bluuebunny/crossref_metadata_2025 huggingface dataset:
Per-fraction planning to enhance optimization degrees of freedom compared to the conventional single-plan approach
Authors: Rossi Linda , Breedveld Sebastiaan , Heijmen Ben
Published: July 2023

Objective. In conventional radiotherapy, a single treatment plan is generated pre-treatment, and delivered in daily fractions. In this study, we propose to generate different treatment plans for all fractions (‘Per-fraction’ planning) to reduce cumulative organs at risk (OAR) doses. Per-fraction planning was compared to the ‘Conventional’ single-plan approach for non-coplanar 4 × 9.5 Gy prostate stereotactic body radiation therapy (SBRT). Approach. An in-house application for fully automated, non-coplanar multi-criterial treatment planning with integrated beam angle and fluence optimization was used for plan generations. For the Conventional approach, a single 12-beam non-coplanar IMRT plan with individualized beam angles was generated for each of the 20 included patients. In Per-fraction planning, four fraction plans were generated for each patient. For each fraction, a different set of patient-specific 12-beam configurations could be automatically selected. Per-fraction plans were sequentially generated by adding dose to already generated fraction plan(s). For each fraction, the cumulative- and fraction dose were simultaneously optimized, allowing some minor constraint violations in fraction doses, but not in cumulative. Main results. In the Per-fraction approach, on average 32.9 ± 3.1 [29;39] unique beams per patient were used. PTV doses in the separate Per-fraction plans were acceptable and highly similar to those in Conventional plans, while also fulfilling all OAR hard constraints. When comparing total cumulative doses, Per-fraction planning showed improved bladder sparing for all patients with reductions in Dmean of 22.6% (p = 0.0001) and in D1cc of 2.0% (p = 0.0001), reductions in patient volumes receiving 30% and 50% of the prescribed dose of 54.7% and 6.3%, respectively, and a 3.1% lower rectum Dmean (p = 0.007). Rectum D1cc was 4.1% higher (p = 0.0001) and Urethra dose was similar. Significance. In this proof-of-concept paper, Per-fraction planning resulted in several dose improvements in healthy tissues compared to the Conventional single-plan approach, for similar PTV dose. By keeping the number of beams per fraction the same as in Conventional planning, reported dosimetric improvements could be obtained without increase in fraction durations. Further research is needed to explore the full potential of the Per-fraction planning approach.
Temperature dependent magnetorelaxometry of magnetic nanoparticle ensembles
Authors: Arsalani Soudabeh , Radon Patricia , Eberbeck Dietmar , Körber Rainer , Jaufenthaler Aaron , Baumgarten Daniel , Wiekhorst Frank
Published: July 2023

Magnetorelaxometry imaging (MRXI) is a non-invasive, quantitative imaging technique for magnetic nanoparticles (MNPs). The image resolution of this technique significantly depends on the relaxation amplitude (ΔB). For this work, we measured the room temperature (299 K) relaxation signals of eight commercial MNP sample systems with different magnetic properties, in both fluid and immobilized states, in order to select the most suitable sample for a particular MRXI setting. Additionally, the effect of elevated temperatures (up to hyperthermia temperature, 335 K) on the relaxation signals of four different MNP systems (Synomag, Perimag, BNF and Nanomag) in both states were investigated. The ΔB values of fluid samples significantly decreased with increasing temperature, and the behaviour for immobilized samples depended on their blocking temperature (T
B). For samples with T
B < 299 K, ΔB also decreased with increasing temperature. Whereas for samples with T
B > 299 K, the opposite behaviour was observed. These results are beneficial for improving the image resolution in MRXI and show, among the investigated systems, and for our setup, Synomag is the best candidate for future in vitro and in vivo studies. This is due to its consistently high ΔB between 299 and 335 K in both states. Our findings demonstrate the feasibility of temperature imaging by MRXI.
Correction of motion tracking errors for PET head rigid motion correction
Authors: Miranda Alan , Kroll Tina , Schweda Vanessa , Staelens Steven , Verhaeghe Jeroen
Published: July 2023

Objective. In positron emission tomography (PET) rigid motion correction, erroneous tracking information translates into reduced quality in motion corrected reconstructions. We aim to improve the accuracy of the motion tracking data, to improve the quality of motion corrected reconstructions. Approach. We developed a method for correction of marker/skin displacement over the skull, for tracking methods which require multiple markers attached on the subject head. Additionally, we correct for small magnitude (∼1–2 mm) residual translation tracking errors that can still be present after other corrections. We performed [18F]FDG scans in awake mice (n = 8) and rats (n = 8), and dynamic [18F]SynVesT-1 scans in awake mice (n = 8). Head tracking was performed with the point source tracking method, attaching 3–4 radioactive fiducial markers on the animals’ heads. List-mode even-by-event motion correction reconstruction was performed using tracking data obtained from the point source tracking method (MC), tracking data corrected for marker displacement (MC-DC), and tracking data with additional correction for residual translation tracking errors (MC-DCT). Image contrast, and the image enhancement metric (IEM, with MC as reference) were calculated in these 3 reconstructions. Main results. In mice [18F]FDG scans, the contrast increased on average 3% from MC to MC-DC (IEM: 1.01), and 5% from MC to MC-DCT (IEM: 1.02). For mice [18F]SynVesT-1 scans the contrast increased 6% from MC to MC-DC (IEM: 1.03), and 7% from MC to MC-DCT (IEM: 1.05). In rat [18F]FDG scans contrast increased 5% (IEM: 1.04), and 9% (IEM: 1.05), respectively. Significance. The methods presented here serve to correct motion tracking errors in PET brain scans, which translates into improved image quality in motion corrected reconstructions.
Combined two-level guided wave structural health monitoring strategy using multifeature integration and machine learning: application to early-age grouted sleeves
Authors: Liu Jiahe , Yi Jun , Li Dongsheng , Cui Xiushi , Zhou Junlong
Published: July 2023

Structural health monitoring of grouted sleeves is one of the assembly industry’s huge challenges. In this study, a combined two-level damage detection was introduced. It comprises defect classification (healthy, rebar eccentricity, and grout leakage) and severity evaluation for early-age grouted sleeves using guided waves. Multiple features (MF) from time-, frequency-, and time-frequency domains were extracted and defined according to the diverse defects and ages of grouted sleeves to represent complex damage characteristics. Moreover, the egret swarm algorithm optimization–extreme learning machine (ESAO-ELM) models were proposed to avoid the influence of subjective experience and judgment from experts. ESAO optimized the initial random parameters (input weights and hidden layer bias) of ELM. Then, two MF-ESAO-ELM models were trained for two-level damage detection on the experimental dataset. The performance of the proposed models was comprehensively evaluated using accuracy, recall, precision, and confusion matrix. MF-ESAO-ELM performs better than ELM and PSO-ELM in accuracy. In this strategy, the defect classification model works in the outer layer to distinguish the state and types of defects of grouted sleeves (healthy, eccentric, or leakage). In comparison, the inner layer starts predicting the severity only if the defect type is leakage. MF-ESAO-ELM offers advantages in terms of accuracy, strategy, and calculation time.
Projection of future carbon benefits by photovoltaic power potential in China using CMIP6 statistical downscaling data
Authors: Niu Jiayun , Wu Jinyang , Qin Wenmin , Wang Lunche , Yang Chao , Zhang Ming , Zhang Yujie , Qi Qinghai
Published: July 2023

Solar photovoltaic (PV) systems is an affordable solution that significantly contribute to climate adaptation and resilience, energy security and greenhouse gas abatement with respect to fossil fuel electricity generation. Currently, available studies on the benefits of PV power generation only consider the electricity consumption and do not account for the possible future benefits from carbon trading under the combined impacts of pollution emissions and socio-economic. In this study, the downscaling and bias correction were applied to the Coupled Model Inter-comparison Project Phase 6 (CMIP6) multi-model mean data based on the historical data from the China Meteorological Administration (CMA) stations. The corrected measurements of meteorology were used to explore the PV power potential and the environmental and economic benefits offset by solar power generation under SSP126, SSP245 and SSP585 in China during 2023–2100. We found that the annual mean PV power potential across mainland China ranged from 1 to 37 Wm−2 and demonstrated a decreasing trend in the Northwest China and an increasing trend in the Southeast China. Compared to thermal power generation, electricity from solar energy will counteract the total emissions of annual mean 139.54 × 105 t CO2, 1702 t SO2, 2562 t NO
X
and 3710 t dust in China in SSP126 scenario. The results of variable importance assessment showed that the West Texas Intermediate crude oil price (47.77%), coal price (41.76%), natural gas price (6.65%) and gross domestic product (2.44%) contribute the most to the carbon emissions allowances (CEAs) price. Against a ‘carbon peak’ background in China, the CEA price will reach 80 CNY/t CO2 by 2030 in China, with the carbon trading value potential ranging from 20 billion to 200 billion CNY of each pixel (10 km × 10 km) by 2030. This study would have important implications for the environmental construction and future investment and construction of PV systems in China.
Breath analysis combined with cardiopulmonary exercise testing and echocardiography for monitoring heart failure patients: the AEOLUS protocol
Authors: Biagini Denise , Pugliese Nicola R , Vivaldi Federico M , Ghimenti Silvia , Lenzi Alessio , De Angelis Francesca , Ripszam Matyas , Bruderer Tobias , Armenia Silvia , Cappeli Federica , Taddei Stefano , Masi Stefano , Francesco Fabio Di , Lomonaco Tommaso
Published: July 2023

This paper describes the AEOLUS pilot study which combines breath analysis with cardiopulmonary exercise testing (CPET) and an echocardiographic examination for monitoring heart failure (HF) patients. Ten consecutive patients with a prior clinical diagnosis of HF with reduced left ventricular ejection fraction were prospectively enrolled together with 15 control patients with cardiovascular risk factors, including hypertension, type II diabetes or chronic ischemic heart disease. Breath samples were collected at rest and during CPET coupled with exercise stress echocardiography (CPET-ESE) protocol by means of needle trap micro-extraction and were analyzed through gas-chromatography coupled with mass spectrometry. The protocol also involved using of a selected ion flow tube mass spectrometer for a breath-by-breath isoprene and acetone analysis during exercise. At rest, HF patients showed increased breath levels of acetone and pentane, which are related to altered oxidation of fatty acids and oxidative stress, respectively. A significant positive correlation was observed between acetone and the gold standard biomarker NT-proBNP in plasma (r= 0.646,p< 0.001), both measured at rest. During exercise, some exhaled volatiles (e.g., isoprene) mirrored ventilatory and/or hemodynamic adaptation, whereas others (e.g., sulfide compounds and 3-hydroxy-2-butanone) depended on their origin. At peak effort, acetone levels in HF patients differed significantly from those of the control group, suggesting an altered myocardial and systemic metabolic adaptation to exercise for HF patients. These preliminary data suggest that concomitant acquisition of CPET-ESE and breath analysis is feasible and might provide additional clinical information on the metabolic maladaptation of HF patients to exercise. Such information may refine the identification of patients at higher risk of disease worsening.
Urbanization and political change in Africa
Authors: Hoelscher Kristian , Dorward Nick , Fox Sean , Lawanson Taibat , Paller Jeffrey W , Phillips Melanie L
Published: July 2023

Urbanization is transforming the human and political geography of Africa. While a growing body of research explores the urban dimensions of clientelism, contentious action, and social mobilization, there has been less attention given to the ways in which this demographic megatrend is influencing political change more broadly. We argue that the political implications of African urbanization are contingent on local conditions and experiences; there are no deterministic associations between urbanization and political change. To better understand the mechanisms linking urbanization to politics, we argue that a place-based approach is needed. We illustrate this by reviewing and highlighting how urbanization may affect (i) the nature and balance of citizen preferences; (ii) the composition, interests, and influence of elite actors; (iii) forms of political mobilization; (iv) shifting gender roles; (v) the role of civil society in political processes; and (vi) the likelihood and manifestations of contentious collective action. We conclude with a discussion of directions for further research.
Model aversiveness and the evolution of imperfect Batesian mimics
Authors: Pike Thomas W , Burman Oliver H P
Published: July 2023

There are numerous examples of Batesian mimics that only imperfectly resemble their models. Given that inaccurate mimics are known to be predated more frequently than accurate ones, imperfect mimicry therefore poses something of a conundrum. One putative explanation, the relaxed selection hypothesis, predicts that when the cost of attacking a model is high relative to the benefit of consuming a mimic, selection against imperfect mimics will be relaxed, allowing mimics to be more imperfect for a given level of fitness. However, empirical support for this hypothesis is equivocal. Here, we report an experimental test of the relaxed selection hypothesis, in which human participants were tasked with discriminating between artificial stimuli representing models and mimics. In response to “attacking” a model (i.e., misclassifying it as palatable, or non-aversive) they received either a mild electric shock (high cost) or vibratory feedback (low cost). Consistent with the predictions of this hypothesis, we found that when the cost of attacking a model was high, mimetic phenotype could deviate more from the model (i.e., be more imperfect) for a given level of fitness than when the cost of attacking a model was low. Moreover, when the cost of attacking a model was high, participants showed an increased latency to attack. This finding shows that given sufficient costs, the relaxed selection hypothesis is a plausible explanation for the evolution of imperfect mimicry.
Evaluation of greenhouse gas emission reduction potential of a demand–response solution: a carbon handprint case study of a virtual power plant
Authors: Sillman J , Lakanen L , Annala S , Grönman K , Luoranen M , Soukka R
Published: July 2023

The transition towards zero-carbon energy production is necessary to limit global warming. Smart energy systems have facilitated the control of demand-side resources to maintain the stability of the power grid and to provide balancing power for increasing renewable energy production. Virtual power plants are examples of demand–response solutions, which may also enable greenhouse gas (GHG) emission reductions due to the lower need for fossil-based balancing energy in the grid and the increased share of renewables. The aim of this study is to show how potential GHG emission reductions can be assessed through the carbon handprint approach for a virtual power plant (VPP) in a grid balancing market in Finland. According to our results, VPP can reduce the hourly based GHG emissions in the studied Finnish grid systems compared with the balancing power without the VPP. Typical energy sources used for the balance power are hydropower and fossil fuels. The reduction potential of GHG emissions varies from 68% to 98% depending on the share of the used energy source for the power balancing, thus VPPs have the potential to significantly reduce GHG emissions of electricity production and hence help mitigate climate change.
The right hemisphere’s capacity for language: evidence from primary progressive aphasia
Authors: Neophytou Kyriaki , Wiley Robert , Litovsky Celia , Tsapkini Kyrana , Rapp Brenda
Published: July 2023

The role of the right hemisphere (RH) in core language processes is still a matter of intense debate. Most of the relevant evidence has come from studies of gray matter, with relatively little research on RH white matter (WM) connectivity. Using Diffusion Tensor Imaging-based tractography, the current work examined the role of the two hemispheres in language processing in 33 individuals with Primary Progressive Aphasia (PPA), aiming to better characterize the contribution of the RH to language processing in the context of left hemisphere (LH) damage. The findings confirm the impact of PPA on the integrity of the WM language tracts in the LH. Additionally, an examination of the relationship between tract integrity and language behaviors provides robust evidence of the involvement of the WM language tracts of both hemispheres in language processing in PPA. Importantly, this study provides novel evidence of a unique contribution of the RH to language processing (i.e. a contribution independent from that of the language-dominant LH). Finally, we provide evidence that the RH contribution is specific to language processing rather than being domain general. These findings allow us to better characterize the role of RH in language processing, particularly in the context of LH damage.
Acute pain drives different effects on local and global cortical excitability in motor and prefrontal areas: insights into interregional and interpersonal differences in pain processing
Authors: De Martino Enrico , Casali Adenauer , Casarotto Silvia , Hassan Gabriel , Rosanova Mario , Graven-Nielsen Thomas , Ciampi de Andrade Daniel
Published: July 2023

Pain-related depression of corticomotor excitability has been explored using transcranial magnetic stimulation-elicited motor-evoked potentials. Transcranial magnetic stimulation-electroencephalography now enables non-motor area cortical excitability assessments, offering novel insights into cortical excitability changes during pain states. Here, pain-related cortical excitability changes were explored in the dorsolateral prefrontal cortex and primary motor cortex (M1). Cortical excitability was recorded in 24 healthy participants before (Baseline), during painful heat (Acute Pain), and non-noxious warm (Warm) stimulation at the right forearm in a randomized sequence, followed by a pain-free stimulation measurement. Local cortical excitability was assessed as the peak-to-peak amplitude of early transcranial magnetic stimulation evoked potential, whereas global-mean field power measured the global excitability. Relative to the Baseline, Acute Pain decreased the peak-to-peak amplitude in M1 and dorsolateral prefrontal cortex compared with Warm (both P < 0.05). A reduced global-mean field power was only found in M1 during Acute Pain compared with Warm (P = 0.003). Participants with the largest reduction in local cortical excitability under Acute Pain showed a negative correlation between dorsolateral prefrontal cortex and M1 local cortical excitability (P = 0.006). Acute experimental pain drove differential pain-related effects on local and global cortical excitability changes in motor and non-motor areas at a group level while also revealing different interindividual patterns of cortical excitability changes, which can be explored when designing personalized treatment plans.
Differential involvement of the anterior and posterior hippocampus, parahippocampus, and retrosplenial cortex in making precise judgments of spatial distance and object size for remotely acquired memories of environments and objects
Authors: Ziegler Marilyne G , Liu Zhong-Xu , Arsenault Jessica , Dang Christa , Grady Cheryl , Rosenbaum R Shayna , Moscovitch Morris
Published: July 2023

The hippocampus is known to support processing of precise spatial information in recently learned environments. It is less clear, but crucial for theories of systems consolidation, to know whether it also supports processing of precise spatial information in familiar environments learned long ago and whether such precision extends to objects and numbers. In this fMRI study, we asked participants to make progressively more refined spatial distance judgments among well-known Toronto landmarks (whether landmark A is closer to landmark B or C) to examine hippocampal involvement. We also tested whether the hippocampus was similarly engaged in estimating magnitude regarding sizes of familiar animals and numbers. We found that the hippocampus was only engaged in spatial judgment. Activation was greater and lasted longer in the posterior than anterior hippocampus, which instead showed greater modulation as discrimination between spatial distances became more fine grained. These findings suggest that the anterior and posterior hippocampus have different functions which are influenced differently by estimation of differential distance. Similarly, parahippocampal-place-area and retrosplenial cortex were involved only in the spatial condition. By contrast, activation of the intraparietal sulcus was modulated by precision in all conditions. Therefore, our study supports the idea that the hippocampus and related structures are implicated in retrieving and operating even on remote spatial memories whenever precision is required, as posted by some theories of systems consolidation.
Mismatch negativity as a marker of auditory pattern separation
Authors: Herman Deena , Baker Stevenson , Chow Ricky , Cazes Jaime , Alain Claude , Rosenbaum R Shayna
Published: July 2023

To what extent does incidental encoding of auditory stimuli influence subsequent episodic memory for the same stimuli? We examined whether the mismatch negativity (MMN), an event-related potential generated by auditory change detection, is correlated with participants’ ability to discriminate those stimuli (i.e. targets) from highly similar lures and from dissimilar foils. We measured the MMN in 30 young adults (18–32 years, 18 females) using a passive auditory oddball task with standard and deviant 5-tone sequences differing in pitch contour. After exposure, all participants completed an incidental memory test for old targets, lures, and foils. As expected, participants at test exhibited high sensitivity in recognizing target items relative to foils and lower sensitivity in recognizing target items relative to lures. Notably, we found a significant correlation between MMN amplitude and lure discrimination, but not foil discrimination. Our investigation shows that our capacity to discriminate sensory inputs at encoding, as measured by the MMN, translates into precision in memory for those inputs.
Short Timeframe Prediction of Kidney Failure among Patients with Advanced Chronic Kidney Disease
Authors: Klamrowski Martin M , Klein Ran , McCudden Christopher , Green James R , Ramsay Tim , Rashidi Babak , White Christine A , Oliver Matthew J , Akbari Ayub , Hundemer Gregory L
Published: July 2023

Background

Development of a short timeframe (6–12 months) kidney failure risk prediction model may serve to improve transitions from advanced chronic kidney disease (CKD) to kidney failure and reduce rates of unplanned dialysis. The optimal model for short timeframe kidney failure risk prediction remains unknown.

Methods

This retrospective study included 1757 consecutive patients with advanced CKD (mean age 66 years, estimated glomerular filtration rate 18 mL/min/1.73 m2). We compared the performance of Cox regression models using (a) baseline variables alone, (b) time-varying variables and machine learning models, (c) random survival forest, (d) random forest classifier in the prediction of kidney failure over 6/12/24 months. Performance metrics included area under the receiver operating characteristic curve (AUC-ROC) and maximum precision at 70% recall (PrRe70). Top-performing models were applied to 2 independent external cohorts.

Results

Compared to the baseline Cox model, the machine learning and time-varying Cox models demonstrated higher 6-month performance [Cox baseline: AUC-ROC 0.85 (95% CI 0.84–0.86), PrRe70 0.53 (95% CI 0.51–0.55); Cox time-varying: AUC-ROC 0.88 (95% CI 0.87–0.89), PrRe70 0.62 (95% CI 0.60–0.64); random survival forest: AUC-ROC 0.87 (95% CI 0.86–0.88), PrRe70 0.61 (95% CI 0.57–0.64); random forest classifier AUC-ROC 0.88 (95% CI 0.87–0.89), PrRe70 0.62 (95% CI 0.59–0.65)]. These trends persisted, but were less pronounced, at 12 months. The random forest classifier was the highest performing model at 6 and 12 months. At 24 months, all models performed similarly. Model performance did not significantly degrade upon external validation.

Conclusions

When predicting kidney failure over short timeframes among patients with advanced CKD, machine learning incorporating time-updated data provides enhanced performance compared with traditional Cox models.
Assessing Lexical and Syntactic Comprehension in Deaf Signing Adults
Authors: Zorzi Giorgia , Aristodemo Valentina , Giustolisi Beatrice , Hauser Charlotte , Donati Caterina , Cecchetto Carlo
Published: July 2023

Among the existing sign language assessment tools, only a small number can be used in clinical settings. This contribution aims at presenting three comprehension assessment tests (two lexical and one syntactic) that offer a solid basis to build tools to assess language impairments in deaf signing adults. We provide the material and guidelines, based on psychometric analyses of the items, to make these tests suitable for clinical assessment. They are available for French Sign Language and Italian Sign Language. So far, the three tests were administered to three groups of deaf participants based on age of exposure (AoE) to sign language: native (AoE from birth), early (AoE = from 1 to 5 years), and late (AoE = from 6 to 15 years) signers. The results showed that the three tests are easy for the typical deaf signing population, and therefore, they can be adapted into tests that assess a deaf signing population with language impairments. Moreover, the results of the syntactic test reveal a categorial difference between native and non-native signers and therefore show the need for baselines that mirror the effect of AoE to sign language when assessing language competence, in particular in clinical assessment.
Transcriptional regulation of the synthesis and secretion of farnesol in the fungus Candida albicans: examination of the Homann transcription regulator knockout collection
Authors: Gutzmann Daniel J , Kramer Jaxon J , Toomey Brigid M , Boone Cory H T , Atkin Audrey L , Nickerson Kenneth W
Published: July 2023

Candida albicans is an efficient colonizer of human gastrointestinal tracts and skin and is an opportunistic pathogen. C. albicans exhibits morphological plasticity, and the ability to switch between yeast and filamentous morphologies is associated with virulence. One regulator of this switch is the quorum sensing molecule farnesol that is produced by C. albicans throughout growth. However, the synthesis, secretion, regulation, and turnover of farnesol are not fully understood. To address this, we used our improved farnesol assay to screen a transcription regulator knockout library for differences in farnesol accumulation in whole cultures, pellets, and supernatants. All screened mutants produced farnesol and they averaged 9.2× more farnesol in the pellet than the supernatant. Nineteen mutants had significant differences with ten mutants producing more farnesol than their SN152+ wild-type control strain while nine produced less. Seven mutants exhibited greater secretion of farnesol while two exhibited less. We examined the time course for farnesol accumulation in six mutants with the greatest accumulation differences and found that those differences persisted throughout growth and they were not time dependent. Significantly, two high-accumulating mutants did not exhibit the decay in farnesol levels during stationary phase characteristic of wild-type C. albicans, suggesting that a farnesol modification/degradation mechanism is absent in these mutants. Identifying these transcriptional regulators provides new insight into farnesol's physiological functions regarding cell cycle progression, white–opaque switching, yeast–mycelial dimorphism, and response to cellular stress.
Characterizing industry payments to US teaching hospitals and affiliated physicians: a cross-sectional analysis of the Open Payments datasets from 2016 to 2022
Authors: Pope Elle , Sehgal Neil
Published: July 2023

Industry payments to US teaching hospitals are common; however, little is known about whether these financial relationships influence affiliated physicians to engage in similar financial relationships with industry. Using national hospital, physician, and industry payment data we investigated trends in industry payments made to US teaching hospitals and affiliated physicians to characterize the magnitude and nature of payments. In addition, we assessed if physicians may be influenced to accept higher value industry payments depending on the value of promotional payments accepted by the teaching hospital they affiliate with. We found that physicians with a US teaching hospital affiliation are associated with accepting higher value industry payments as the total value of industry payments of the teaching hospital increases. Our findings varied by specialty, with surgeons accepting the highest value payments. These results highlight the need for greater public disclosure and awareness of payments to better manage and mitigate industry-biased clinical decision making.
Human herpesvirus 8 ORF57 protein is able to reduce TDP-43 pathology: network analysis identifies interacting pathways
Authors: Webber Chelsea J , Murphy Caroline N , Rondón-Ortiz Alejandro N , van der Spek Sophie J F , Kelly Elena X , Lampl Noah M , Chiesa Giulio , Khalil Ahmad S , Emili Andrew , Wolozin Benjamin
Published: July 2023

Aggregation of TAR DNA-binding protein 43 kDa (TDP-43) is thought to drive the pathophysiology of amyotrophic lateral sclerosis and some frontotemporal dementias. TDP-43 is normally a nuclear protein that in neurons translocates to the cytoplasm and can form insoluble aggregates upon activation of the integrated stress response (ISR). Viruses evolved to control the ISR. In the case of Herpesvirus 8, the protein ORF57 acts to bind protein kinase R, inhibit phosphorylation of eIF2α and reduce activation of the ISR. We hypothesized that ORF57 might also possess the ability to inhibit aggregation of TDP-43. ORF57 was expressed in the neuronal SH-SY5Y line and its effects on TDP-43 aggregation characterized. We report that ORF57 inhibits TDP-43 aggregation by 55% and elicits a 2.45-fold increase in the rate of dispersion of existing TDP-43 granules. These changes were associated with a 50% decrease in cell death. Proteomic studies were carried out to identify the protein interaction network of ORF57. We observed that ORF57 directly binds to TDP-43 as well as interacts with many components of the ISR, including elements of the proteostasis machinery known to reduce TDP-43 aggregation. We propose that viral proteins designed to inhibit a chronic ISR can be engineered to remove aggregated proteins and dampen a chronic ISR.
Spermatogenesis after gonadotoxic childhood treatment: follow-up of 12 patients
Authors: Delgouffe E , Braye A , Vloeberghs V , Mateizel I , Ernst C , Ferster A , Devalck C , Tournaye H , Gies I , Goossens E
Published: July 2023

STUDY QUESTION

What is the long-term impact of presumed gonadotoxic treatment during childhood on the patient’s testicular function at adulthood?

SUMMARY ANSWER

Although most patients showed low testicular volumes and some degree of reproductive hormone disruption 12.3 (2.3–21.0) years after gonadotoxic childhood therapy, active spermatogenesis was demonstrated in the semen sample of 8 out of the 12 patients.

WHAT IS KNOWN ALREADY

In recent decades, experimental testicular tissue banking programmes have been set up to safeguard the future fertility of young boys requiring chemo- and/or radiotherapy with significant gonadotoxicity. Although the risk of azoospermia following such therapies is estimated to be high, only limited long-term data are available on the reproductive potential at adulthood.

STUDY DESIGN, SIZE, DURATION

This single-centre prospective cohort study was conducted between September 2020 and February 2023 and involved 12 adult patients.

PARTICIPANTS/MATERIALS, SETTING, METHODS

This study was carried out in a tertiary care centre and included 12 young adults (18.1–28.3 years old) who had been offered testicular tissue banking prior to gonadotoxic treatment during childhood. All patients had a consultation and physical examination with a fertility specialist, a scrotal ultrasound to measure the testicular volumes and evaluate the testicular parenchyma, a blood test for assessment of reproductive hormones, and a semen analysis.

MAIN RESULTS AND THE ROLE OF CHANCE

Testicular tissue was banked prior to the gonadotoxic treatment for 10 out of the 12 included patients. Testicular volumes were low for 9 patients, and 10 patients showed some degree of reproductive hormone disruption. Remarkably, ongoing spermatogenesis was demonstrated in 8 patients at a median 12.3 (range 2.3–21.0) years post-treatment.

LIMITATIONS, REASONS FOR CAUTION

This study had a limited sample size, making additional research with a larger study population necessary to verify these preliminary findings.

WIDER IMPLICATIONS OF THE FINDINGS

These findings highlight the need for multicentric research with a larger study population to establish universal inclusion criteria for immature testicular tissue banking.

STUDY FUNDING/COMPETING INTEREST(S)

This study was conducted with financial support from the Research Programme of the Research Foundation-Flanders (G010918N), Kom Op Tegen Kanker, and Scientific Fund Willy Gepts (WFWG19-03). The authors declare no competing interests.

TRIAL REGISTRATION NUMBER

NCT04202094; https://clinicaltrials.gov/ct2/show/NCT04202094?id=NCT04202094&draw=2&rank=1 This study was registered on 6 December 2019, and the first patient was enrolled on 8 September 2020.
Experimental and histological evaluation of different clamp technique for pulmonary artery
Authors: Chiba Yoshiki , Takahashi Yuki , Takase Yoshiaki , Tsuruta Kodai , Maki Ryunosuke , Miyajima Masahiro , Ohnishi Hirofumi , Watanabe Atsushi
Published: July 2023

OBJECTIVES

The double-loop technique has been used in our clinical settings for pulmonary arterioplasty and/or injured artery repair during thoracoscopic anatomical lung resection. We evaluated the pressure resistance capacity and intimal load to determine the effectiveness and safety of the double-loop technique.

METHODS

The double-loop technique, DeBakey clamp, Fogarty clamp, endovascular clips and vessel loop technique were evaluated. During an experimental study, a polyvinyl alcohol main pulmonary artery model, manometer and in-deflation device were used to measure the burst pressure. The maximum clamp pressure was measured using a pressure-measuring film. Each measurement was performed 10 times. During the histological study, we measured the burst pressure and evaluated the intimal damage of the human pulmonary artery associated with the double-loop technique and DeBakey clamp.

RESULTS

The experimental burst pressure (mmHg) and maximum clamp pressure (MPa) between the double-loop technique and DeBakey at the third notch were not significantly different (24.6 ± 2.8 and 21.8 ± 2.8, P = 0.094; 1.54 ± 0.12 and 1.49 ± 0.12, P = 0.954). During the histological study, the burst pressures of the double-loop technique and DeBakey at the third notch were also not significantly different (P = 0.754). Furthermore, the double-loop technique resulted in only intimal deformation in each five samples.

CONCLUSIONS

The double-loop technique is feasible for thoracoscopic anatomical lung resection because it has similar pressure resistance capacity and intimal load as DeBakey at the 3rd notch.
A Method for Change. Lacanian Discourse Analysis: A Glimpse into Climate Policy
Authors: Tolis Valeria
Published: July 2023

In this article, I propose a return to Jacques Lacan, I develop a Lacanian discourse analysis (LDA) as one possible method in international relations and demonstrate its potential by sketching out the case of climate change policy within the European Union. Lacan’s theory of the four discourses as conceptual “mind maps” informs a method of discourse analysis enabling researchers to empirically investigate how a hegemonic discourse can be challenged and potentially subverted. A Lacanian perspective emphasizes the “subject of the enunciation” and conceptualizes subjects as socially produced but lacking: Discourse provides an historicized socio-linguistic structure sustaining the subject’s societal relations, but the speaking activity always produces a cut within subjectivity, which manifests as an excess-loss of meaning in the enunciation. Via the case study of the energy efficiency policy in the EU, I first illustrate how an LDA allows us to investigate climate knowledge and the authority of the discourse. Then, by looking at how energy efficiency is spoken in the enunciation, I expose the excess of meaning produced as an effect of language, which “fractures” the discourse. Finally, I show how to leverage on these produced fractures to assess the transformative and empowering potential of the observed discourse.
Pulmonary microbiota intervention alleviates fine particulate matter-induced lung inflammation in broilers
Authors: Zhou Zilin , Shen Dan , Wang Kai , Liu Junze , Li Mingyang , Win-Shwe Tin-Tin , Nagaoka Kentaro , Li Chunmei
Published: July 2023

Fine particulate matter (PM2.5) released during the livestock industry endangers the respiratory health of animals. Our previous findings suggested that broilers exposed to PM2.5 exhibited lung inflammation and changes in the pulmonary microbiome. Therefore, this study was to investigate whether the pulmonary microbiota plays a causal role in the pathogenesis of PM2.5-induced lung inflammation. We first used antibiotics to establish a pulmonary microbiota intervention broiler model, which showed a significantly reduced total bacterial load in the lungs without affecting the microbiota composition or structure. Based on it, 45 AA broilers of similar body weight were randomly assigned to three groups: control (CON), PM2.5 (PM), and pulmonary microbiota intervention (ABX-PM). From 21 d of age, broilers in the ABX-PM group were intratracheally instilled with antibiotics once a day for 3 d. Meanwhile, broilers in the other two groups were simultaneously instilled with sterile saline. On 24 and 26 d of age, broilers in the PM and ABX-PM groups were intratracheally instilled with PM2.5 suspension to induce lung inflammation, and broilers in the CON group were simultaneously instilled with sterile saline. The lung histomorphology, inflammatory cytokines’ expression levels, lung microbiome, and microbial growth conditions were analyzed to determine the effect of the pulmonary microbiota on PM2.5-induced lung inflammation. Broilers in the PM group showed lung histological injury, while broilers in the ABX-PM group had normal lung histomorphology. Furthermore, microbiota intervention significantly reduced mRNA expression levels of interleukin-1β, tumor necrosis factor-α, interleukin-6, interleukin-8, toll-like receptor 4 and nuclear factor kappa-B. PM2.5 induced significant changes in the β diversity and structure of the pulmonary microbiota in the PM group. However, no significant changes in microbiota structure were observed in the ABX-PM group. Moreover, the relative abundance of Enterococcus cecorum in the PM group was significantly higher than that in the CON and ABX-PM groups. And sterile bronchoalveolar lavage fluid from the PM group significantly promoted the growth of E. cecorum, indicating that PM2.5 altered the microbiota’s growth condition. In conclusion, pulmonary microbiota can affect PM2.5-induced lung inflammation in broilers. PM2.5 can alter the bacterial growth environment and promote dysbiosis, potentially exacerbating inflammation.
Bilateral adrenal hemorrhage after pancreaticoduodenectomy
Authors: Andres Sarah , Suchak Nikki , Brady Maureen , Kukar Moshim , Sarkar Joy
Published: July 2023

The incidence of bilateral adrenal hemorrhage (BAH) in the postoperative setting is rare, but potentially life threatening. A literature review of postoperative BAH reveals that there is limited data on BAH following abdominal surgery. We present a case of BAH following pancreaticoduodenectomy, which has not been previously documented in the literature. A 70-year-old male patient with no previous history of adrenal disease underwent an uncomplicated pancreaticoduodenectomy and was discharged after a typical postoperative course. He was readmitted with abdominal pain and ileus on POD 8 and a computed tomography (CT) scan was initially unremarkable, but a repeat CT scan on POD 11 demonstrated BAH. He was found to have adrenal insufficiency and was successfully treated with steroids. Clinicians should be aware of the possibility of adrenal hemorrhage postoperatively as it can potentially be a fatal surgical complication. To enhance patient outcomes, early detection and appropriate treatment are essential.
Maximizing the Potential of Air National Guard International Health Specialists for Global Health Engagement
Authors: Moore David C , Harder Amanda M , Peterson Matthew J , Blum Scott A
Published: July 2023

The Air Force International Health Specialist program provides expert medical and public health support to enhance global health engagement efforts. National Guardsmen possess unique civilian health care expertise to support global health engagement. The DoD must increase support for Air National Guard International Health Specialist involvement, including training and development opportunities.
Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab
Authors: Colombo Nicoletta , Lorusso Domenica , Monk Bradley J , Slomovitz Brian , Hasegawa Kosei , Nogueira-Rodrigues Angélica , Zale Melissa , Okpara Chinyere E , Barresi Gianmaria , McKenzie Jodi , Makker Vicky
Published: July 2023

Background

Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation.

Materials and Methods

In Study-309/KEYNOTE-775, patients received lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). The incidence and median time to the first onset of ARs, dose modifications, and concomitant medications are described. Key ARs characterized include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome.

Results

As expected, the most common any-grade key ARs included: hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Grades 3-4 key ARs with incidence ≥10% included: hypertension, fatigue, and weight decreased. Key ARs first occurred within approximately 3 months of treatment initiation. AR management strategies consistent with the prescribing information and the study protocol are discussed.

Conclusion

Successful AR management strategies for lenvatinib plus pembrolizumab include education of the patient and entire treatment team, preventative measures and close monitoring, and judicious use of dose modifications and concomitant medications.

Clinicaltrials.gov ID

NCT03517449
Quality of Life and Treatment-Related Side Effects in Patients With HR+/HER2− Advanced Breast Cancer: Findings From a Multicountry Survey
Authors: Cardoso Fatima , Rihani Julie , Harmer Victoria , Harbeck Nadia , Casas Ana , Rugo Hope S , Fasching Peter A , Moore Adam , de Courcy Joanna , Pathak Purnima , Haftchenary Sina , Aubel Dawn , Schumacher-Wulf Eva
Published: July 2023

Background

Quality of life (QOL) is a critical factor in decision-making for advanced breast cancer (ABC). There is a need to improve how QOL and treatment-related side effects (SEs) that impact it are clinically assessed. We examined healthcare professionals’ (HCPs’) and patients’ perspectives on the importance of QOL discussions and the impact of SEs on QOL in clinical settings.

Patients and Methods

A cross-sectional online survey was conducted (7/2020-5/2021) among oncologists, nurses, and patients with HR+/HER2− ABC in 7 countries.

Results

The survey was completed by 502 HCPs and 467 patients. Overall, 88% of oncologists and 49% of patients recalled QOL discussions at follow-up. In the first- through fourth-line (1L, 2L, 3L, and 4L) settings, respectively, 48%, 57%, 79%, and 85% of oncologists reported QOL was very important; 73% and 45% of patients receiving 1L and 2L treatment and 40% receiving 3L+ treatment indicated QOL was important. Patients reported that insomnia, anxiety, back pain, fatigue, diarrhea, hot flashes, low sexual interest, and loss of appetite had a moderate/severe impact on QOL. Of patients experiencing certain SEs, ≥64% did not discuss them with HCPs until there was a moderate/severe impact on QOL. In patients receiving a CDK4/6 inhibitor, SEs, including insomnia, diarrhea, back pain, and fatigue, had a moderate/severe impact on QOL.

Conclusions

This survey discovered disconnects between HCPs and patients with ABC on the importance of QOL discussions and the impact of SEs on QOL. These data support the use of ABC-specific QOL questionnaires that closely monitor SEs impacting QOL.