bluuebunny/crossref_metadata_2025 huggingface dataset:
Entrepreneurship and misallocation in production network economies
Authors: Cavalcanti Tiago , Mendes Angelo , Pannella Pierluca
Published: November 2023

This paper investigates how sectoral linkages amplify or diminish misallocation at the intensive and extensive margins. Our analysis is based on a multisector general equilibrium model with input–output linkages, heterogeneous entrepreneurial abilities, and endogenous occupational choice. Distortions affect the intensive use of production inputs and they also impact the agents’ occupational decisions, misallocating the mass and type of entrepreneurs in different sectors of production. When the most distorted sectors are upstream (downstream), input–output linkages amplify (diminish) the loss from entreprenurial misallocation. We calibrate the model to the US and quantify the output losses from sectoral corporate taxes, decomposing the role of networks and the extensive margin decisions. We find that sectoral linkages quadruple the loss from the misallocation of entrepreneurs. We study an entry subsidy program, showing that it should target those sectors whose marginal entrepreneurs suffer larger profit losses, even if they are not necessarily the most distorted.
Arthroscopic biceps tenodesis using press-fit bony plug: a case series study
Authors: Gad Ahmed Mahmoud , Zawam Sherif Hamdy
Published: November 2023

Purpose

To assess the feasibility, operative time, clinical outcomes, possible complications, and failure rates of all-through arthroscopic biceps tenodesis using press-fit bony plug technique.

Methods

This prospective case series study involved 30 skeletally mature patients with long head of biceps pathology (tendinitis after failure of conservative treatment, subluxation, dislocation, or tendon tears). All patients were followed up for 24 months at least.

Results

Twenty-nine patients regained full shoulder and elbow range of motion; one case suffered from reflex sympathetic dystrophy. There was a significant improvement in the constant, ASES, and VAS scores when comparing the pre-operative and post-operative values. The average biceps strength was 96% compared to the opposite healthy side. No cases were complicated by neuro-vascular deficits or failure of the tenodesis.

Conclusion

Press-fit biceps tenodesis is safe and accessible with low economic demands. We recommend this technique to be used more often when addressing patients with long head of biceps pathologies.

Registration data

Registration number: N-1562023.

Registration date: June 2022 “Retrospectively registered”.
Training and external validation of pre-treatment FDG PET-CT-based models for outcome prediction in anal squamous cell carcinoma
Authors: Frood Russell , Mercer Joseph , Brown Peter , Appelt Ane , Mistry Hitesh , Kochhar Rohit , Scarsbrook Andrew
Published: November 2023

Objectives

The incidence of anal squamous cell carcinoma (ASCC) is increasing worldwide, with a significant proportion of patients treated with curative intent having recurrence. The ability to accurately predict progression-free survival (PFS) and overall survival (OS) would allow for development of personalised treatment strategies. The aim of the study was to train and external test radiomic/clinical feature derived time-to-event prediction models.

Methods

Consecutive patients with ASCC treated with curative intent at two large tertiary referral centres with baseline FDG PET-CT were included. Radiomic feature extraction was performed using LIFEx software on the pre-treatment PET-CT. Two distinct predictive models for PFS and OS were trained and tuned at each of the centres, with the best performing models externally tested on the other centres’ patient cohort.

Results

A total of 187 patients were included from centre 1 (mean age 61.6 ± 11.5 years, median follow up 30 months, PFS events = 57/187, OS events = 46/187) and 257 patients were included from centre 2 (mean age 62.6 ± 12.3 years, median follow up 35 months, PFS events = 70/257, OS events = 54/257). The best performing model for PFS and OS was achieved using a Cox regression model based on age and metabolic tumour volume (MTV) with a training c-index of 0.7 and an external testing c-index of 0.7 (standard error = 0.4).

Conclusions

A combination of patient age and MTV has been demonstrated using external validation to have the potential to predict OS and PFS in ASCC patients.

Clinical relevance statement

A Cox regression model using patients’ age and metabolic tumour volume showed good predictive potential for progression-free survival in external testing. The benefits of a previous radiomics model published by our group could not be confirmed on external testing.

Key Points

• A predictive model based on patient age and metabolic tumour volume showed potential to predict overall survival and progression-free survival and was validated on an external test cohort.

• The methodology used to create a predictive model from age and metabolic tumour volume was repeatable using external cohort data.

• The predictive ability of positron emission tomography-computed tomography–derived radiomic features diminished when the influence of metabolic tumour volume was accounted for.
Beyond femininity or masculinity: gender typologies and healthy eating in early adulthood
Authors: González-Pascual Juan Luis , Esteban-Gonzalo Sara , Veiga Óscar Luis , Esteban-Gonzalo Laura
Published: November 2023

Purpose

In the field of health sciences gender is often confused with biological sex (male/female) or reduced to a dichotomous classification (masculinity/femininity). The concepts of sex and gender interact with each other, but they are not equivalent. According to Sandra Bem four gender typologies can be established (androgynous, masculine, feminine and undifferentiated).

A relationship has been shown to exist between gender and health. Yet, there is little evidence as to the relationship between gender typologies and adherence to the Mediterranean diet. The aim of this research is to evaluate the association between Bem’s gender typologies and adherence to the Mediterranean diet.

Methods

Mediterranean Diet Adherence Screener (MEDAS) and Bem’s gender typologies were the main variables. Sex, age, socioeconomic status (SES), body mass index (BMI) and obesity were analyzed as covariates.

Results

Multilevel multivariate analysis showed that androgynous typology was associated with increased adherence to Mediterranean diet (β = 0.46 (SE 0.21), p = 0.033), adjusting by covariates, in a university population in Spain. Moreover, this was not the case with masculinity or femininity typologies.

Conclusion

Thus, the results of this study suggest (1) that androgynous typology is not only associated with better mental health but also with healthy/healthier lifestyles, and (2) the complexity of the relationship between sex-gender and health would advise researchers avoid dichotomies such as male/female or masculinity/femininity.
Does multiple gastric aspirate collection increase sensitivity of M. tuberculosis detection in children with pulmonary tuberculosis?
Authors: Venturini Elisabetta , Bortone Barbara , Cini Gianmaria , Venanzi Jacopo , Pellegrino Roberta , Bartolesi Anna Maria , Vaggelli Guendalina , Trapani Sandra , Indolfi Giuseppe , Bianchi Leila , Montagnani Carlotta , Chiappini Elena , Rossolini Gian Maria , Galli Luisa
Published: November 2023

This study aims to investigate the sensitivity of microscopy, culture and polymerase chain reaction on three gastric aspirates (GAs) in the microbiological confirmation of active pulmonary tuberculosis (TB) and to identify possible changes in sensitivity derived from the collection of a different number of aspirates. Children with clinical and radiological diagnoses of active pulmonary TB who underwent three GAs between March 2007 and June 2019 were retrospectively evaluated. Clinical, radiological, and microbiological data were collected. The sensitivity of microbiological tests on GAs was calculated. Moreover, differences in sensitivity according to age and radiological pattern were investigated. Overall, 156 children with active pulmonary TB were enrolled with a median age of 51.5 (IQR: 25.2–113.2) months. Microbiological investigations on the first GA showed a sensitivity of 34% (95%CI 26.7, 42), the cumulative sensitivity of first and second GAs was 40.4% (95%CI 32.7, 48.5) and of the three GAs was 47.4% (95%CI 39.8, 55.2). The collection of three GAs leads to an overall increase in sensitivity of the first GA by 13.4% (95%CI 2.8, 24.1%; p=0.014). Moreover, the increase in sensitivity was significantly higher in children ≤ 4 years of age and in those with uncomplicated TB (p=0.008).

Conclusions: Performing a higher number of GAs increases the sensitivity of microbiological confirmation of active pulmonary TB, particularly in children ≤ 4 years and with an uncomplicated radiological pattern.

What is known:• The diagnosis of paediatric tuberculosis is a challenge for paediatricians• Despite their low sensitivity gastric aspirates represent the standard sample for microbiological confirmation of active pulmonary tuberculosis in children• Most international guidelines recommend performing three sequential gastric aspirates on three consecutive days

What is new:• A significant increase in global sensitivity by 13.4% was found by the collection of three gastric aspirates compared to the first one• Performing a higher number of gastric aspirates increases the sensitivity of microbiological confirmation, particularly in children ≤ 4 years and with an uncomplicated radiological pattern
Effect of exercise across the head and neck cancer continuum: a systematic review of randomized controlled trials
Authors: Avancini Alice , Borsati Anita , Belluomini Lorenzo , Giannarelli Diana , Nocini Riccardo , Insolda Jessica , Sposito Marco , Schena Federico , Milella Michele , Pilotto Sara
Published: November 2023

Purpose

This study aims to systematically explore the impact of physical exercise as supportive therapy for head and neck cancer.

Methods

A systematic search on PubMed/MEDLINE, Cochrane, and SPORTDiscus was conducted. Randomized controlled trials exploring the effects of a physical exercise intervention in comparison with usual care on outcomes in patients with head and neck cancer were selected. The RoB 2 tool was used to determine the study quality. The extracted data are reported as qualitative synthesis.

Results

Among the 527 records examined, nine studies were included. No trials investigating exercise as prehabilitation were found, whereas eight studies involving 452 patients with head and neck cancer were conducted during anticancer treatment. Most trials did not report improvements in body mass index or body composition, while 2/4 and 3/5 investigations found a significant increase in muscle strength and cardiorespiratory fitness, respectively. Regarding the patients’ reported outcomes, 4 out of 7 studies observed enhancements in some domains of quality of life, and two trials out of 3 detected an amelioration in fatigue following the exercise intervention. Analyzing the exercise programs, it seems that combining aerobic and resistance training could be more beneficial compared to a single type of full-body exercise in counteracting physical decline and controlling symptoms in the anticancer therapy phase. One trial has investigated the effect of resistance exercise on patients who had terminated the anticancer treatments, reporting significant improvements in lean mass, muscle strength, and quality of life.

Conclusion

Exercise may be a promising approach in patients with head and neck cancer. Future studies are needed to consolidate these results.
Accounting for forest fire risks: global insights for climate change mitigation
Authors: Chu Long , Grafton R. Quentin , Nelson Harry
Published: November 2023

Fire is an important risk in global forest loss and contributed 20% to 25% of the global anthropogenic greenhouse gas emissions between 1997 and 2016. Forest fire risks will increase with climate change in some locations, but existing estimates of the costs of using forests for climate mitigation do not yet fully account for these risks or how these risks change inter-temporally. To quantify the importance of forest fire risks, we undertook a global study of individual country fire risks, combining economic datasets and global remote sensing data from 2001 to 2020. Our estimates of forest fire risk premia better account for the risk of forest burning that would be additional to the risk-free and break-even price of credits or offsets to promote carbon sequestration and storage in forests. Our results show the following: (1) forest fire risk premia can be much larger than the historical forest area burned; (2) for some countries, forest fire risk premia have a large impact on the relative country-level break-even price of carbon credits or offsets; (3) a large spatial and inter-temporal heterogeneity of forest fires across countries between 2001 and 2020; and (4) the importance of properly incorporating forest fire risk premia into carbon credits/offset programs. As part of our analysis, and to emphasise the possible sub-national scale differences, our results highlight the heterogeneity in fire risk premia across 10 Canadian provinces.
Relationship between circadian rhythm-related genes and extracellular matrix: implications for sleep deprivation
Authors: Liu Xuejuan , Sun Jia , Ling Zexia , Dong Tong
Published: November 2023

Background

Sleep deprivation (SD) can lead to the development of various pathological disorders. The extracellular matrix (ECM) compositions and circadian rhythm genes are two pivotal variables of SD. However, their relationships remain undefined during SD.

Methods

A mouse SD model was established using a modified multiplatform water environment method. The expression of nerve growth factor (NGF) in mouse hippocampus was detected by an immunofluorescence (IF) method. Protein expression was assessed by western blot, and mRNA analysis was performed by quantitative real-time PCR (qRT-PCR). The differentially expressed genes after SD, the genes associated with stromal score, and gene expression correlation were analyzed by bioinformatic analysis.

Results

The mouse model of SD was successfully established, as evidenced by the changed morphology, increased Bax and NGF levels, and downregulated Bcl-2 in mouse hippocampus after SD. The differentially expressed genes after SD were closely associated with the ECM compositions. The ECM composition metalloproteinase 9 (MMP9) was under-expressed in mouse hippocampus after SD. The hippocampal MMP9 expression was correlated with the expression levels of circadian genes PER2, PER3, TIMELESS, FBXL3, and NFIL3. PER2 and TIMELESS were upregulated in mouse hippocampus after SD.

Conclusion

The current findings suggest a correlation between ECM composition MMP9 and circadian rhythm-related genes PER2 and TIMELESS in mouse hippocampus after SD, providing a novel understanding of the disorders after SD.
SIGAA: signaling automated analysis: a new tool for Ca2+ signaling quantification using ratiometric Ca2+ dyes
Authors: Lopes Rafael Faria , Gonçalves-Ribeiro Joana , Sebastião Ana M. , Meneses Carlos , Vaz Sandra H.
Published: November 2023

Astrocytes are non-neural cells, restricted to the brain and spinal cord, whose functions and morphology depend on their location. Astrocyte–astrocyte and astrocyte–neuron interactions occur through cytoplasmic Ca2+ level changes that are assessed to determine cell function and response (i.e., drug testing). The evaluation of alterations in intracellular Ca2+ levels primarily relies on fluorescence imaging techniques, performed through video recording of cells incubated with Ca2+-sensitive dyes. By observing ion concentration shifts over time in a delimited region of interest (ROI) encompassing a single cell, it is possible to draw conclusions on cell responses to specific stimuli. Our work describes a tool named SIGAA—signaling automated analysis, for astrocyte ROI-based fluorescent imaging. This tool is specifically tailored for two wavelengths excited dyes by using two inputs of Ca2+ signaling recorded frames/videos and outputting a set of features relevant to the experiment’s conclusions and cell characterization. SIGAA performs automatic drift correction for the two recorded videos with a template matching algorithm, followed by astrocyte identification (ROI) using morphological reconstruction techniques. Subsequently, SIGAA extracts intracellular Ca2+ evolution functions for all identified ROIs detects function transients, and estimates a set of features for each signal. These features closely resemble those obtained through traditional methods and software used thus far. SIGAA is a new fully automated tool, which can speed up hour-long studies and analysis to a few minutes, showing reliable results as the validity tests indicate.
Numerical modeling of vadose zone electrical resistivity to evaluate its hydraulic parameters
Authors: Masria Ali , Seif Ahmed Khaled , Ghareeb Mohamed , Abd-Elmaboud Mahmoud E. , Soliman Karim , Ammar A. I.
Published: November 2023

Studying and determining the physical properties and hydraulic parameters of vadose zone sediments is an important key to evaluate the infiltration rate into them and assessing the extent to which aquifer sediments benefit from rainwater harvesting in arid and semi-arid areas. Due to the lack of sufficient data on the characteristics of this zone depths, a numerical modeling was used to simulate the electrical resistivity of these sediments by applying the electrical resistivity method, because it is the most affected by the physical properties of dry and wet sediments. This study was applied as a proposal for application in northwestern KSA to calculate the vertical hydraulic conductivity and transmissivity for the vadose zone. This was implemented by assuming a three-layer model using COMSOL Multiphysics model with different electrical resistivity values depending on some in situ electrical resistivity measurements for shallow depths. Hence, the infiltration rate of sediments in this area can be predicted with depth and its effect on aquifer recharge. The focus was on calculating the vertical hydraulic parameters of the most widespread surface sediments with depth and comparing the results of calculating these parameters for some sediments laboratory-wise to ensure their accuracy. Then, their infiltration rate was inferred separately with depth, predicting their ability to aquifer recharge and make the most of rainwater harvesting. Finally, this study can be considered as a preliminary study to determine the expected forward model of electrical resistivity and hydraulic parameters values for the vadose zone sediments with depth along the area and in any other areas, and then apply them accurately in situ to estimate the extent of its usefulness in rainwater harvesting, especially aquifer recharge.
Spatiotemporal trends of urban-induced land use and land cover change and implications on catchment surface imperviousness
Authors: Andualem Tesfa Gebrie , Peters Stefan , Hewa Guna A. , Boland John , Myers Baden R.
Published: November 2023

Urbanization, changes in land use and land cover (LULC), and an increase in population collectively have significant impacts on urban catchments. However, a vast majority of LULC studies have been conducted using readily available satellite imagery, which often presents limitations due to its coarse spatial resolution. Such imagery fails to accurately depict the surface characteristics and diverse spectrum of LULC classifications contained within a single pixel. This study focused on the highly urbanized Dry Creek catchment in Adelaide, South Australia and aimed to determine the impact of urbanization on spatiotemporal changes in LULC and its implications for the land surface condition of the catchment. Very high spatial resolution imagery was utilized to examine changes in LULC over the past four decades. Support Vector Machine-learning-based image classification was utilized to classify and identify the changes in LULC over the study area. The classification accuracy showed strong agreement, with a kappa value greater than 0.8. The findings of this analysis showed that extensive urban development, which expanded the built-up area by 34 km2, were responsible for the decline in grass cover by 43.1 km2over the last 40 years (1979–2019). Moreover, built-up areas, plantation, and water features, in contrast to grass cover, have demonstrated an increasing trend during the study period. The overall urban expansion over the study period was 136.6%. Urbanization intensified impervious area coverage, increasing the runoff coefficient, equivalent impervious area, and curve number by 60.6%, 60.6%, and 7.9%, respectively, while decreasing the retention capacity by 38.6%. These modifications suggest a potential variability in catchment surface runoff, prompting the need for further research to understand the surface runoff changes brought by the changes in LULC resulting from urbanization. The findings of this study can be used for land use planning and flood management.
Cancer/testis-45A1 promotes cervical cancer cell tumorigenesis and drug resistance by activating oncogenic SRC and downstream signaling pathways
Authors: Meng Mei , Guo Yan , Chen Yu , Li Xu , Zhang Bin , Xie Zhijia , Liu Juntao , Zhao Zhe , Liu Yuxi , Zhang Tong , Qiao Yingnan , Shang Bingxue , Zhou Quansheng
Published: November 2023

Background

Cancer/testis antigen-45A1 (CT45A1) is overexpressed in various types of cancer but is not expressed in healthy women. The role of CT45A1 in cervical cancer has not yet been described in the literature.

Purpose

The aim of this research was to study the role of CT45A1 in cervical cancer progression and drug resistance, elucidate the mechanisms underlying CT45A1-mediated tumorigenesis and investigate CT45A1 as a biomarker for cervical cancer diagnosis, prognostic prediction, and targeted therapy.

Methods

The CT45A1 levels in the tumors from cervical cancer patients were measured using immunohistochemical staining. The role and mechanisms underlying CT45A1-mediated cervical cancer cell tumor growth, invasion, and drug resistance were studied using xenograft mice, cervical cancer cells, immunohistochemistry, RNA-seq, real-time qPCR, Chromatin immunoprecipitation and Western blotting.

Results

CT45A1 levels were notably high in the tumor tissues of human cervical cancer patients compared to the paracancerous tissues (p < 0.001). Overexpression of CT45A1 was closely associated with poor prognosis in cervical cancer patients. CT45A1 promoted cervical cancer cell tumor growth, invasion, neovascularization, and drug resistance. Mechanistically, CT45A1 promoted the expression of 128 pro-tumorigenic genes and concurrently activated key signaling pathways, including the oncogenic SRC, ERK, CREB, and YAP/TAZ signaling pathways. Furthermore, CT45A1-mediated tumorigenesis and drug resistance were markedly inhibited by the small molecule lycorine.

Conclusion

CT45A1 promotes cervical cancer cell tumorigenesis, neovascularization, and drug resistance by activating oncogenic SRC and downstream tumorigenic signaling pathways. These findings provide new insight into the pathogenesis of cervical cancer and offer a new platform for the development of novel therapeutics against cervical cancer.
Osteoporosis and major fragility fractures (MOF) in sarcoidosis patients: association with disease severity
Authors: Caffarelli Carla , Cameli Paolo , Al Refaie Antonella , Mondillo Caterina , Versienti Alessandro , Manasse Giuditta , Bargagli Elena , Gonnelli Stefano
Published: November 2023

Background

The reports on bone mineral loss or major osteoporosis fracture (MOF) in sarcoidosis are scarce and have conflicting outcomes. This study aimed to evaluate the prevalence and risk factors of MOF in sarcoidosis patients.

Methods

In a single-center cohort of 382 patients with sarcoidosis (55.8 ± 11.6 years) we evaluated bone mineral density at lumbar spine, at femoral neck and at total hip and the presence of MOF. Lung function measurements including diffusion capacity for carbon monoxide (DLCO) were assessed. Chest X-rays were performed and radiological staging was done by Scadding score.

Results

Ninety patients (23.6%) with sarcoidosis have history of a MOF. BMD T-scores were lower in sarcoidosis with MOF with respect to those without MOF, but the difference was statistically significant only for BMD at femoral neck (p < 0.05). Moreover, BMD values at total hip was positively correlated with DLCO (%) (p < 0.001). Prevalence of MOF was higher in patients with sarcoidosis with lung parenchymal involvement (radiological stages 2–4) than in patients with sarcoidosis in chest X-ray stages 0 and 1 (28.3 vs 19.2% respectively, p < 0.05). Moreover, multiple regression analyses showed that X-ray Scadding score was positively associated with MOF.

Conclusions

This study shows that MOF represent a common and important complication in patients with moderate/severe sarcoidosis. The chest X-ray evaluation and the pulmonary function test could allow to define the risk of MOF in sarcoidosis patients.
Taking embodiment seriously in public policy and practice: adopting a procedural approach to health and welfare
Authors: Roberts Joseph T F
Published: November 2023

It is a common refrain amongst phenomenologists, disability theorists, and feminist legal theorists that medical practice pays insufficient attention to people’s embodiment. The complaint that we take insufficient account of people’s embodiment isn’t limited to the clinical interaction. It has also been directed at healthcare regulation and welfare policy. In this paper, I examine the arguments for taking embodiment seriously in both medical practice and welfare policy, concluding we have good reasons to take better account of people’s embodiment. I then set out two challenges to taking embodiment seriously in public policy. First, given the amount of variation in how people are embodied, there is strong possibility that adjusting policy to benefit particular individuals based on an appreciation of their embodied experiences could be detrimental towards other individuals. The second challenge concerns how to ensure that people’s testimony about their first-person embodied experience is subject to adequate scrutiny without this resulting in epistemic injustice. I argue that the solution to both of these challenges is to devise a just procedure for soliciting people’s testimony and taking it into account in the policy development process. As such, I also provide an outline of what a just procedure should look like.
Simulation study of hydrogen sulfide removal in underground gas storage converted from the multilayered sour gas field
Authors: Yang Yi , Li Longxin , Wang Xia , Qin Nan , Zhang Ruihan , Zhao Yulong , Tian Ye
Published: November 2023

A simulation study was carried out to investigate the temporal evolution of H2S in the Huangcaoxia underground gas storage (UGS), which is converted from a depleted sulfur-containing gas field. Based on the rock and fluid properties of the Huangcaoxia gas field, a multilayered model was built. The upper layer Jia-2 contains a high concentration of H2S (27.2 g/m3), and the lower layer Jia-1 contains a low concentration of H2S (14.0 mg/m3). There is also a low-permeability interlayer between Jia-1 and Jia-2. The multi-component fluid characterizations for Jia-1 and Jia-2 were implemented separately using the Peng-Robinson equation of state in order to perform the compositional simulation. The H2S concentration gradually increased in a single cycle and peaked at the end of the production season. The peak H2S concentration in each cycle showed a decreasing trend when the recovery factor (RF) of the gas field was lower than 70%. When the RF was above 70%, the peak H2S concentration increased first and then decreased. A higher reservoir RF, a higher maximum working pressure, and a higher working gas ratio will lead to a higher H2S removal efficiency. Similar to developing multi-layered petroleum fields, the operation of multilayered gas storage can also be divided into multi-layer commingled operation and independent operation for different layers. When the two layers are combined to build the storage, the sweet gas produced from Jia-1 can spontaneously mix with the sour gas produced from Jia-2 within the wellbore, which can significantly reduce the overall H2S concentration in the wellstream. When the working gas volume is set constant, the allocation ratio between the two layers has little effect on the H2S removal. After nine cycles, the produced gas’s H2S concentration can be lowered to 20 mg/m3. Our study recommends combining the Jia-2 and Jia-1 layers to build the Huangcaoxia underground gas storage. This plan can quickly reduce the H2S concentration of the produced gas to 20 mg/m3, thus meeting the gas export standards as well as the HSE (Health, Safety, and Environment) requirements in the field. This study helps the engineers understand the H2S removal for sulfur-containing UGS as well as provides technical guidelines for converting other multilayered sour gas fields into underground storage sites.
Shinmi (親身): a Distinctive Japanese Medical Virtue?
Authors: Ozeki-Hayashi Reina , Wilkinson Dominic J. C.
Published: November 2023

In Western countries, the ideal professional and ethical attributes of healthcare providers and the ideal patient-doctor relationship have been analysed in detail. Other cultures, however, may have different norms, arising in response to diverse healthcare needs, cultural values and offering alternative perspectives. In this paper, drawing a case study, we introduce the concept of Shinmi, used in Japan to describe a desirable approach to medical care. Shinmi means kind or cordial in Japanese. In the medical context, it refers to doctors treating patients with a degree of emotional closeness as if they were the doctors’ own family. We analyse the concept of Shinmi, drawing on virtue ethics. We distinguish two different elements to a Shinmi-na attitude. As illustrated in our example, excessive Shinmi can be problematic for patients and doctors. Furthermore, elements of Shinmi may conflict with existing Western values (for example, norms that encourage emotional detachment and discourage doctors’ treatment of family members). However, if pursued appropriately, we argue that a balanced Shinmi-na approach can be conducive to the goals of medicine. The concept of Shinmi may be valuable for medical students, in Japanese and potentially other health care systems, and help them to cultivate a virtuous approach to meeting the emotional needs of patients.
Rivers Are Warming Up and Losing Oxygen
Authors: Cutts Elise
Published: November 2023

Researchers used deep learning to fill in the gaps of “patchy” water quality data, revealing decades-long trends toward warmer and less oxygenated rivers that could have worrisome consequences.
Rapid white matter changes in children with conduct problems during a parenting intervention
Authors: O’ Brien Suzanne , Sethi Arjun , Blair James , Viding Essi , Beyh Ahmad , Mehta Mitul A. , Dallyn Robert , Ecker Christine , Petrinovic Marija M. , Doolan Moira , Blackwood Nigel , Catani Marco , Murphy Declan G. M. , Scott Stephen , Craig Michael C.
Published: November 2023

Studies report that the microstructural integrity of the uncinate fasciculus (UF; connecting the anterior temporal lobe to the orbitofrontal cortex) is abnormal in adults with psychopathy and children with conduct problems (CP), especially those with high callous-unemotional (CU) traits. However, it is unknown if these abnormalities are ‘fixed’ or ‘reversible’. Therefore, we tested the hypothesis that a reduction in CP symptoms, following a parenting intervention, would be associated with altered microstructural integrity in the UF. Using diffusion tensor imaging tractography we studied microstructural differences (mean diffusivity (MD) and radial diffusivity (RD)) in the UF of 43 typically developing (TD) and 67 boys with CP before and after a 14-week parenting intervention. We also assessed whether clinical response in CP symptoms or CU traits explained changes in microstructure following the intervention. Prior to intervention, measures of MD and RD in the UF were increased in CP compared to TD boys. Following intervention, we found that the CP group had a significant reduction in RD and MD. Further, these microstructural changes were driven by the group of children whose CU traits improved (but not CP symptoms as hypothesized). No significant microstructural changes were observed in the TD group. Our findings suggest, for the first time, that microstructural abnormalities in the brains of children with CP may be reversible following parenting intervention.
ADRB2 inhibition combined with antioxidant treatment alleviates lung fibrosis by attenuating TGFβ/SMAD signaling in lung fibroblasts
Authors: Wan Ruyan , Wang Lan , Duan Yudi , Zhu Miaomiao , Li Wenwen , Zhao Mengxia , Yuan Hongmei , Xu Kai , Li Zhongzheng , Zhang Xiao , Yu Guoying
Published: November 2023

Idiopathic pulmonary fibrosis is a progressive and fatal interstitial lung disease with a poor prognosis and limited therapeutic options, which is characterized by aberrant myofibroblast activation and pathological remodeling of the extracellular matrix, while the mechanism remains elusive. In the present investigation, we observed a reduction in ADRB2 expression within both IPF and bleomycin-induced fibrotic lung samples, as well as in fibroblasts treated with TGF-β1. ADRB2 inhibition blunted bleomycin-induced lung fibrosis. Blockage of the ADRB2 suppressed proliferation, migration, and invasion and attenuated TGF-β1-induced fibroblast activation. Conversely, the enhancement of ADRB2 expression or functionality proved capable of inducing fibroblast-to-myofibroblast differentiation. Subsequent mechanistic investigation revealed that inhibition of ADRB2 suppressed the activation of SMAD2/3 in lung fibroblasts and increased phos-SMAD2/3 proteasome degradation, and vice versa. Finally, ADRB2 inhibition combined with antioxidants showed increased efficacy in the therapy of bleomycin-induced lung fibrosis. In short, these data indicate that ADRB2 is involved in lung fibroblast differentiation, and targeting ADRB2 could emerge as a promising and innovative therapeutic approach for pulmonary fibrosis.
Spatial transcriptomics reveals unique gene expression changes in different brain regions after sleep deprivation
Authors: Vanrobaeys Yann , Peterson Zeru J. , Walsh Emily. N. , Chatterjee Snehajyoti , Lin Li-Chun , Lyons Lisa C. , Nickl-Jockschat Thomas , Abel Ted
Published: November 2023

Sleep deprivation has far-reaching consequences on the brain and behavior, impacting memory, attention, and metabolism. Previous research has focused on gene expression changes in individual brain regions, such as the hippocampus or cortex. Therefore, it is unclear how uniformly or heterogeneously sleep loss affects the brain. Here, we use spatial transcriptomics to define the impact of a brief period of sleep deprivation across the brain in male mice. We find that sleep deprivation induced pronounced differences in gene expression across the brain, with the greatest changes in the hippocampus, neocortex, hypothalamus, and thalamus. Both the differentially expressed genes and the direction of regulation differed markedly across regions. Importantly, we developed bioinformatic tools to register tissue sections and gene expression data into a common anatomical space, allowing a brain-wide comparison of gene expression patterns between samples. Our results suggest that distinct molecular mechanisms acting in discrete brain regions underlie the biological effects of sleep deprivation.
c-Myc uses Cul4b to preserve genome integrity and promote antiviral CD8+ T cell immunity
Authors: Dar Asif A. , Kim Dale D. , Gordon Scott M. , Klinzing Kathleen , Rosen Siera , Guha Ipsita , Porter Nadia , Ortega Yohaniz , Forsyth Katherine S. , Roof Jennifer , Fazelinia Hossein , Spruce Lynn A. , Eisenlohr Laurence C. , Behrens Edward M. , Oliver Paula M.
Published: November 2023

During infection, virus-specific CD8+ T cells undergo rapid bursts of proliferation and differentiate into effector cells that kill virus-infected cells and reduce viral load. This rapid clonal expansion can put T cells at significant risk for replication-induced DNA damage. Here, we find that c-Myc links CD8+ T cell expansion to DNA damage response pathways though the E3 ubiquitin ligase, Cullin 4b (Cul4b). Following activation, c-Myc increases the levels of Cul4b and other members of the Cullin RING Ligase 4 (CRL4) complex. Despite expressing c-Myc at high levels, Cul4b-deficient CD8+ T cells do not expand and clear the Armstrong strain of lymphocytic choriomeningitis virus (LCMV) in vivo. Cul4b-deficient CD8+ T cells accrue DNA damage and succumb to proliferative catastrophe early after antigen encounter. Mechanistically, Cul4b knockout induces an accumulation of p21 and Cyclin E2, resulting in replication stress. Our data show that c-Myc supports cell proliferation by maintaining genome stability via Cul4b, thereby directly coupling these two interdependent pathways. These data clarify how CD8+ T cells use c-Myc and Cul4b to sustain their potential for extraordinary population expansion, longevity and antiviral responses.
Cell volume controlled by LRRC8A-formed volume-regulated anion channels fine-tunes T cell activation and function
Authors: Wang Yuman , Sun Zaiqiao , Ping Jieming , Tang Jianlong , He Boxiao , Chang Teding , Zhou Qian , Yuan Shijie , Tang Zhaohui , Li Xin , Lu Yan , He Ran , He Ximiao , Liu Zheng , Yin Lei , Wu Ning
Published: November 2023

Biosynthesis drives the cell volume increase during T cell activation. However, the contribution of cell volume regulation in TCR signaling during T lymphoblast formation and its underlying mechanisms remain unclear. Here we show that cell volume regulation is required for optimal T cell activation. Inhibition of VRACs (volume-regulated anion channels) and deletion of leucine-rich repeat-containing protein 8A (LRRC8A) channel components impair T cell activation and function, particularly under weak TCR stimulation. Additionally, LRRC8A has distinct influences on mRNA transcriptional profiles, indicating the prominent effects of cell volume regulation for T cell functions. Moreover, cell volume regulation via LRRC8A controls T cell-mediated antiviral immunity and shapes the TCR repertoire in the thymus. Mechanistically, LRRC8A governs stringent cell volume increase via regulated volume decrease (RVD) during T cell blast formation to keep the TCR signaling molecules at an adequate density. Together, our results show a further layer of T cell activation regulation that LRRC8A functions as a cell volume controlling “valve” to facilitate T cell activation.
Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs
Authors: Rosso Ilaria , Jones-Weinert Corey , Rossiello Francesca , Cabrini Matteo , Brambillasca Silvia , Munoz-Sagredo Leonel , Lavagnino Zeno , Martini Emanuele , Tedone Enzo , Garre’ Massimiliano , Aguado Julio , Parazzoli Dario , Mione Marina , Shay Jerry W. , Mercurio Ciro , d’Adda di Fagagna Fabrizio
Published: November 2023

Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism activated in ~10–15% of cancers, characterized by telomeric damage. Telomeric damage-induced long non-coding RNAs (dilncRNAs) are transcribed at dysfunctional telomeres and contribute to telomeric DNA damage response (DDR) activation and repair. Here we observed that telomeric dilncRNAs are preferentially elevated in ALT cells. Inhibition of C-rich (teloC) dilncRNAs with antisense oligonucleotides leads to DNA replication stress responses, increased genomic instability, and apoptosis induction selectively in ALT cells. Cell death is dependent on DNA replication and is increased by DNA replication stress. Mechanistically, teloC dilncRNA inhibition reduces RAD51 and 53BP1 recruitment to telomeres, boosts the engagement of BIR machinery, and increases C-circles and telomeric sister chromatid exchanges, without increasing telomeric non-S phase synthesis. These results indicate that teloC dilncRNA is necessary for a coordinated recruitment of DDR factors to ALT telomeres and it is essential for ALT cancer cells survival.
Metal-free photoanodes for C–H functionalization
Authors: Zhang Junfang , Zhu Yuntao , Njel Christian , Liu Yuxin , Dallabernardina Pietro , Stevens Molly M. , Seeberger Peter H. , Savateev Oleksandr , Loeffler Felix F.
Published: November 2023

Organic semiconductors, such as carbon nitride, when employed as powders, show attractive photocatalytic properties, but their photoelectrochemical performance suffers from low charge transport capability, charge carrier recombination, and self-oxidation. High film-substrate affinity and well-designed heterojunction structures may address these issues, achieved through advanced film generation techniques. Here, we introduce a spin coating pretreatment of a conductive substrate with a multipurpose polymer and a supramolecular precursor, followed by chemical vapor deposition for the synthesis of dual-layer carbon nitride photoelectrodes. These photoelectrodes are composed of a porous microtubular top layer and an interlayer between the porous film and the conductive substrate. The polymer improves the polymerization degree of carbon nitride and introduces C-C bonds to increase its electrical conductivity. These carbon nitride photoelectrodes exhibit state-of-the-art photoelectrochemical performance and achieve high yield in C-H functionalization. This carbon nitride photoelectrode synthesis strategy may be readily adapted to other reported processes to optimize their performance.
The ultra-thin, minimally invasive surface electrode array NeuroWeb for probing neural activity
Authors: Lee Jung Min , Pyo Young-Woo , Kim Yeon Jun , Hong Jin Hee , Jo Yonghyeon , Choi Wonshik , Lin Dingchang , Park Hong-Gyu
Published: November 2023

Electrophysiological recording technologies can provide valuable insights into the functioning of the central and peripheral nervous systems. Surface electrode arrays made of soft materials or implantable multi-electrode arrays with high electrode density have been widely utilized as neural probes. However, neither of these probe types can simultaneously achieve minimal invasiveness and robust neural signal detection. Here, we present an ultra-thin, minimally invasive neural probe (the “NeuroWeb”) consisting of hexagonal boron nitride and graphene, which leverages the strengths of both surface electrode array and implantable multi-electrode array. The NeuroWeb open lattice structure with a total thickness of 100 nm demonstrates high flexibility and strong adhesion, establishing a conformal and tight interface with the uneven mouse brain surface. In vivo electrophysiological recordings show that NeuroWeb detects stable single-unit activity of neurons with high signal-to-noise ratios. Furthermore, we investigate neural interactions between the somatosensory cortex and the cerebellum using transparent dual NeuroWebs and optical stimulation, and measure the times of neural signal transmission between the brain regions depending on the pathway. Therefore, NeuroWeb can be expected to pave the way for understanding complex brain networks with optical and electrophysiological mapping of the brain.
A computational model for structural dynamics and reconfiguration of DNA assemblies
Authors: Lee Jae Young , Koh Heeyuen , Kim Do-Nyun
Published: November 2023

Recent advances in constructing a structured DNA assembly whose configuration can be dynamically changed in response to external stimuli have demanded the development of an efficient computational modeling approach to expedite its design process. Here, we present a computational framework capable of analyzing both equilibrium and non-equilibrium dynamics of structured DNA assemblies at the molecular level. The framework employs Langevin dynamics with structural and hydrodynamic finite element models that describe mechanical, electrostatic, base stacking, and hydrodynamic interactions. Equilibrium dynamic analysis for various problems confirms the solution accuracy at a near-atomic resolution, comparable to molecular dynamics simulations and experimental measurements. Furthermore, our model successfully simulates a long-time-scale close-to-open-to-close dynamic reconfiguration of the switch structure in response to changes in ion concentration. We expect that the proposed model will offer a versatile way of designing responsive and reconfigurable DNA machines.
Petal size is controlled by the MYB73/TPL/HDA19-miR159-CKX6 module regulating cytokinin catabolism in Rosa hybrida
Authors: Jing Weikun , Gong Feifei , Liu Guoqin , Deng Yinglong , Liu Jiaqi , Yang Wenjing , Sun Xiaoming , Li Yonghong , Gao Junping , Zhou Xiaofeng , Ma Nan
Published: November 2023

The size of plant lateral organs is determined by well-coordinated cell proliferation and cell expansion. Here, we report that miR159, an evolutionarily conserved microRNA, plays an essential role in regulating cell division in rose (Rosa hybrida) petals by modulating cytokinin catabolism. We uncover that Cytokinin Oxidase/Dehydrogenase6 (CKX6) is a target of miR159 in petals. Knocking down miR159 levels results in the accumulation of CKX6 transcripts and earlier cytokinin clearance, leading to a shortened cell division period and smaller petals. Conversely, knocking down CKX6 causes cytokinin accumulation and a prolonged developmental cell division period, mimicking the effects of exogenous cytokinin application. MYB73, a R2R3-type MYB transcription repressor, recruits a co-repressor (TOPLESS) and a histone deacetylase (HDA19) to form a suppression complex, which regulates MIR159 expression by modulating histone H3 lysine 9 acetylation levels at the MIR159 promoter. Our work sheds light on mechanisms for ensuring the correct timing of the exit from the cell division phase and thus organ size regulation by controlling cytokinin catabolism.
Inulin-enriched Megamonas funiformis ameliorates metabolic dysfunction-associated fatty liver disease by producing propionic acid
Authors: Yang Xinyue , Zhang Meihong , Liu Yan , Wei Fuxiao , Li Xin , Feng Yuqing , Jin Xiaolu , Liu Dan , Guo Yuming , Hu Yongfei
Published: November 2023

Accumulated evidence supports the beneficial role of inulin in alleviating metabolic dysfunction-associated fatty liver disease (MAFLD) by modulating gut microbiota. However, the underlying mechanisms are not fully understood. Here we used high-fat diet (HFD)-induced laying hen model of MAFLD to investigate the effect of inulin on ameliorating MAFLD and found that the inulin-enriched Megamonas genus was inversely correlated with hepatic steatosis-related parameters. Oral administration of a newly isolated commensal bacterium by culturomics, M. funiformis CML154, to HFD-fed hens and mice ameliorated MAFLD, changed liver gene expression profiles, and increased intestinal propionate concentration. Further evidence demonstrated that the anti-MAFLD effect of M. funiformis CML154 is attributed to propionate-mediated activation of the APN-AMPK-PPARα signaling pathway, thereby inhibiting fatty acid de novo synthesis and promoting β-oxidation. These findings establish the causal relationships among inulin, M. funiformis, and MAFLD, and suggest that M. funiformis CML154 is a probiotic candidate for preventative or therapeutic intervention of MAFLD.