bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between intimate partner violence and leukocyte telomere length: a retrospective cohort study of 144 049 UK Biobank participants
Authors: Chan Ko Ling , Lo Camilla K. M. , Chen Xiao-Yan , Ip Patrick , Leung Wing Cheong , Shiels Paul G. , Pell Jill P. , Minnis Helen , Ho Frederick K.
Published: April 2023

Aims

Intimate partner violence (IPV) is a public health challenge negatively affecting victims’ health. Telomere length (TL), a marker for biological ageing, might be reflective of the mechanisms through which IPV leads to adverse health outcomes. The objective of the current study was to explore the association between IPV and leucocyte TL.

Methods

We conducted an analysis using a subset of the UK Biobank (N = 144 049). Physical, sexual and emotional IPV were reported by the participants. DNA was extracted from peripheral blood leukocytes. TL was assayed by quantitative polymerase chain reaction. We used multivariable linear regressions to test the associations between IPV and TL adjusted for age, sex, ethnicity, deprivation, education, as well as symptoms of depression and post-traumatic stress disorder in a sensitivity analysis.

Results

After adjusting for sociodemographic factors, any IPV was associated with 0.02-s.d. shorter TL (β = −0.02, 95% CI −0.04 to −0.01). Of the three types of IPV, physical violence had a marginally stronger association (β = −0.05, 95% CI −0.07 to −0.02) than the other two types. The associations of numbers of IPV and TL showed a dose–response pattern whereby those who experienced all three types of IPV types had the shortest TL (β = −0.07, 95% CI −0.12 to −0.03), followed by those who experienced two types (β = −0.04, 95% CI −0.07 to −0.01). Following additional adjustment for symptoms of depression and PTSD, the associations were slightly attenuated but the general trend by number of IPVs remained.

Conclusions

Victims of IPV, particularly those exposed to multiple types of IPVs, had shorter TL indicative of accelerated biological ageing. Given that all three types of IPV are linked to TL, clinical practitioners need to comprehensively identify all types of IPV and those who received multiple types. Further studies should explore the association of violence with changes in TL over time, as well as to which extent biological ageing is a mechanistic factor.
Terrestrial Heat Flow Variation With Depth Caused by Anomalously High Radiogenic Heat Production
Authors: Wang Yibo , Furlong Kevin , Fuchs Sven , He Lijuan , Hu Shengbiao
Published: April 2023

Surface Heat flow (HF) can be calculated from the accumulation of radiogenic heat production (RHP) of arbitrarily subdivided thin layers of the crust and the residual HF. However, geothermal studies of scientific drilling projects around the world do not have clear vertical correspondence between HF and RHP, which has created a great controversy for the relationship between the two. For the first time, continuous temperature data, thermal conductivity and RHP measurements from the 3,008‐m‐deep Lujiang‐Zongyang Scientific Drilling in the northeastern Yangtze Craton, demonstrate that the abnormal HF is determined by high RHP rock (mean value, 10 μW/m3). The detailed spatial‐temporal study of magmatic activity in the Lujiang‐Zongyang basin shows the high RHP rock are concentrated in the early syenite‐monzonite period (133–131 Ma) in the northern basin. Two enrichment processes caused by late Neoproterozoic and Mesozoic subduction contribute to the formation.
Improving E3SM Land Model Photosynthesis Parameterization via Satellite SIF, Machine Learning, and Surrogate Modeling
Authors: Chen Anping , Ricciuto Daniel , Mao Jiafu , Wang Jiawei , Lu Dan , Meng Fandong
Published: April 2023

The parameterization of key photosynthesis parameters is one of the key uncertain sources in modeling ecosystem gross primary productivity (GPP). Solar‐induced chlorophyll fluorescence (SIF) offers a good proxy for GPP since it marks the actual process of photosynthesis; while machine learning (ML) provides a robust approach to model the GPP‐SIF relationship. Here, we trained the boosted regressing tree (BRT) and the Random Forest ML models with Greenhouse Gases Observing Satellite SIF data and in situ GPP observations from 49 eddy covariance towers. These trained ML GPP‐SIF models were fed into the Energy Exascale Earth System Model (E3SM) Land Model (ELM) to generate ELM‐simulated global SIF estimates, which were then benchmarked against satellite SIF observations with a surrogate modeling approach. Our results indicated good modeling performance of the ML‐based GPP‐SIF relationship. The ELM model when fed with the ML GPP‐SIF models also can well predict the spatial‐temporal variations in SIF. We also found high model accuracy for the surrogate modeling. Model parameter sensitivity analysis suggested that the fraction of leaf nitrogen in RuBisCO (flnr) is the most sensitive parameter to the SIF; other sensitive parameters include the Ball‐Berry stomatal conductance slope (mbbopt) and the vcmax entropy (vcmaxse). The posterior uncertainty in simulated GPP was greatly reduced after benchmarking, and the model produced improved spatial patterns of mean GPP relative to FLUXCOM GPP. Our integrated approach provides a new avenue for improving land models and using remote‐sensing SIF, which can be further improved in the future with more ground‐ and satellite‐based observations.
Tropical Forcing of Barents‐Kara Sea Ice During Autumn
Authors: Warner James L. , Screen James A. , Scaife Adam A. , Maidens Anna , Knight Jeff
Published: April 2023

The causality of the link between Autumn Barents‐Kara (BK) sea ice and the winter North Atlantic Oscillation (NAO) is uncertain, given teleconnections stemming from the tropics may influence both the extra‐tropics and the Arctic. We explore the relationship between tropical rainfall and BK sea ice in autumn, by nudging the tropics to follow observed variability in otherwise free running ensemble simulations. Tropical forcing alone can skillfully reproduce a significant fraction of observed interannual NAO variability in late autumn. We also show that interannual variability in the NAO is strongly related to simulated BK sea ice. As a result, we are able to reproduce some of the observed link between tropical rainfall and autumn BK sea ice. However, only during the strong 1997 El Niño are clear tropical influences at high latitudes found. Large ensembles and strong tropical forcing are required to detect tropical forced variability in models at high latitudes.
Blocking the CD47-SIRPα interaction reverses the disease phenotype in a polycythemia vera mouse model
Authors: Lysenko Veronika , Schürch Patrick M. , Tuzlak Selma , van Wijk Nicole Wildner-Verhey , Kovtonyuk Larisa V. , Becher Burkhard , Manz Markus G. , Kreutmair Stefanie , Theocharides Alexandre P. A.
Published: April 2023

Polycythemia vera (PV) is a hematopoietic stem cell neoplasm driven by somatic mutations in JAK2, leading to increased red blood cell (RBC) production uncoupled from mechanisms that regulate physiological erythropoiesis. At steady-state, bone marrow macrophages promote erythroid maturation, whereas splenic macrophages phagocytose aged or damaged RBCs. The binding of the anti-phagocytic (“don’t eat me”) CD47 ligand expressed on RBCs to the SIRPα receptor on macrophages inhibits phagocytic activity protecting RBCs from phagocytosis. In this study, we explore the role of the CD47-SIRPα interaction on the PV RBC life cycle. Our results show that blocking CD47-SIRPα in a PV mouse model due to either anti-CD47 treatment or loss of the inhibitory SIRPα-signal corrects the polycythemia phenotype. Anti-CD47 treatment marginally impacted PV RBC production while not influencing erythroid maturation. However, upon anti-CD47 treatment, high-parametric single-cell cytometry identified an increase of MerTK+ splenic monocyte-derived effector cells, which differentiate from Ly6Chi monocytes during inflammatory conditions, acquire an inflammatory phagocytic state. Furthermore, in vitro, functional assays showed that splenic JAK2 mutant macrophages were more “pro-phagocytic,” suggesting that PV RBCs exploit the CD47-SIRPα interaction to escape innate immune attacks by clonal JAK2 mutant macrophages.
Which one is better for refractory/relapsed acute B-cell lymphoblastic leukemia: Single-target (CD19) or dual-target (tandem or sequential CD19/CD22) CAR T-cell therapy?
Authors: Liu Sining , Zhang Xinyue , Dai Haiping , Cui Wei , Yin Jia , Li Zheng , Yang Xiao , Yang Chunxiu , Xue Shengli , Qiu Huiying , Miao Miao , Chen Suning , Jin Zhengming , Fu Chengcheng , Li Caixia , Sun Aining , Han Yue , Wang Ying , Yu Lei , Wu Depei , Cui Qingya , Tang Xiaowen
Published: April 2023

CD19 chimeric antigen receptor (CAR) T-cell therapy has shown great success against B-cell acute lymphoblastic leukemia (B-ALL). Tandem and sequential CD19/CD22 dual-target CAR T-cell therapies have been developed to reduce the possibility of CD19-negative relapse; however, the superior strategy is still uncertain. This study screened 219 patients with relapsed/refractory B-ALL who were enrolled in clinical trials of either CD19 (NCT03919240) or CD19/CD22 CAR T-cell therapy (NCT03614858). The complete remission (CR) rates in the single CD19, tandem CD19/CD22, and sequential CD19/CD22 groups were 83.0% (122/147), 98.0% (50/51), and 95.2% (20/21), respectively (single CD19 vs. tandem CD19/CD22, P = 0.006). Patients with high-risk factors achieved a higher rate of CR in the tandem CD19/CD22 group than in the single CD19 group (100.0% vs. 82.4%, P = 0.017). Tandem CD19/CD22 CAR T-cell therapy was one of the significant favorable factors in the multivariate analysis of the CR rate. The incidence of adverse events was similar among the three groups. Multivariable analysis in CR patients showed that a low frequency of relapse, a low tumor burden, minimal residual disease-negative CR and bridging to transplantation were independently associated with better leukemia-free survival. Our findings suggested that tandem CD19/CD22 CAR T-cell therapy obtains a better response than CD19 CAR T-cell therapy and a similar response to sequential CD19/CD22 CAR T-cell therapy.
Combined inhibition of BCL-2 and MCL-1 overcomes BAX deficiency-mediated resistance of TP53-mutant acute myeloid leukemia to individual BH3 mimetics
Authors: Carter Bing Z. , Mak Po Yee , Tao Wenjing , Ayoub Edward , Ostermann Lauren B. , Huang Xuelin , Loghavi Sanam , Boettcher Steffen , Nishida Yuki , Ruvolo Vivian , Hughes Paul E. , Morrow Phuong K. , Haferlach Torsten , Kornblau Steven , Muftuoglu Muharrem , Andreeff Michael
Published: April 2023

TP53-mutant acute myeloid leukemia (AML) respond poorly to currently available treatments, including venetoclax-based drug combinations and pose a major therapeutic challenge. Analyses of RNA sequencing and reverse phase protein array datasets revealed significantly lower BAX RNA and protein levels in TP53-mutant compared to TP53–wild-type (WT) AML, a finding confirmed in isogenic CRISPR-generated TP53-knockout and -mutant AML. The response to either BCL-2 (venetoclax) or MCL-1 (AMG176) inhibition was BAX-dependent and much reduced in TP53-mutant compared to TP53-WT cells, while the combination of two BH3 mimetics effectively activated BAX, circumventing survival mechanisms in cells treated with either BH3 mimetic, and synergistically induced cell death in TP53-mutant AML and stem/progenitor cells. The BH3 mimetic–driven stress response and cell death patterns after dual inhibition were largely independent of TP53 status and affected by apoptosis induction. Co-targeting, but not individual targeting of BCL-2 and MCL-1 in mice xenografted with TP53-WT and TP53-R248W Molm13 cells suppressed both TP53-WT and TP53-mutant cell growth and significantly prolonged survival. Our results demonstrate that co-targeting BCL-2 and MCL-1 overcomes BAX deficiency-mediated resistance to individual BH3 mimetics in TP53-mutant cells, thus shifting cell fate from survival to death in TP53-deficient and -mutant AML. This concept warrants clinical evaluation.
Unravelling rechargeable zinc-copper batteries by a chloride shuttle in a biphasic electrolyte
Authors: Xu Chen , Lei Chengjun , Li Jinye , He Xin , Jiang Pengjie , Wang Huijian , Liu Tingting , Liang Xiao
Published: April 2023

The zinc-copper redox couple exhibits several merits, which motivated us to reconstruct the rechargeable Daniell cell by combining chloride shuttle chemistry in a zinc chloride-based aqueous/organic biphasic electrolyte. An ion-selective interface was established to restrict the copper ions in the aqueous phase while ensuring chloride transfer. We demonstrated that the copper-water-chloro solvation complexes are the descriptors, which are predominant in aqueous solutions with optimized concentrations of zinc chloride; thus, copper crossover is prevented. Without this prevention, the copper ions are mostly in the hydration state and exhibit high spontaneity to be solvated in the organic phase. The zinc-copper cell delivers a highly reversible capacity of 395 mAh g−1 with nearly 100% coulombic efficiency, affording a high energy density of 380 Wh kg−1 based on the copper chloride mass. The proposed battery chemistry is expandable to other metal chlorides, which widens the cathode materials available for aqueous chloride ion batteries.
Addressable and adaptable intercellular communication via DNA messaging
Authors: Marken John P. , Murray Richard M.
Published: April 2023

Engineered consortia are a major research focus for synthetic biologists because they can implement sophisticated behaviors inaccessible to single-strain systems. However, this functional capacity is constrained by their constituent strains’ ability to engage in complex communication. DNA messaging, by enabling information-rich channel-decoupled communication, is a promising candidate architecture for implementing complex communication. But its major advantage, its messages’ dynamic mutability, is still unexplored. We develop a framework for addressable and adaptable DNA messaging that leverages all three of these advantages and implement it using plasmid conjugation in E. coli. Our system can bias the transfer of messages to targeted receiver strains by 100- to 1000-fold, and their recipient lists can be dynamically updated in situ to control the flow of information through the population. This work lays the foundation for future developments that further utilize the unique advantages of DNA messaging to engineer previously-inaccessible levels of complexity into biological systems.
Solution epitaxy of polarization-gradient ferroelectric oxide films with colossal photovoltaic current
Authors: Lin Chen , Zhang Zijun , Dai Zhenbang , Wu Mengjiao , Liu Shi , Chen Jialu , Hua Chenqiang , Lu Yunhao , Zhang Fei , Lou Hongbo , Dong Hongliang , Zeng Qiaoshi , Ma Jing , Pi Xiaodong , Zhou Dikui , Wu Yongjun , Tian He , Rappe Andrew M. , Ren Zhaohui , Han Gaorong
Published: April 2023

Solution growth of single-crystal ferroelectric oxide films has long been pursued for the low-cost development of high-performance electronic and optoelectronic devices. However, the established principles of vapor-phase epitaxy cannot be directly applied to solution epitaxy, as the interactions between the substrates and the grown materials in solution are quite different. Here, we report the successful epitaxy of single-domain ferroelectric oxide films on Nb-doped SrTiO3 single-crystal substrates by solution reaction at a low temperature of ~200 oC. The epitaxy is mainly driven by an electronic polarization screening effect at the interface between the substrates and the as-grown ferroelectric oxide films, which is realized by the electrons from the doped substrates. Atomic-level characterization reveals a nontrivial polarization gradient throughout the films in a long range up to ~500 nm because of a possible structural transition from the monoclinic phase to the tetragonal phase. This polarization gradient generates an extremely high photovoltaic short-circuit current density of ~2.153 mA/cm2 and open-circuit voltage of ~1.15 V under 375 nm light illumination with power intensity of 500 mW/cm2, corresponding to the highest photoresponsivity of ~4.306×10−3 A/W among all known ferroelectrics. Our results establish a general low-temperature solution route to produce single-crystal gradient films of ferroelectric oxides and thus open the avenue for their broad applications in self-powered photo-detectors, photovoltaic and optoelectronic devices.
Associations between in vitro, in vivo and in silico cell classes in mouse primary visual cortex
Authors: Wei Yina , Nandi Anirban , Jia Xiaoxuan , Siegle Joshua H. , Denman Daniel , Lee Soo Yeun , Buchin Anatoly , Van Geit Werner , Mosher Clayton P. , Olsen Shawn , Anastassiou Costas A.
Published: April 2023

The brain consists of many cell classes yet in vivo electrophysiology recordings are typically unable to identify and monitor their activity in the behaving animal. Here, we employed a systematic approach to link cellular, multi-modal in vitro properties from experiments with in vivo recorded units via computational modeling and optotagging experiments. We found two one-channel and six multi-channel clusters in mouse visual cortex with distinct in vivo properties in terms of activity, cortical depth, and behavior. We used biophysical models to map the two one- and the six multi-channel clusters to specific in vitro classes with unique morphology, excitability and conductance properties that explain their distinct extracellular signatures and functional characteristics. These concepts were tested in ground-truth optotagging experiments with two inhibitory classes unveiling distinct in vivo properties. This multi-modal approach presents a powerful way to separate in vivo clusters and infer their cellular properties from first principles.
Wafer-scale high-κ dielectrics for two-dimensional circuits via van der Waals integration
Authors: Lu Zheyi , Chen Yang , Dang Weiqi , Kong Lingan , Tao Quanyang , Ma Likuan , Lu Donglin , Liu Liting , Li Wanying , Li Zhiwei , Liu Xiao , Wang Yiliu , Duan Xidong , Liao Lei , Liu Yuan
Published: April 2023

The practical application of two-dimensional (2D) semiconductors for high-performance electronics requires the integration with large-scale and high-quality dielectrics—which however have been challenging to deposit to date, owing to their dangling-bonds-free surface. Here, we report a dry dielectric integration strategy that enables the transfer of wafer-scale and high-κ dielectrics on top of 2D semiconductors. By utilizing an ultra-thin buffer layer, sub-3 nm thin Al2O3 or HfO2 dielectrics could be pre-deposited and then mechanically dry-transferred on top of MoS2 monolayers. The transferred ultra-thin dielectric film could retain wafer-scale flatness and uniformity without any cracks, demonstrating a capacitance up to 2.8 μF/cm2, equivalent oxide thickness down to 1.2 nm, and leakage currents of ~10−7 A/cm2. The fabricated top-gate MoS2 transistors showed intrinsic properties without doping effects, exhibiting on-off ratios of ~107, subthreshold swing down to 68 mV/dec, and lowest interface states of 7.6×109 cm−2 eV−1. We also show that the scalable top-gate arrays can be used to construct functional logic gates. Our study provides a feasible route towards the vdW integration of high-κ dielectric films using an industry-compatible ALD process with well-controlled thickness, uniformity and scalability.
Targeted and high-throughput gene knockdown in diverse bacteria using synthetic sRNAs
Authors: Cho Jae Sung , Yang Dongsoo , Prabowo Cindy Pricilia Surya , Ghiffary Mohammad Rifqi , Han Taehee , Choi Kyeong Rok , Moon Cheon Woo , Zhou Hengrui , Ryu Jae Yong , Kim Hyun Uk , Lee Sang Yup
Published: April 2023

Synthetic sRNAs allow knockdown of target genes at translational level, but have been restricted to a limited number of bacteria. Here, we report the development of a broad-host-range synthetic sRNA (BHR-sRNA) platform employing the RoxS scaffold and the Hfq chaperone from Bacillus subtilis. BHR-sRNA is tested in 16 bacterial species including commensal, probiotic, pathogenic, and industrial bacteria, with >50% of target gene knockdown achieved in 12 bacterial species. For medical applications, virulence factors in Staphylococcus epidermidis and Klebsiella pneumoniae are knocked down to mitigate their virulence-associated phenotypes. For metabolic engineering applications, high performance Corynebacterium glutamicum strains capable of producing valerolactam (bulk chemical) and methyl anthranilate (fine chemical) are developed by combinatorial knockdown of target genes. A genome-scale sRNA library covering 2959 C. glutamicum genes is constructed for high-throughput colorimetric screening of indigoidine (natural colorant) overproducers. The BHR-sRNA platform will expedite engineering of diverse bacteria of both industrial and medical interest.
Circulating cytokine levels in systemic sclerosis related interstitial lung disease and idiopathic pulmonary fibrosis
Authors: Zheng Boyang , Keen Kevin J. , Fritzler Marvin J. , Ryerson Christopher J. , Wilcox Pearce , Whalen Beth A. , Sahin Basak , Yao Iris , Dunne James V.
Published: April 2023

Exploration of cytokine levels in systemic sclerosis-associated interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF) is needed to find common and diverse biomolecular pathways. Circulating levels of 87 cytokines were compared amongst 19 healthy controls and consecutive patients with SSc-ILD (n = 39), SSc without ILD (n = 29), and IPF (n = 17) recruited from a Canadian centre using a log-linear model adjusted for age, sex, baseline forced vital capacity (FVC), and immunosuppressive or anti-fibrotic treatment at time of sampling. Also examined was annualized change in FVC. Four cytokines had Holm’s corrected p-values less than 0.05. Eotaxin-1 levels were increased approximately two-fold in all patient categories compared to healthy controls. Interleukin-6 levels were eight-fold higher in all ILD categories compared to healthy controls. MIG/CXCL9 levels increased two-fold more in all but one patient category compared to healthy controls. Levels of a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13, (ADAMTS13) were lower for all categories of patients compared to controls. No substantial association was found for any of the cytokines with FVC change. Observed cytokine differences suggest both common and diverse pathways leading to pulmonary fibrosis. Further studies evaluating longitudinal change of these molecules would be informative.
Wave optics of imaging with contact ball lenses
Authors: Maslov A. V. , Jin B. , Astratov V. N.
Published: April 2023

Recent progress in microspherical superlens nanoscopy raises a fundamental question about the transition from super-resolution properties of mesoscale microspheres, which can provide a subwavelength resolution $$\sim \lambda /7$$

∼
λ
/
7

, to macroscale ball lenses, for which the imaging quality degrades because of aberrations. To address this question, this work develops a theory describing the imaging by contact ball lenses with diameters $$30<D/\lambda <4000$$

30
<
D
/
λ
<
4000

covering this transition range and for a broad range of refractive indices $$1.3<n<2.1$$

1.3
<
n
<
2.1

. Starting from geometrical optics we subsequently proceed to an exact numerical solution of the Maxwell equations explaining virtual and real image formation as well as magnification M and resolution near the critical index $$n\approx 2$$

n
≈
2

which is of interest for applications demanding the highest M such as cellphone microscopy. The wave effects manifest themselves in a strong dependence of the image plane position and magnification on $$D/\lambda $$

D
/
λ

, for which a simple analytical formula is derived. It is demonstrated that a subwavelength resolution is achievable at $$D/\lambda \lesssim 1400$$

D
/
λ
≲
1400

. The theory explains the results of experimental contact-ball imaging. The understanding of the physical mechanisms of image formation revealed in this study creates a basis for developing applications of contact ball lenses in cellphone-based microscopy.
mRNA markers associated with malignant pleural effusion
Authors: Hsu Shih-Chang , Chang Shan-Yueh , Hwang Yi-Ting , Terng Harn-Jing , Tsai Chen-Liang , Shen Chih-Hao , Huang Shau Ku , Chian Chih‑Feng
Published: April 2023

Malignant pleural effusions (MPE) commonly result from malignant tumors and represent advanced-stage cancers. Thus, in clinical practice, early recognition of MPE is valuable. However, the current diagnosis of MPE is based on pleural fluid cytology or histologic analysis of pleural biopsies with a low diagnostic rate. This research aimed to assess the diagnostic ability of eight previously identified Non-Small Cell Lung Cancer (NSCLC)-associated genes for MPE. In the study, eighty-two individuals with pleural effusion were recruited. There were thirty-three patients with MPE and forty-nine patients with benign transudate. mRNA was isolated from the pleural effusion and amplified by Quantitative real-time PCR. The logistic models were further applied to evaluate the diagnostic performance of those genes. Four significant MPE-associated genes were discovered in our study, including Dual-specificity phosphatase 6 (DUSP6), MDM2 proto-oncogene (MDM2), Ring finger protein 4 (RNF4), and WEE1 G2 Checkpoint Kinase (WEE1). Pleural effusion with higher expression levels of MDM2 and WEE1 and lower expression levels of RNF4 and DUSP6 had a higher possibility of being MPE. The four-gene model had an excellent performance distinguishing MPE and benign pleural effusion, especially for pathologically negative effusions. Therefore, the gene combination is a suitable candidate for MPE screening in patients with pleural effusion. We also identified three survival-associated genes, WEE1, Neurofibromin 1 (NF1), and DNA polymerase delta interacting protein 2 (POLDIP2), which could predict the overall survival of patients with MPE.
Water and heat exchanges in mammalian lungs
Authors: Haut Benoit , Karamaoun Cyril , Mauroy Benjamin , Sobac Benjamin
Published: April 2023

A secondary function of the respiratory system of the mammals is, during inspiration, to heat the air to body temperature and to saturate it with water before it reaches the alveoli. Relying on a mathematical model, we propose a comprehensive analysis of this function, considering all the terrestrial mammals (spanning six orders of magnitude of the body mass, M) and focusing on the sole contribution of the lungs to this air conditioning. The results highlight significant differences between the small and the large mammals, as well as between rest and effort, regarding the spatial distribution of heat and water exchanges in the lungs, and also in terms of regime of mass transfer taking place in the lumen of the airways. Interestingly, the results show that the mammalian lungs appear to be designed just right to fully condition the air at maximal effort (and clearly over-designed at rest, except for the smallest mammals): all generations of the bronchial region of the lungs are mobilized for this purpose, with calculated values of the local evaporation rate of water from the bronchial mucosa that can be very close to the maximal ability of the serous cells to replenish this mucosa with water. For mammals with a mass above a certain threshold ($$\simeq 5$$

≃
5

kg at rest and $$\simeq 50$$

≃
50

g at maximal effort), it appears that the maximal value of this evaporation rate scales as $$M^{-1/8}$$

M

-
1
/
8

at rest and $$M^{-1/16}$$

M

-
1
/
16

at maximal effort and that around 40% (at rest) or 50% (at maximal effort) of the water/heat extracted from the lungs during inspiration is returned to the bronchial mucosa during expiration, independently of the mass, due to a subtle coupling between different phenomena. This last result implies that, above these thresholds, the amounts of water and heat extracted from the lungs by the ventilation scale with the mass such as the ventilation rate does (i.e. as $$M^{3/4}$$

M

3
/
4

at rest and $$M^{7/8}$$

M

7
/
8

at maximal effort). Finally, it is worth to mention that these amounts appear to remain limited, but not negligible, when compared to relevant global quantities, even at maximal effort (4–6%).
Plasma mineral status after a six-month intervention providing one egg per day to young Malawian children: a randomized controlled trial
Authors: Perez-Plazola Marina , Diaz Jenna , Stewart Christine P. , Arnold Charles D. , Caswell Bess L. , Lutter Chessa K. , Werner E. Rochelle , Maleta Kenneth , Turner Jay , Prathibha Pradeep , Liu Xuan , Gyimah Emmanuel , Iannotti Lora
Published: April 2023

Mineral deficiencies are common in children living in low-resource areas. Eggs are a rich source of essential nutrients and have been shown to improve growth in young children, although little is known about their impact on mineral status. Children aged 6–9 months (n = 660) were randomized to receive either one egg/day for 6-months or no intervention. Anthropometric data, dietary recalls, and venous blood were collected at baseline and 6-months follow-up. Quantification of plasma minerals (n = 387) was done using inductively coupled plasma-mass spectroscopy. Difference-in-difference mean plasma mineral concentrations was determined from baseline and follow-up values and assessed between groups by intention-to-treat using ANCOVA regression models. Prevalence of zinc deficiency was 57.4% at baseline and 60.5% at follow-up. Mean difference (MD) of plasma magnesium, selenium, copper, and zinc levels were not different between groups. Plasma iron concentrations were significantly lower in the intervention compared to the control group (MD = − 9.29; 95% CI: − 15.95, − 2.64). Zinc deficiency was widely prevalent in this population. Mineral deficiencies were not addressed with the egg intervention. Further interventions are needed to improve the mineral status of young children.
Food allergens in oral care products
Authors: Coimbra Luísa , Costa Isabel Margarida , Evangelista José Grillo , Figueiredo Alexandra
Published: April 2023

Food allergies are a growing concern, especially in Western societies and can dramatically impact the quality of life of affected individuals. In recent years, various food allergens have been introduced into the oral care industry to improve product properties and provide the best possible treatment. Since small doses of food allergens may be sufficient to trigger allergic reactions, the non-discrimination of the sources of certain excipients in the product composition can compromise the patient's health. Therefore, knowledge and awareness of allergies and product composition among health professionals are critical on behalf of patients’ and consumers’ health. This study aimed to ascertain the presence of dairy products (e.g., cow's milk proteins and lactose), cereals (e.g., gluten, soy, and oats), fruits, nuts, spices, shellfish, and additives as excipients in oral care products for outpatients and products for professional use in the Dental Office. Among the 387 surveyed products, the highest prevalence of food allergens was found in toothpaste, fluoride varnishes, and alginates, mostly in spices and fresh fruits. As food allergies may occur because of erroneous information or a lack of labeling on the allergen list, manufacturers should be more rigorous in declaring allergens on product labeling regarding the safety of consumers.
Non-carcinogenic and cumulative risk assessment of exposure of kitchen workers in restaurants and local residents in the vicinity of polycyclic aromatic hydrocarbons
Authors: Shamsedini Narges , Dehghani Mansooreh , Samaei Mohammad Reza , Nozari Majid , Bahrany Shayan , Tabatabaei Zeynab , Azhdarpoor Aboolfazl , Hoseini Mohammad , Fararoei Mohammad , Roosta Sareh
Published: April 2023

Polycyclic aromatic hydrocarbons (PAHs) are often formed when organic substances do not burn completely. This study evaluates the non-carcinogenic and cumulative risks associated with PAHs levels by testing blood and urine samples in kitchen workers and residents near restaurants in Shiraz, Iran. Metabolites of PAH in the urine samples as well as clinical parameters in the blood samples were measured. The non-carcinogenic and cumulative risk assessments from exposure of the study groups to PAH metabolites were also evaluated. The highest average concentrations of PAH metabolites were related to kitchen workers (2126.7 ng/g creatinine (ng/g cr)). The metabolites of 1-Hydroxypyrene (1-OHP) and 9-Phenanthrene (9-OHPhe) had the highest and lowest mean concentrations, respectively. A direct correlation was observed between the levels of PAH metabolites with malondialdehyde (MDA) and total antioxidation capacity (TAC) levels (p < 0.05). Hazard Index (HIi) was obtained less than one (HIi < 1), indicating low-risk negative health impacts on the target groups. Nevertheless, conducting more studies to determine the health status of these people is quite evident.
High concentrations of soluble endoglin can inhibit BMP9 signaling in non-endothelial cells
Authors: Andersson-Rusch Clara , Liu Bin , Quist-Løkken Ingrid , Upton Paul D. , Olsen Oddrun Elise , Hella Hanne , Yang Xudong , Tong Zhen , Morrell Nicholas W. , Holien Toril , Li Wei
Published: April 2023

Endoglin (ENG) is a single-pass transmembrane protein highly expressed on vascular endothelial cells, although low expression levels can be detected in many other cell types. Its extracellular domain can be found in circulation known as soluble endoglin (sENG). Levels of sENG are elevated in many pathological conditions, in particular preeclampsia. We have shown that while loss of cell surface ENG decreases BMP9 signaling in endothelial cells, knocking down ENG in blood cancer cells enhances BMP9 signaling. Despite sENG binding to BMP9 with high affinity and blocking the type II receptor binding site on BMP9, sENG did not inhibit BMP9 signaling in vascular endothelial cells, but the dimeric form of sENG inhibited BMP9 signaling in blood cancer cells. Here we report that in non-endothelial cells such as human multiple myeloma cell lines and the mouse myoblast cell line C2C12, both monomeric and dimeric forms of sENG inhibit BMP9 signaling when present at high concentrations. Such inhibition can be alleviated by the overexpression of ENG and ACVRL1 (encoding ALK1) in the non-endothelial cells. Our findings suggest that the effects of sENG on BMP9 signaling is cell-type specific. This is an important consideration when developing therapies targeting the ENG and ALK1 pathway.
Movements and spatial usage of harbour seals in the Elbe estuary in Germany
Authors: van Neer Abbo , Nachtsheim Dominik , Siebert Ursula , Taupp Thomas
Published: April 2023

Harbour seals are top predators in the North Sea and regarded as sentinels for ecosystem health. A few hundred also occur in adjacent estuaries, such as the Elbe estuary, Germany. However, only little is known about how these animals use this dynamic tidally influenced habitat, which has been under high anthropogenic pressure for decades. In this context, nine harbour seals (Phoca vitulina) from the Elbe estuary were equipped with biotelemetry devices to track their movements over multiple months. Harbour seal movements were characterised by short trips (trip length outside pupping season for females: 9.0 ± 1.12 km, males: 7.0 ± 1.24 km) as well as small home ranges (median 50% home range for females: 16.3 km2, males: 36.1 km2) compared to harbour seals from marine regions. Within the estuary, the animals utilised the fairway, river branches and tributaries. During the pupping season in June and July, four seals showed strongly reduced trip lengths and durations, increased daily haul out durations as well as smaller home ranges. Even though a continuous exchange with harbour seals from the Wadden Sea likely occurs, most individuals in this study spent the entire deployment duration inside the estuary. This indicates that the Elbe estuary provides a suitable habitat for harbour seals, despite extensive anthropogenic usage, calling for further studies on the consequences of living in such an industrialised habitat.
Pioglitazone use increases risk of Alzheimer's disease in patients with type 2 diabetes receiving insulin
Authors: Lin Hsin-Chung , Chung Chi-Hsiang , Chen Lih-Chyang , Wang Jui-Yang , Chen Chien-Chou , Huang Kuo-Yang , Tsai Ming-Hang , Chien Wu-Chien , Lin Hsin-An
Published: April 2023

Pioglitazone is an insulin resistance inhibitor widely used as monotherapy or combined with metformin or insulin in treating type 2 diabetes mellitus (T2DM). This study further investigated the relationship between pioglitazone use and the risk of developing Alzheimer's disease (AD) in patients newly diagnosed with T2DM, and examined the potential impact of insulin use on this association. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Our data exhibited that the risk of developing AD in the pioglitazone group was 1.584-fold (aHR = 1.584, 95% CI 1.203–1.967, p < 0.05) higher than that in the non-pioglitazone controls. Compared to patients without both insulin and pioglitazone, higher cumulative risk of developing AD was found in patients receiving both insulin and pioglitazone (aHR = 2.004, 95% CI = 1.702–2.498), pioglitazone alone (aHR = 1.596, 95% CI = 1.398–1.803), and insulin alone (aHR = 1.365, 95% CI = 1.125–1.572), respectively (all p < 0.05). A similar observation also found in the evaluation the use of diabetic drugs with a cumulative defined daily dose (cDDD). No interaction between pioglitazone and major risk factors (comorbidities) of AD was observed. In conclusion, alternative drug therapies may be an effective strategy for reducing risk of developing AD in T2DM patients.
Reclassification of moderate aortic stenosis based on data-driven phenotyping of hemodynamic progression
Authors: Cho Iksung , Kim William D. , Kim Subin , Ko Kyu-Yong , Seong Yeonchan , Kim Dae-Young , Seo Jiwon , Shim Chi Young , Ha Jong-Won , Mori Makoto , Gupta Aakriti , You Seng Chan , Hong Geu-Ru , Krumholz Harlan M.
Published: April 2023

The management and follow-up of moderate aortic stenosis (AS) lacks consensus as the progression patterns are not well understood. This study aimed to identify the hemodynamic progression of AS, and associated risk factors and outcomes. We included patients with moderate AS with at least three transthoracic echocardiography (TTE) studies performed between 2010 and 2021. Latent class trajectory modeling was used to classify AS groups with distinctive hemodynamic trajectories, which were determined by serial systolic mean pressure gradient (MPG) measurements. Outcomes were defined as all-cause mortality and aortic valve replacement (AVR). A total of 686 patients with 3093 TTE studies were included in the analysis. Latent class model identified two distinct AS trajectory groups based on their MPG: a slow progression group (44.6%) and a rapid progression group (55.4%). Initial MPG was significantly higher in the rapid progression group (28.2 ± 5.6 mmHg vs. 22.9 ± 2.8 mmHg, P < 0.001). The prevalence of atrial fibrillation was higher in the slow progression group; there was no significant between-group difference in the prevalence of other comorbidities. The rapid progression group had a significantly higher AVR rate (HR 3.4 [2.4–4.8], P < 0.001); there was no between-group difference in mortality (HR 0.7 [0.5–1.0]; P = 0.079). Leveraging longitudinal echocardiographic data, we identified two distinct groups of patients with moderate AS: slow and rapid progression. A higher initial MPG (≥ 24 mmHg) was associated with more rapid progression of AS and higher rates of AVR, thus indicating the predictive value of MPG in management of the disease.
Effects of biochar, zeolite and mycorrhiza inoculation on soil properties, heavy metal availability and cowpea growth in a multi-contaminated soil
Authors: Ibrahim Ehab A. , El-Sherbini Mohamed A. A. , Selim El-Metwally M.
Published: April 2023

Heavy metal pollution of agricultural soil has become a major serious concern. The development of suitable control and remediation strategies for heavy metal contaminated soil has become critical. The outdoor pot experiment was conducted to investigate the effect of biochar, zeolite, and mycorrhiza on the bioavailability reduction of heavy metals and its subsequent effects on soil properties and bioaccumulation in plants as well as the growth of cowpea grown in highly polluted soil. Zeolite, biochar, mycorrhiza, zeolite with mycorrhiza, biochar with mycorrhiza, and soil without any modifications were the six treatments used. The experiment was conducted with a completely randomized design and four replications. The results indicated that the combination of biochar with mycorrhiza had the highest values of root and shoot dry weight and the lowest heavy metal concentrations in root and shoot as well as bioconcentration and translocation factors for all heavy metals. The highest significant reductions in the availability of heavy metals over the control were found with biochar with mycorrhiza, which were 59.1%, 44.3%, 38.0%, 69.7%, 77.8%, 77.2% and 73.6% for Cd, Co, Cr, Cu, Ni, Pb and Zn, respectively. The application of biochar and zeolite either alone or in combination with mycorrhiza increased significantly soil pH and EC compared to mycorrhiza treatment and untreated soil. It can be concluded that the combination of biochar and mycorrhizal inoculation has great potential as a cost-effective and environmentally technique for enhancing heavy metal immobilization, lowering heavy metal availability and plant uptake, and improving cowpea plant growth.
Long-term uptake rate of a breast cancer screening program in Fukushima, Japan, following the 2011 Triple Disaster: a retrospective observational study
Authors: Ozaki Akihiko , Saito Hiroaki , Kaneda Yudai , Sawano Toyoaki , Nishikawa Yoshitaka , Murakami Michio , Tsubokura Masaharu , Hirai Kei , Ohira Hiromichi
Published: April 2023

Little is known about how crises might affect the long-term uptake of breast cancer screening programs. This study aimed to clarify the long-term trend of breast cancer screening program uptake in Minamisoma City following the 2011 Triple Disaster in Fukushima, Japan (earthquake, tsunami, and nuclear disaster), and to evaluate the factors associated with this uptake. This study retrospectively analyzed data from the Basic Resident Registry and Breast Cancer Screening Program in Minamisoma City following the Triple Disaster. We calculated the annual breast cancer screening uptake rate for women aged 40–74 years who were of an even-numbered age at the end of each fiscal year and the incidence of at least one instance of uptake of the breast cancer screening initiative during the biennial intervals. We further performed cross-sectional and longitudinal regression analyses for the biannual screening uptake and investigated its associated factors. Breast cancer screening participation rates were 19.8% and 18.2% in 2009 and 2010, respectively. They decreased to 4.2% in 2011, and gradually increased thereafter, reaching the pre-disaster level of 20.0% in 2016. Similar but longer decrease of the uptake was observed in the biannual screening uptake rate. No pre-disaster screening uptake between 2009 and 2010, those living alone, or those who were evacuated, were factors that were found to be associated with non-uptake of the breast cancer screening program following the 2011 disaster. This study showed a long-term decline in breast cancer screening uptake in the area affected by the Triple Disaster, which was the most severe among those under evacuation, those who were isolated, and those without previous uptake. The insights emerging from this study could be used to increase awareness of this issue and establish potential countermeasures.
A ready-to-use machine learning tool for symmetric multi-modality registration of brain MRI
Authors: Iglesias Juan Eugenio
Published: April 2023

Volumetric registration of brain MRI is routinely used in human neuroimaging, e.g., to align different MRI modalities, to measure change in longitudinal analysis, to map an individual to a template, or in registration-based segmentation. Classical registration techniques based on numerical optimization have been very successful in this domain, and are implemented in widespread software suites like ANTs, Elastix, NiftyReg, or DARTEL. Over the last 7–8 years, learning-based techniques have emerged, which have a number of advantages like high computational efficiency, potential for higher accuracy, easy integration of supervision, and the ability to be part of a meta-architectures. However, their adoption in neuroimaging pipelines has so far been almost inexistent. Reasons include: lack of robustness to changes in MRI modality and resolution; lack of robust affine registration modules; lack of (guaranteed) symmetry; and, at a more practical level, the requirement of deep learning expertise that may be lacking at neuroimaging research sites. Here, we presentEasyReg, an open-source, learning-based registration tool that can be easily used from the command line without any deep learning expertise or specific hardware.EasyRegcombines the features of classical registration tools, the capabilities of modern deep learning methods, and the robustness to changes in MRI modality and resolution provided by our recent work in domain randomization. As a result,EasyRegis: fast; symmetric; diffeomorphic (and thus invertible); agnostic to MRI modality and resolution; compatible with affine and nonlinear registration; and does not require any preprocessing or parameter tuning. We present results on challenging registration tasks, showing thatEasyRegis as accurate as classical methods when registering 1 mm isotropic scans within MRI modality, but much more accurate across modalities and resolutions.EasyRegis publicly available as part of FreeSurfer; seehttps://surfer.nmr.mgh.harvard.edu/fswiki/EasyReg.
Intensity-dependent cardiopulmonary response during and after strength training
Authors: Lässing Johannes , Maudrich Tom , Kenville Rouven , Uyar Zarah , Bischoff Christian , Fikenzer Sven , Busse Martin , Falz Roberto
Published: April 2023

Whereas cardiopulmonary responses are well understood in endurance training, they are rarely described in strength training. This cross-over study examined acute cardiopulmonary responses in strength training. Fourteen healthy male strength training-experienced participants (age 24.5 ± 2.9 years; BMI 24.1 ± 2.0 kg/m2) were randomly assigned into three strength training sessions (three sets of ten repetitions) with different intensities (50%, 62,5%, and 75% of the 3-Repetition Maximum) of squats in a smith machine. Cardiopulmonary (impedance cardiography, ergo-spirometry) responses were continuously monitored. During exercise period, heart rate (HR 143 ± 16 vs. 132 ± 15 vs. 129 ± 18 bpm, respectively; p < 0.01; η2p 0.54) and cardiac output (CO: 16.7 ± 3.7 vs. 14.3 ± 2.5 vs. 13.6 ± 2.4 l/min, respectively; p < 0.01; η2p 0.56) were higher at 75% of 3-RM compared to those at the other intensities. We noted similar stroke volume (SV: p = 0.08; η2p 0.18) and end-diastolic volume (EDV: p = 0.49). Ventilation (VE) was higher at 75% compared to 62.5% and 50% (44.0 ± 8.0 vs. 39.6 ± 10.4 vs. 37.6 ± 7.7 l/min, respectively; p < 0.01; η2p 0.56). Respiration rate (RR; p = .16; η2p 0.13), tidal volume (VT: p = 0.41; η2p 0.07) and oxygen uptake (VO2: p = 0.11; η2p 0.16) did not differ between intensities. High systolic and diastolic blood pressure were evident (62.5% 3-RM 197 ± 22.4/108.8 ± 13.4 mmHG). During the post-exercise period (60 s), SV, CO, VE, VO2, and VCO2 were higher (p < 0.01) than during the exercise period, and the pulmonary parameters differed markedly between intensities (VE p < 0.01; RR p < 0.01; VT p = 0.02; VO2 p < 0.01; VCO2 p < 0.01). Despite the differences in strength training intensity, the cardiopulmonary response reveals significant differences predominantly during the post-exercise period. Intensity-induced breath holding induces high blood pressure peaks and cardiopulmonary recovery effects after exercise.