practice of transformative education or Bildung, but also—more relevant from a philosophical point of view—enable an analysis of the conceptual core of the idea of a transformative journey. As will be shown, far from being a special case of education or Bildung, this conceptual structure lies at the very heart of both.
Deciphering the mechanism of Chaihu Shugan San in the treatment of nonalcoholic steatohepatitis using network pharmacology and molecular docking
Authors: Ren Yi , Xiao Kaihui , Lu Yujia , Chen Wei , Li Li , Zhao Jingjie
Published: September 2024

Objectives

In China, there is a long history and rich clinical experience in treating nonalcoholic steatohepatitis (NASH) with traditional Chinese herbal medicines, including Chai Hu Shu Gan San. This study aims to investigate the potential regulatory effects of Chaihu Shugan San (CSS) on liver lipid metabolism and inflammatory damage in mice with experimental nonalcoholic steatohepatitis (NASH) induced by a choline-deficient high-fat diet (CDHFD). Utilizing network pharmacology, we systematically explore the mechanisms of action and therapeutic potential of CSS against NASH.

Methods

Potential targets in CSS and targets for NASH were identified using online databases. Functional enrichment and protein–protein interaction analyses were conducted to identify hub-targeted genes and elucidate the underlying molecular mechanisms. The affinities of active compounds in CSS with hub-targeted genes were evaluated using molecular docking. Finally, hub-targeted genes were validated through real-time polymerase chain reaction, western blotting, and immunofluorescence in choline-deficient high-fat diet mice, both with and without CSS treatment.

Key findings

CSS reduces serum ALT and AST levels in NASH mice(P < 0.05) and ameliorates ballooning degeneration in the livers of NASH mice, thereby lowering the NAS score(P < 0.05). Including naringenin, high-performance liquid chromatography/mass spectrometrys identified 12 chromatographic peaks. Based on network pharmacology analysis, CSS contains a total of 103 active compounds and 877 target genes. Transferase activity represents a potential mechanism for therapeutic intervention of CSS in NASH. The transcriptional levels and protein expression of the SIRT1 gene in NASH mice are significantly increased by CSS (P < 0.05).

Conclusions

Naringenin is probable active compound in CSS and SIRT1 is the hub gene by which CSS is involved in NASH treatment.
‘Stumped’ by stump appendicitis—a case report and literature review
Authors: Soh Chien Lin , Shetty Shraddha , Abdalla Sala , Soggiu Fiammetta
Published: September 2024

Stump appendicitis, a rare postoperative complication of appendicectomy, is inflammation of the remnant appendix tissue due to incomplete removal of the appendix at the index operation. Due to a past surgical history of appendicectomy, there is often a diagnostic delay. This delay can result in increased morbidity and mortality for patients. This series seeks to describe two cases encountered in a London district general hospital to elucidate the diagnostic, management, and operative challenges of stump appendicitis. Our case series demonstrates the importance of recognition of stump appendicitis as a differential for patients presenting with abdominal pain and previous appendicectomy. Active exclusion of this differential diagnosis in a patient with previous appendicectomy who presents with right iliac fossa pain is vital. Early identification and treatment can prevent morbidity in the patient population. We highlight that complete operative documentation and access to medical records are useful for this diagnosis.
Transcription factor CpWRKY50 enhances anthracnose resistance by promoting jasmonic acid signaling in papaya
Authors: Yang Min , Zhou Chenping , Kuang Ruibin , Wu Xiaming , Liu Chuanhe , He Han , Wei Yuerong
Published: September 2024

Colletotrichum brevisporum is an important fungal pathogen that causes anthracnose and has led to serious postharvest losses of papaya (Carica papaya L.) fruit in recent years. WRKY transcription factors (TFs) play vital roles in regulating plant resistance to pathogens, but their functions in papaya anthracnose resistance need further exploration. In this study, we identified a WRKY TF, CpWRKY50, which belongs to the WRKY IIc subfamily. During infection with C. brevisporum, expression of CpWRKY50 in anthracnose-resistant papaya cultivars was significantly higher than that in susceptible cultivars. CpWRKY50 was induced by methyl jasmonate, and CpWRKY50 localized in the nucleus. In yeast, full-length CpWRKY50 had transactivation activity, but CpWRKY50 variants truncated at the N or C termini did not. CpWRKY50 positively regulated papaya resistance to C. brevisporum, as demonstrated by transient overexpression of CpWRKY50 in papaya and heterologous expression of CpWRKY50 in tomato. Moreover, endogenous jasmonic acid (JA) and JA-isoleucine levels in the fruits of transgenic tomato OE lines were higher than in wild type both before and after inoculation with C. brevisporum, indicating that increased CpWRKY50 expression promotes JA accumulation. Furthermore, our results revealed CpWRKY50 directly binds to W-box motifs (TTGACC) in the promoters of two JA signaling-related genes, CpMYC2 and pathogenesis-related 4 CpPR4, thereby activating their expression. Our data support that CpWRKY50 positively regulates anthracnose resistance in papaya by promoting JA signaling. These results broaden our understanding of papaya disease resistance mechanisms and will facilitate the genetic improvement of papaya through molecular breeding.
Endoplasmic reticulum membrane remodeling by targeting reticulon-4 induces pyroptosis to facilitate antitumor immune
Authors: Zhao Mei-Mei , Ren Ting-Ting , Wang Jing-Kang , Yao Lu , Liu Ting-Ting , Zhang Ji-Chao , Liu Yang , Yuan Lan , Liu Dan , Xu Jiu-Hui , Tu Peng-Fei , Tang Xiao-Dong , Zeng Ke-Wu
Published: September 2024

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the “bubble” structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Extreme precipitation reduces the recent photosynthetic carbon isotope signal detected in ecosystem respiration in an old-growth temperate forest
Authors: Diao Haoyu , Wu Jiabing
Published: September 2024

The successful utilization of stable carbon isotope approaches in investigating forest carbon dynamics has relied on the assumption that the carbon isotope compositions (δ13C) therein have detectable temporal variations. However, interpreting the δ13C signal transfer can be challenging, given the complexities involved in disentangling the effect of a single environmental factor, the isotopic dilution effect from background CO2 and the lack of high-resolution δ13C measurements. In this study, we conducted continuous in situ monitoring of atmospheric CO2 (δ13Ca) across a canopy profile in an old-growth temperate forest in northeast China during the normal year 2020 and the wet year 2021. Both years exhibited similar temperature conditions in terms of both seasonal variations and annual averages. We tracked the natural carbon isotope composition from δ13Ca to photosynthate (δ13Cp) and to ecosystem respiration (δ13CReco). We observed significant differences in δ13Ca between the two years. Contrary to in 2020, in 2021 there was a δ13Ca valley in the middle of the growing season, attributed to surges in soil CO2 efflux induced by precipitation, while in 2020 values peaked during that period. Despite substantial and similar seasonal variations in canopy photosynthetic discrimination (Δ13Ccanopy) in the two years, the variability of δ13Cp in 2021 was significantly lower than in 2020, due to corresponding differences in δ13Ca. Furthermore, unlike in 2020, we found almost no changes in δ13CReco in 2021, which we ascribed to the imprint of the δ13Cp signal on above-ground respiration and, more importantly, to the contribution of stable δ13C signals from soil heterotrophic respired CO2. Our findings suggest that extreme precipitation can impede the detectability of recent photosynthetic δ13C signals in ecosystem respiration in forests, thus complicating the interpretation of above- and below-ground carbon linkage using δ13CReco. This study provides new insights for unravelling precipitation-related variations in forest carbon dynamics using stable isotope techniques.
Does the Source of FDI Matter? The Case of Tax Havens
Authors: Shpak Solomiya
Published: September 2024

This paper estimates the benefits of FDI for firm performance, differentiating source countries between tax havens and non–tax havens. Using longitudinal data on more than 300,000 initially domestic firms in Ukraine between 1999 and 2013 and employing propensity score matching and panel data methods, this study finds that firms acquired by non–tax haven foreign investors experience substantial increases in employment, productivity, exports, and wages, but the gains are much lower and shorter-lived for firms receiving FDI from tax havens. These findings, based on econometric analysis of nearly the universe of Ukrainian businesses, are consistent with macroeconomic studies and anecdotal evidence that much of the tax-haven FDI in Ukraine actually represents domestic ownership channeled through offshore companies. This “round-trip FDI” results in negligible effects on firm performance and, at a macro level, it overstates the amount of genuine FDI flows into Ukraine.
Unraveling the role of MiR‐181 in skin fibrosis pathogenesis by targeting NUDT21
Authors: Mills Tingting W. , Wu Minghua , Alonso Jerry , Puente Hydia , Charles Julio , Chen Zheng , Yoo Seung‐hee , Mayes Maureen D. , Assassi Shervin
Published: September 2024

Systemic sclerosis (SSc) is a life‐threatening autoimmune disease characterized by widespread fibrosis in the skin and several internal organs. Nudix Hydrolase 21 (NUDT2 or CFIm25) downregulation in fibroblasts is known to play detrimental roles in both skin and lung fibrosis. This study aims to investigate the upstream mechanisms that lead to NUDT21 repression in skin fibrosis. We identified transforming growth factor β (TGFβ1) as the primary cytokine that downregulated NUDT21 in normal skin fibroblasts. In the bleomycin‐induced dermal fibrosis model, consistent with the peak activation of TGFβ1 at the late fibrotic stage, NUDT21 was downregulated at this stage, and delayed NUDT21 knockdown during this fibrotic phase led to enhanced fibrotic response to bleomycin. Further investigation suggested TGFβ downregulated NUDT21 through microRNA (miRNA) 181a and 181b induction. Both miR‐181a and miR‐181b were elevated in bleomycin‐induced skin fibrosis in mice and primary fibroblasts isolated from SSc patients, and they directly targeted NUDT21 and led to its downregulation in skin fibroblasts. Functional studies demonstrated that miR‐181a and miR‐181b inhibitors attenuated bleomycin‐induced skin fibrosis in mice in association with decreased NUDT21 expression, while miR‐181a and miR‐181b mimics promoted bleomycin‐induced fibrosis. Overall, these findings suggest a novel role for miR‐181a/b in SSc pathogenesis by repressing NUDT21 expression.
Why Make the Cut? The Anconeus Triceps Hemipeel Approach for Distal Humerus Exposure Without Olecranon Osteotomy
Authors: Rees Andrew B. , Dombrowsky Alexander R. , Posey Samuel L. , Wally Meghan K. , Kempton Laurence B. , Hsu Joseph R. , Phelps Kevin D.
Published: September 2024

Articular visualization is a challenging aspect of treating comminuted intraarticular distal humerus fractures (AO/OTA types 13B and 13C). Multiple surgical approaches have been described to improve articular visualization while minimizing morbidity to the patient. The anconeus hemipeel approach is a modified approach to the distal humerus involving retrograde reflection of the anconeus to provide improved exposure to the distal humerus. The anconeus hemipeel approach can be used in place of the olecranon osteotomy—which adds additional morbidity and complicates future arthroplasty options. This study describes the approach as a technical trick and reports the first clinical outcomes of patients treated with the anconeus hemipeel approach for exposure of the distal humerus without an olecranon osteotomy for the treatment of comminuted, intraarticular distal humerus fractures.
Endocrine therapy for early breast cancer in the era of oral selective estrogen receptor degraders: challenges and future perspectives
Authors: Ascione Liliana , Castellano Grazia , Curigliano Giuseppe , Zagami Paola
Published: September 2024

Purpose of review

Growth and survival of hormone receptor positive breast cancer cells are dependent on circulating hormones (e.g., estrogen and progesterone). Endocrine therapy improved outcomes in both early and advanced hormone receptor positive breast cancer. These treatments include drugs with different mechanisms of action, namely selective estrogen receptor modulators (SERM), aromatase inhibitors, and selective estrogen receptor degraders (SERDs). SERDs represent estrogen receptor antagonists, favoring its degradation and thus interfering with proliferation genes transcription and activation. Fulvestrant is the first approved SERD, administered intramuscularly for treating advanced breast cancer.

Recent findings

Oral SERDs have been tested to overcome the limitation of the intramuscular administration, and to increase SERD bioavailability. Recently, an oral SERD, Elacestrant, has been approved by the Food and Drug Administration (FDA) for patients carrying an ESR1 mutation. In fact, oral SERDs seem to be effective in tumors harboring ESR1 mutations, a well known mechanism of resistance to endocrine therapy (especially aromatase inhibitors).

More recently, oral SERDs have been tested in patients with early hormone receptor positive breast cancer, although their impact on survival and in this curative setting compared to standard endocrine therapy still needs to be elucidated. The best timing and duration of SERD administration and specific biomarkers in (neo)adjuvant setting remain largely unknown.
Immunotherapy in first line treatment of adult acute lymphoblastic leukemia
Authors: Torrent Anna , Ribera Josep-Maria
Published: September 2024

Purpose of review

The use of immunotherapy in recent years has changed the paradigm of treatment in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), improving outcomes in the relapsed/refractory setting. New strategies are incorporating immunotherapy into front-line regimens to reduce the toxicity of chemotherapy, prolong survival and increase the possibility of treating older patients. The aim of this review was to describe the new strategies, which have incorporated these drugs into front-line regimens for BCP-ALL patients.

Recent findings

Recent studies have demonstrated that immunotherapy can be included in front-line induction, consolidation and/or maintenance regimens for the treatment of BCP-ALL patients by its addition to chemotherapy, by substituting some chemotherapy cycles or even including immunotherapy in chemotherapy-free strategies.

The implications of these relevant findings will allow treating older patients, reducing the toxicity of chemotherapy and increasing patient outcomes. In addition, these findings have raised the possibility of avoiding the need for hematologic stem cell transplant in some selected patients.
When do I ask for a DNA methylation array for primary brain tumor diagnosis?
Authors: Barresi Valeria , Poliani Pietro Luigi
Published: September 2024

Purpose of review

Despite remarkable advances in molecular characterization, the diagnosis of brain tumors remains challenging, particularly in cases with ambiguous histology or contradictory molecular features. In this context, DNA methylation profiling plays an important role in improving diagnostic and prognostic accuracy. This review aims to provide diagnostic guidance regarding when DNA methylation arrays represent a useful tool for the diagnosis of primary brain tumors.

Recent findings

Large-scale profiling has revealed that DNA methylation profiles of brain tumors are highly reproducible and stable. Therefore, DNA methylation profiling has been successfully used to classify brain tumors and identify new entities. This approach seems to be particularly promising for heterogeneous groups of tumors, such as IDH-wildtype gliomas, and glioneuronal and embryonal tumors, which include a variety of entities that are still under characterization.

As underlined in the fifth edition of the WHO classification of central nervous system tumors, the diagnosis of brain tumors requires the integration of histological, molecular, clinical, and radiological features. Although advanced imaging and histological examination remain the standard diagnostic tools, DNA methylation analysis can significantly improve diagnostic accuracy, with a substantial impact on patient management.
The emerging role of melflufen and peptide-conjugates in multiple myeloma
Authors: Moukalled Nour , Abou Dalle Iman , El Cheikh Jean , Ye Yishan , Malarad Florent , Mohty Mohamad , Bazarbachi Ali
Published: September 2024

Purpose of review

The past two decades have witnessed an impressive expansion in the treatment landscape of multiple myeloma, leading to significant improvements in progression-free; as well as overall survival. However, almost all patients still experience multiple relapses during their disease course, with biological and cytogenetic heterogeneity affecting response to subsequent treatments. The purpose of this review is to provide a historical background regarding the role of alkylating agents and an updated data regarding the use of peptide–drug conjugates such as melflufen for patients with multiple myeloma.

Recent findings

The combination of daratumumab–melflufen–dexamethasone evaluated in the LIGHTHOUSE study showed a statistically significant improvement in progression-free survival compared to single-agent daratumumab (not reached vs. 4.9 months respectively; P = 0.0032), with improvement in overall response rate to 59% vs. 30% respectively; P = 0.03.

There have been an interest in developing and utilizing peptide–drug conjugates such as melflufen for treatment of patients with multiple myeloma, especially in the relapsed setting given historical results with alkylating agents, the use of which has been limited by dose-related toxicities in a disease that remains largely incurable. Single agent melflufen initially showed promising results especially in specific subgroups of heavily pretreated patients before the decision to suspend all clinical trials evaluating this agent after results from the OCEAN phase 3 trial. Subsequent reported analyses especially for melflufen-based combinations appear promising and suggest a potential use of peptide–drug conjugates provided optimal patient selection, as well as identification of the best companion agent.
Duodenal-type follicular lymphoma: comprehensive insights into disease characteristics and established treatment strategies
Authors: Alnughmush Ahmed , Fakih Riad El , Alyamany Ruah , Bakshi Nasir , Alhayli Saud , Aljurf Mahmoud
Published: September 2024

Purpose of review

This review aims to detail the characteristics and outcomes of duodenal-type follicular lymphoma (DTFL), a rare lymphoma variant. It focuses on integrating recent reports in treatment modalities and highlights emerging insights into the unique biological features of the disease.

Recent finding

Recent studies confirm the indolent nature of DTFL, with extended follow-up periods showing favorable outcomes under watchful waiting strategies and a notable proportion of patients experiencing spontaneous remission. Additionally, advancements in understanding the disease's biology revealed that the tumor microenvironment is marked by specific genomic expressions indicative of chronic inflammation.

The observations of spontaneous resolution and the generally favorable progression of DTFL call for a conservative approach in initiating treatment. Clinical management should judiciously consider the disease's typically benign course against the potential risks of intervention, promoting customized treatment protocols tailored for cases with clinical necessity. Additionally, the discovery of an inflammatory tumor microenvironment and molecular evidence suggesting an antigen-driven process highlight critical areas for future research.
Advances in the pathogenesis of FLT3-mutated acute myeloid leukemia and targeted treatments
Authors: Travaglini Serena , Gurnari Carmelo , Ottone Tiziana , Voso Maria Teresa
Published: September 2024

Purpose of review

FLT3 mutations are among the most common myeloid drivers identified in adult acute myeloid leukemia (AML). Their identification is crucial for the precise risk assessment because of the strong prognostic significance of the most recurrent type of FLT3 alterations, namely internal tandem duplications (ITDs). Recent advances in the pathogenesis and biology of FLT3-mutated AML have opened an opportunity for development and application of selective inhibition of FLT3 pathway.

Recent findings

In the last decade, at least three targeted treatments have been approved by regulatory agencies and several others are currently under investigations. Here, we review the latest advance in the role of FLT3 mutations in AML, providing an outline of the available therapeutic strategies, their mechanisms of actions and of resistance, as well as routes for potential improvement.

The availability of FLT3 inhibitors has improved outcomes in AML harboring such mutations, currently also reflected in disease stratification and recommendations. Newer inhibitors are under investigations, and combinations with chemotherapy or other targeted treatments are being explored to further improve disease outcomes.
Formula-led methods using first morning fasting spot urine to assess usual salt intake: a secondary analysis of PURE study data
Authors: McLean Rachael M. , Song Jing , Wang Changqiong , He Feng J. , Cappuccio Francesco P. , Campbell Norm RC. , MacGregor Graham A.
Published: September 2024

Objectives:

Observational studies that assess the relationship between salt intake and long-term outcomes require a valid estimate of usual salt intake. The gold-standard measure in individuals is sodium excretion in multiple nonconsecutive 24-h urines. Multiple studies have demonstrated that random spot urine samples are not valid for estimating usual salt intake; however, some researchers believe that fasting morning spot urine samples produce a better measure of usual salt intake than random spot samples.

Methods:

We have used publicly available data from a PURE China validation study to compare estimates of usual salt intake from morning spot urine samples and three published formulae with mean of two 24-h urine samples (reference). We estimated the means and 95% confidence intervals of absolute and relative errors for each formula-led method and the degree to which estimates were able to be classified into the correct quartile of intake. Bland-Altman plots were used to test the level of agreement.

Results:

The results show that compared with the reference method, all formulae-led estimates from spot urine collections have high error rates: both random and systematic. This is demonstrated for individual estimates, as well as by quartiles of reference salt intake. This study conclusively demonstrates the unsuitability of morning spot urine formula-led estimates of usual salt intake.

Conclusion:

Our findings support international recommendations to not conduct, fund, or publish research studies that use spot urine samples with estimating equations to assess individuals’ salt intake in association with health outcomes.