bluuebunny/crossref_metadata_2025 huggingface dataset:
Does training beget training over the life course? Cumulative advantage in work-related non-formal training participation in Germany and the UK
Authors: dos Santos Sascha , Dieckhoff Martina , Ehlert Martin , Mertens Antje
Published: April 2024

Continuous training participation over the career becomes ever more important. However, most existing research mainly analyzed training at single points in time. This article investigates training dynamics and hence asks the question of whether training begets training. We provide two contributions to the literature: First, we analyze if previous training participation has an effect on later participation, leading to strict cumulative advantages. Second, by comparing Germany and the United Kingdom, we aim to explore whether these processes differ between countries with divergent skill formation systems. Using dynamic random effects probit models, which control for time-constant unobserved factors, and panel data (NEPS and UKHLS), we find that the accumulation of training experiences is mainly determined by initial education as well as job and firm characteristics. Still, previous participation plays a secondary yet noteworthy role, signifying dynamic growth in both countries, with higher effects for the United Kingdom. Thus, we show that only considering worker, job, and firm characteristics when analyzing inequality in training participation neglects a significant further mechanism that is rooted in previous training participation. We come to three main conclusions: (i) There is a potential amplification of early inequalities over time. Individuals who are initially on career paths that promote regular training participation are likely to keep and even enhance their advantage over time. (ii) On the other hand, our results also suggest the potential for individuals to break free from non-participation patterns. (iii) The inequality-generating pathways can be influenced by institutions.
Microbial Diversity and Open Questions about the Deep Tree of Life
Authors: Eme Laura , Tamarit Daniel
Published: April 2024

In this perspective, we explore the transformative impact and inherent limitations of metagenomics and single-cell genomics on our understanding of microbial diversity and their integration into the Tree of Life. We delve into the key challenges associated with incorporating new microbial lineages into the Tree of Life through advanced phylogenomic approaches. Additionally, we shed light on enduring debates surrounding various aspects of the microbial Tree of Life, focusing on recent advances in some of its deepest nodes, such as the roots of bacteria, archaea, and eukaryotes. We also bring forth current limitations in genome recovery and phylogenomic methodology, as well as new avenues of research to uncover additional key microbial lineages and resolve the shape of the Tree of Life.
Evolution of Phenotypic Variance Provides Insights into the Genetic Basis of Adaptation
Authors: Lai Wei-Yun , Nolte Viola , Jakšić Ana Marija , Schlötterer Christian
Published: April 2024

Most traits are polygenic, and the contributing loci can be identified by genome-wide association studies. The genetic basis of adaptation (adaptive architecture) is, however, difficult to characterize. Here, we propose to study the adaptive architecture of traits by monitoring the evolution of their phenotypic variance during adaptation to a new environment in well-defined laboratory conditions. Extensive computer simulations show that the evolution of phenotypic variance in a replicated experimental evolution setting can distinguish between oligogenic and polygenic adaptive architectures. We compared gene expression variance in male Drosophila simulans before and after 100 generations of adaptation to a novel hot environment. The variance change in gene expression was indistinguishable for genes with and without a significant change in mean expression after 100 generations of evolution. We suggest that the majority of adaptive gene expression evolution can be explained by a polygenic architecture. We propose that tracking the evolution of phenotypic variance across generations can provide an approach to characterize the adaptive architecture.
The endosymbiont of Epithemia clementina is specialized for nitrogen fixation within a photosynthetic eukaryote
Authors: Moulin Solène L Y , Frail Sarah , Braukmann Thomas , Doenier Jon , Steele-Ogus Melissa , Marks Jane C , Mills Matthew M , Yeh Ellen
Published: April 2024

Epithemia spp. diatoms contain obligate, nitrogen-fixing endosymbionts, or diazoplasts, derived from cyanobacteria. These algae are a rare example of photosynthetic eukaryotes that have successfully coupled oxygenic photosynthesis with oxygen-sensitive nitrogenase activity. Here, we report a newly-isolated species, E. clementina, as a model to investigate endosymbiotic acquisition of nitrogen fixation. We demonstrate that the diazoplast, which has lost photosynthesis, provides fixed nitrogen to the diatom host in exchange for fixed carbon. To identify the metabolic changes associated with this endosymbiotic specialization, we compared the Epithemia diazoplast with its close, free-living cyanobacterial relative, Crocosphaera subtropica. Unlike C. subtropica, in which nitrogenase activity is temporally separated from photosynthesis, we show that nitrogenase activity in the diazoplast is continuous through the day (concurrent with host photosynthesis) and night. Host and diazoplast metabolism are tightly coupled to support nitrogenase activity: Inhibition of photosynthesis abolishes daytime nitrogenase activity, while nighttime nitrogenase activity no longer requires cyanobacterial glycogen storage pathways. Instead, import of host-derived carbohydrates supports nitrogenase activity throughout the day-night cycle. Carbohydrate metabolism is streamlined in the diazoplast compared to C. subtropica with retention of the oxidative pentose phosphate pathway and oxidative phosphorylation. Similar to heterocysts, these pathways may be optimized to support nitrogenase activity, providing reducing equivalents and ATP and consuming oxygen. Our results demonstrate that the diazoplast is specialized for endosymbiotic nitrogen fixation. Altogether, we establish a new model for studying endosymbiosis, perform a functional characterization of this diazotroph endosymbiosis, and identify metabolic adaptations for endosymbiotic acquisition of a critical biological function.
2-Fluorodeschloroketamine consumption: About two deaths and a case of self-mutilation
Authors: Riess Salomé , Chèze Marjorie , Muckensturm Aurelie , Klinger Nadine , Roussel Olivier , Cirimele Vincent
Published: April 2024

2-Fluorodeschloroketamine (2-FDCK) is a new psychoactive substance (NPS), close to the ketamine structure. Few cases of 2-FDCK intake are described in the forensic literature, especially concerning death cases. We report here a case of self-mutilation (Case 1) and two forensic deaths linked to 2-FDCK consumption. The second case involved a man found dead in the street, having been stabbed. The third case was a man found dead following a suspected overdose and in an advanced state of putrefaction. For all three cases, biological fluids such as blood and urine were analyzed, as was hair for the two fatal cases. The aim of this study was to identify and quantify 2-FDCK and its main metabolites in different matrices. Biological fluids and hair were analyzed by liquid chromatography coupled with tandem mass spectrometry after decontamination and extraction. Seized products were analyzed by gas chromatography–mass spectrometry and assayed, when possible, by ultra-performance liquid chromatography with diode-array detection. 2-FDCK was detected and quantified in the peripheral blood of Cases 1, 2 and 3 (457, 758 and 5885 µg/L, respectively), as were its main metabolites nor-2-FDCK, dihydro-nor-2-FDCK and dihydro-2-FDCK. In the 1 cm long hair of Cases 2 and 3, 2-FDCK was also detected (approximately 4149 and 79824 pg/mg, respectively). Deschloroketamine (DCK) was found in the biological fluids of Cases 1, 2 and 3 (10, 8 and 350 µg/L, respectively), as well as in hair of Cases 2 and 3 (65 and around 8119 pg/mg, respectively). In Case 3, as a small bag containing DCK powder was seized from his home, we can assume that DCK was taken. On the contrary, to our knowledge, it has not been established that Case 2 took DCK alone, so we can assume that it may be the first case to report DCK from 2-FDCK metabolism in fluids as well as in hair.
RANKL signaling drives skeletal muscle into the oxidative profile
Authors: Cavalcanti de Araújo Paulo Henrique , Cezine Maria Eduarda Ramos , Vulczak Anderson , Vieira Luiz Carlos , Matsuo Flávia Sayuri , Remoto Júlia Maranghetti , Santos Audrei dos Reis , Miyabara Elen Haruka , Alberici Luciane Carla , Osako Mariana Kiomy
Published: April 2024

The bone–muscle unit refers to the reciprocal regulation between bone and muscle by mechanical interaction and tissue communication via soluble factors. The RANKL stimulation induces mitochondrial biogenesis and increases the oxidative capacity in osteoclasts and adipocytes. RANKL may bind to the membrane bound RANK or to osteoprotegerin (OPG), a decoy receptor that inhibits RANK–RANKL activation. RANK is highly expressed in skeletal muscle, but the contribution of RANKL to healthy skeletal muscle fiber remains elusive. Here we show that RANKL stimulation in C2C12-derived myotubes induced activation of mitochondrial biogenesis pathways as detected by RNA-seq and western blot. RANKL expanded the mitochondrial reticulum, as shown by mitochondrial DNA quantification and MitoTracker staining, and boosted the spare respiratory capacity. Using MEK and MAPK inhibitors, we found that RANKL signals via ERK and p38 to induce mitochondrial biogenesis. The soleus from OPG−/− and OPG+/− mice showed higher respiratory rates compared to C57BL6/J WT mice, which correlates with high serum RANKL levels. RANKL infusion using a mini-osmotic pump in WT mice increased the number of mitochondria, boosted the respiratory rate, increased succinate dehydrogenase activity in skeletal muscle, and improved the fatigue resistance of gastrocnemius. Therefore, our findings reveal a new role of RANKL as an osteokine-like protein that impacts muscle fiber metabolism.
Decolonization in South African universities: storytelling as subversion and reclamation
Authors: Davids Nuraan
Published: April 2024

Underscoring recurrent calls for the decolonization of university curricula in South Africa are underexplored presumptions that by only disrupting theoretical content, universities might release themselves from a colonialist grasp, that continues to dominate and distort higher education discourse. While it might be the case that certain theories hold enormous authoritative, ‘truthful’ sway, as propagated through Western interpretations and norms, there are inherent problems in exclusively approaching the decolonization project as a content-based hurdle, removed from the subjectivities of students’ social, lived, and learning realities. The argument advanced in this article is that until the epistemic harm of colonialism and apartheid are afforded careful recognition and attention—as in focusing on the lived experiences, realities, and stories of individuals—the hard work of delegitimizing coloniality, and its implicit structures of hegemonies and binaries cannot unfold. In addressing these harms, I commence by describing some of the contexts of epistemic harm, promulgated through colonialism and apartheid. This is followed by a consideration of decolonization, both as theory and practice-within-context. Here, I also foreground the #Rhodesmustfall campaign, as a particular moment of painful clarity about why decolonization, as well as transformation, has faltered in higher education in South Africa. In the second half, I focus on the necessity of prioritizing storytelling as a deep manifestation of decolonization. Stories, I maintain, provide access into unknown lives, and can subvert the invisible, normative framings, which dictate how we live in this world. As a manifestation of decolonization, students’ stories hold profound implications for the recognition and affirmation of pluralist identities, histories, knowledge, values, and world-views.
Evaluating the Acceptability and Feasibility of Collecting Passive Smartphone Data to Estimate Psychological Functioning in U.S. Service Members and Veterans: A Pilot Study
Authors: Schultz Lauren S , Murphy Mikela A , Donegan Macayla , Knights Jonathan , Baker Justin T , Thompson Matthew F , Waters Andrew J , Roy Michael , Gray Joshua C
Published: April 2024

Introduction

This study investigated the acceptability and feasibility of digital phenotyping in a military sample with a history of traumatic brain injury and co-occurring psychological and cognitive symptoms. The first aim was to evaluate the acceptability of digital phenotyping by (1a) quantifying the proportion of participants willing to download the app and rates of dropout and app discontinuation and (1b) reviewing the stated reasons for both refusing and discontinuing use of the app. The second aim was to investigate technical feasibility by (2a) characterizing the amount and frequency of transferred data and (2b) documenting technical challenges. Exploratory aim 3 sought to leverage data on phone and keyboard interactions to predict if a participant (a) is depressed and (b) has depression that improves over the course of the study.

Materials and Methods

A passive digital phenotyping app (Mindstrong Discovery) functioned in the background of the participants’ smartphones and passively collected phone usage and typing kinematics data.

Results

Fifteen out of 16 participants (93.8%) consented to install the app on their personal smartphone devices. Four participants (26.7%) discontinued the use of the app partway through the study, primarily because of keyboard usability and technical issues. Fourteen out of 15 participants (93.3%) had at least one data transfer, and the median number of days with data was 40 out of a possible 57 days. The exploratory machine learning models predicting depression status and improvement in depression performed better than chance.

Conclusions

The findings of this pilot study suggest that digital phenotyping is acceptable and feasible in a military sample and provides support for future larger investigations of this technology.
Safety and effectiveness of certolizumab pegol in Japanese patients with rheumatoid arthritis: Up to 3-year results from a postmarketing surveillance study
Authors: Kameda Hideto , Nishida Keiichiro , Nanki Toshihiro , Watanabe Akira , Oshima Yukiya , Momohara Shigeki
Published: April 2024

Objectives

To report up to 3-year safety and effectiveness of certolizumab pegol (CZP) in Japanese patients with rheumatoid arthritis from a postmarketing surveillance study.

Methods

Patients enrolled previously completed 24 weeks of CZP in the 24-week postmarketing surveillance study. Adverse drug reactions (ADRs) were recorded for patients who received ≥1 CZP dose. Effectiveness outcomes were 28-joint Disease Activity Score with erythrocyte sedimentation rate and European Alliance of Associations for Rheumatology response. Week 24–156 safety and Week 0–52 effectiveness data are reported here.

Results

A total of 781 patients were enrolled, with 735 and 376 patients evaluated for safety and effectiveness, respectively. Within the safety set, 17.8% (131/735) of patients reported ADRs; 9.4% (69/735) reported serious ADRs. Among patients with history of respiratory, thoracic, and mediastinal disorders, 38.4% (28/73) reported ADRs. The most frequent ADRs were infections and infestations (11.8%; 87/735); skin and subcutaneous tissue disorders (1.9%; 14/735); respiratory, thoracic, and mediastinal disorders (1.6%; 12/735). Mean 28-joint Disease Activity Score with erythrocyte sedimentation rate reduced from 4.6 (Week 0) to 2.8 (Week 52). At Week 52, 51.8% (161/311) of patients achieved European Alliance of Associations for Rheumatology Good response.

Conclusions

The long-term safety and effectiveness of CZP in the real-world setting in Japan were consistent with previously reported data; no new safety signals were identified.
The impact of ribosome biogenesis in cancer: from proliferation to metastasis
Authors: Hwang Sseu-Pei , Denicourt Catherine
Published: April 2024

The dysregulation of ribosome biogenesis is a hallmark of cancer, facilitating the adaptation to altered translational demands essential for various aspects of tumor progression. This review explores the intricate interplay between ribosome biogenesis and cancer development, highlighting dynamic regulation orchestrated by key oncogenic signaling pathways. Recent studies reveal the multifaceted roles of ribosomes, extending beyond protein factories to include regulatory functions in mRNA translation. Dysregulated ribosome biogenesis not only hampers precise control of global protein production and proliferation but also influences processes such as the maintenance of stem cell-like properties and epithelial-mesenchymal transition, contributing to cancer progression. Interference with ribosome biogenesis, notably through RNA Pol I inhibition, elicits a stress response marked by nucleolar integrity loss, and subsequent G1-cell cycle arrest or cell death. These findings suggest that cancer cells may rely on heightened RNA Pol I transcription, rendering ribosomal RNA synthesis a potential therapeutic vulnerability. The review further explores targeting ribosome biogenesis vulnerabilities as a promising strategy to disrupt global ribosome production, presenting therapeutic opportunities for cancer treatment.
Examining the Predictive Utility of Behavioral Economic Demand Indices and Subjective Effects on the Actualized Reinforcing Value of Menthol Cigarettes and Potential Alternatives
Authors: Erath Tyler G , Schulz Jonathan A , Hinton Alice , Mehta Toral , Reed Derek D , Tidey Jennifer W , Wagener Theodore L , Villanti Andrea C
Published: April 2024

Introduction

Considering recent and proposed bans on menthol cigarettes, methods are needed to understand the substitutability of potential menthol cigarette alternatives (MCAs) for menthol cigarettes. This study examined the prospective relationship between behavioral economic demand indices and subjective effects of usual brand menthol cigarettes (UBMC) and preferred MCAs with subsequent performance on a laboratory-based concurrent-choice task comparing UBMC and MCAs.

Methods

Eighty participants who typically smoked menthol cigarettes completed this clinical laboratory study. After sampling each product, participants completed the cigarette purchase task (CPT) and modified cigarette evaluation questionnaire (mCEQ). Following 1 week of substituting their preferred MCA for their UBMC, participants completed a 90-minute concurrent-choice self-administration (SA) task comparing their UBMC and preferred MCA. Linear regression models explored associations between CPT demand indices and mCEQ subjective effects in the laboratory with subsequent response effort for UBMCs on the concurrent-choice task.

Results

Three demand indices for UBMC were positively associated with UBMC response effort: essential value (EV; p = .02), Omax (p = .02), and breakpoint (p = .04). Four CPT demand indices for the preferred MCA significantly corresponded with UBMC response effort: EV (p = .03), price associated with maximal expenditure (Pmax) (p = .04), maximal expenditure (Omax) (p = .03), and breakpoint (p = .03). Subjective effects captured by the mCEQ were not associated with response effort.

Conclusions

Demand indices reflecting Persistence (ie, sensitivity to escalating price) predicted effort to obtain UBMC puffs on the concurrent-choice task. Among this sample, the CPT captured information on the relative reinforcing value (ie, addiction potential) of combustible tobacco products similar to the longer SA task.

Implications

In an ever-changing product market, assessing the reinforcing efficacy of menthol cigarettes and putative substitutes quickly and with validity is an important methodological tool for understanding abuse liability. Results suggest that behavioral economic demand indices of CPT efficiently capture information on the relative reinforcing value of UBMC and plausible alternative tobacco products, similar to a 90-minute in-laboratory SA task.
Variation in nuptial color in relation to sex, individual quality and mating success in the sex-role reversed Phalaropus fulicarius (Red Phalarope)
Authors: Delhey Kaspar , Krietsch Johannes , Parisi Andrea , Valcu Mihai , Kempenaers Bart
Published: April 2024

In most bird species, males are more ornamented and compete for females, who contribute more to offspring care. In a minority of species, this pattern is reversed, with more colorful females competing for mates and males taking care of parental duties. In such sex-role reversed species, the links between colorful ornamentation, individual quality and mating success are not well established. Phalaropus fulicarius (Red Phalarope) is a colorful sex-role reversed migratory shorebird with regular social polyandry, in which both sexes show considerable color variation. Here, we describe sex differences in color and quantify associations between color variation and indicators of quality and mating success in both sexes. Using a large sample of photos collected across 3 consecutive years on the Arctic breeding grounds, we scored color variation for 4 body parts (bill, crown, cheek, and breast), and analyzed scores separately and combined into an overall color score. Females were more colorful and larger than males, and individuals could be unambiguously sexed by crown color. Nevertheless, there was substantial variation within sexes and some overlap between males and females in bill, cheek, breast, and overall color scores. Assortative mating by color was only found for the bill. Color variation did not correlate with plasma testosterone levels, except for male cheek color. Females in better body condition had yellower bills and higher overall color scores, while early-arriving birds had higher breast and overall scores. Phalaropus fulicarius that bred locally were heavier than those that did not, but they did not have higher color scores. Female color variation did not predict the probability of local social polyandry nor variation in clutch size, and male coloration did not predict the probability of nest predation. In conclusion, P. fulicarius color variation showed modest correlations with individual quality and was unrelated to variation in local reproductive success.
Analytical Methods for Brassinosteroid Analysis: Recent Advances and Applications
Authors: Oklestkova Jana , Kvasnica Miroslav , Strnad Miroslav
Published: April 2024

Brassinosteroids (BRs) are plant steroidal hormones that play crucial roles in plant growth and development. Accurate quantification of BRs in plant tissues is essential for understanding their biological functions. This study presents a comprehensive overview of the latest methods used for the quantification of BRs in plants. We discuss the principles, advantages and limitations of various analytical techniques, including immunoassays, gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry that are used for the detection and quantification of BRs from complex plant matrixes. We also explore the use of isotopically labeled internal standards to improve the accuracy and reliability of BR quantification.
The Role of FtsH Complexes in the Response to Abiotic Stress in Cyanobacteria
Authors: Krynická Vendula , Komenda Josef
Published: April 2024

FtsH proteases (FtsHs) belong to intramembrane ATP-dependent metalloproteases which are widely distributed in eubacteria, mitochondria and chloroplasts. The best-studied roles of FtsH in Escherichia coli include quality control of membrane proteins, regulation of response to heat shock, superoxide stress and viral infection, and control of lipopolysaccharide biosynthesis. While heterotrophic bacteria mostly contain a single indispensable FtsH complex, photosynthetic cyanobacteria usually contain three FtsH complexes: two heterocomplexes and one homocomplex. The essential cytoplasmic FtsH1/3 most probably fulfills a role similar to other bacterial FtsHs, whereas the thylakoid FtsH2/3 heterocomplex and FtsH4 homocomplex appear to maintain the photosynthetic apparatus of cyanobacteria and optimize its functionality. Moreover, recent studies suggest the involvement of all FtsH proteases in a complex response to nutrient stresses. In this review, we aim to comprehensively evaluate the functions of the cyanobacterial FtsHs specifically under stress conditions with emphasis on nutrient deficiency and high irradiance. We also point to various unresolved issues concerning FtsH functions, which deserve further attention.
The Verticillium dahliae Effector VdPHB1 Promotes Pathogenicity in Cotton and Interacts with the Immune Protein GhMC4
Authors: Song Qingwei , Han Song , Hu Shi , Xu Yiyang , Zuo Kaijing
Published: April 2024

Verticillium dahliae is a kind of pathogenic fungus that brings about wilt disease and great losses in cotton. The molecular mechanism of the effectors in V. dahliae regulating cotton immunity remains largely unknown. Here, we identified an effector of V. dahliae, VdPHB1, whose gene expression is highly induced by infection. The VdPHB1 protein is localized to the intercellular space of cotton plants. Knock-out of the VdPHB1 gene in V. dahliae had no effect on pathogen growth, but decreased the virulence in cotton. VdPHB1 ectopically expressed Arabidopsis plants were growth-inhibited and significantly susceptible to V. dahliae. Further, VdPHB1 interacted with the type II metacaspase GhMC4. GhMC4 gene-silenced cotton plants were more sensitive to V. dahliae with reduced expression of pathogen defense-related and programmed cell death genes. The accumulation of GhMC4 protein was concurrently repressed when VdPHB1 protein was expressed during infection. In summary, these results have revealed a novel molecular mechanism of virulence regulation that the secreted effector VdPHB1 represses the activity of cysteine protease for helping V. dahliae infection in cotton.
Functions and Mechanisms of Brassinosteroids in Regulating Crop Agronomic Traits
Authors: Chen Xu , Hu Xiaotong , Jiang Jianjun , Wang Xuelu
Published: April 2024

Brassinosteroids (BRs) perform crucial functions controlling plant growth and developmental processes, encompassing many agronomic traits in crops. Studies of BR-related genes involved in agronomic traits have suggested that BRs could serve as a potential target for crop breeding. Given the pleiotropic effect of BRs, a systematic understanding of their functions and molecular mechanisms is conducive for application in crop improvement. Here, we summarize the functions and underlying mechanisms by which BRs regulate the several major crop agronomic traits, including plant architecture, grain size, as well as the specific trait of symbiotic nitrogen fixation in legume crops. For plant architecture, we discuss the roles of BRs in plant height, branching number and leaf erectness, and propose how progress in these fields may contribute to designing crops with optimal agronomic traits and improved grain yield by accurately modifying BR levels and signaling pathways.
Fermionic quantum turbulence: Pushing the limits of high-performance computing
Authors: Wlazłowski Gabriel , Forbes Michael McNeil , Sarkar Saptarshi Rajan , Marek Andreas , Szpindler Maciej
Published: April 2024

Ultracold atoms provide a platform for analog quantum computer capable of simulating the quantum turbulence that underlies puzzling phenomena like pulsar glitches in rapidly spinning neutron stars. Unlike other platforms like liquid helium, ultracold atoms have a viable theoretical framework for dynamics, but simulations push the edge of current classical computers. We present the largest simulations of fermionic quantum turbulence to date and explain the computing technology needed, especially improvements in the Eigenvalue soLvers for Petaflop Applications library that enable us to diagonalize matrices of record size (millions by millions). We quantify how dissipation and thermalization proceed in fermionic quantum turbulence by using the internal structure of vortices as a new probe of the local effective temperature. All simulation data and source codes are made available to facilitate rapid scientific progress in the field of ultracold Fermi gases.
Wage Risk and Government and Spousal Insurance
Authors: De Nardi Mariacristina , Fella Giulio , Paz-Pardo Gonzalo
Published: April 2024

The extent to which households can self-insure depends on family structure and wage risk. We calibrate a model of couples and singles’ savings and labour supply under two types of wage processes. The first wage process is the canonical—age-independent, linear—one that is typically used to evaluate government insurance provision. The second wage process is a flexible one. We use our model to evaluate the optimal mix of the two most common types of means-tested benefits—IW versus income floor. The canonical wage process underestimates wage persistence for women and thus implies that IW benefits should account for most benefit income. In contrast, the richer wage process that matches the wage data well, implies that the income floor should be the main benefit source, similarly to the system in place in the U.K. This stresses that allowing for rich wage dynamics is important to properly evaluate policy.
Development and Implementation of a Novel CAPS Assay Reveals High Prevalence of a Boscalid Resistance Marker and Its Co-Occurrence with an Azole Resistance Marker in Erysiphe necator
Authors: Seress Diána , Molnár Orsolya , Matolcsi Fruzsina , Pintye Alexandra , Kovács Gábor M. , Németh Márk Z.
Published: April 2024

Succinate dehydrogenase inhibitors (SDHIs) are frequently used against powdery mildew (PM) fungi, such as Erysiphe necator, the causal agent of grapevine PM. Fungicide resistance, however, hinders effective control. DNA-based monitoring facilitates the recognition of resistance. We aimed (i) to adapt an effective method to detect a widespread genetic marker of resistance to boscalid, a commonly used SDHI, and (ii) to study the co-occurrence of the marker with a marker of resistance to demethylase inhibitor (DMI) fungicides. Sequencing of the sdhB gene identified a nonsynonymous substitution, denoted as sdhB-A794G, leading to an amino acid change (H242R) in the sdhB protein. In vitro fungicide resistance tests showed that E. necator isolates carrying sdhB-A794G were resistant to boscalid. We adopted a cleaved amplified polymorphic sequence-based method and screened more than 500 field samples collected from five Hungarian wine regions in two consecutive years. The sdhB-A794G marker was detected in all wine regions and in both years, altogether in 61.7% of samples, including 20.5% in which both sdhB-A794G and the wild-type were present. The frequency of sdhB-A794G was higher in SDHI-treated vineyards than in vineyards without any SDHI application. A significant difference in the presence of the marker was detected among wine regions; its prevalence ranged from none to 100%. We identified significant co-occurrence of sdhB-A794G with the CYP51-A495T (Y136F) mutation of the CYP51 gene, a known marker of resistance to DMIs. The monitoring of fungicide resistance is fundamental for the successful control of E. necator. Our rapid, cost-effective diagnostic method will support decision-making and fungicide resistance monitoring and management.
ADOPTERs of Innovation in a Crisis: The History of Vera Gedroits, Kanehiro Takaki and the Russo-Japanese War of 1904–1905
Authors: Raichurkar Pratik , Kaushal Devesh , Wilson Robert Beaumont
Published: April 2024

The 1904–1905 Russo-Japanese War was the first “modern” conflict, using rapid-firing artillery and machine guns, fought over imperial ambitions in Korea and Manchuria. During the war, Princess Vera Gedroits pioneered early laparotomy for penetrating abdominal wounds with unprecedented success. Her techniques were then adopted by the Russian Society of Military Doctors. However, Allied forces took 10 years to adopt operative management of penetrating abdominal wounds over conservative management. Gedroits was later appointed in Kyiv as the world’s first female Professor of Surgery. Kanehiro Takaki, a Japanese Naval surgeon, showed in 1884 a diet of barley, meat, milk, bread, and beans, rather than polished white rice, eliminated beriberi in the Japanese Navy. Despite this success, the Japanese Army failed to change the white rice rations until March 1905. During the 1904–1905 Russo-Japanese War, an estimated 250,000 Japanese soldiers developed beriberi, of whom 27,000 died. Japan’s 1905 defeat of Russia sowed the seeds of discontent with Tsar Nicholas’ rule, culminating in the 1917 Russian Revolution. Although the Russian Navy was destroyed, Japan ceded North Sakhalin Island to Russia in peace negotiations, and Russia seized Manchuria, South Sakhalin, and the Kuril Islands in 1945. We highlight the contributions of Gedroits and Takaki, 2 intellectual prodigies who respectively pioneered rapid triage and surgical management of trauma and a cure for beriberi. We aim to show how both these surgeons challenged entrenched dogma and the cultural and political zeitgeist, and risked their professional reputations and their lives in being ADOPTERs of innovation during a crisis.
Benchmark Values for Construct Survival and Complications by Type of ASD Surgery
Authors: Bass Robert Daniel , Lafage Renaud , Smith Justin S. , Ames Christopher , Bess Shay , Eastlack Robert , Gupta Munish , Hostin Richard , Kebaish Khaled , Kim Han Jo , Klineberg Eric , Mundis Gregory , Okonkwo David , Shaffrey Christopher , Schwab Frank , Lafage Virginie , Burton Douglas ,   On behalf of the International Spine Study Group
Published: April 2024

Objective.

The aim of this study was to provide benchmarks for the rates of complications by type of surgery performed.

Study Design.

Prospective multicenter database.

Background.

We have previously examined overall construct survival and complication rates for ASD surgery. However, the relationship between type of surgery and construct survival warrants more detailed assessment.

Materials and Methods.

Eight surgical scenarios were defined based on the levels treated, previous fusion status [primary (P)vs.revision (R)], and three-column osteotomy use (3CO): short lumbar fusion, LT-pelvis with 5 to 12 levels treated (P, R, or 3CO), UT-pelvis with 13 levels treated (P, R, or 3CO), and thoracic to lumbar fusion without pelvic fixation, representing 92.4% of the case in the cohort. Complication rates for each type were calculated and Kaplan-Meier curves with multivariate Cox regression analysis was used to evaluate the effect of the case characteristics on construct survival rate, while controlling for patient profile.

Results.

A total of 1073 of 1494 patients eligible for 2-year follow-up (71.8%) were captured. Survival curves for major complications (with or without reoperation), while controlling for demographics differed significantly among surgical types (P<0.001). Fusion procedures short of the pelvis had the best survival rate, while UT-pelvis with 3CO had the worst survival rate. Longer fusions and more invasive operations were associated with lower 2-year complication-free survival, however, there were no significant associations between type of surgery and renal, cardiac, infection, wound, gastrointestinal, pulmonary, implant malposition, or neurological complications (allP>0.5).

Conclusions.

This study suggests that there is an inherent increased risk of complication for some types of ASD surgery independent of patient profile. The results of this paper can be used to produce a surgery-adjusted benchmark for ASD surgery with regard to complications and survival. Such a tool can have very impactful applications for surgical decision-making and more informed patient counseling.

Level of Evidence.

Level III.
Socioeconomic inequalities in cancer incidence and mortality: An analysis of GLOBOCAN 2022
Authors: Cao Wei , Qin Kang , Li Feng , Chen Wanqing
Published: April 2024

Background:

Given the recent updates in cancer burden estimates by GLOBOCAN 2022, this study was undertaken to provide pertinent perspectives within the context of the Human Development Index (HDI) and major world economies.

Methods:

Datasets sourced from GLOBOCAN encompassed cancer cases and deaths across all cancer types in 2022, alongside projections up to 2050. Cancer incidences and deaths of the top 10 cancers within China and four distinct HDI-classified regions were compared using descriptive analyses. Age-standardized incidence rates (ASIRs) and mortality rates (ASMRs) worldwide for the most prevalent cancers in 2022 across ten largest economies and four-tier HDIs were examined. The top five cancer types concerning both incidence and mortality in China were delineated by sex and age group.

Results:

In males, prostate cancer predominated in countries with low, high (except China), and very high HDI. Prostate and liver cancers were prominent causes of death in countries with low HDI. In females, breast and cervical cancers predominated in countries with low-to-medium HDI. Lung and colorectal cancer incidence and deaths increased with high HDI for both sexes. ASIRs and ASMRs for breast, prostate, lung, and colorectal cancers in the top 10 economies were higher than the global average. However, liver, stomach, and cervical cancers in most Western countries exhibited lower rates. In China, hematologic malignancies (43%) were prevalent among children aged 0–14 years, whereas thyroid cancer led among adolescents and young adults aged 15–39 years. Regarding incidence and mortality, lung cancer predominated for individuals over 40 years, except for females aged 40–59 years, in whom breast cancer predominated. Projected trends indicated substantial increases in new cancer cases (76.6%) and deaths (89.7%) over the next three decades.

Conclusions:

Infection- and poverty-related cancer burdens are offset by increased prostate, breast, colorectal, and lung cancer incidence associated with rapid societal and economic transitions. Cancer incidence and mortality patterns in China feature characteristics of developed and developing countries, necessitating tailored, evidence-based, and comprehensive strategies for effective cancer prevention and control.
Postoperative myocardial injury after major head and neck cancer surgery
Authors: Amir Duaa , Inam Hina
Published: April 2024

Background/objective:

This narrative review aims to assess the causes and evaluate the scientific evidence concerning the increased risk of postoperative myocardial infarction (PMI) in patients undergoing major head and neck surgery.

Method:

A comprehensive review of literature was conducted and findings from clinical trials, meta-analysis as well as observational studies were incorporated to explore the risk factors associated with PMI after a major head and neck surgery. Preoperative risk factors, appropriate diagnostic plans, biomarkers, risk stratification strategies, and treatment options were also assessed.

Result:

The review highlights that patients undergoing head and neck surgery are at a significant risk of developing PMI primarily due to surgical trauma, anesthesia, and the extensive nature of head and neck surgeries. However, pre-existing conditions like renal insufficiency, cerebrovascular diseases, and diabetes may also exacerbate this risk. Moreover, ECG and regular observation of troponin has proven to be successful in detecting PMI, which can be easily masked due to its ambiguous symptoms in postoperative patients that are receiving pain reducing medications. Once diagnosed, PMI is treated with standard medication for myocardial infarction, however, more emphasis has been put on its timely diagnosis through routine troponin testing.

Conclusion:

Head and neck cancers are prevalent in developing nations such as Pakistan where the use of tobacco is widespread. As a result of such aggressive cancer, patients may undergo surgery, which places them at a risk of developing PMI. This can be avoided through routine troponin testing which still requires further research on localized patient population considering the physiologic differences.
Alpha-fetoprotein: Past, present, and future
Authors: Yeo Yee Hui , Lee Yi-Te , Tseng Hsian-Rong , Zhu Yazhen , You Sungyong , Agopian Vatche G. , Yang Ju Dong
Published: April 2024

Alpha-fetoprotein (AFP) is a glycoprotein that plays an important role in immune regulation with critical involvement in early human development and maintaining the immune balance during pregnancy. Postfetal development, the regulatory mechanisms controlling AFP undergo a shift and AFP gene transcription is suppressed. Instead, these enhancers refocus their activity to maintain albumin gene transcription throughout adulthood. During the postnatal period, AFP expression can increase in the setting of hepatocyte injury, regeneration, and malignant transformation. It is the first oncoprotein discovered and is routinely used as part of a screening strategy for HCC. AFP has been shown to be a powerful prognostic biomarker, and multiple HCC prognosis models confirmed the independent prognostic utility of AFP. AFP is also a useful predictive biomarker for monitoring the treatment response of HCC. In addition to its role as a biomarker, AFP plays important roles in immune modulation to promote tumorigenesis and thus has been investigated as a therapeutic target in HCC. In this review article, we aim to provide an overview of AFP, encompassing the discovery, biological role, and utility as an HCC biomarker in combination with other biomarkers and how it impacts clinical practice and future direction.
Optic Disc Microvasculature Dropout in Preperimetric Glaucoma
Authors: Suh Min Hee , Weinreb Robert N. , Zangwill Linda M.
Published: April 2024

Précis:

Optic disc microvasculature dropout (MvD-D) was associated with worse disease severity in pre-perimetric glaucoma. MvD-D was not accompanied by focal lamina cribrosa defect or parapapillary deep-layer microvasculature dropout in 62.3% and 71.0% of eyes, respectively.

Purpose:

To investigate factors associated with optic disc microvasculature dropout (MvD-D) in patients with preperimetric primary open angle glaucoma (PPG).

Methods:

One hundred thirty nine eyes of PPG patients were categorized according to the presence of MvD-D with optical coherence tomography angiography (OCTA). Factors including visual field (VF) mean deviation (MD), retinal nerve fiber layer (RNFL) thickness, focal lamina cribrosa (LC) defect, optic disc hemorrhage (DH), and parapapillary deep-layer microvasculature dropout (MvD-P) were compared between eyes with and without MvD-D.

Results:

MvD-D was observed in 69 PPG eyes (49.6%). Compared with eyes without MvD-D, the ones with MvD-D had a significantly thinner RNFL in all areas except the nasal sector, worse VF MD, and a focal LC defect and MvD-P (P<0.05): male gender also was more highly prevalent. A considerable number of eyes with MvD-D lacked focal LC defect (62.3% [43/69]) or MvD-P (71.0% [49/69]), while a few eyes without MvD-D had focal LC defect (10.0% [7/70]) or MvD-P (2.9% [2/70]). In a multivariable logistic regression analysis, male gender (odds ratio [OR], 3.96; P<0.001), worse VF MD (OR, 1.44; P=0.019), thinner global RNFL (OR, 1.13; P<0.001), higher prevalence of focal LC defect (OR, 3.71; P=0.014) and MvD-P (OR, 7.85; P<0.001) were significantly associated with MvD-D.

Conclusions:

MvD-D was related to worse disease severity in patients with PPG, and often was not accompanied by focal LC defect or MvD-P. This suggests that impaired optic disc circulation can be an early sign of glaucoma without noticeable changes in functional or structural features (i.e., VF, focal LC defect, MvD-P).
Catheter-related Infections in Pediatric Patients Due to a Rare Pathogen: Herbaspirillum huttiense
Authors: Özen Seval , Kanik Yüksek Saliha , Dinç Bedia , Üçkardeş Fatih , Konca Hatice Kübra , Erat Tuğba , Güney Ahmet Yasin , Güneş Ömer , Coşkun Zehra Nihan , Gülhan Belgin , Bayhan Gülsüm İclal , Çöplü Nilay , Parlakay Aslı Nur Özkaya , Özbek Namık Yaşar
Published: April 2024

Background:

Herbaspirillum species are nonfermenting, aerobic, helical or curved, Gram-negative bacteria belonging to the class Betaproteobacteria, order Burkholderiales. To date, only a few studies have reported on the epidemiology, clinical symptoms, antibiotic susceptibility profiles, treatment and outcomes of Herbaspirillum huttiense-related infections in pediatric patients.

Methods:

The aim of this study was to present 3 years of H.huntiense data, antibiotic susceptibility profiles, systemic antibiotics and antibiotic lock therapy (ALT) options and clinical outcomes.

Results:

Fourteen episodes of infection in 12 patients were included in this retrospective study. The patients had a male/female ratio of 1:1 and a median age of 160.5 months (range, 3–198 months). Catheter-related bloodstream infection (CRBSI) was detected in 11 patients. Only 1 patient developed catheter-related infective endocarditis. The patient’s catheter was removed, and she was successfully treated with systemic antibiotics for 4 weeks. Systemic antibiotics were used in all infections related to H. huttiense. In septic, critically ill patients, the catheter was removed, and systemic antibiotics were started. Port catheters were removed in 5 patients. ALT was performed in clinically stable patients. ALT using amikacin was administered to 6 patients through the port catheter. Two patients had a 2nd attack. After the 2nd ALT treatment, 1 patient cured, and the catheter of the other patient was removed due to persistent microbial growth in cultures. Antimicrobial susceptibility testing of the reported isolates showed susceptibility to meropenem (90%), ceftazidime (87%) and piperacillin/tazobactam (65%), with 92% resistance to colistin.

Conclusion:

H. huttiense is an emerging pathogen in CRBSI. Piperacillin/tazobactam, ceftazidime and meropenem appear to be good therapeutic options for the treatment of H. huttiense infections. ALT and systemic antibiotics can be used in H. huttiense-CRBSI to sterilize and preserve the central venous catheter.
Clinical Course and Outcomes of Infants with Streptococcus bovis/Streptococcus Gallolyticus subspecies pasteurianus Infection: A Systematic Review and Meta-analysis
Authors: Jaya-Bodestyne Sandra Lynn , Tan Yee Yin , Sultan Rehena , Yeo Kee Thai , Kong Juin Yee
Published: April 2024

Background:

Streptococcus gallolyticus subspecies pasteurianus (SGP), a subtype of Streptococcus bovis, is an uncommon but important cause of neonatal sepsis. Although uncommon, SGP infections during infancy have been associated with an increased risk of morbidity and mortality.

Methods:

This is a systematic review and meta-analysis of available literature on the clinical course and outcomes of infants with SGP infection. Studies were identified using the following MeSH keywords: “Streptococcus gallolyticus,” “Streptococcus bovis,” “newborn” and “infant.” Data including perinatal factors, clinical presentation, investigations, treatment and outcomes were extracted and analyzed.

Results:

A total of 46 articles were identified (116 cases: 60 S. bovis, 56 SGP). The cases were predominantly term (52%), male (57%) and born via vaginal delivery (67%). The most common symptom was fever [67% (95% confidence interval (CI): 43%–84%)], lethargy [66% (95% CI: 32%–89%)], tachypnea [59% (95% CI: 27%–85%)] and irritability [59% (95% CI: 34%–79%)]. Infants with early-onset infections (<3 days of life) were more likely to have respiratory symptoms and bacteremia (73%), whereas late-onset infections presented predominantly with gastrointestinal symptoms. Four mortalities were reported which occurred before antibiotic administration. Isolated bacteria were mostly penicillin-susceptible [95% (95% CI: 78–99%)] and cases treated with penicillin derivative had good recovery.

Conclusions:

SGP is an important cause of neonatal sepsis and meningitis. Penicillin derivative is an effective treatment for SGP, and outcomes appear to be favorable.