bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Modern Irrigation Methods on Groundwater Storage and Land Subsidence in High-water Stress Regions
Authors: Abd-Elaty Ismail , Fathy Ismail , Kuriqi Alban , John Am Pris , Straface Salvatore , Ramadan Elsayed M.
Published: February 2023

Water resources management in high-stress regions is a large-scale problem affecting food and water security. Therefore, modern irrigation systems such as sprinklers, subsurface, and drip irrigations are applied to manage the water shortage in regions of the Nile delta. Because of the increase in population rate and climate change, freshwater supplies are significantly limited and must be efficiently managed. Consequently, Egypt plans to implement MIS in the old land of the Nile delta. The current study aims to investigate and model the recharge from the excess irrigation system that affects groundwater storage and land subsidence unexpectedly. The visual modflow was applied to investigate the groundwater heads and drawdown. At the same time, the analytical solution based on Terzaghi theory, and the surfer software was used to estimate and map the land subsidence.

For this reason, we investigated the groundwater drawdown in the high-water shortage of Egypt’s Nile delta. Three scenarios were considered by changing irrigation methods and their Impact on land subsidence in the Nile Delta Aquifer (NDA). Therefore, the results of this study demonstrated that the groundwater drawdown reached 2.60 m, 4.20 m, and 6.50 m, respectively. In contrast, the land subsidence outstretched 26 m, 44 m, and 65 cm for the sprinkle sub-surface. Future design infrastructures such as pipelines, roads, irrigation networks, canals, and water structures should consider land subsidence due to modern irrigation systems (MIS).
Severe hyponatraemia (P-Na < 116 mmol/l) in the emergency department: a series of 394 cases
Authors: Mustajoki Sami
Published: February 2023

Aim

To evaluate the significance of severe hyponatraemia presented at the emergency department (ED).

Methods

A retrospective hospital
records study of all patients with plasma sodium levels of < 116 mmol/l from 2016 to 2020 in a single tertiary referral centre.

Results

A total of 394 visits of 363 individual severely hyponatraemic patients represented 0.08% of all ED visits. The
mean age was 68 years and the male-to-female ratio was 1:1.3. The symptoms and signs were diffuse and varying, while half of
the patients had neurologic symptoms. The aetiology of hyponatraemia was often multifactorial. The aetiologies varied by age,
and the most common ones were the syndrome of inappropriate antidiuresis (34%), diuretic use (27%), alcohol-related (19%)
and dehydration (19%). The mean sodium correction rates were 6.6, 4.9 and 3.8 mmol/l/24 h at 24, 48 and 72 h, respectively.
The mean maximum correction rate over any 24-h time interval was 10.2 mmol/l. The vital signs (National Early Warning
Score, NEWS) of severely hyponatraemic patients were mostly normal. All-cause mortality was 18% for 1-year follow-up.
Malignancies, especially small-cell lung cancer, and end-stage liver disease caused most of the deaths. Osmotic demyelination
syndrome (ODS) was diagnosed in five (1.4%) patients.

Conclusion

Patients with severe hyponatraemia in the ED presented with non-specific complaints. The aetiology of hyponatraemia was often multifactorial and varied by age. The need
for intensive care was poorly predicted by NEWS. The one-year mortality rate was 18% and the incidence of ODS 1.4% after
an episode of severe hyponatraemia.
Myocardial Metabolism in Heart Failure
Authors: Ng Sher May , Neubauer Stefan , Rider Oliver J
Published: February 2023

Purpose of Review

Myocardial metabolism is intricately linked to cardiac function. Perturbations of cardiac energy metabolism result in an energy-starved heart and the development of contractile dysfunction. In this review, we discuss alterations in myocardial energy supply, transcriptional changes in response to different energy demands, and mitochondrial function in the development of heart failure.

Recent Findings

Recent studies on substrate modulation through modifying energy substrate supply have shown cardioprotective properties. In addition, large cardiovascular outcome trials of anti-diabetic agents have demonstrated prognostic benefit, suggesting the importance of myocardial metabolism in cardiac function.

Understanding molecular and transcriptional controls of cardiac metabolism promises new research avenues for metabolic treatment targets. Future studies assessing the impact of substrate modulation on cardiac energetic status and function will better inform development of metabolic therapies.
Effect of chilling and salinity stress on photosynthetic performance and ultrastructure of chloroplast in faba beans (Vicia faba L.) leaves
Authors: El-Dakak Rehab A. , Badr Reem H. , Zeineldein Marwa H. , Swedan Eman A. , Batrawy Omnia El , Hassaballah Amany F. , Hassan Ibrahim A.
Published: February 2023

Chilling (Ch) and salinity (S) are challenging stresses affecting plant physiology, growth, and productivity. The current study investigated the effects of these two stresses, singly and in combination, on photosynthetic performance and ultrastructure of chloroplast of faba beans (Vicia faba L. Cv. Aspani). Plants were exposed to 3 °C and 120 mM NaCl for 16 h in an optimized soil mixture (sand:clay 2:1) under optimized conditions. Results showed that both Ch and S significantly reduced photosynthetic rates, Fv/Fm, chlorophyll content, stomatal index, and stomatal conductance. Chilling caused changes in chloroplast ultrastructure (swelling, ruptured envelopes, and shrunk lamellae), while salinity caused more deformation of the thylakoid membrane and disorganization of the grana structure. However, there was an antagonistic effect between Ch x S. The tolerance of plant to 120 mM NaCl, in the present study, was improved by exposure to Ch which rather allowed the maintenance of chloroplast ultrastructure and morphology of stomata. Moreover, using SEM and TEM gave an effective insight of the ultrastructural damage in plant cells under stress and helps to consider the underlying mechanisms of stress effects. Our results suggest that Ch mitigates the noxious effect of S on the photosynthetic performance of Vicia faba plants.
Glutamine is a substrate for glycosylation and CA19-9 biosynthesis through hexosamine biosynthetic pathway in pancreatic cancer
Authors: Liu Chen , Deng Shengming , Xiao Zhiwen , Lu Renquan , Cheng He , Feng Jingjing , Shen Xuxia , Ni Quanxing , Wu Weiding , Yu Xianjun , Luo Guopei
Published: February 2023

Background

Carbohydrate antigen 19–9 (CA19-9) is the most widely used biomarker for pancreatic cancer. Since CA19-9 closely correlates with patient outcome and tumor stage in pancreatic cancer, the deciphering of CA19-9 biosynthesis provides a potential clue for treatment.

Methods

Concentration of amino acids was detected by ultrahigh-performance liquid chromatography tandem mass spectrometry. Metabolic flux of glutamine was examined by isotope tracing untargeted metabolomics. Label-free quantitative n-glycosylation proteomics was used to examine n-glycosylation alterations.

Results

Among all amino acids, glutamine was higher in CA19-9-high pancreatic cancers (> 37 U/mL, 66 cases) than in CA19-9-normal clinical specimens (≤ 37 U/mL, 37 cases). The glutamine concentration in clinical specimens was positively correlated with liver metastasis or lymphovascular invasion. Glutamine blockade using diazooxonorleucine suppressed pancreatic cancer growth and intraperitoneal and lymphatic metastasis. Glutamine promotes O-GlcNAcylation, protein glycosylation, and CA19-9 biosynthesis through the hexosamine biosynthetic pathway. UDP-n-acetylglucosamine (UDP-GlcNAc) levels correlated with the glutamine influx through hexosamine biosynthetic pathway and supported CA19-9 biosynthesis.

Conclusions

Glutamine is a substrate for CA19-9 biosynthesis in pancreatic cancer. Glutamine blockade may be a potential therapeutic strategy for pancreatic cancer.
Numerical modeling constrained by environmental isotopes for sustainable development of partially renewable aquifers in desert area
Authors: Hagagg Kamilia , Hussien Rasha Abdallah , Sadek Mostafa Abdel Hamid
Published: February 2023

Sustainable groundwater resources are a critical issue for national development in developing countries like Egypt, which is characterized by a semi-arid to arid climate and low per capita share of fresh water as a result of progressive population increase and especially after the construction of the Great Ethiopian Renaissance Dam. It is mandatory to adopt and modify methods suitable for preserving and efficient use of available water resources. The Eocene carbonate aquifer in the desert area under study (West El-Minia, Mid-Upper Egypt) is partially renewable; its sustainable development in irrigation is explored in this work. The (recharge–withdraw–exploit) regimes have been optimized by keeping the well abstraction below the fraction of renewable recharge and maximizing the exploit by selecting low water -consuming crops of high economic value. A novel approach is introduced in this work by integrating isotope hydrology techniques with numerical modeling; environmental isotopes (18O and D) contents of 62 groundwater samples have been used to determine and map the contribution of recent recharge in the study area (from 10 to 95%) and to constrain the acceptable reduction in hydraulic head allowed under an optimized withdraw and usage regime. Different scenarios were proposed by changing (rate of pumping, number of wells, wells distribution and irrigated crops) and simulating aquifer behavior to achieve the sustainable yield goals and the best plan for groundwater management in the study area.

Graphical abstract
Development and Feasibility Testing of a Multilevel Intervention to Increase Hepatitis C Virus Screening Among Baby Boomers in Primary Care
Authors: Kasting Monica L. , Laily Alfu , Nephew Lauren D. , Shields Cleveland G. , Shedd-Steele Rivienne , Rawl Susan M.
Published: February 2023

Chronic infection with hepatitis C virus (HCV) results in an increased risk of cirrhosis and hepatocellular carcinoma (HCC). Only 15% of baby boomers (born 1945–1965) have ever been screened. We aimed to develop a multilevel intervention to increase HCV screening for baby boomers in a primary care setting. This study included two phases: intervention development (phase 1) and feasibility testing (phase 2). In phase 1, we partnered with a Community Advisory Board and a Provider Advisory Board to develop a multilevel intervention to increase HCV screening to be delivered to both providers and patients in primary care. Phase 2 assessed intervention feasibility, acceptability, and usability by conducting Concurrent Think Aloud (CTA) interviews and surveys using previously validated scales with patients (n = 8) and providers (n = 7). Phase 1 results: The patient-level intervention included a mailed reminder letter and CDC pamphlet and a 7-min in-clinic educational video. The provider-level intervention included a 30-min educational session and monthly performance feedback e-mails. Phase 2 results: Qualitatively, both the patient and provider-level intervention were feasible, acceptable, and usable by the target audiences. Quantitatively, on a 1–4 scale, the range of patient-level scores was 3.00–4.00 and provider level was 3.50–4.00 for feasibility, acceptability, and usability. This intervention could improve HCV screening among a high-risk population and therefore reduce HCV-related morbidity and mortality. This project developed a feasible, acceptable, and usable multilevel intervention aimed at increasing HCV screening in primary care.
Authoritarian Successor Parties, Supporters, and Protest: Lessons from Asian Democracies
Authors: Lee Myunghee
Published: February 2023

Are authoritarian successor party (ASP) supporters more likely to protest? I propose that ASP supporters are less likely to protest in general. The post-democratization mobilization environment is shaped upon the pre-democratization mobilization basis. During the pre-democratization period, protest was organized around the democracy movement. Thus, protest tactics and networks were accumulated through it. As former authoritarian ruling party supporters, ASP supporters are less likely to have legacies of participating in the democracy movement, which prevents them from accessing the accumulated protest resources from the democracy movement. However, I argue that this negative association varies based on the ASP qualities and supporters’ age. Supporters of ASPs that maintain strong pre-democratization legacies are more likely to participate in protests than supporters of ASPs that do not strongly highlight their authoritarian legacies. Also, when the ASPs’ characteristics are considered, older ASP supporters are more likely to participate in protests than younger supporters. Using both single-level and multilevel statistical analyses, I examine four Asian countries with politically powerful ASPs and find evidence supporting my hypotheses. Lastly, I compare two South Korean mass movements, the Candlelight movement and theTaegeukgirallies to unpack the relationships between ASP supporters, protest resources, and mobilization. This study reveals authoritarian legacies among post-democratization citizens through ASP supporters’ protesting behavior.
Effect of three crop rotations and four residue levels on canola and bean grain yield and residue production
Authors: Hirzel Juan , Undurraga Pablo , León Lorenzo , Matus Iván
Published: February 2023

Crop rotation in agriculture can lead to increased crop productivity in the rotation and improved soil fertility as a result of residue incorporation. Unfortunately, residue incorporation is not a common practice in crop production systems under the Mediterranean regime, largely due to the lack of information on the effect of the follow-up crops. Therefore, this study was conducted with six biannual rotations (bread wheat–canola, bread wheat–bean, durum wheat–canola, durum wheat–bean, corn–canola and corn–bean) using four residue incorporation levels (0, 50, 100 and 200%) in an Andisol in south central Chile. Grain yield and residue production were evaluated in the canola and bean crops 5 years after initiating crop rotation. The previous crop affected canola grain yield and residue production, which were both higher after corn. Meanwhile, the residue incorporation level had a slight effect on residue production after bread wheat. Only bean grain yield was affected by the previous crop, which was higher after the durum wheat and corn crops. The residue incorporation has marginally affected residue production after bread wheat. Finally, residue incorporation at different levels under the conditions of the present experiment had a minimal effect on bean and canola residue production following the bread wheat crop. The best crop rotation for canola grain yield was corn–canola, which produced 0.54 Mg/ha (18.3%) higher yield than the average of the other two rotations. The best crop rotation for achieving higher bean grain yield was corn–bean, which yielded 0.52 Mg/ha (12.3%) higher than the average of the other two rotations.
Atypical hemispheric lateralization of brain function and structure in autism: a comprehensive meta-analysis study
Authors: Li Qingqing , Zhao Wei , Palaniyappan Lena , Guo Shuixia
Published: February 2023

Background

Characteristic changes in the asymmetric nature of the human brain are associated with neurodevelopmental differences related to autism. In people with autism, these differences are thought to affect brain structure and function, although the structural and functional bases of these defects are yet to be fully characterized.

Methods

We applied a comprehensive meta-analysis to resting-state functional and structural magnetic resonance imaging datasets from 370 people with autism and 498 non-autistic controls using seven datasets of the Autism Brain Imaging Data Exchange Project. We studied the meta-effect sizes based on standardized mean differences and standard deviations (s.d.) for lateralization of gray matter volume (GMV), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo). We examined the functional correlates of atypical laterality through an indirect annotation approach followed by a direct correlation analysis with symptom scores.

Results

In people with autism, 85, 51, and 51% of brain regions showed a significant diagnostic effect for lateralization in GMV, fALFF, and ReHo, respectively. Among these regions, 35.7% showed overlapping differences in lateralization in GMV, fALFF, and ReHo, particularly in regions with functional annotations for language, motor, and perceptual functions. These differences were associated with clinical measures of reciprocal social interaction, communication, and repetitive behaviors. A meta-analysis based ons.d.showed that people with autism had lower variability in structural lateralization but higher variability in functional lateralization.

Conclusion

These findings highlight that atypical hemispheric lateralization is a consistent feature in autism across different sites and may be used as a neurobiological marker for autism.
Embodied world construction: a phenomenology of ritual
Authors: Williams Jack
Published: February 2023

This article presents a new approach to understanding ritual: embodied world construction. Informed by phenomenology and a philosophy of embodiment, this approach argues that rituals can (re)shape the structure of an individual's perceptual world. Ritual participation transforms how the world appears for an individual through the inculcation of new perceptual habits, enabling the perception of objects and properties which could not previously be apprehended. This theory is then applied to two case studies from an existing ethnographic study of North American evangelicalism, indicating how the theory of embodied world construction can shed new light on how individuals are shaped by ritual practice.
The scaffolded evolution of human communication
Authors: Veit Walter , Browning Heather
Published: February 2023

Heintz & Scott-Phillips provide a useful synthesis for constructing a bridge between work by both cognitive scientists and evolutionary biologists studying the diversity of human communication. Here, we aim to strengthen their bridge from the side of evolutionary biology, to argue that we can best understand ostensive communication as a scaffold for more complex forms of intentional expressions.
The central problem is still evolutionary stability
Authors: Wacewicz Sławomir , Żywiczyński Przemysław
Published: February 2023

We applaud Heintz & Scott-Phillips's guiding metaphor of “unleashing leashed expression,” and we value the unified explanation for the emergence of not only language, but also other forms of unleashed expression, such as multimodal communication. We are more critical of the authors' discussion of the selection pressures acting towards unleashed expression, which are proposed to hinge on partner choice ecology.
No unleashed expression without language
Authors: Carston Robyn
Published: February 2023

While the metarepresentational structure of ostensive communication may explain the unleashing of human expression, it neither explains the open-endedness of the thoughts expressed/communicated, nor how the multiply embedded nature of the metarepresentational structure invoked arose. These both require the recursivity of human language, a capacity which must be distinguished from external (public) languages and their use in communication.
Poset Ramsey numbers: large Boolean lattice versus a fixed poset
Authors: Axenovich Maria , Winter Christian
Published: February 2023

Given partially ordered sets (posets)

$(P, \leq _P\!)$

and

$(P^{\prime}, \leq _{P^{\prime}}\!)$

, we say that

$P^{\prime}$

contains a copy of

$P$

if for some injective function

$f\,:\, P\rightarrow P^{\prime}$

and for any

$X, Y\in P$

,

$X\leq _P Y$

if and only if

$f(X)\leq _{P^{\prime}} f(Y)$

. For any posets

$P$

and

$Q$

, the poset Ramsey number

$R(P,Q)$

is the least positive integer

$N$

such that no matter how the elements of an

$N$

-dimensional Boolean lattice are coloured in blue and red, there is either a copy of

$P$

with all blue elements or a copy of

$Q$

with all red elements. We focus on a poset Ramsey number

$R(P, Q_n)$

for a fixed poset

$P$

and an

$n$

-dimensional Boolean lattice

$Q_n$

, as

$n$

grows large. We show a sharp jump in behaviour of this number as a function of

$n$

depending on whether or not

$P$

contains a copy of either a poset

$V$

, that is a poset on elements

$A, B, C$

such that

$B\gt C$

,

$A\gt C$

, and

$A$

and

$B$

incomparable, or a poset

$\Lambda$

, its symmetric counterpart. Specifically, we prove that if

$P$

contains a copy of

$V$

or

$\Lambda$

then

$R(P, Q_n) \geq n +\frac{1}{15} \frac{n}{\log n}$

. Otherwise

$R(P, Q_n) \leq n + c(P)$

for a constant

$c(P)$

. This gives the first non-marginal improvement of a lower bound on poset Ramsey numbers and as a consequence gives

$R(Q_2, Q_n) = n + \Theta \left(\frac{n}{\log n}\right)$

.
Working in a UK national proton radiotherapy facility: the therapeutic radiographer perspective
Authors: Bailey R.
Published: February 2023

The first national UK proton beam therapy centre opened at The Christie NHS Foundation Trust in 2018, which alongside University College London Hospitals NHS Foundation Trust (UCLH) proton beam therapy centre, is expected to treat approximately seven-hundred and fifty patients per year at service ramp up.

The aim of this editorial is to share with a wider audience the role of a Band 6 proton senior treatment radiographer working in a national NHS service and future developments of the service. Prior to the service being clinical, a range of processes were followed, including the creation of quality documents, departmental training and end-to-end testing, with the first patient receiving treatment in December 2018.

Proton senior radiographers are responsible for the delivery of safe and accurate radiotherapy and ensuring a smooth patient pathway, through a multi-collaborative team approach. Although there are key differences between proton and photon radiotherapy, the fundamental aspects, including radiation principles, governance and patient advice are the same. The training package for proton senior radiographers includes an individual local induction as part of the proton education and competency framework, which incorporates practical learning, including clinical supervision and workshops, plus audio-visual presentations and workbooks to complete.

Future developments of proton beam therapy include proton arc therapy and flash therapy, alongside educational developments, such as training the future workforce and advanced practice consultant radiographer roles. Shared learning through multi-collaboration of international proton beam therapy centres is crucial to improve care for future service users.
Strategies for and Barriers to Collaboratively Developing Anti‐Racist Policies and Resources as Described by Geoscientists of Color Participating in the Unlearning Racism in Geoscience (URGE) Program
Authors: Burton Carlene , Duran Gabriel , Wright Vashan , Chmiel Rebecca
Published: February 2023

The Unlearning Racism in Geosciences (URGE) program guides groups of geoscientists as they draft, implement, and assess anti‐racist policies and resources for their workplace. Some participating Geoscientists of Color (GoC) shared concerns about microaggression, tokenism, and power struggles within their groups. These reports led us to collect and analyze data that describe the experiences of GoC in URGE. The data are from five discussion groups and two surveys. Our analyses revealed that participating GoC want to continue working with White colleagues on anti‐racist work. GoC want White colleagues not to shy away from doing anti‐racist work. Instead, GoC want White colleagues (a) to create and adhere to robust behavioral codes of conduct, (b) to focus discussions on anti‐racism, (c) to act on anti‐racism initiatives, (d) not to prompt GoC to educate them or reveal trauma, and (e) to refrain from microaggressions and tokenism. These desired outcomes were achieved in some groups with varying degrees of success. Correcting a history of mistrust relating to racism and anti‐racism action is key to implementing and assessing effective anti‐racist policies and resources. This requires leadership support, following through on anti‐racism action, and deepening relationships between GoC and White colleagues. Future anti‐racist programs should spend a substantial amount of time on and demonstrate the importance of training participants how to discuss racism effectively and how to create and adhere to robust behavioral codes of conduct. Future programs should also explore developing a robust program‐wide code of conduct that includes a policy for reporting offenses.
Statistical Properties of Lower Hybrid Waves in the Magnetopause Reconnection Exhaust Region
Authors: Ren Yong , Dai Lei , Wang Chi , Lavraud Benoit
Published: February 2023

Lower hybrid waves (LHWs) are frequently observed associated with magnetic reconnection. A general picture of the statistical properties of LHWs in magnetopause reconnection, however, has not yet been established. Here we report such a statistical study of LHWs using magnetospheric multiscale mission data in the magnetopause reconnection exhaust region. LHWs are identified in reconnection outflow regions over a broad range of magnetic local time. Most of the LHWs are near strong density gradients located on the low‐density magnetospheric side of the reconnection layer. The wave amplitude is typically several mV/m but can occasionally reach a few tens of mV/m. Compared with intervals that do not exhibit LHWs, intervals with LHWs show a ∼50% increase in parallel electron temperature, providing statistical evidence that LHWs contribute to parallel electron heating in reconnection exhausts and the dayside low‐latitude boundary layer.
Generating in vitro models of NTRK-fusion mesenchymal neoplasia as tools for investigating kinase oncogenic activation and response to targeted therapy
Authors: Vanoli Fabio , Herviou Laurie , Tsuda Yusuke , Sung Patricia , Xie Ziyu , Fishinevich Eve , Min Soe S. , Mallen William , de Wardin Henry de Traux , Zhang Yanming , Jasin Maria , Antonescu Cristina R.
Published: February 2023

The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as pan-tumor oncogenic drivers has led to new personalized therapies in oncology. Recent studies investigating NTRK fusions among mesenchymal neoplasms have identified several emerging soft tissue tumor entities displaying various phenotypes and clinical behaviors. Among them, tumors resembling lipofibromatosis or malignant peripheral nerve sheath tumors often harbor intra-chromosomal NTRK1 rearrangements, while most infantile fibrosarcomas are characterized by canonical ETV6::NTRK3 fusions. However, appropriate cellular models to investigate mechanisms of how kinase oncogenic activation through gene fusions drives such a wide spectrum of morphology and malignancy are lacking. Progress in genome editing has facilitated the efficient generation of chromosomal translocations in isogenic cell lines. In this study we employ various strategies to model NTRK fusions, including LMNA::NTRK1 (interstitial deletion) and ETV6::NTRK3 (reciprocal translocation) in human embryonic stem (hES) cells and mesenchymal progenitors (hES-MP). Here, we undertake various methods to model non-reciprocal, intrachromosomal deletions/translocations by induction of DNA double strand breaks (DSBs) exploiting either the repair mechanisms of homology directed repair (HDR) or non-homologous end joining (NHEJ). Expression of LMNA::NTRK1 or ETV6::NTRK3 fusions in either hES cells or hES-MP did not affect cell proliferation. However, the level of mRNA expression of the fusion transcripts was significantly upregulated in hES-MP, and phosphorylation of the LMNA::NTRK1 fusion oncoprotein was noted only in hES-MP but not in hES cells. Similarly, an NTRK1-driven transcriptional profile related to neuronal and neuroectodermal lineage was upregulated mainly in hES-MP, supporting the importance of appropriate cellular context in modeling cancer relevant aberrations. As proof of concept of the validity of our in vitro models, phosphorylation was depleted by two TRK inhibitors, Entrectinib and Larotrectinib, currently used as targeted therapy for tumors with NTRK fusions.
Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions
Authors: Chen Zhou , Han Fangfang , Du Yan , Shi Huaqing , Zhou Wence
Published: February 2023

Having a hypoxic microenvironment is a common and salient feature of most solid tumors. Hypoxia has a profound effect on the biological behavior and malignant phenotype of cancer cells, mediates the effects of cancer chemotherapy, radiotherapy, and immunotherapy through complex mechanisms, and is closely associated with poor prognosis in various cancer patients. Accumulating studies have demonstrated that through normalization of the tumor vasculature, nanoparticle carriers and biocarriers can effectively increase the oxygen concentration in the tumor microenvironment, improve drug delivery and the efficacy of radiotherapy. They also increase infiltration of innate and adaptive anti-tumor immune cells to enhance the efficacy of immunotherapy. Furthermore, drugs targeting key genes associated with hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, and drugs targeting hypoxia-inducible factors and downstream targets, can be used for visualization and quantitative analysis of tumor hypoxia and antitumor activity. However, the relationship between hypoxia and cancer is an area of research that requires further exploration. Here, we investigated the potential factors in the development of hypoxia in cancer, changes in signaling pathways that occur in cancer cells to adapt to hypoxic environments, the mechanisms of hypoxia-induced cancer immune tolerance, chemotherapeutic tolerance, and enhanced radiation tolerance, as well as the insights and applications of hypoxia in cancer therapy.
Artificial intelligence-enabled screening strategy for drug repurposing in monoclonal gammopathy of undetermined significance
Authors: Ryu Alexander J. , Kumar Shaji , Dispenzieri Angela , Kyle Robert A. , Rajkumar S. Vincent , Kingsley Thomas C.
Published: February 2023

Monoclonal gammopathy of undetermined significance (MGUS) is a benign hematological condition with the potential to progress to malignant conditions including multiple myeloma and Waldenstrom macroglobulinemia. Medications that modify progression risk have yet to be identified. To investigate, we leveraged machine-learning and electronic health record (EHR) data to screen for drug repurposing candidates. We extracted clinical and laboratory data from a manually curated MGUS database, containing 16,752 MGUS patients diagnosed from January 1, 2000 through December 31, 2021, prospectively maintained at Mayo Clinic. We merged this with comorbidity and medication data from the EHR. Medications were mapped to 21 drug classes of interest. The XGBoost module was then used to train a primary Cox survival model; sensitivity analyses were also performed limiting the study group to those with non-IgM MGUS and those with M-spikes >0.3 g/dl. The impact of explanatory features was quantified as hazard ratios after generating distributions using bootstrapping. Medication data were available for 12,253 patients; those without medications data were excluded. Our model achieved a good fit of the data with inverse probability of censoring weights concordance index of 0.883. The presence of multivitamins, immunosuppression, non-coronary NSAIDS, proton pump inhibitors, vitamin D supplementation, opioids, statins and beta-blockers were associated with significantly lower hazard ratio for MGUS progression in our primary model; multivitamins and non-coronary NSAIDs remained significant across both sensitivity analyses. This work could inform subsequent prospective studies, or similar studies in other disease states.
‘Potentially curative therapies’ for hepatocellular carcinoma: how many patients can actually be cured?
Authors: Cucchetti Alessandro , Elshaarawy Omar , Han Guohong , Chong Charing C. N. , Serra Carla , O’Rourke Joanne Marie , Crew Richard , Felicani Cristina , Ercolani Giorgio , Shah Tahir , Vogel Arndt , Lai Paul B. S. , Johnson Philip J.
Published: February 2023

Background

Treatment of hepatocellular carcinoma (HCC) is predicated on early diagnosis such that ‘curative therapies’ can be successfully applied. The term ‘curative’ is, however, poorly quantitated. We aimed to complement our previous work by developing a statistical model to predict cure after ablation and to use this analysis to compare the true curative potential of the various ‘curative’ therapies.

Methods

We accessed data from 1571 HCC patients treated in 5 centres receiving radiofrequency (RFA) or microwave (MWA) ablation and used flexible parametric modelling to determine the curative fraction. The results of this analysis were then combined with our previous estimations to provide a simple calculator applicable to all patients undergoing potentially curative therapies.

Results

The cure fraction was 18.3% rising to about 40% in patients with good liver function and very small tumours.

Conclusion

Cure for HCC treated with ablation occurs in the order of 20% to 30%, similar to that achievable by resection but much inferior to transplantation where the analogous figure is >70%. We provide a ‘calculator’ that permits clinicians to estimate the chance of cure for any individual patient, based on readily available clinical features.
Single cell epigenomic and transcriptomic analysis uncovers potential transcription factors regulating mitotic/meiotic switch
Authors: Zhang Fa-Li , Feng Yan-Qin , Wang Jing-Ya , Zhu Ke-Xin , Wang Lu , Yan Jia-Mao , Li Xiu-Xiu , Wang Jun-Jie , Ge Wei , De Felici Massimo , Shen Wei
Published: February 2023

In order to reveal the complex mechanism governing the mitotic/meiotic switch in female germ cells at epigenomic and genomic levels, we examined the chromatin accessibility (scATAC-seq) and the transcriptional dynamics (scRNA-seq) in germ cells of mouse embryonic ovary between E11.5 to 13.5 at single-cell resolution. Adopting a strict transcription factors (TFs) screening framework that makes it easier to understand the single-cell chromatin signature and a TF interaction algorithm that integrates the transcript levels, chromatin accessibility, and motif scores, we identified 14 TFs potentially regulating the mitotic/meiotic switch, including TCFL5, E2F1, E2F2, E2F6, E2F8, BATF3, SP1, FOS, FOXN3, VEZF1, GBX2, CEBPG, JUND, and TFDP1. Focusing on TCFL5, we constructed Tcfl5+/− mice which showed significantly reduced fertility and found that decreasing TCFL5 expression in cultured E12.5 ovaries by RNAi impaired meiotic progression from leptotene to zygotene. Bioinformatics analysis of published results of the embryonic germ cell transcriptome and the finding that in these cells central meiotic genes (Stra8, Tcfl5, Sycp3, and E2f2) possess open chromatin status already at the mitotic stage together with other features of TCFL5 (potential capability to interact with core TFs and activate meiotic genes, its progressive activation after preleptotene, binding sites in the promoter region of E2f2 and Sycp3), indicated extensive amplification of transcriptional programs associated to mitotic/meiotic switch with an important contribution of TCFL5. We conclude that the identified TFs, are involved in various stages of the mitotic/meiotic switch in female germ cells, TCFL5 primarily in meiotic progression. Further investigation on these factors might give a significant contribution to unravel the molecular mechanisms of this fundamental process of oogenesis and provide clues about pathologies in women such as primary ovarian insufficiency (POI) due at least in part to meiotic defects.
Association between levels of exposure to heavy metals and renal function indicators of residents in environmentally vulnerable areas
Authors: Kwon Jung-Yeon , Lee Seungho , Surenbaatar Ulziikhishig , Lim Hyoun-Ju , Kim Byoung-Gwon , Eom Sang-Yong , Cho Yong Min , Kim Woo Jin , Yu Byeng-Chul , Lee Kwan , Hong Young-Seoub
Published: February 2023

Abandoned metal mines and refineries are considered environmentally vulnerable areas owing to high levels of exposure to heavy metals. This study examined the association between heavy metal exposure and renal function indicators. We studied a total of 298 participants, of which 74 and 68 resided in low- and high-exposure abandoned metal mine areas, respectively, with 121 in the refinery area and 35 in the control area. Blood and urine samples were collected from the participants to analyze the levels of blood lead, cadmium, and creatinine and urinary cadmium, NAG, and β2-MG. The estimated glomerular filtration rate, which is calculated using the Chronic Kidney Disease Epidemiology Collaboration equation, was used for assessments. The study participants comprised more females than males, and their mean age was 70.3 years. The blood lead and cadmium as well as urinary cadmium levels were 2.12 μg/dL, 1.89 μg/L, and 2.11 μg/L, respectively, in the heavy metal-exposure areas, and 1.18 μg/dL, 0.89 μg/L, and 1.11 μg/L, respectively, in the control area. The odds ratio (OR) for exceeding the reference value showed that blood cadmium in the refinery area was 38 times higher than that in the control area. Urinary cadmium was seven times higher in the low-exposure abandoned metal mine area than in the control area. NAG showed a positive correlation with urinary cadmium in all areas. In the refinery area, correlations were observed between β2-MG and urinary cadmium levels and the eGFR and blood cadmium level; in the high-exposure abandoned metal mine area, correlations were observed between NAG, β2-MG, and the eGFR and blood cadmium. In this study, the association between Cd exposure and some renal function indicators was observed. This study’s findings and the obtained biological samples can serve as a basis for future molecular biological research.
Identifying ways of producing pigs more sustainably: tradeoffs and co-benefits in land and antimicrobial use
Authors: Bartlett Harriet , Balmford Andrew , Wood James L. N. , Holmes Mark A.
Published: February 2023

Pork accounts for the largest proportion of meat consumed globally and demand is growing rapidly. Two important externalities of pig farming are land use and antimicrobial resistance (AMR) driven by antimicrobial use (AMU). Land use and AMU are commonly perceived to be negatively related across different production systems, so those with smaller land footprints pose greater risk to human health. However, the relationship between land use and AMU has never been systematically evaluated. We addressed this by measuring both outcomes for 74 highly diverse pig production systems. We found weak evidence of an AMU/land use tradeoff. We also found several systems characterized by low externality costs in both domains. These potentially promising systems were spread across different label and husbandry types and indeed no type was a reliable indicator of low-cost systems in both externalities. Our findings highlight the importance of using empirical evidence in decision-making, rather than relying on assumptions.
Corrosion damage and life prediction of concrete structure in the coking ammonium sulfate workshop of iron and steel industry
Authors: Lv Yao , Niu Ditao , Liu Xiguang , Lin Mingqiang , Li Yue-chen
Published: February 2023

Iron and steel plants emit a large amount of CO2 and SO2 in the production process, and the high concentrations of acid gases lead to serious corrosion damage of concrete structures. In this paper, the environmental characteristics and corrosion damage degree of concrete in a 7-year-old coking ammonium sulfate workshop were investigated, and the neutralization life prediction of the concrete structure was carried out. Besides, the corrosion products were analyzed through concrete neutralization simulation test. The average temperature and relative humidity in the workshop were 34.7 °C and 43.4%, and they were 1.40 times higher and 1.70 times less than those of the general atmospheric environment, respectively. Both the concentrations of CO2 and SO2 were significantly different in various sections of the workshop, and they were much higher than those of the general atmospheric environment. The appearance corrosion and compressive strength loss of concrete were more serious in the sections with high SO2 concentration, such as vulcanization bed section and crystallization tank section. The neutralization depth of concrete in the crystallization tank section was the largest, with an average value of 19.86 mm. The corrosion products gypsum and CaCO3 were obviously visible in the surface layer of concrete, while only CaCO3 could be observed at 5 mm. The prediction model of concrete neutralization depth was established, and the remaining neutralization service life in the warehouse, synthesis section (indoor), synthesis section (outdoor), vulcanization bed section, and crystallization tank section were 69.21 a, 52.01 a, 88.56 a, 29.62 a, and 7.84 a, respectively.
Inflammatory biomarkers, angiogenesis and lymphangiogenesis in epicardial adipose tissue correlate with coronary artery disease
Authors: Si Yueqiao , Feng Zengbin , Liu Yixiang , Fan Wenjun , Shan Weichao , Zhang Ying , Shi Fei , Xing Enhong , Sun Lixian
Published: February 2023

In this study, we explored the relationship between inflammatory adipokine levels and coronary artery disease (CAD). We collected subcutaneous adipose tissues(SAT), pericardial adipose tissues(PAT), and epicardial adipose tissues (EAT) and serum samples from 26 inpatients with CAD undergone coronary artery bypass grafting and 20 control inpatients without CAD. Serum inflammatory adipokines were measured by ELISA. Quantitative real-time PCR and western blot were used to measure gene and protein expression. Adipocyte morphology was assessed by H&E staining. Immunohistochemistry and immunofluorescence were used to measure endothelial and inflammatory markers. Serum pro- and anti-inflammatory adipokine levels were higher and lower, respectively, in the CAD group than those in the control group (P < 0.05). In CAD, the pro-inflammatory adipokine levels via ELISA in EAT and PAT were elevated. Pro-inflammatory adipokine mRNA expression was increased, while anti-inflammatory adipokine mRNA expression decreased, in CAD relative to NCAD in EAT and PAT rather than SAT. In EAT, adipocyte area and macrophage-specific staining were lower, while lymphatic vessel marker expression was higher in CAD. Additionally, the endothelial marker expression in EAT was higher than PAT in CAD. The three tissue types had different blood vessel amounts in CAD. The regulation and imbalance expression of the novel biomarkers, including inflammatory adipokine, macrophage infiltration, angiogenesis, and lymphangiogenesis in EAT and PAT, may be related to the pathogenesis of CAD. The serum levels of inflammatory adipokines may correlate to CAD, which requires large sample size studies to get further validation before clinic practice.
Machine learning intelligence to assess the shear capacity of corroded reinforced concrete beams
Authors: Kumar Aman , Arora Harish Chandra , Kapoor Nishant Raj , Kumar Krishna , Hadzima-Nyarko Marijana , Radu Dorin
Published: February 2023

The ability of machine learning (ML) techniques to forecast the shear strength of corroded reinforced concrete beams (CRCBs) is examined in the present study. These ML techniques include artificial neural networks (ANN), adaptive-neuro fuzzy inference systems (ANFIS), decision tree (DT) and extreme gradient boosting (XGBoost). A thorough databank with 140 data points about the shear capacity of CRCBs with various degrees of corrosion was compiled after a review of the literature. The inputs parameters of the implemented models are the width of the beam, the effective depth of the beam, concrete compressive strength (CS), yield strength of reinforcement, percentage of longitudinal reinforcement, percentage of transversal reinforcement (stirrups), yield strength of stirrups, stirrups spacing, shear span-to-depth ratio (a/d), corrosion degree of main reinforcement, and corrosion degree of stirrups. The coefficient of determination of the ANN, ANFIS, DT, and XGBoost models are 0.9811, 0.9866, 0.9799, and 0.9998, respectively. The MAPE of the XGBoost model is 99.39%, 99.16%, and 99.28% lower than ANN, ANFIS, and DT models. According to the results of the sensitivity examination, the shear strength of the CRCBs is most affected by the depth of the beam, stirrups spacing, and the a/d. The graphical displays of the Taylor graph, violin plot, and multi-histogram plot additionally support the XGBoost model's dependability and precision. In addition, this model demonstrated good experimental data fit when compared to other analytical and ML models. Accurate prediction of shear strength using the XGBoost approach confirmed that this approach is capable of handling a wide range of data and can be used as a model to predict shear strength with higher accuracy. The effectiveness of the developed XGBoost model is higher than the existing models in terms of precision, economic considerations, and safety, as indicated by the comparative study.
The association between muscle architecture and muscle spindle abundance
Authors: Kissane Roger W. P. , Charles James P. , Banks Robert W. , Bates Karl T.
Published: February 2023

Across the human body, skeletal muscles have a broad range of biomechanical roles that employ complex proprioceptive control strategies to successfully execute a desired movement. This information is derived from peripherally located sensory apparatus, the muscle spindle and Golgi tendon organs. The abundance of these sensory organs, particularly muscle spindles, is known to differ considerably across individual muscles. Here we present a comprehensive data set of 119 muscles across the human body including architectural properties (muscle fibre length, mass, pennation angle and physiological cross-sectional area) and statistically test their relationships with absolute spindle number and relative spindle abundance (the residual value of the linear regression of the log-transformed spindle number and muscle mass). These data highlight a significant positive relationship between muscle spindle number and fibre length, emphasising the importance of fibre length as an input into the central nervous system. However, there appears to be no relationship between muscles architecturally optimised to function as displacement specialists and their provision of muscle spindles. Additionally, while there appears to be regional differences in muscle spindle abundance, independent of muscle mass and fibre length, our data provide no support for the hypothesis that muscle spindle abundance is related to anatomical specialisation.