bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid in-motion heading alignment using time-differenced carrier phases from a single GNSS antenna and a low-grade IMU
Authors: Wu Qing , Chai Hongzhou , Xiang Minzhi , Zhang Yong , Zhang Fan , Feng Xu
Published: June 2024

Despite advancements in global navigation satellite system/inertial navigation system (GNSS/INS) integrated systems, the challenge of achieving rapid and accurate initial heading alignment remains, particularly in low-grade IMUs and marine applications with swaying conditions. This study introduces an innovative in-motion heading alignment method utilizing time-differenced carrier phases (TDCP) from a single GNSS antenna and a low-grade IMU based on the fundamental principle of trajectory similarity. The heading angle is determined by comparing the dead reckoning (DR)-derived trajectory with the TDCP-derived trajectory. This is achieved using gyro measurements and the delta position from TDCP solutions. The proposed alignment method can be implemented in real-time and the alignment period is just 1 s, which indicates that the method could continuously output heading when the carrier is in motion. We not only validate the effectiveness of the proposed alignment method in land vehicle applications, but also in maritime vessels, like unmanned surface vessels (USV), and unmanned underwater vehicles (UUV). In addition, we evaluated the impact of challenging ocean conditions and mounting angle errors on the proposed alignment method. Experimental results show that the heading could be determined with an accuracy of 0.49°, 3.10°, and 2.31° at a 95% confidence level for the land vehicle, USV, and UUV tests, respectively. Besides, the RMS of the alignment errors calculated by our method reaches 0.24°, 1.42°, and 1.19° for the land vehicle, USV, and UUV tests, respectively.
Thoughts on the transformation and development of mechanized and intelligent construction of pumped storage power stations under the dual carbon goal
Authors: Liu Xueshan , Huang Yufei , Shi Yunli , Zheng Yueyang
Published: June 2024

How to shorten the construction cycle of pumped storage power plants under the dual carbon target is an urgent core problem that needs to be studied and solved under the current situation of large-scale and high proportion development of pumped storage power plants. At the same time, based on the fact that the traditional construction methods and processes in the pumped storage industry are still in the primary stage at present, China Southern power grid peak shaving and frequency modulation power generation Co., Ltd. proposed and carried out the research on the transformation of the mechanized and intelligent construction of pumped storage power stations. It plans to rely on the pumped storage power stations under construction and to be built, combined with their respective engineering characteristics, to study the complete set of construction equipment for the construction of pumped storage power stations and the matching intelligent application platform, Gradually achieve the long-term goals of mechanized replacement, automatic personnel reduction and intelligent unmanned construction of pumped storage power stations.
Modal decomposition of the shedding mechanism of partial cavitation in a Venturi Tube
Authors: Xia Gaoju , You Weibin , Xuan Xiaoxu , Chen Songying , Yoon Joon Yong , Sun Xun
Published: June 2024

The present paper studies the shedding mechanism of partial cavitation in a Venturi Tube, dominated by re-entrant jet and bubbly shock mechanisms, by using two data-driven modal decomposition methods: proper orthogonal decomposition (POD) and dynamic mode decomposition (DMD). According to the snapshot data series obtained by high-speed photography, the modal decomposition and reconstruction of the grey image are carried out. The POD results indicate that the main frequency of the re-entrant jet is higher than that of the shock under the sixth-order mode, and the energy amplitude of the latter is about 20 times that of the former. Furthermore, as the cavitation number increases, the condensation shock mechanism eventually replaces the re-entrant jet mechanism. The DMD results show that the shock behaves obvious traveling wave mode, because the frequency is higher and the phase of the spatial distribution changes evenly under the fourth-order mode. POD and DMD can help to understand the shedding mechanism of partial cavitation.
The influence of reservoir water level on the hydraulic characteristics of spillway tunnel
Authors: Funan Chen , Weijie Cui , Yang Xue , Gaohui Li
Published: June 2024

The spillway tunnel for water discharging is very important in water conservancy and hydropower engineering. Spillway tunnel with inclined and elbow part near the outlet can be more easily adapted to the topographic and geological conditions than that near the inlet, and can limit the cavitation damage to the short tunnel near outlet. Therefore, it has been widely used in the case of discharging water with high head and large discharge. Cavitation induced by high speed flow may cause severe damage to the spillway tunnel surface. And aeration is a common measure for surface protection. Study on the hydraulic characteristics of water-air two-phase flow is of great significance for improving aeration effect. In this paper, the velocity, depth of water and Froude Number of spillway tunnel under different reservoir water levels are studied by using VOF method. The results show that the Froude Number decreases at first and then increases as reservoir water level becomes lower.
Cavitating flow around a low aspect ratio NACA0012 hydrofoil with regular grooves
Authors: Tsoy M , Skripkin S , Kravtsova A
Published: June 2024

The purpose of this work is to study the influence of the periodic grooves applied to the surface of the hydrofoil as passive control method on the cavitation dynamics and development. The cavitating flow in the slit channel around NACA 0012 hydrofoil is investigated. An experimental study of the flow was carried out using the high-speed visualization followed by image processing of acquired data. Attached cavity length is substantially reduced by 25% - 30% by using grooves on hydrofoil surface. However, cavitation inception for grooved hydrofoil occurs at almost two-time lower flowrate.
Vibration of Variable Speed Pump-Turbine in Turbine Operating Range: Simulation by CFD+FEM
Authors: Xue Song , Cheng Yongguang , Liu Demin , Chen Hongyu , Lin Yunfa
Published: June 2024

Variable speed pumped-storage unit can operate efficiently and stably in wide range of power and head through the coordinated control of the rotational speed and guide vanes. The regulation in rotational speed brings about frequency and amplitude changes of pressure pulsations, which further influence the avoidance margin of vibration and the dynamic response of the runner. The vibration characteristics of the variable-speed pump-turbine need to be studied when it runs in the wider operating region. Selecting an actual pumped-storage unit as the subject and using the CFD+FEM coupled simulation method as a tool, we conducted three-dimensional pump-turbine vibration simulations and analyse the flow patterns, pressure pulsations, and runner vibration characteristics of several typical operating points in turbine mode. The study focused on the variation laws of pressure pulsations and dynamic stresses when rotational speed is regulated. Comparison with the results for the constant speed unit under the corresponding working conditions was conducted. It is shown that the variable speed operation can effectively avoid the severe vibration conditions that the constant speed unit encounters; the amplitudes of pressure pulsations and dynamic stresses of the runner are small at low rotational speed; in the condition of high speed, low head, and small load, the vibration is the most obvious. This study can provide a reference for the design and operation of variable speed pump-turbine.
Study on Cavitation Determination of Pump Turbine Model Test
Authors: Han Wenfu , Zhang Fei , Zhao Yifeng , Man Zhe , Ding Jinghua , Sun Xiaoxia , Wang Gang
Published: June 2024

At present, it is difficult to determine whether cavitation has occurred in the pump turbine model test, with a large human error and no more accurate judgment guidelines, this paper proposes an intelligent algorithm based on image recognition to determine when cavitation has occurred. The method collects images of water bodies in the recognition area, extracts and processes the features of fixed parts, and compares them with database image data to finally realize the recognition of cavitation phenomena. The results show that the method captures the cavitation phenomenon more accurately and efficiently, and achieves the intelligent judgment of the cavitation phenomenon.
Natural selection through genetics
Authors: Madgwick Philip G
Published: June 2024

The chapter presents a historical account of the development of the understanding of how evolution by natural selection operates through the genetic mechanism of inheritance. The contrasting examples of the evolution of peppered moth colourations and protection against malaria (and sickle-cell anaemia) are established to identify the challenge of explaining trait evolution. First, transmission genetics is presented as identifying the logical structure of inheritance, following its development from its Mendelian foundations through to the Modern Synthesis. The colouration and protection traits are identified as having different patterns of dominance and linkage. Second, evolutionary genetics is discussed, from ideas relating to inclusive fitness through to selfish genes. Such reasoning established how traits are favoured by natural selection. Third, molecular genetics is discussed to identify what heritable entity really changes when there is evolution by natural selection. The basis of genes in DNA is described, as well as its implications for understanding pleiotropy. Intrinsic and extrinsic pleiotropy are distinguished and used to explain the different evolutionary trajectories of the colouration and protection traits.
Maladaptation in social behaviour
Authors: Madgwick Philip G
Published: June 2024

The chapter discusses the challenges and opportunities in seeking evidence of maladaptation among the social behaviours of individual organisms, focusing on the analysis of intraspecific competition, spite, and greenbeards. Numerous examples of maladaptation are critically evaluated. The presence of intraspecific competition is argued to be insufficient evidence of maladaptation due to its allocative effects, as demonstrated through the discussion of examples including sexual characters, tragedies of the commons and sexual conflict. Spite is argued to be distinct from maladaptation, as inclusive fitness is framed around relative fitness. The historical development of spite as a long unproven theory is discussed, characterising its conceptual development away from its maladaptive intimations. Lastly, the transition of the greenbeard concept from a thought-experiment to a real phenomenon is reviewed. The existential, selection, and detection arguments against their reality are discussed in contrast to the new wave of examples of greenbeard genes. Ultimately, genetic conflict is argued not to be evidence of maladaptation.
Neoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study
Authors: Dent Rebecca , Cortés Javier , Pusztai Lajos , McArthur Heather , Kümmel Sherko , Bergh Jonas , Denkert Carsten , Park Yeon Hee , Hui Rina , Harbeck Nadia , Takahashi Masato , Untch Michael , Fasching Peter A , Cardoso Fatima , Haiderali Amin , Jia Liyi , Nguyen Allison Martin , Pan Wilbur , O’Shaughnessy Joyce , Schmid Peter
Published: June 2024

Background

In KEYNOTE-522 (NCT03036488), neoadjuvant pembrolizumab plus chemotherapy and then adjuvant pembrolizumab significantly improved pathological complete response and event-free survival vs neoadjuvant chemotherapy in early-stage triple-negative breast cancer (TNBC). We report patient-reported outcomes (PROs) from KEYNOTE-522.

Methods

Patients were randomized 2:1 to neoadjuvant pembrolizumab 200 mg or placebo every 3 weeks, plus 4 cycles of paclitaxel plus carboplatin and then 4 cycles of doxorubicin (or epirubicin) plus cyclophosphamide. After surgery, patients received adjuvant pembrolizumab or placebo for up to 9 cycles. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (EORTC QLQ-C30) and EORTC Breast Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23) were prespecified secondary objectives. Between-group differences in least squares (LS) mean change from baseline (day 1 of cycle 1 in both neoadjuvant and adjuvant phases) to the prespecified latest time point with at least 60% completion and at least 80% compliance were assessed using a longitudinal model (no alpha error assigned).

Results

Week 21 (neoadjuvant phase) and week 24 (adjuvant phase) were the latest time points at which completion/compliance rates were ≥60%/80%. In the neoadjuvant phase, between-group differences (pembrolizumab plus chemotherapy [n = 762] vs placebo plus chemotherapy [n = 383]) in LS mean change from baseline to week 21 in QLQ-C30 global health status/quality of life (GHS/QoL), emotional functioning, and physical functioning were −1.04 (95% confidence interval = −3.46 to 1.38), −0.69 (95% CI = −3.13 to 1.75), and −2.85 (95% CI = −5.11 to −0.60), respectively. In the adjuvant phase, between-group differences (pembrolizumab [n = 539] vs placebo [n = 308]) in LS mean change from baseline to week 24 were −0.41 (95% CI = −2.60 to 1.77), −0.60 (95% CI = −2.99 to 1.79), and −1.57 (95% CI = −3.36 to 0.21).

Conclusions

No substantial differences in PRO assessments were observed between neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab vs neoadjuvant placebo plus chemotherapy in early-stage TNBC.

Trial registration

ClinicalTrials.gov, NCT03036488.
Effect of smoking on melanoma incidence: a systematic review with meta-analysis
Authors: Friedman Erica B , Williams Gabrielle J , Lo Serigne N , Thompson John F
Published: June 2024

Background

There is a strong correlation between cigarette smoking and the development of many cancer types. It is therefore paradoxical that multiple reports have suggested a reduced incidence of melanoma in smokers. This study aimed to analyze all existing studies of melanoma incidence in smokers relative to nonsmokers.

Methods

Searches of MEDLINE and Embase were conducted for studies reporting data on melanoma in smokers and never-smokers. No study design limitations or language restrictions were applied. The outcome examined was the association between smoking status and melanoma. Analyses focused on risk of melanoma in smokers and never-smokers generated from multivariable analyses, and these analyses were pooled using a fixed-effects model. Risk of bias was assessed using the Newcastle-Ottawa tool.

Results

Forty-nine studies that included 59 429 patients with melanoma were identified. Pooled analyses showed statistically significant reduced risks of melanoma in male smokers (risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.56 to 0.65, P < .001) and female smokers (RR = 0.79, 95% CI = 0.73 to 0.86, P < .001). Male former smokers had a 16% reduction in melanoma risk compared with male never-smokers (RR = 0.84, 95% CI = 0.77 to 0.93, P < .001), but no risk reduction was observed in female former smokers (RR = 1.0, 95% CI = 0.92 to 1.08).

Conclusions

Current smokers have a statistically significant reduced risk of developing melanoma compared with never-smokers, with a reduction in melanoma risk of 40% in men and 21% in women.
A case report on the management of neglected and forgotten DJ stent for 18 years with severe encrustation and giant bladder stone
Authors: Nigusie Alemu Tsiyon , Aderaw Habtamu , Sheiferawe Yacob , Tsehaye Kinfe
Published: June 2024

Ureteral stents play a vital role in urologic surgeries, aiding in urinary flow maintenance, obstruction alleviation and facilitating healing. However, when stents are forgotten, they can lead to encrustation, resulting in significant patient morbidity and posing challenges for urologists Stent-related complications have been shown to increase with the duration of time the stent is left in place. This report details the clinical presentation, diagnostic process, and treatment of a 68-year-old male patient had a neglected stent placed 18 years ago after extracorporeal shockwave lithotripsy. He presented with severe stent encrustation, a solitary giant bladder stone, and renal stones. The patient underwent a cystolithotomy to remove the bladder stone followed by an ultrasound-guided percutaneous nephrolithotomy with pneumatic lithotripsy in a separate procedure. Preventive strategies such as implementing a stent registry, enhancing patient education, and encouraging follow-up appointments are crucial to avoid such complications.
Prey Shifts Drive Venom Evolution in Cone Snails
Authors: Koch Thomas Lund , Robinson Samuel D , Salcedo Paula Flórez , Chase Kevin , Biggs Jason , Fedosov Alexander E , Yandell Mark , Olivera Baldomero M , Safavi-Hemami Helena
Published: June 2024

Venom systems are complex traits that have independently emerged multiple times in diverse plant and animal phyla. Within each venomous lineage there typically exists interspecific variation in venom composition where several factors have been proposed as drivers of variation, including phylogeny and diet. Understanding these factors is of broad biological interest and has implications for the development of antivenom therapies and venom-based drug discovery. Because of their high species richness and the presence of several major evolutionary prey shifts, venomous marine cone snails (genus Conus) provide an ideal system to investigate drivers of interspecific venom variation. Here, by analyzing the venom gland expression profiles of ∼3,000 toxin genes from 42 species of cone snail, we elucidate the role of prey-specific selection pressures in shaping venom variation. By analyzing overall venom composition and individual toxin structures, we demonstrate that the shifts from vermivory to piscivory in Conus are complemented by distinct changes in venom composition independent of phylogeny. In vivo injections of venom from piscivorous cone snails in fish further showed a higher potency compared with venom of nonpiscivores demonstrating a selective advantage. Together, our findings provide compelling evidence for the role of prey shifts in directing the venom composition of cone snails and expand our understanding of the mechanisms of venom variation and diversification.
No benefit from TMZ treatment in glioblastoma with truly unmethylated MGMT promoter: Reanalysis of the CE.6 and the pooled Nordic/NOA-08 trials in elderly glioblastoma patients
Authors: Hegi Monika E , Oppong Felix B , Perry James R , Wick Wolfgang , Henriksson Roger , Laperriere Norman J , Gorlia Thierry , Malmström Annika , Weller Michael
Published: June 2024

Background

The treatment of elderly/ frail patients with glioblastoma is a balance between avoiding undue toxicity, while not withholding effective treatment. It remains debated, whether these patients should receive combined chemo-radiotherapy with temozolomide (RT/TMZ→TMZ) regardless of the O6-methylguanine DNA methyltransferase gene promoter (MGMTp) methylation status. MGMT is a well-known resistance factor blunting the treatment effect of TMZ, by repairing the most genotoxic lesion. Epigenetic silencing of the MGMTp sensitizes glioblastoma to TMZ. For risk-adapted treatment, it is of utmost importance to accurately identify patients, who will not benefit from TMZ treatment.

Methods

Here, we present a reanalysis of the clinical trials CE.6 and the pooled NOA-08 and Nordic trials in elderly glioblastoma patients that compared RT to RT/TMZ→TMZ, or RT to TMZ, respectively. For 687 patients with available MGMTp methylation data, we applied a cutoff discerning truly unmethylated glioblastoma, established in a pooled analysis of 4 clinical trials for glioblastoma, with RT/TMZ→TMZ treatment, using the same quantitative methylation-specific MGMTp PCR assay.

Results

When applying this restricted cutoff to the elderly patient population, we confirmed that glioblastoma with truly unmethylated MGMTp derived no benefit from TMZ treatment. In the Nordic/NOA-08 trials, RT was better than TMZ, suggesting little or no benefit from TMZ.

Conclusions

For evidence-based treatment of glioblastoma patients validated MGMTp methylation assays should be used that accurately identify truly unmethylated patients. Respective stratified management of patients will reduce toxicity without compromising outcomes and allow testing of more promising treatment options.
Medulloblastoma in children with Fanconi anemia: Association with FA-D1/FA-N, SHH type and poor survival independent of treatment strategies
Authors: Sönksen Marthe , Obrecht-Sturm Denise , Hernáiz Driever Pablo , Sauerbrey Axel , Graf Norbert , Kontny Udo , Reimann Christian , Langhein Mina , Kordes Uwe R , Schwarz Rudolf , Obser Tobias , Boschann Felix , Schüller Ulrich , Altendorf Lea , Goschzik Tobias , Pietsch Torsten , Mynarek Martin , Rutkowski Stefan
Published: June 2024

Background

The outcome of children with medulloblastoma (MB) and Fanconi Anemia (FA), an inherited DNA repair deficiency, has not been described systematically. Treatment is complicated by high vulnerability to treatment-associated side effects, yet structured data are lacking. This study aims to give a comprehensive overview of clinical and molecular characteristics of pediatric FA MB patients.

Methods

Clinical data including detailed information on the treatment and toxicities of 6 previously unreported FA MB patients were supplemented with data of 16 published cases.

Results

We identified 22 cases of children with FA and MB with clinical data available. All MBs with subgroup reporting were SHH-activated (n = 9), confirmed by methylation profiling in 5 patients. FA MB patients exclusively belonged to complementation groups FA-D1 (n = 16) or FA-N (n = 3). Patients were treated with postoperative chemotherapy only (50%) or radiotherapy (RT) ± chemotherapy (27%). Of 23% did not receive adjuvant therapy. Excessive treatment-related toxicities were frequent. Severe hematological toxicity occurred in 91% of patients treated with alkylating chemotherapy, while non-alkylating agents and RT were less toxic. Median overall survival (OS) was 1 year (95%CI: 0.3–1.8). 1-year-progression-free-survival (PFS) was 26.3% ± 10.1% and 1-year-OS was 42.1% ± 11.3%. Adjuvant therapy prolonged survival (1y-OS/1y-PFS 0%/0% without adjuvant therapy vs. 53.3% ± 12.9%/33.3 ± 12.2% with adjuvant therapy, P = .006/P = .086).

Conclusions

MB in FA patients is strongly associated with SHH activation and FA-D1/FA-N. Despite the dismal prognosis, adjuvant therapy may prolong survival. Non-alkylating chemotherapy and RT are feasible in selected patients with careful monitoring of toxicities and dose adjustments. Curative therapy for FA MB-SHH remains an unmet medical need.
Crossing the Ludo-Cinematic Continuum
Authors: Atkinson Sean
Published: June 2024

Sean Atkinson outlines three challenges faced when applying western music theory to the analysis of video game music: the theory was developed to analyze western art music; video game music is an art form that makes use of such art music but that also makes use of other musics; and the interactivity of video game music is a specific problem that must be accounted for. Regarding this last, and concentrating on the link to film music, Atkinson presents a ludo-cinematic continuum model that describes not the video game music itself but rather its function and use in the game. Thus, music with a more ludic function is more interactive and less choreographed compared to the scripted and choreographed cinematic function. In using the model to conduct a preliminary assessment of the music to be analyzed, Atkinson provides the means to determine the most appropriate analytical tools when it comes to the music itself.
Ambient Ecologies
Authors: Kamp Michiel
Published: June 2024

In a chapter on ambient ecologies of music in video games, Michiel Kamp argues for including nondynamic musical cues as part of the ecology of the game. Such music, unlike the dynamic music that is typically the subject of much academic discourse and media attention, provides no ludic signals about the gameplay state; it is an ambient cue that is “just there.” Kamp argues that, far from being dismissed as mere background music, this ambient music is a key part of the ecology of the game, providing stability and persistence and a space within which to achieve the game’s goals.
Ode to Joysticks
Authors: Gibbons William
Published: June 2024

On the back of the 2020 Game Awards recognition of that year’s Final Fantasy VII Remake in the “Best Score and Music” category, William Gibbons explores the meaning of labels such as “the Beethoven of game music” applied to the composer Nobuo Uematsu. Gibbons is concerned with our understanding of Uematsu’s place in music history, but more generally in how and why these labels develop in music history, as well as how they shape audience perceptions of musical value over time. Cycles of canonization emphasizing one composer as exceptional risk overshadowing the relevance and importance of other video game music composers.
A History of Early US Pinball Sound, 1871–1939
Authors: Lerner Neil
Published: June 2024

Neil Lerner explores the roots of video game sound practices through an investigation of the sound of US pinball machines from 1871 to 1939. Lerner suggests that pinball and its predecessors always had sound as an element of play. Along with the introduction of electromechanical sound-producing devices in 1934 (Harry Williams’ Contact), this established several conventions of sounds in games that influenced the early video game designers in the 1970s, several of whom worked for companies that had originally been pinball manufacturers. In 1935, Big Game became the first pinball machine to include a sound effect intended to increase the realism of the theme; in this case, it was a synchronizing of a light and a quickly struck metal plate that simulated a gunshot. Bells remained the principal sound in pinball machines until the solid-state era began in the 1970s.
The fine-tuning argument against the multiverse
Authors: Boyce Kenneth , Swenson Philip
Published: June 2024

It is commonly argued that the fact that our universe is fine-tuned for life favors both a design hypothesis as well as a non-teleological multiverse hypothesis. The claim that the fine-tuning of this universe supports a non-teleological multiverse hypothesis has been forcefully challenged however by Ian Hacking and Roger White. In this paper we take this challenge even further by arguing that if it succeeds, then not only does the fine-tuning of this universe fail to support a multiverse hypothesis, but it tends to favor a single-universe hypothesis instead.
Poverty Governance in the Delegated Welfare State: Privatization, Commodification, and the U.S. Health Care Safety Net
Authors: Parker Emily
Published: June 2024

Due to forces of retrenchment and fiscal austerity in the contemporary U.S. welfare state, the federal government has increasingly delegated the funding of public programs to private entities. How does privatization influence the way marginalized populations experience the social safety net? To develop insights on delegated poverty governance, this study examines a longstanding public-private program—Federally Qualified Health Centers (FQHCs)—which comprise a nationwide network of clinics serving over thirty million predominantly low-income patients in medically underserved areas. I conducted a case study drawing on in-depth interviews with patients and staff in a small-town FQHC in the Rust Belt. Unlike other social welfare programs, I found a pronounced absence of stigma associated with the FQHC, largely due to features of the delegated policy design, the blended institutional setting, and strategic organizational decisions. However, low-income patients were also unaware of their rights to treatment when encountering paternalistic enforcement of overdue billing rules, which resulted in delayed or foregone health care. Due to underlying tensions surrounding commodification, I argue that privatization of the safety net may quell the stigma of government programs among the poor while simultaneously disentitling individuals from their rights of social citizenship.
Evaluation of significantly changed chemokine factors of idiopathic granulomatous mastitis in non‐puerperal patients
Authors: Li Fangyuan , Nie Longzhu , Huang Junying , Sin Tat‐Hang , Wang Xuejing , Zhang Fan , Ma Jia , Shi Xiaoguang , Chen Linlin , Niu Kunying , Zhang Xiaohui , Zhou Yidong
Published: June 2024

Idiopathic granulomatous mastitis (IGM), a recurrent inflammation disease of the non‐lactating breast, has had an increasing clinical morbidity rate in recent years, and its complicated symptoms and unclear etiology make it challenging to treat. This rare benign inflammatory breast disease, centered on the lobules, represents the most challenging type of non‐puerperal mastitis (NPM), also known as non‐lactating mastitis. In this study, patients diagnosed with IGM (M, n = 23) were recruited as cases, and patients with benign control breast disease (C, n = 17) were enrolled as controls. Cytokine microarray detection measured and analyzed the differentially expressed cytokine factors between IGM and control patients. Then, we verified the mRNA and protein expression levels of the significantly changed cytokine factors using Q‐RT‐PCR, ELISA, western blot, and IHC experiments. The cytokine factor expression levels significantly changed compared to the control group. We observed a significant increase between IGM and control patients in cytokine factors expression, such as interleukin‐1β (IL‐1β), monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)‐1α, MIP‐1β, tumor necrosis factor receptor 2 (TNF RII). Then, we verified the expression of these top five dysregulated factors in both mRNA and protein levels. Our results demonstrated the cytokine map in IGM and indicated that several cytokines, especially chemokines, were associated with and significantly dysregulated in IGM tissues compared to the control group. The chemokine factors involved might be essential in developing and treating IGM. These findings would be helpful for a better understanding of IGM and offer valuable insights for devising novel diagnostic and therapeutic strategies.
Food poisoning due to money tree seeds: a case report of toxic encephalopathy
Authors: Zhao Yue , Quan Xiaojiao , Wang Tao
Published: June 2024

Background

The money tree is a favored indoor potted plant in China. Its seeds resemble chestnuts in both shape and flavor when cooked, which are generally considered non-toxic and safe for consumption.

Case presentation

This report presents the first published case of food poisoning due to the ingestion of large amounts of money tree seeds. A 67-year-old man exhibited toxic encephalopathy symptoms and dyspnea after consuming the seeds for approximately 6 months. After empirical mechanical ventilation, therapeutic plasma exchange, and other medical interventions, the patient’s clinical status improved significantly. He was subsequently discharged from the hospital.

Conclusion

Consuming a substantial quantity of money tree seeds within a limited timeframe can lead to poisoning, resulting in adverse outcomes, particularly toxic encephalopathy. Moreover, plasma exchange may have some therapeutic effect.
Associations of Local Cannabis Control Policies With Harmful Cannabis Exposures Reported to the California Poison Control System
Authors: Matthay Ellicott C. , Mousli Leyla M. , Sun Chloe , Lewis Justin , Jacobs Laurie M. , Heard Stuart , Ho Raymond , Schmidt Laura A. , Apollonio Dorie E.
Published: June 2024

Background:

Cannabis exposures reported to the California Poison Control System increased following the initiation of recreational cannabis sales on 1 January 2018 (i.e., “commercialization”). We evaluated whether local cannabis control policies adopted by 2021 were associated with shifts in harmful cannabis exposures.

Methods:

Using cannabis control policies collected for all 539 California cities and counties in 2020–2021, we applied a differences-in-differences design with negative binomial regression to test the association of policies with harmful cannabis exposures reported to California Poison Control System (2011–2020), before and after commercialization. We considered three policy categories: bans on storefront recreational retail cannabis businesses, overall restrictiveness, and specific recommended provisions (restricting product types or potency, packaging and labeling restrictions, and server training requirements).

Results:

Localities that ultimately banned storefront recreational retail cannabis businesses had fewer harmful cannabis exposures for children aged <13 years (rate ratio = 0.82; 95% confidence interval = 0.65, 1.02), but not for people aged >13 years (rate ratio = 0.97; 95% confidence interval = 0.85, 1.11). Of 167 localities ultimately permitting recreational cannabis sales, overall restrictiveness was not associated with harmful cannabis exposures among children aged <13 years, but for people aged >13 years, a 1-standard deviation increase in ultimate restrictiveness was associated with fewer harmful cannabis exposures (rate ratio = 0.93; 95% confidence interval = 0.86, 1.01). For recommended provisions, estimates were generally too imprecise to detect associations with harmful cannabis exposures.

Conclusion:

Bans on storefront retail and other restrictive approaches to regulating recreational cannabis may be associated with fewer harmful cannabis exposures for some age groups following statewide commercialization.
Multimodal Imaging in Mucolipidosis Type IV: Siblings With Novel Genetic Variant
Authors: Yangzes Sonam , Verma Anjali , Kaur Anupriya , Spalkit Stanzin , Kakkar Nandita , Gupta Amit
Published: June 2024

Purpose:

Utilization of multimodal imaging techniques to diagnose cases of mucolipidosis type IV (ML-IV) and report a new genetic variant.

Methods:

This study is a case report.

Results:

Case 1 involves a 4-year-old boy with corneal haziness and global developmental delay who showed an increased reflectivity of the corneal epithelium on anterior segment optical coherence tomography (AS-OCT). In addition, neurologic evaluation was suggestive of ML-IV. Further genetics evaluation confirmed ML-IV. Histology of the button revealed a thickened epithelial basement membrane. Case 2, the younger sibling, showed a milder corneal haze with similar changes on AS-OCT prompting us to further evaluate for ML-IV by genetics (positive MCOLN1 gene mutation). Both instances highlighted varied ML-IV presentations, but a persistent feature was hyperreflective epithelium.

Conclusions:

Our study emphasizes AS-OCT's role in screening ML-IV and advocates the role of genetic counseling of affected parents. We present 2 South-Asian siblings with ML-IV with a new genetic variant, emphasizing the utility of detailed ophthalmic and neurologic assessments using multimodal imaging.
Role of 18F-Fluorodeoxyglucose Positron Emission Tomography in Children With Germ Cell Tumor After Chemotherapy
Authors: De Pasquale Maria Debora , D’Angelo Paolo , Crocoli Alessandro , Vallero Stefano G. , Bertolini Patrizia , Miele Evelina , Terenziani Monica
Published: June 2024

Background/Aim:

18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a diagnostic tool widely used in adult oncology and some pediatric oncological settings. There are no established recommendations for the use of this imaging modality in pediatric malignant germ cell tumors (mGCT), however. Our aim is to evaluate the role of 18F-FDG PET/CT in the restaging of mGCT after chemotherapy in children and adolescents.

Methods:

We retrospectively reviewed patients with mGCT treated in Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers who underwent 18F-FDG PET/CT between 2011 and 2021.

Results:

Seventeen patients (median age 13 y) were included in the study. In 14 patients, 18F-FDG PET/CT was performed at diagnosis; 12 showed pathologic uptake. The 2 18F-FDG PET/CT negative cases were histologically defined as yolk sac tumor (YST) and mixed (chorioncarcinoma, YST). Nine of the 12 patients who had pathologic 18F-FDG PET/CT at diagnosis repeated the examination after neoadjuvant chemotherapy, before, second look surgery. In 5 cases, no pathologic uptake was evident. Histology showed necrosis alone in 4 cases and necrosis and mature teratoma in 1. In 3 of the 6 cases with pathologic uptake (2 of 6 patients did not perform the examination at diagnosis), histology showed persistence of malignant component, whereas in the remaining 3 cases, necrosis and mature teratoma were present.

Conclusion:

In our review of a series of children with mGCT, 18F-FDG PET/CT after neoadjuvant chemotherapy showed 1 of 5 false negatives and was unable to discriminate between residual malignant component and mature teratoma.
177Lu-DOTATATE PRRT Safety and Organ-at-Risk Dosimetry in Patients With Gastroenteropancreatic Neuroendocrine Tumors
Authors: Mileva Magdalena , Van Bogaert Camille , Marin Gwennaëlle , Danieli Rachele , Artigas Carlos , Levillain Hugo , Ameye Lieveke , Taraji-Schiltz Loubna , Stathopoulos Konstantinos , Wimana Zéna , Hendlisz Alain , Flamen Patrick , Karfis Ioannis
Published: June 2024

Purpose

The aim of this study was to assess the association among toxicity, dosimetry of organs-at-risk, and disease progression in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with 177Lu-DOTATATE.

Patients and Methods

Thirty-seven patients with GEP-NETs underwent 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in a single-arm, prospective, phase 2 study, where patients were followed up with blood tests, isotopic glomerular filtration rate (iGFR), and imaging examinations (CT/MRI and PET) every 6 months until disease progression. Adverse events (AEs) graded per CTCAEv4.03 and occurring during treatment were collected and followed up until resolution. Dosimetry, including biologically effective doses (BEDs) to kidneys, BED to bone marrow, and absorbed dose (AD) to spleen, was performed after each PRRT cycle. Statistical analyses explored associations among dosimetry, toxicity, and patient progression free-survival.

Results

The most common AEs were anemia and lymphopenia (65%), followed by thrombocytopenia and fatigue (each 51%), alopecia (46%), and nausea (41%). The most common grade ≥3 AE was lymphopenia (43%). There was no grade ≥3 nephrotoxicity. The median iGFR % decrease was 11% (P < 0.001), at a median follow-up of 23 months. iGFR %decrease and renal BED did not correlate (Spearman ρ = −0.09). Similarly, no significant association was found between bone marrow BED or spleen AD and the grades of hematological toxicities. We observed no association between progression free-survival and either the decline of renal function or the occurrence of hematological toxicities during PRRT.

Conclusions

This study confirms the safety profile of 177Lu-DOTATATE PRRT in patients with GEP-NETs irrespective of the dosimetry of organs at risk. Kidney, bone marrow, and spleen dosimetry measures were not associated with renal or hematological toxicity.
Acute microtubule changes linked to DMD pathology are insufficient to impair contractile function or enhance contraction-induced injury in healthy muscle
Authors: Vanegas Camilo , Ursitti Jeanine , Kallenbach Jacob G. , Pinto Kaylie , Harriot Anicca , Coleman Andrew K. , Shi Guoli , Ward Christopher W.
Published: June 2024

Duchenne muscular dystrophy (DMD) is marked by the genetic deficiency of the dystrophin protein in striated muscle whose consequence is a cascade of cellular changes that predispose the susceptibility to contraction injury central to DMD pathology. Recent evidence identified the proliferation of microtubules enriched in post-translationally modified tubulin as a consequence of dystrophins absence that increases the passive mechanics of the muscle fiber and the excess mechanotransduction elicited reactive oxygen species and calcium signals that promote contraction injury. Motivated by evidence that acutely normalizing the disease microtubule alterations reduced contraction injury in murine DMD muscle (mdx), here we sought the direct impact of these microtubule alterations independent of dystrophins absence and the multitude of other changes consequent to dystrophic disease. To this end we used acute pharmacologic (epithiolone-D, EpoD; 4 hours) or genetic (vashohibin-2 and small vasohibin binding protein overexpression via AAV9; 2 weeks) strategies to effectively model the proliferation of detyrosination enriched microtubules in themdxmuscle. Quantifyingin vivonerve evoked plantarflexor function we find no alteration in peak torque nor contraction kinetics in WT mice modeling these DMD relevant MT alterations. Quantifying the susceptibility to eccentric contraction injury we show EpoD treatment proffered a small but significant protection from contraction injury while VASH/SVBP had no discernable impact. We conclude that the disease dependent MT alterations act in concert with additional cellular changes to predispose contraction injury in DMD.
Self-healing, biocompatible bioinks from self-assembled peptide and alginate hybrid hydrogels
Authors: Field Emily H. , Ratcliffe Julian , Johnson Chad J. , Binger Katrina J. , Reynolds Nicholas P.
Published: June 2024

1.

There is a pressing need for new biomaterials that are printable, stiff and highly biocompatible. This is primarily due to the inverse relationship between the printability and viscosity of hydrogels. Cell-laden, printable, rigid biomaterials are needed for replicating stiffer tissues such as cartilage in regenerative medicine, modelling the fibrosis of tissue and cancer microenvironments, as well as in non-cellular research fields such as biosensors. Here, we have designed a hybrid material compromised of self-assembled Fmoc-FF peptide assemblies dispersed throughout a sodium alginate matrix. The resultant hybrid bioink has a stiffness up to 10 times greater than sodium alginate alone but remains highly printable, even when laden with high concentrations of cells. In addition, the thixotropic self-assembled peptide assemblies gave the hybrid bioinks highly desirable self-healing capabilities. The choice of solvent used to initially dissolve the peptides made significant differences to both the physical properties and the biocompatibility of the bioinks, with the best performing able to support the growth of encapsulated macrophages over 5 days. Our developed hybrid materials allow the bioprinting of materials previously considered too stiff to extrude without causing shear induced cytotoxicity with applications in tissue engineering and biosensing.
High-dimensional causal mediation analysis by partial sum statistic and sample splitting strategy in imaging genetics application
Authors: Hung-Ching Chang , Yusi Fang , Gorczyca Michael T. , Kayhan Batmanghelich , Tseng George C.
Published: June 2024

Causal mediation analysis provides a systematic approach to explore the causal role of one or more mediators in the association between exposure and outcome. In omics or imaging data analysis, mediators are often high-dimensional, which brings new statistical challenges. Existing methods either violate causal assumptions or fail in interpretable variable selection. Additionally, mediators are often highly correlated, presenting difficulties in selecting and prioritizing top mediators. To address these issues, we develop a framework using Partial Sum Statistic and Sample Splitting Strategy, namely PS5, for high-dimensional causal mediation analysis. The method provides a powerful global mediation test satisfying causal assumptions, followed by an algorithm to select and prioritize active mediators with quantification of individual mediation contributions. We demonstrate its accurate type I error control, superior statistical power, reduced bias in mediation effect estimation, and accurate mediator selection using extensive simulations of varying levels of effect size, signal sparsity, and mediator correlations. Finally, we apply PS5 to an imaging genetics dataset of chronic obstructive pulmonary disease (COPD) patients (N=8,897) in the COPDGene study to examine the causal mediation role of lung images (p=5,810) in the associations between polygenic risk score and lung function and between smoking exposure and lung function, respectively. Both causal mediation analyses successfully estimate the global indirect effect and detect mediating image regions. Collectively, we find a region in the lower lobe of the right lung with a strong and concordant mediation effect for both genetic and environmental exposures. This suggests that targeted treatment toward this region might mitigate the severity of COPD due to genetic and smoking effects.
Reproducibility of radiomic features of the brain on ultrahigh-resolution MRI at 7 Tesla: a comparison of different segmentation techniques
Authors: Klinger Julian H. , Leithner Doris , Woo Sungmin , Weber Michael , Vargas H. Alberto , Mayerhoefer Marius E.
Published: June 2024

Objectives

To determine the impact of segmentation techniques on radiomic features extracted from ultrahigh-field (UHF) MRI of the brain.

Materials and Methods

Twenty-one 7T MRI scans of the brain, including a 3D magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) T1-weighted sequence with an isotropic 0.63 mm³ voxel size, were analyzed. Radiomic features (histogram, texture, and shape; total n=101) from six brain regions -cerebral gray and white matter, basal ganglia, ventricles, cerebellum, and brainstem-were extracted from segmentation masks constructed with four different techniques: the iGT (reference standard), based on a custom pipeline that combined automatic segmentation tools and expert reader correction; the deep-learning algorithm Cerebrum-7T; the Freesurfer-v7 software suite; and the Nighres algorithm. Principal components (PCs) were calculated for histogram and texture features. To test the reproducibility of radiomic features, intraclass correlation coefficients (ICC) were used to compare Cerebrum-7, Freesurfer-v7, and Nighres to the iGT, respectively.

Results

For histogram PCs, median ICCs for Cerebrum-7T, Freesurfer-v7, and Nighres were 0.99, 0.42, and 0.11 for the gray matter; 0.84, 0.25, and 0.43 for the basal ganglia; 0.89, 0.063, and 0.036 for the white matter; 0.84, 0.21, and 0.33 for the ventricles; 0.94, 0.64, and 0.93 for the cerebellum; and 0.78, 0.21, and 0.53 for the brainstem. For texture PCs, median ICCs for Cerebrum-7T, Freesurfer-v7, and Nighres were 0.95, 0.21, and 0.15 for the gray matter; 0.70, 0.36, and 0.023 for the basal ganglia; 0.91, 0.25, and 0.023 for the white matter; 0.80, 0.75, and 0.59 for the ventricles; 0.95, 0.43, and 0.86 for the cerebellum; and 0.72, 0.39, and 0.46 for the brainstem. For shape features, median ICCs for Cerebrum-7T, FreeSurfer-v7, and Nighres were 0.99, 0.91, and 0.36 for the gray matter; 0.89, 0.90, and 0.13 for the basal ganglia; 0.98, 0.91, and 0.027 for the white matter; 0.91, 0.91, and 0.36 for the ventricles; 0.80, 0.68, and 0.47 for the cerebellum; and 0.79, 0.17, and 0.15 for the brainstem.

Conclusions

Radiomic features in UHF MRI of the brain show substantial variability depending on the segmentation algorithm. The deep learning algorithm Cerebrum-7T enabled the highest reproducibility. Dedicated software tools for UHF MRI may be needed to achieve more stable results.