bluuebunny/crossref_metadata_2025 huggingface dataset:
Durability and Underlying Physiological Factors: How Do They Change Throughout a Cycling Season in Semiprofessional Cyclists?
Authors: Voet Jens G. , Lamberts Robert P. , Viribay Aitor , de Koning Jos J. , van Erp Teun
Published: June 2024

Purpose: To investigate how cycling time-trial (TT) performance changes over a cycling season, both in a “fresh” state and in a “fatigued” state (durability). Additionally, the aim was to explore whether these changes are related to changes in underlying physiological factors such as gross efficiency, energy expenditure (EE), and substrate oxidation (fat oxidation [FatOx] and carbohydrate oxidation [CarbOx]). Methods: Sixteen male semiprofessional cyclists visited the laboratory on 3 occasions during a cycling season (PRE, START, and IN) and underwent a performance test in both fresh and fatigued states (after 38.1 [4.9] kJ/kg), containing a submaximal warm-up for the measurement of gross efficiency, EE, FatOx, and CarbOx and a maximal TT of 1 (TT1min) and 10 minutes (TT10min). Results were compared across states (fresh vs fatigued) and periods (PRE, START, and IN). Results: The average power output (PO) in TT1min decreased (P < .05) from fresh to fatigued state across all observed periods, whereas there was no change in the PO in TT10min. Over the course of the season, the PO in TT1min in the fatigued state improved more compared with the PO in TT1min in the fresh state. Furthermore, while EE did not significantly change, there was an increase in FatOx and a decrease in CarbOx toward the fatigued state. These changes diminished during the cycling season (IN), indicating a greater contribution of CarbOx in the fatigued state. Conclusions: TT1min performance is more sensitive to fatigue compared with TT10min. Also, during a cycling season, durability improves more when compared with fresh maximal POs, which is also observed in the changes in substrate oxidation.
The Evolution of Physical Activity and Health Research in China: A Bibliometric Analysis of Study Areas and Sex Balance in Authorship
Authors: Zhang Kaiyue , Morales Diana , Chen Junshi , Zhao Wenhua , Tang Anne , Kohn Eduardo , Ding Ding , Ramirez Varela Andrea , Pratt Michael , Hallal Pedro C.
Published: June 2024

Background: This article evaluates the evolution of physical activity and health research in China through a bibliometric analysis focused on number of publications, study areas, and sex balance in authorship. Methods: A systematic review was conducted by the Global Observatory for Physical Activity for “physical activity and health” publications between 1950 and 2019. Here, we focus on the 610 Chinese publications identified, defined as those in which data collection took place in China. We assessed the number of publications, classified them into 5 areas (1) surveillance, (2) correlates and determinants, (3) health consequences, (4) interventions, and (5) policy, and analyzed female participation in authorship. Results: The first Chinese publication identified in the review was in 1990. Since, the average number of physical activity and health publications increased from one per year in the 1990s to 7.6 per year in the 2000s, and to 47 per year in the 2010s. Most publications focused on the correlates and determinants (38.7%) and the health consequences of physical activity (35.9%). Physical activity policy accounted for 2.3% of the publications. In the 1990s, 64% of the publications included at least one female author; this proportion increased to 90% in the 2010s. Conclusion: Despite a slow start, China’s research on physical activity and health has grown rapidly since 2000. The distribution of publications by study areas and female participation in authorship is similar to that observed globally, with fewer publications focused on interventions and policy as compared with other topics.
Two-dimensional perovskite templates for durable, efficient formamidinium perovskite solar cells
Authors: Sidhik Siraj , Metcalf Isaac , Li Wenbin , Kodalle Tim , Dolan Connor J. , Khalili Mohammad , Hou Jin , Mandani Faiz , Torma Andrew , Zhang Hao , Garai Rabindranath , Persaud Jessica , Marciel Amanda , Muro Puente Itzel Alejandra , Reddy G. N. Manjunatha , Balvanz Adam , Alam Muhammad A. , Katan Claudine , Tsai Esther , Ginger David , Fenning David P. , Kanatzidis Mercouri G. , Sutter-Fella Carolin M. , Even Jacky , Mohite Aditya D.
Published: June 2024

We present a design strategy for fabricating ultrastable phase-pure films of formamidinium lead iodide (FAPbI
3
) by lattice templating using specific two-dimensional (2D) perovskites with FA as the cage cation. When a pure FAPbI
3
precursor solution is brought in contact with the 2D perovskite, the black phase forms preferentially at 100°C, much lower than the standard FAPbI
3
annealing temperature of 150°C. X-ray diffraction and optical spectroscopy suggest that the resulting FAPbI
3
film compresses slightly to acquire the (011) interplanar distances of the 2D perovskite seed. The 2D-templated bulk FAPbI
3
films exhibited an efficiency of 24.1% in a p-i-n architecture with 0.5–square centimeter active area and an exceptional durability, retaining 97% of their initial efficiency after 1000 hours under 85°C and maximum power point tracking.
Speciation patterns of zinc in ocean particles
Authors: Cutter Gregory
Published: June 2024

Different particulate zinc forms ultimately affect marine biological productivity
Impaired interferon response in senecavirus A infection and identification of 3C
pro
as an antagonist
Authors: Zhang Xiangle , Li Pengfei , Chen Wenzhe , Zhang Shilei , Li Kangli , Ru Yi , Zhao Zhenxiang , Cao Weijun , Yang Fan , Tian Hong , Guo Jianhong , He Jijun , Zhu Zixiang , Zheng Haixue
Published: June 2024

Senecavirus A (SVA), a picornavirus, causes vesicular diseases and epidemic transient neonatal losses in swine, resulting in a multifaceted economic impact on the swine industry. SVA counteracts host antiviral response through multiple strategies facilitatng viral infection and transmission. However, the mechanism of how SVA modulates interferon (IFN) response remains elusive. Here, we demonstrate that SVA 3C protease (3C
pro
) blocks the transduction of Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway to antagonize type I IFN response. Mechanistically, 3C
pro
selectively cleaves and degrades STAT1 and STAT2 while does not target JAK1, JAK2, and IRF9, through its protease activity. Notably, SVA 3C
pro
cleaves human and porcine STAT1 on a Leucine (L)-Aspartic acid (D) motif, specifically L693/D694. In the case of STAT2, two cleavage sites were identified: glutamine (Q) 707 was identified in both human and porcine, while the second cleavage pattern differed, with residues 754–757 (Valine-Leucine-Glutamine-Serine motifs) in human STAT2 and Q758 in porcine STAT2. These cleavage patterns by SVA 3C
pro
partially differ from previously reported classical motifs recognized by other picornaviral 3C
pro
, highlighting the distinct characteristics of SVA 3C
pro
. Together, these results reveal a mechanism by which SVA 3C
pro
antagonizes IFN-induced antiviral response but also expands our knowledge about the substrate recognition patterns for picornaviral 3C
pro
.

IMPORTANCE

Senecavirus A (SVA), the only member in the
Senecavirus
genus within the
Picornaviridae
family, causes vesicular diseases in pigs that are clinically indistinguishable from foot-and-mouth disease (FMD), a highly contagious viral disease listed by the World Organization for Animal Health (WOAH). Interferon (IFN)-mediated antiviral response plays a pivotal role in restricting and controlling viral infection. Picornaviruses evolved numerous strategies to antagonize host antiviral response. However, how SVA modulates the JAK-STAT signaling pathway, influencing the type I IFN response, remains elusive. Here, we identify that 3C
pro
, a protease of SVA, functions as an antagonist for the IFN response. 3C
pro
utilizes its protease activity to cleave STAT1 and STAT2, thereby diminishing the host IFN response to promote SVA infection. Our findings underscore the significance of 3C
pro
as a key virulence factor in the antagonism of the type I signaling pathway during SVA infection.
Globally significant mass of terrestrial organic carbon efficiently transported by canyon-flushing turbidity currents
Authors: Baker Megan L. , Hage Sophie , Talling Peter J. , Acikalin Sanem , Hilton Robert G. , Haghipour Negar , Ruffell Sean C. , Pope Ed L. , Jacinto Ricardo Silva , Clare Michael A. , Sahin Sefa
Published: June 2024

Burial of organic carbon in marine sediments is a long-term sink of atmospheric CO2, and submarine turbidity currents are volumetrically the most important sediment transport process on Earth. Yet the processes, amounts, and efficiency of organic carbon transfer by turbidity currents through submarine canyons to the deep sea are poorly documented and understood. We present an organic carbon budget for the submarine Congo Canyon, offshore West Africa, constrained with time-lapse bathymetry, sediment cores, and flow monitoring, including the effects of two >1000-km-runout canyon-flushing turbidity currents. In one year, flows eroded an estimated 6.09 ± 2.70 Mt of previously buried terrestrial organic carbon in the canyon, primarily from fine-grained and vegetation-rich muddy sand facies with high organic carbon contents (as high as 11%). The age and composition of organic carbon in the Congo Canyon is comparable to those in the Congo River, indicating that transfer is efficient. Over the whole canyon-channel system, we extrapolate that 43 ± 15 Mt of organic carbon was eroded and transported to the deep (>5 km) sea, equivalent to 22% of the annual global particulate organic carbon export from rivers to oceans and 54%–108% of the predicted annual terrestrial organic carbon burial in the oceans. Canyon-flushing turbidity currents carried a globally significant mass of terrestrial organic carbon down just one submarine canyon in a single year, indicating their importance for redistribution and delivery of organic carbon to the deep sea.
Excitation functions and isomeric cross-section ratios of (d,xn) reactions on $$^{86}$$Sr
Authors: Uddin Md. Shuza , Sudár Sándor , Basunia M. Shamsuzzoha , Scholten Bernhard , Spellerberg Stefan , Voyles Andrew S. , Morrell Jonathan T. , Spahn Ingo , Hermanne Alex , Bernstein Lee A. , Neumaier Bernd , Qaim Syed M.
Published: June 2024

Excitation functions of the $$^{86}$$

86

Sr(d,n)$$^{87m,87g}$$

87
m
,
87
g

Y, $$^{86}$$

86

Sr(d,2n)$$^{86m,86g}$$

86
m
,
86
g

Y and $$^{86}$$

86

Sr(d,3n)$$^{85m,85g}$$

85
m
,
85
g

Y reactions on enriched $$^{86}$$

86

Sr target were measured by the activation technique up to deuteron energies of 49 MeV. The isomeric cross-section ratios as a function of projectile energy were deduced from the measured data for $$^{87m}$$

87
m

Y, $$^{87g}$$

87
g

Y(cum), $$^{86m}$$

86
m

Y, $$^{86g}$$

86
g

Y(cum), $$^{85m}$$

85
m

Y and $$^{85g}$$

85
g

Y pairs for the same energy range. All measurements are reported for the first time. The experimental data were compared with the data from the TENDL library which is based on TALYS calculation with default parameters. No satisfactory agreement was observed. Nuclear model calculations were then performed using the codes TALYS and EMPIRE with some parameter adjustments, and compared with the experimental data. The quality of the agreement between experimental data and model calculations was numerically quantified. In general, the data as well as the isomeric cross-section ratios are partially reproduced by the model calculations, provided the input model parameters are properly chosen and the level structure of the product nucleus is thoughtfully considered.
A cosmological model formulated in Lyra geometry incorporating Ricci dark energy and a deceleration parameter that varies linearly
Authors: Alkaoud A. , Bakry M. A. , Eid A. , Khader M. M.
Published: June 2024

This research focuses on exploring the dynamics of a cosmos model under the influence of Ricci dark energy within the framework of modified Lyra geometry. The modified field equations of Einstein for Lyra’s geometry are introduced, and specific solutions are obtained for a Big Rip cosmos scenario. Additionally, various physical and geometrical aspects of the cosmos are comprehensively investigated and discussed.
Information transparency and stock sentiment beta: Evidence from China
Authors: Wang Jian , Xu Jiatuo , Wang Xiaoting , Liu Ting , Yang Jun
Published: June 2024

Stock returns demonstrate different levels of sensitivity to marketwide sentiment fluctuations. Previous studies argue that stock sentiment risk is caused by information opacity and that companies lacking information transparency tend to be young, small, paying no dividend, volatile, and fast growing. However, little direct evidence exists regarding the impact of information transparency on stock sentiment sensitivity/beta. This paper contributes to fill this gap by employing proximate measures of information transparency: quality of accruals and earnings, and accuracy of analyst forecast. Empirical results validate that information transparency indeed helps curb stock sentiment beta. Such an impact is more pronounced during periods of low market sentiment when irrational investors are mostly sidelined. Two mediating factors are identified: noise trading and stable institutional shareholding. Additionally, improving information transparency on corporate governance also constrains stock sentiment sensitivity. Our results are robust to alternative measures and the endogeneity concern.
Correlation and stratigraphic implications of the lowermost Cambrian small shelly fossils from new sites of South China
Authors: Luo Mei , Brock Glenn A. , Liang Yue , Song Baopeng , Hu Yazhou , Liu Fan , Zhang Zhifei
Published: June 2024

Early Cambrian small shelly fossils (SSFs) represent some of the earliest biomineralized examples of metazoans and are often extremely abundant and diverse, so can be useful for regional and intercontinental correlation in pre-trilobitic carbonate or phosphorite deposits. New SSF assemblages chemically extracted from the Cambrian Yangjiagou Member carbonates in the Fucheng area, southern Shaanxi Province, China. The SSFs include anabaritids, protoconodonts, hyolitheminths, maikhanellids,
Quadrapyrgites
,
Archaeooides
,
Olivooides
and
Siphogonuchites
. The recovered SSFs represent two previously identified SSF assemblage zones: the
Anabarites trisulcatus
–
Protohertzina anabarica
assemblage zone and the succeeding
Paragloborilus subglobosa
–
Purella squamulosa
assemblage zone. The early Cambrian fossil assemblage zones described from this locality are correlated on a regional scale across the Yangtze Platform from eastern Yunnan, the Three Gorge region of western Hubei, northern Sichuan, the Ningqiang and Xixiang regions of southern Shaanxi and the Nemakit–Daldynian Stages of Siberia. The results reveal that the Yangjiagou Member is provisionally equivalent to the Zhongyicun Member of Yunnan, the Yanjiahe Formation of Hubei, the Maidiping Formation of Sichuan and the Kuanchuanpu Formation of Shaanxi. This paper offers new evidence and fossil data for the location of the Precambrian–Cambrian boundary in the Micangshan area of South China.
Learning Domain Invariant Features for Unsupervised Indoor Depth Estimation Adaptation
Authors: Zhang Jiehua , Li Liang , Yan Chenggang , Wang Zhan , Xu Changliang , Zhang Jiyong , Chen Chuqiao
Published: June 2024

Predicting depth maps from monocular images has made an impressive performance in the past years. However, most depth estimation methods are trained with paired image-depth map data or multi-view images (e.g., stereo pair and monocular sequence), which suffer from expensive annotation costs and poor transferability. Although unsupervised domain adaptation methods are introduced to mitigate the reliance on annotated data, rare works focus on the unsupervised cross-scenario indoor monocular depth estimation. In this article, we propose to study the generalization of depth estimation models across different indoor scenarios in an adversarial-based domain adaptation paradigm. Concretely, a domain discriminator is designed for discriminating the representation from source and target domains, while the feature extractor aims to confuse the domain discriminator by capturing domain-invariant features. Further, we reconstruct depth maps from latent representations with the supervision of labeled source data. As a result, the feature extractor learned features possess the merit of both domain-invariant and low source risk, and the depth estimator can deal with the domain shift between source and target domains. We conduct the cross-scenario and cross-dataset experiments on the ScanNet and NYU-Depth-v2 datasets to verify the effectiveness of our method and achieve impressive performance.
Keeper: Automated Testing and Fixing of Machine Learning Software
Authors: Wan Chengcheng , Liu Shicheng , Xie Sophie , Liu Yuhan , Hoffmann Henry , Maire Michael , Lu Shan
Published: June 2024

The increasing number of software applications incorporating machine learning (ML) solutions has led to the need for testing techniques. However, testing ML software requires tremendous human effort to design realistic and relevant test inputs and to judge software output correctness according to human common sense. Even when misbehavior is exposed, it is often unclear whether the defect is inside ML API or the surrounding code and how to fix the implementation. This article tackles these challenges by proposing Keeper, an automated testing and fixing tool for ML software. The core idea of Keeper is designing pseudo-inverse functions that semantically reverse the corresponding ML task in an empirical way and proxy common human judgment of real-world data. It incorporates these functions into a symbolic execution engine to generate tests. Keeper also detects code smells that degrade software performance. Once misbehavior is exposed, Keeper attempts to change how ML APIs are used to alleviate the misbehavior.

Our evaluation on a variety of applications shows that Keeper greatly improves branch coverage, while identifying 74 previously unknown failures and 19 code smells from 56 out of 104 applications. Our user studies show that 78% of end-users and 95% of developers agree with Keeper’s detection and fixing results.
Self-Planning Code Generation with Large Language Models
Authors: Jiang Xue , Dong Yihong , Wang Lecheng , Fang Zheng , Shang Qiwei , Li Ge , Jin Zhi , Jiao Wenpin
Published: June 2024

Although large language models (LLMs) have demonstrated impressive ability in code generation, they are still struggling to address the complicated intent provided by humans. It is widely acknowledged that humans typically employ planning to decompose complex problems and schedule solution steps prior to implementation. To this end, we introduce planning into code generation to help the model understand complex intent and reduce the difficulty of problem-solving. This paper proposes a self-planning code generation approach with large language models, which consists of two phases, namely planning phase and implementation phase. Specifically, in the planning phase, LLM plans out concise solution steps from the intent combined with few-shot prompting. Subsequently, in the implementation phase, the model generates code step by step, guided by the preceding solution steps. We conduct extensive experiments on various code-generation benchmarks across multiple programming languages. Experimental results show that self-planning code generation achieves a relative improvement of up to 25.4% in Pass@1 compared to direct code generation, and up to 11.9% compared to Chain-of-Thought of code generation. Moreover, our self-planning approach also enhances the quality of the generated code with respect to correctness, readability, and robustness, as assessed by humans.
Non-voltage-gated Ca2+ channel signaling in glomerular cells in kidney health and disease
Authors: Ma Rong , Tao Yu , Wade Michael L. , Mallet Robert T.
Published: June 2024

Positioned at the head of the nephron, the renal corpuscle generates a plasma ultrafiltrate to initiate urine formation. Three major cell types within the renal corpuscle, the glomerular mesangial cells, podocytes, and glomerular capillary endothelial cells, communicate via endocrine- and paracrine-signaling mechanisms to maintain the structure and function of the glomerular capillary network and filtration barrier. Ca2+ signaling mediated by several distinct plasma membrane Ca2+ channels impacts the functions of all three cell types. The past two decades have witnessed pivotal advances in understanding of non-voltage-gated Ca2+ channel function and regulation in the renal corpuscle in health and renal disease. This review summarizes the current knowledge of the physiological and pathological impact of non-voltage-gated Ca2+ channel signaling in mesangial cells, podocytes and glomerular capillary endothelium. The main focus is on transient receptor potential and store-operated Ca2+ channels, but ionotropic N-methyl-d-aspartate receptors and purinergic receptors also are discussed. This update of Ca2+ channel functions and their cellular signaling cascades in the renal corpuscle is intended to inform the development of therapeutic strategies targeting these channels to treat kidney diseases, particularly diabetic nephropathy.
Comparing the efficacy of different climate indices for prediction of labor loss, body temperatures, and thermal perception in a wide variety of warm and hot climates
Authors: Havenith George , Smallcombe James W. , Hodder Simon , Jay Ollie , Foster Josh
Published: June 2024

There is an urgent need to determine the optimal heat stress metric when forecasting the impact of heat stress on human performance, physiological stress, and perception. We analyzed a wealth of laboratory data, simulating heart rate (HR)-paced work with wide variations in air temperature, humidity, wind speed, solar radiation, and clothing. We conclude that the universal thermal climate index (UTCI) [followed by wet-bulb globe temperature (WBGT)] is the optimal heat index to reliably predict reductions in performance, and elevations in physiological and perceptual stress.
Can General Anesthesia Facilitate the Detection of Clinically Significant Prostate Cancer in Prostate Fusion Biopsy?
Authors: Yakut Emrah
Published: June 2024

Background. Although the use of anesthetics in prostate biopsy on pain has been well studied, its effect on the diagnosis of clinically significant prostate cancer (csCPa) is not well known. We aimed to investigate the contribution of performing the prostate fusion biopsy (PFB) procedure under general anesthesia (GA) to diagnosing csCPa. Materials and Methods. We retrospectively analyzed the data of 252 patients who underwent multiparametric magnetic resonance imaging (MpMRI)—guided PFB. Patients were divided into two groups: those under local anesthesia (LA) and GA. For LA and GA groups, csCPa capture rates in PFB were evaluated separately and in total for Prostate Imaging Reporting and Data System (PIRADS) 3, PIRADS 4, and PIRADS 5 lesions. It was investigated whether the PFB application under GA increases the chance of csCPa capture. Chi‐square and z‐ratio analysis was performed to determine the change in pathological diagnosis according to the anesthesia method. Results. A total of 411 lesions were detected by MpMRI in 252 men included in the study. LA was applied to 61.5% and GA to 38.5% of the patients. We found that the type of anesthesia affected the frequency of csCPa detection only for anterior lesions. Clinically insignificant prostate cancer (CIPC) was detected more frequently in the GA group than in the LA group. Considering PIRADS 3, PIRADS 4, and all lesion groups, benign pathology was statistically significantly more frequent in the LA group, while CIPC was statistically significantly more frequent in the GA group (p  = 0.000). Conclusion. Our study showed that performing PFB under GA may contribute to the diagnosis of csCPa in anterior region lesions. However, this effect could not be demonstrated when all lesions were examined. In fact, it causes more CIPCs to be caught. Considering that the CIPC approach is contradictory in the literature; multicenter, prospective studies with large participation are needed, taking into account patient and lesion characteristics.
Biological Sample Collection to Advance Research and Treatment: A Fight Osteosarcoma Through European Research and Euro Ewing Consortium Statement
Authors: Green Darrell , van Ewijk Roelof , Tirtei Elisa , Andreou Dimosthenis , Baecklund Fredrik , Baumhoer Daniel , Bielack Stefan S. , Botchu Rajesh , Boye Kjetil , Brennan Bernadette , Capra Michael , Cottone Lucia , Dirksen Uta , Fagioli Franca , Fernandez Natalia , Flanagan Adrienne M. , Gambarotti Marco , Gaspar Nathalie , Gelderblom Hans , Gerrand Craig , Gomez-Mascard Anne , Hardes Jendrik , Hecker-Nolting Stefanie , Kabickova Edita , Kager Leo , Kanerva Jukka , Kester Lennart A. , Kuijjer Marieke L. , Laurence Valérie , Lervat Cyril , Marchais Antonin , Marec-Berard Perrine , Mendes Cristina , Merks Johannes H.M. , Ory Benjamin , Palmerini Emanuela , Pantziarka Pan , Papakonstantinou Evgenia , Piperno-Neumann Sophie , Raciborska Anna , Roundhill Elizabeth A. , Rutkauskaite Vilma , Safwat Akmal , Scotlandi Katia , Staals Eric L. , Strauss Sandra J. , Surdez Didier , Sys Gwen M.L. , Tabone Marie-Dominique , Toulmonde Maud , Valverde Claudia , van de Sande Michiel A.J. , Wörtler Klaus , Campbell-Hewson Quentin , McCabe Martin G. , Nathrath Michaela
Published: June 2024

Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and biobanking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientific progress, promote collaboration, and improve outcomes.
A 5-Year Follow-up Clinical Study of the B-cell Maturation Antigen Chimeric Antigen Receptor T-cell Therapy HDS269B in Patients with Relapsed or Refractory Multiple Myeloma
Authors: Chen Dongjian , Zhu Yu , Chen Zhi , Jiang Songfu , He Haiyan , Qiang Wanting , Xiang Fang , Sun Xuedong , Du Juan
Published: June 2024

Purpose:

This study aimed to report the 5-year clinical outcomes of anti–B-cell maturation antigen chimeric antigen receptor (CAR) T-cell (HDS269B) therapy in patients with relapsed/refractory multiple myeloma (RRMM), including those with poor performance status [Eastern Cooperative Oncology Group (ECOG) scores 3 to 4], and to identify factors influencing long-term outcomes.

Patients and Methods:

Forty-nine patients with RRMM enrolled from 2016 to 2020 received HDS269B (9 × 106 cells/kg) after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine. The overall response, long-term outcomes, and safety were assessed, as were their associations with clinical and disease characteristics.

Results:

With a median follow-up of 59.0 months, the overall response rate was 77.55%. The median progression-free survival (PFS) and overall survival (OS) were 9.5 months [95% confidence interval (CI), 5.01–13.99] and 20.0 months (95% CI, 11.26–28.74), respectively. The 5-year PFS and OS rates were 21.3% (95% CI, 12.3%–36.7%) and 34.1% (95% CI, 22.7%–51.3%), respectively. Patients with ECOG 0 to 2 had marked longer survival, with a median PFS of 11.0 months and a median OS of 41.8 months. Early minimal residual disease negativity, higher and persistent CAR T-cell expansion, and the absence of extramedullary disease were associated with better survival outcomes. No new CAR T-cell therapy–associated toxicities were observed. Importantly, ECOG scores 0 to 2, prior therapy lines <4, and CAR T-cell persistence at ≥6 months were independently associated with longer OS.

Conclusions:

HDS269B is effective and safe, especially for patients with ECOG scores 0 to 2. Early CAR T-cell intervention may improve prognosis in patients with RRMM.
GD2 Target Antigen and CAR T Cells: Does It Take More Than Two to Tango?
Authors: Locatelli Franco , Quintarelli Concetta
Published: June 2024

Over the past decade, chimeric antigen receptor T cells have emerged as a breakthrough cancer therapy in selected hematologic malignancies. Translating the success of this therapy to solid tumors is challenging. In this issue, we discuss strategies potentially useful to increase the chimeric antigen receptor T-cell efficacy in this clinical indication.

See related article by Fischer-Riepe et al., p. 3564
Double-Stranded RNA to Mimic Viral Infection for Cancer Immunotherapy
Authors: Martínez-Riaño Ana , Mosteo Laura , Molero-Glez Paula , Márquez-Rodas Iván , Melero Ignacio
Published: June 2024

The presence of moieties denoting viral infection is crucial to mount powerful cytotoxic T-cell immune responses acting through innate receptors such as Toll-like receptor 3. For cancer immunotherapy, several safe analogues of viral double-stranded RNA are under clinical development following compelling evidence for efficacy in mouse models.

See related article by van Eijck et al., p. 3447
Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children’s Oncology Group
Authors: Stieglitz Elliot , Lee Alex G. , Angus Steven P. , Davis Christopher , Barkauskas Donald A. , Hall David , Kogan Scott C. , Meyer Julia , Rhodes Steven D. , Tasian Sarah K. , Xuei Xiaoling , Shannon Kevin , Loh Mignon L. , Fox Elizabeth , Weigel Brenda J.
Published: June 2024

Juvenile myelomonocytic leukemia (JMML) is a hematologic malignancy of young children caused by mutations that increase Ras signaling output. Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment, but patients with relapsed or refractory (advanced) disease have dismal outcomes. This phase II trial evaluated the safety and efficacy of trametinib, an oral MEK1/2 inhibitor, in patients with advanced JMML. Ten infants and children were enrolled, and the objective response rate was 50%. Four patients with refractory disease proceeded to HSCT after receiving trametinib. Three additional patients completed all 12 cycles permitted on study and continue to receive off-protocol trametinib without HSCT. The remaining three patients had progressive disease with two demonstrating molecular evolution by the end of cycle 2. Transcriptomic and proteomic analyses provided novel insights into the mechanisms of response and resistance to trametinib in JMML. ClinicalTrials.gov Identifier: NCT03190915.

Significance: Trametinib was safe and effective in young children with relapsed or refractory JMML, a lethal disease with poor survival rates. Seven of 10 patients completed the maximum 12 cycles of therapy or used trametinib as a bridge to HSCT and are alive with a median follow-up of 24 months.

See related commentary by Ben-Crentsil and Padron, p. 1574
Cerebrovascular Endothelial Dysfunction: Role of BACE1
Authors: Katusic Zvonimir S. , d’Uscio Livius V. , He Tongrong
Published: June 2024

Dysfunctional endothelium is increasingly recognized as a mechanistic link between cardiovascular risk factors and dementia, including Alzheimer disease. BACE1 (β-site amyloid-β precursor protein-cleaving enzyme 1) is responsible for β-processing of APP (amyloid-β precursor protein), the first step in the production of Aβ (amyloid-β) peptides, major culprits in the pathogenesis of Alzheimer disease. Under pathological conditions, excessive activation of BACE1 exerts detrimental effects on endothelial function by Aβ-dependent and Aβ-independent mechanisms. High local concentration of Aβ in the brain blood vessels is responsible for the loss of key vascular protective functions of endothelial cells. More recent studies recognized significant contribution of Aβ-independent proteolytic activity of endothelial BACE1 to the pathogenesis of endothelial dysfunction. This review critically evaluates existing evidence supporting the concept that excessive activation of BACE1 expressed in the cerebrovascular endothelium impairs key homeostatic functions of the brain blood vessels. This concept has important therapeutic implications. Indeed, improved understanding of the mechanisms of endothelial dysfunction may help in efforts to develop new approaches to the protection and preservation of healthy cerebrovascular function.
Occurrence and associated agronomic factors of mycotoxin contamination in silage maize in the Great Lakes region of the United States
Authors: Kaur H. , Durst P. , Kaatz P. , Singh M.P.
Published: June 2024

Silage maize in Michigan and the Great Lakes region is exposed to in-field ear and stalk rot fungal infections by Fusarium spp. which may result in production of toxic secondary metabolites called mycotoxins. These toxins can cause severe health complications in livestock but might remain unidentified as most silage maize is fed on-farm and not sold in formal markets. This study was conducted to quantify the status of mycotoxins and the agronomic management practices impacting their concentration in silage maize across Michigan farms. Samples (n = 122) were collected from across the state for three years (2019-2021). Results show that 100% of the samples tested positive for deoxynivalenol (DON) at detectable levels. Other mycotoxins that occurred frequently were zearalenone (ZEN), fumonisins, enniatins, and beauvericin (BEA). Mycotoxin concentration was found to vary across regions due to differences in weather parameters such as temperature and humidity, driven partly by the proximity of some regions to the Great Lakes. Mycotoxins were also found to co-occur, with an average of 13 mycotoxins in each sample. Strong correlations were observed between DON, ZEN, and BEA (r > 0.40). Crop rotation and planting date explained 91 and 68% variability in DON and fumonisin, respectively. Deoxynivalenol and fumonisin concentration was 20 and 67% higher in silage maize following a host crop of Fusarium spp. than a non-host crop. Planting silage maize between May 10 and May 30 increased the mycotoxin concentration by at least 50% than outside this window. However, tillage did not significantly impact mycotoxin occurrence and concentration. Overall, multiple mycotoxins were found in silage maize across the region and knowledge of their presence and contributing factors can help growers develop integrated management strategies to mitigate mycotoxin accumulation.
The Aftermath – What Future for African Studies (in Europe?). A View From Behind the Scenes of ECAS9
Authors: van Wolputte Steven , Bollig Michael Thomas , Gockel Martina , Greiner Clemens , Kahindi Noah
Published: June 2024

In the spring of 2023, the ninth European Conference on African Studies (ECAS) took place in Cologne. Though not unexpected (or unusual) this event sparked critical comments and questions. As the organisers, we understand and appreciate this criticism. We, therefore, felt the need to respond to at least some of them, partly because we also asked ourselves many of these questions before, during, and after the conference. At the same time, we want to call for a certain degree of pragmatism when it comes to organising an event this size by providing a look behind the scenes.
Impostor Phenomenon Among Recently Graduated General Surgeons
Authors: Halgas Barret , Horton John , Cancio Leopoldo
Published: June 2024

Background

Imposter phenomenon can occur in highly competitive fields causing internal feelings of fraud and self-doubt. Significant imposterism has been recently reported amongst general surgery residents.

Study Design

We hypothesized that attending surgeons, navigating the transition into independent practice, would report a similar experience. We surveyed and collected Clance Imposter Phenomenon Scale (CIPS) scores from 24 Army general surgeons within 4 years of graduation.

Results

Nearly all exhibited at least moderate imposterism, and over half reported significant or intense imposterism. Women reported statistically higher scores than men. Surgeons who engaged in off-duty employment or participated in mentorship were less likely to have significant or intense imposterism.

Conclusion

Transition to practice is a challenging and highly variable time for new surgeons. Identifying factors that attenuate these feelings could help with early career advancement.
Surgical Urgency, Patient Comorbidities, and Socioeconomic Factors in Surgical Site Infections in Pediatric Surgery
Authors: Quintero Luis Alejandro , Hernandez Jennifer , Orduno Villa Nancy , Romero Dino , Spector Chelsea , Ngo Lisa , Shatawi Zaineb , Levene Tamar , Lao Oliver , Parreco Joshua P.
Published: June 2024

Background

The rise of value-based purchasing has led to decreased compensation for hospital-acquired conditions, including surgical site infections (SSI). This study aims to assess the risk factors for SSI in children and teenagers undergoing gastrointestinal surgery across US hospitals.

Methods

The 2018-2020 Nationwide Readmissions Database was queried for patients undergoing gastrointestinal surgery under the age of 18. The primary outcome was SSI during index admission or readmission within a year. Comparison groups were elective, trauma, and emergent surgery based on anatomic location and urgency. Univariable comparison used chi-squared tests for relevant variables. Confounders were addressed through multivariable logistic regression with significant variables from univariable analysis.

Results

113 108 total patients met the study criteria. The SSI rate during admission or readmission was 2.9% (n = 3254). Infections during admission and readmission were 1.4% (n = 1560) and 1.5% (n = 1694), respectively. The most common site was organ space (48.6%, n = 1657). Increased infection risk was associated with trauma (OR 1.80 [1.51-2.16] P < .001), emergency surgery (OR 1.31 [1.17-1.47] P < .001), large bowel surgery (OR 2.78 [2.26-3.43] P < .001), and those with three or more comorbidities (OR 2.03 [1.69-2.45] P < .001). Investor-owned hospitals (OR .65 [.56-.76] P < .001) and highest quartile income (OR .80 [.73-.88] P < .001) were associated with decreased infection risk.

Conclusions

Pediatric patients undergoing gastrointestinal surgery face an elevated risk of SSI, especially in trauma and emergency surgeries, particularly with multiple comorbidities. Meanwhile, a reduced risk is observed in high-income and investor-owned hospital settings. Hospitals and surgeons caring for high risk patients should advocate for risk adjustment in value-based payment systems.
The Long-Term Results of Proximal Gastrectomy for Proximal Gastric Cancer: A Propensity Score Matching Analysis Based on SEER Database
Authors: Dai Wei , Wen Feng , Li Xiang , Fu Zhongxue
Published: June 2024

Background

Proximal gastrectomy (PG) is one of function‐preserving gastrectomy (FPG). In this study, we compared the long-term results of proximal gastric cancer (PGC) patients undergoing proximal gastrectomy and total gastrectomy (TG).

Method

Patients diagnosed with PGC and receiving PG or TG between 2004 and 2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was applied to minimize confounding factors. Kaplan-Meier analysis and log-rank test were used to compare overall survival (OS) and cancer-specific survival (CSS) between the PG and TG groups. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting OS.

Result

A total of 3916 patients were recruited according to the inclusion and exclusion criteria, with 2614 undergoing PG and 1302 undergoing TG. After 1:1 PSM matching, 912 pairs of data were included for analysis. Before PSM matching, PG group tended to have better OS and CSS outcomes. However, after PSM matching, both surgical approaches showed similar long-term results.

Conclusion

PG for PGC yields comparable long-term outcomes to TG and demonstrates safety in terms of oncologic outcomes.
Needs assessment and patient-guided development of a video-based diabetic retinopathy patient education tool
Authors: Ahmed Osama M , Applebaum Serina S , Ahmad Maham , Ahmed Danya M , Juthani Prerak , Nwanyanwu Kristen
Published: June 2024

Objective:

To gain retina physicians’ and diabetic retinopathy (DR) patients’ perspectives on needs and opportunities in DR education, and then develop and pilot test an educational video.

Design:

This study utilised qualitative interview data for video creation, and interview and survey data for assessment.

Setting:

This study was conducted in a single large academic medical centre.

Method:

We conducted semi-structured interviews with attending retina physicians and DR patients (Cohort A) which were coded for themes about needs in DR patient education. Using these interviews, we designed and piloted a 6-minute user-centred animated video among a second patient cohort (Cohort B), who completed post-intervention interviews.

Results:

Four physicians and 14 DR patients participated in the study. Themes from Cohort A included accessible information, early management, lifestyle factors and emotional context. Physician themes included effective communication, visual information delivery and individual-level diabetes management. Cohort B commented on the subsequently created video’s improved accessibility, engagement and supplementation of their existing DR knowledge.

Conclusion:

Physicians and patients showed an interest in video education and identified unique educational needs. We used these insights to create a video that demonstrated positive patient uptake. Close attention to retina physicians’ and DR patients’ perspectives can offer a valuable approach in developing materials to increase patients’ health knowledge. Within the context studied, videos may be more accessible and engaging than the use of traditional print-based education materials.
Exports, Employment and Conflict: Evidence From the Second Intifada
Authors: Calì Massimiliano , Miaari Sami H.
Published: June 2024

Do export shocks affect conflict? The evidence on this question has so far focused mainly on commodity price shocks. This paper uses data from the entire export basket to examine whether shocks to Palestinian exports in the second half of the 1990s affected the intensity of the subsequent Palestinian uprising (‘Second Intifada’). The analysis uses sector-specific changes in Chinese and global exports to instrument Palestinian exports to minimize potential endogeneity bias of export changes with respect to conflict. The findings suggest that an increase of USD 10 million in Palestinian exports of a sector employing 10% of the locality’s private employment reduces the number of Palestinians killed by Israel in that locality by 13.9 percent. The paper provides evidence that these results are consistent with the opportunity cost mechanism of conflict participation.
New Monomer Capable of Dual Chemical Binding with Dentin to Improve Bonding Durability
Authors: Wang H.M. , Li K.X. , Tian Z.L. , Zhu Y.L. , Liu X.Y. , Yang S.H. , Qiao S.W. , Zhu S. , Shi Z.S.
Published: June 2024

The water-rich nature of the dentin bonding microenvironment, coupled with the stresses on the bonding interface, contributes to the hydrolytic degradation of the hybrid layer, resulting in a decline in bonding durability and, ultimately, restoration failure. Currently, the 3-step etch-and-rinse technique remains the gold standard for dentin bonding, and the bonding mechanism mainly involves a physical interaction with little chemical bonding. In this study, we have developed a siloxane-modified polyurethane monomer (SPU) with acrylate and siloxane modifications that chemically binds to both collagen and hydroxyapatite in dentin. Formulated as a bisphenol A-glycidyl methacrylate alternative, the SPU monomer-based adhesive was designed to improve dentin bonding quality and durability. Attenuated total reflection Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscope, and hydroxyproline release assays were performed on SPU-treated collagen, hydroxyapatite, and acid-etched dentin slices to dentin. The physicochemical properties of the configured SPU adhesives were profiled for polymerization behavior, water contact angle, and tensile strain and strength. The bonding effectiveness was assessed through micro-tensile strength, nano-leakage tests conducted on the bonded samples before and after thermal cycle aging. Finally, we further conducted in vivo and in vitro experiments to assess the biocompatibility of adhesives. The results showed that the siloxane groups of SPU monomer could covalently bind to dentin collagen and hydroxyapatite. The incorporation of SPU in the adhesive led to a significant increase in adhesive polymerization ( P < 0.05) and tensile strain at break up to 134.11%. Furthermore, the SPU adhesive significantly improved dentin bond strength ( P < 0.05), reduced interfacial nano-leakage ( P < 0.05), and displayed good biocompatibility. In conclusion, the application of SPU, which achieves dual chemical bonding with dentin, can improve the quality of the hybrid layer, buffer the interfacial stresses, enhance the interfacial resistance to hydrolysis, and provide a feasible strategy to extend the service life of adhesive restorations.