bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic and photosynthetic analyses of Synechocystis sp. PCC6803 and Chlorogloeopsis fritschii sp. PCC6912 exposed to an M-dwarf spectrum under an anoxic atmosphere
Authors: Battistuzzi Mariano , Morlino Maria Silvia , Cocola Lorenzo , Trainotti Livio , Treu Laura , Campanaro Stefano , Claudi Riccardo , Poletto Luca , La Rocca Nicoletta
Published: January 2024

Introduction

Cyanobacteria appeared in the anoxic Archean Earth, evolving for the first time oxygenic photosynthesis and deeply changing the atmosphere by introducing oxygen. Starting possibly from UV-protected environments, characterized by low visible and far-red enriched light spectra, cyanobacteria spread everywhere on Earth thanks to their adaptation capabilities in light harvesting. In the last decade, few cyanobacteria species which can acclimate to far-red light through Far-Red Light Photoacclimation (FaRLiP) have been isolated. FaRLiP cyanobacteria were thus proposed as model organisms to study the origin of oxygenic photosynthesis as well as its possible functionality around stars with high far-red emission, the M-dwarfs. These stars are astrobiological targets, as their longevity could sustain life evolution and they demonstrated to host rocky terrestrial-like exoplanets within their Habitable Zone.

Methods

We studied the acclimation responses of the FaRLiP strain Chlorogloeopsis fritschii sp. PCC6912 and the non-FaRLiP strain Synechocystis sp. PCC6803 to the combination of three simulated light spectra (M-dwarf, solar and far-red) and two atmospheric compositions (oxic, anoxic). We first checked their growth, O2 production and pigment composition, then we studied their transcriptional responses by RNA sequencing under each combination of light spectrum and atmosphere conditions.

Results and discussion

PCC6803 did not show relevant differences in gene expression when comparing the responses to M-dwarf and solar-simulated lights, while far-red caused a variation in the transcriptional level of many genes. PCC6912 showed, on the contrary, different transcriptional responses to each light condition and activated the FaRLiP response under the M-dwarf simulated light. Surprisingly, the anoxic atmosphere did not impact the transcriptional profile of the 2 strains significantly. Results show that both cyanobacteria seem inherently prepared for anoxia and to harvest the photons emitted by a simulated M-dwarf star, whether they are only visible (PCC6803) or also far-red photons (PCC6912). They also show that visible photons in the simulated M-dwarf are sufficient to keep a similar metabolism with respect to solar-simulated light.

Conclusion

Results prove the adaptability of the cyanobacterial metabolism and enhance the plausibility of finding oxygenic biospheres on exoplanets orbiting M-dwarf stars.
Validation of the digital health literacy assessment among the university students in China
Authors: Nie Limei , Zhao Jiajia , Pan Lutong , Pang Mingli , Wang Jieru , Zhou Yue , Chen Rui , Liu Hui , Xu Xixing , Su Baochen , Kong Fanlei
Published: January 2024

Purpose

With the development of the internet, digital health literacy (DHL) has become increasingly important for managing health. Consequently, various digital health literacy scales have been created for different groups. The purpose of this study was to verify the reliability and validity of the simplified Chinese version of the Digital Health Literacy Assessment (DHLA) scale among university students in China.

Method

Snowball sampling was used to recruit the participants via an online platform (Wenjuan.com), and finally 304 university students were included in the survey. Demographic information and the status of DHL were collected through the online questionnaire. Cronbach’s alpha and split-half reliability were used to test the internal consistency of the scale, while the structural validity was verified by exploratory factor analysis and confirmatory factor analysis. Additionally, the convergence of the scale was tested by composite reliability (CR) and average variance extracted (AVE).

Result

Two dimensions were generated from 10 entries in the scale, named Self-rated Digital Health Literacy and Trust Degree of Online Health Information, respectively. The Cronbach’s alpha and split-half reliability of the total scale were 0.912 and 0.828, while the Cronbach’s alpha of the two dimensions were 0.913 and 0.830, respectively. The structural validity-related indexes of the scale met the standards (RMSEA = 0.079, GFI = 0.943, AGFI = 0.902, CFI = 0.971). In each dimension, the CR and AVE also reached critical values (CR > 0.7 and AVE > 0.5).

Conclusion

The scale had high reliability and validity, indicating the simplified Chinese DHLA scale could be used to evaluate the DHL of university students in China.
High resolution and contrast 7 tesla MR brain imaging of the neonate
Authors: Bridgen Philippa , Tomi-Tricot Raphael , Uus Alena , Cromb Daniel , Quirke Megan , Almalbis Jennifer , Bonse Beya , De la Fuente Botella Miguel , Maggioni Alessandra , Cio Pierluigi Di , Cawley Paul , Casella Chiara , Dokumaci Ayse Sila , Thomson Alice R. , Willers Moore Jucha , Bridglal Devi , Saravia Joao , Finck Thomas , Price Anthony N. , Pickles Elisabeth , Cordero-Grande Lucilio , Egloff Alexia , O’Muircheartaigh Jonathan , Counsell Serena J. , Giles Sharon L. , Deprez Maria , De Vita Enrico , Rutherford Mary A. , Edwards A. David , Hajnal Joseph V. , Malik Shaihan J. , Arichi Tomoki
Published: January 2024

Introduction

Ultra-high field MR imaging offers marked gains in signal-to-noise ratio, spatial resolution, and contrast which translate to improved pathological and anatomical sensitivity. These benefits are particularly relevant for the neonatal brain which is rapidly developing and sensitive to injury. However, experience of imaging neonates at 7T has been limited due to regulatory, safety, and practical considerations. We aimed to establish a program for safely acquiring high resolution and contrast brain images from neonates on a 7T system.

Methods

Images were acquired from 35 neonates on 44 occasions (median age 39 + 6 postmenstrual weeks, range 33 + 4 to 52 + 6; median body weight 2.93 kg, range 1.57 to 5.3 kg) over a median time of 49 mins 30 s. Peripheral body temperature and physiological measures were recorded throughout scanning. Acquired sequences included T2 weighted (TSE), Actual Flip angle Imaging (AFI), functional MRI (BOLD EPI), susceptibility weighted imaging (SWI), and MR spectroscopy (STEAM).

Results

There was no significant difference between temperature before and after scanning (p = 0.76) and image quality assessment compared favorably to state-of-the-art 3T acquisitions. Anatomical imaging demonstrated excellent sensitivity to structures which are typically hard to visualize at lower field strengths including the hippocampus, cerebellum, and vasculature. Images were also acquired with contrast mechanisms which are enhanced at ultra-high field including susceptibility weighted imaging, functional MRI, and MR spectroscopy.

Discussion

We demonstrate safety and feasibility of imaging vulnerable neonates at ultra-high field and highlight the untapped potential for providing important new insights into brain development and pathological processes during this critical phase of early life.
Econometric modeling of tobacco exports in the milieu of changing global and national policy regimes: repercussions on the Indian tobacco sector
Authors: Reddy K. Viswanatha , Paramesha V. , Kumar K. N. Ravi , Asci S. , Immanuelraj T. K. , Madhav M. Sheshu , Sendhil R. , Konduru S. , Rao K. Prabhakara , Ramasundaram P.
Published: January 2024

Introduction

Tobacco, an important commercial crop, plays a crucial role in farmers' incomes and livelihoods to a sizable population and contributes significant exchange earnings to the Indian economy. Currently, India is the second-largest tobacco producer after China, with a production of 758 million kg (13% of global production) and exports of ~190 million kg of tobacco (9% of global tobacco export volume). However, there are uncertainties surrounding the tobacco sector, such as growing public health and environmental issues associated with tobacco production and consumption and changing national and international tobacco-related policy regimes. In this context, the current study investigates the determinants of tobacco exports and geographical shifts in export destinations over the years.

Methods

The statistical models employed are co-integration, and vector error-correlation models to test the short-run and long-run dynamics relationship between tobacco exports and the explanatory variables, and the Markov chain approach to find out geographical shifts in export destinations.

Results and discussion

The econometric model estimated the relationship between the tobacco export volume with domestic production, export price, and global demand for Indian tobacco, and investigated the geographical shift in export destinations of tobacco in the context of changing global and national policy regimes on the sector. The econometric modeling framework confirms that there exists a statistically significant relationship between Indian tobacco export demand, domestic production, export price, and world demand for Indian tobacco. The geographical shift was evident in major export destinations during the post-WHO-FCTC (Framework Convention on Tobacco Control) regime. The model findings direct that India should take advantage of the export price, and global demand for tobacco as India ratified WHO-FCTC; there is no scope for horizontal expansion of the area under tobacco. This modeling framework aids as a tool to direct and explore the possible options with a greater emphasis on export-centric farming system in tobacco production by augmenting crop compliance and quality to meet the standards of international markets.
“Early intervention isn't an option, it's a necessity”: learning from implementation facilitators and challenges from the rapid scaling of an early intervention eating disorders programme in England
Authors: Hyam Lucy , Torkelson Claire , Richards Katie , Semple Amy , Allen Karina L. , Owens Jill , Jackson Aileen , Semple Laura , Glennon Danielle , Di Clemente Giulia , Schmidt Ulrike
Published: January 2024

Introduction

The First Episode Rapid Early Intervention for Eating Disorders (FREED) service has shown promising outcomes for young people with an eating disorder, leading to national scaling and implementation across England. Between 2020 and 2023, the national implementation of FREED was supported by the Academic Health Science Networks (AHSNs), which are publicly funded organisations with the mission to spread innovations at scale and pace. This study aimed to investigate the views and experiences of AHSN programme leads on the national roll-out of FREED and the perceived sustainability of the model.

Methods and results

Semi-structured interviews were conducted with 13 programme leads across the AHSNs with direct experience supporting the national implementation of FREED. Thematic analysis was adopted using a critical realist approach. Initial sub-themes were inductively generated and then organised under seven larger themes representing the domains of the Non-adoption, Abandonment, and Challenges to Scale-Up, Spread and Sustainability (NASSS) framework. Each sub-theme was classified as a facilitator and/or barrier and then each larger theme/domain was assessed for its complexity (simple, complicated, complex). Data analysis revealed 28 sub-themes, 10 identified as facilitators, 13 as barriers, and five as both. Two domains were classed as simple, three as complicated, and two as complex. Sub-themes ranged from illness-related complexities to organisational pressures. Key facilitators included a high-value proposition for FREED and a supportive network. Key barriers included staffing issues and illness-related factors that challenge early intervention.

Discussion

Participants described broad support for FREED but desired sustained investment for continued provision and improving implementation fidelity. Future development areas raised by participants included enlarging the evidence base for early intervention, increasing associated training opportunities, and widening the reach of FREED. Results offer learning for early intervention in eating disorders and the scaling of new health initiatives.
What is an Herbarium and How Does it Help Us Protect Biodiversity?
Authors: Fortier Riley P. , Heberling J. Mason , Feeley Kenneth J.
Published: January 2024

When scientists study plants, they often collect, preserve, and store parts of the plants in a big collection called an herbarium. These plant specimens serve as proof that a species was growing in a certain place at a certain time. Herbaria (“herbaria” is the plural of herbarium) are where scientists describe new plant species and study how different species are related. Herbaria also contain lots of information about where certain plant species grow, what type of habitats species like, and at what time of year plants bloom and make fruits. Finally, herbaria are powerful tools for helping us understand how plants are affected by disturbances like habitat destruction and climate change. For all of these reasons, herbaria allow us to better understand and protect plant species all over the world. To continue benefitting from herbaria, we need to keep collecting plants and make these collections accessible to the world.
Trends and climate response in the yield of staple crops across Northeast China
Authors: Xiao Dengpan , Yang Xiaohui , Bai Huizi , Tang Jianzhao , Tao Fulu
Published: January 2024

Understanding how climate change has been affecting crop yield is a prerequisite to inform adaptation decisions and to ensure global food security. The Northeast China (NEC), located in high-latitude area, is significantly affected by climate change. There is a high demand for quantitative information on impacts of climate variability on crop yields in NEC. In this study, we applied panel regression models to explore the yield-climate relationship and its spatial variations based on experimentally observed yield (Ys) and the county-scale statistical yield (Yc) of three typical crops (e.g., maize, rice and soybean) across NEC from 1981 to 2010, as well as contemporary climate data. The results indicated that Ys (Yc) of maize, rice and soybean during the past three decades increased by 64.2% (82.0%), 47.5% (55.3%), and 59.2% (58.0%), respectively. Moreover, we found climate during crop growth period had changed significantly and the change had caused measurable impacts on crop yields. Changes in temperature, precipitation and solar radiation jointly decreased Ys (Yc) of maize and soybean by 1.3% (0.7%) and 0.3% (1.1%), respectively, however increased Ys (Yc) of rice by 1.2% (2.2%), with a large spatial difference. Therefore, the impact of climate change on yields of three crops was far less than the actual increase in crop yields. Our finding suggest that other factors, mainly improved management practices, may be the main reason for the significant increase in crop yields in NEC over the past few decades. Although historical climate change also played an important role in the yields of three crops, certain improvement in management measures not only compensated for the negative impact of climate change, but also greatly promoted the increase in crop yields. Therefore, in proposing strategies for crop production to cope with climate change, we need in-depth assessments of the role of improved management.
Influences of nitrogen input forms and levels on phosphorus availability in karst grassland soils
Authors: Zhou Jing , Yang Fugui , Zhao Xuechun , Gu Xinyao , Chen Chao , Chen Jihui
Published: January 2024

The availability of soil phosphorus (P), a crucial nutrient influencing plant productivity and ecosystem function, is impacted by continuously increasing nitrogen (N) enrichment, which changes the soil P cycle. The effect of varying forms of N input on soil P dynamics in P-limited karst grassland ecosystems remains unclear. To address this knowledge gap, we conducted a greenhouse experiment to explore the effects of various forms of N addition [Ca(NO3)2, NH4Cl, NH4NO3, Urea] on soil P fractions in these ecosystems, applying two levels (N1: 50 mg N kg−1soil, N2: 100 mg N kg−1soil) of N input in two soils (yellow soil, limestone soil). Results indicated that P fractions in both soil types were significantly affected by N additions, with yellow soil demonstrating a higher sensitivity to these additions, and this effect was strongly modulated by the form and level of N added. High N addition, rather than low N, significantly affect the P fractions in both soil types. Specially, except for Ca(NO3)2, high N addition significantly increased the available P in both soils, following the order: Urea and NH4NO3 > NH4Cl > Ca(NO3)2, and decreased NaHCO3-Pi in both soils. High N addition also significantly reduced NaOH-Po and C.HCl-Po fractions in yellow soil. Additionally, the response of root biomass and alkaline phosphatase activity in both soils to N input paralleled the trends observed in the available P fractions. Notably, changes in soil available P were strongly correlated with plant root biomass and soil alkaline phosphatase activity. Our study highlights that the N addition form significantly influences soil P availability, which is closely tied to plant root biomass and alkaline phosphatase activity. This finding underscores the importance of considering N input form to boost soil fertility and promote sustainable agriculture.
Glucose Concentration in Regulating Induced Pluripotent Stem Cells Differentiation Toward Insulin-Producing Cells
Authors: Wang Chencheng , Abadpour Shadab , Olsen Petter Angell , Wang Daxin , Stokowiec Justyna , Chera Simona , Ghila Luiza , Ræder Helge , Krauss Stefan , Aizenshtadt Aleksandra , Scholz Hanne
Published: January 2024

The generation of insulin-producing cells from human-induced pluripotent stem cells holds great potential for diabetes modeling and treatment. However, existing protocols typically involve incubating cells with un-physiologically high concentrations of glucose, which often fail to generate fully functional IPCs. Here, we investigated the influence of high (20 mM) versus low (5.5 mM) glucose concentrations on IPCs differentiation in three hiPSC lines. In two hiPSC lines that were unable to differentiate to IPCs sufficiently, we found that high glucose during differentiation leads to a shortage of NKX6.1+ cells that have co-expression with PDX1 due to insufficient NKX6.1 gene activation, thus further reducing differentiation efficiency. Furthermore, high glucose during differentiation weakened mitochondrial respiration ability. In the third iPSC line, which is IPC differentiation amenable, glucose concentrations did not affect the PDX1/NKX6.1 expression and differentiation efficiency. In addition, glucose-stimulated insulin secretion was only seen in the differentiation under a high glucose condition. These IPCs have higher KATP channel activity and were linked to sufficient ABCC8 gene expression under a high glucose condition. These data suggest high glucose concentration during IPC differentiation is necessary to generate functional IPCs. However, in cell lines that were IPC differentiation unamenable, high glucose could worsen the situation.
Integrated Microbiome and Metabolomics Analysis of the Effects of Dietary Supplementation with Corn-Steep-Liquor-Derived Candida utilis Feed on Black Pigs
Authors: Qi Huiyu , Wang Ruqi , Wang Chuanqi , Wang Rui , Shen Jinglin , Fang Hengtong , Zhang Jing
Published: January 2024

In this experiment, glucose master liquor and corn steep liquor were used as carbon and nitrogen sources, and Candida utilis was used as a strain to ferment yeast feed. The OD value and number of yeast cells were used as response values to optimize the medium components of the yeast feed through a response surface methodology. The optimal medium components were a glucose master liquor concentration of 8.3%, a corn steep liquor concentration of 1.2%, and a KH2PO4 concentration of 0.14%. Under this condition of fermentation, the OD value was 0.670 and the number of yeast cells was 2.72 × 108/mL. Then, we fed Candida utilis feed to Dongliao black piglets, and the effects of the yeast feed on the piglets’ growth performance, fecal microbiota, and plasma metabolic levels were investigated through 16S rDNA sequencing and metabolomics. In total, 120 black piglets with an average initial weight of 6.90 ± 1.28 kg were randomly divided into two groups. One group was fed the basic diet (the CON group), and the other was supplemented with 2.5% Candida utilis add to the basic diet (the 2.5% CU group). After a pre-feeding period, the formal experiments were performed for 21 days. The results showed that the addition of Candida utilis to the diet did not affect growth performance compared with the control group. Meanwhile, no significant differences were observed in the serum biochemical indices. However, piglets in the 2.5% CU group had a significantly altered fecal microbiota, with an increased abundance of Clostridium_sensu_stricto_1, Lactobacillus, and Muribaculaceae_unclassified. Regarding the plasma metabolome, the 12 differential metabolites detected were mainly enriched in the histidine, tryptophan, primary bile acid, and caffeine metabolic pathways. Regarding the integrated microbiome–metabolome analysis, differential metabolites correlated with fecal flora to variable degrees, but most of them were beneficial bacteria of Firmicutes. Collectively, dietary Candida utilis feed had no adverse effect on growth performance; however, it played an important role in regulating fecal flora and maintaining metabolic levels.
Laboratory Evolution of Antimicrobial Resistance in Bacteria to Develop Rational Treatment Strategies
Authors: Maeda Tomoya , Furusawa Chikara
Published: January 2024

Laboratory evolution studies, particularly with Escherichia coli, have yielded invaluable insights into the mechanisms of antimicrobial resistance (AMR). Recent investigations have illuminated that, with repetitive antibiotic exposures, bacterial populations will adapt and eventually become tolerant and resistant to the drugs. Through intensive analyses, these inquiries have unveiled instances of convergent evolution across diverse antibiotics, the pleiotropic effects of resistance mutations, and the role played by loss-of-function mutations in the evolutionary landscape. Moreover, a quantitative analysis of multidrug combinations has shed light on collateral sensitivity, revealing specific drug combinations capable of suppressing the acquisition of resistance. This review article introduces the methodologies employed in the laboratory evolution of AMR in bacteria and presents recent discoveries concerning AMR mechanisms derived from laboratory evolution. Additionally, the review outlines the application of laboratory evolution in endeavors to formulate rational treatment strategies.
Brain Frontal-Lobe Misery Perfusion in COVID-19 ICU Survivors: An MRI Pilot Study
Authors: Song Jie , Khanduja Shivalika , Rando Hannah , Shi Wen , Hazel Kaisha , Pottanat George Paul , Jones Ebony , Xu Cuimei , Hu Zhiyi , Lin Doris , Yasar Sevil , Lu Hanzhang , Cho Sung-Min , Jiang Dengrong
Published: January 2024

Post-acute COVID-19 syndrome (PCS) is highly prevalent. Critically ill patients requiring intensive care unit (ICU) admission are at a higher risk of developing PCS. The mechanisms underlying PCS are still under investigation and may involve microvascular damage in the brain. Cerebral misery perfusion, characterized by reduced cerebral blood flow (CBF) and elevated oxygen extraction fraction (OEF) in affected brain areas, has been demonstrated in cerebrovascular diseases such as carotid occlusion and stroke. This pilot study aimed to examine whether COVID-19 ICU survivors exhibited regional misery perfusion, indicating cerebral microvascular damage. In total, 7 COVID-19 ICU survivors (4 female, 20–77 years old) and 19 age- and sex-matched healthy controls (12 female, 22–77 years old) were studied. The average interval between ICU admission and the MRI scan was 118.6 ± 30.3 days. The regional OEF was measured using a recently developed technique, accelerated T2-relaxation-under-phase-contrast MRI, while the regional CBF was assessed using pseudo-continuous arterial spin labeling. COVID-19 ICU survivors exhibited elevated OEF (β = 5.21 ± 2.48%, p = 0.047) and reduced relative CBF (β = −0.083 ± 0.025, p = 0.003) in the frontal lobe compared to healthy controls. In conclusion, misery perfusion was observed in the frontal lobe of COVID-19 ICU survivors, suggesting microvascular damage in this critical brain area for high-level cognitive functions that are known to manifest deficits in PCS. Physiological biomarkers such as OEF and CBF may provide new tools to improve the understanding and treatment of PCS.
Positive Well-Being, Work-Related Rumination and Work Engagement among Chinese University Logistics Staff
Authors: Zheng Siyao , Tan Shuyue , Tan Xiaotong , Fan Jialin
Published: January 2024

Logistics personnel in Chinese universities are facing unbalanced costs and benefit from overloaded work with minimum wages, which impede school development and their well-being. However, the logistics staff population has been neglected in past investigations pertaining to psychological health conditions. The present study aimed to examine the positive well-being, work-related rumination, and work engagement of logistics staff, their correlations, and the factors affecting well-being in 282 Chinese university logistics staff via the Smith Well-being Questionnaire, the Work-Related Rumination Questionnaire, and the Utrecht Work Engagement Scale. The results indicated low levels of well-being and high levels of work-related rumination and work engagement among Chinese university logistics staff. The presence of positive attitudes towards life and work and high levels of work engagement predicts enhanced well-being, while the presence of negative characteristics and work-related rumination predicts decreased well-being. In situations where the working hours and work duties are challenging to change, universities can regularly schedule psychological counselling sessions for logistics staff to improve their well-being.
Intramedullary Spinal Cord Tumors: Whole-Genome Sequencing to Assist Management and Prognosis
Authors: Mayol del Valle Miguel , Morales Bryan , Philbrick Brandon , Adeagbo Segun , Goyal Subir , Newman Sarah , Frontera Natasha L. , Nduom Edjah , Olson Jeffrey , Neill Stewart , Hoang Kimberly
Published: January 2024

Intramedullary spinal cord tumors (IMSCTs) harbor unique genetic mutations which may play a role in prognostication and management. To this end, we present the largest cohort of IMSCTs with genetic characterization in the literature from our multi-site institutional registry. A total of 93 IMSCT patient records were reviewed from the years 1999 to 2020. Out of these, 61 complied with all inclusion criteria, 14 of these patients had undergone genetic studies with 8 undergoing whole-genomic sequencing. Univariate analyses were used to assess any factors associated with progression-free survival (PFS) using the Cox proportional hazards model. Firth’s penalized likelihood approach was used to account for the low event rates. Fisher’s exact test was performed to compare whole-genome analyses and specific gene mutations with progression. PFS (months) was given as a hazard ratio. Only the absence of copy neutral loss of heterozygosity (LOH) was shown to be significant (0.05, p = 0.008). Additionally, higher risk of recurrence/progression was associated with LOH (p = 0.0179). Our results suggest LOH as a genetic predictor of shorter progression-free survival, particularly within ependymoma and glioblastoma tumor types. Further genomic research with larger multi-institutional datasets should focus on these mutations as possible prognostic factors.
Predictive Factors for Critical Weight Loss in Saudi Head and Neck Cancer Patients Undergoing (Chemo)Radiotherapy
Authors: Redwan Alaa S. , Kattan Fayrooz A. , Alidrisi Maha A. , Ali Gayur A. , Ghaith Mazen M. , Arbaeen Ahmad F. , Almasmoum Hussain A. , Almohmadi Najlaa H. , Alkholy Sarah O. , Alhassani Walaa E. , Abusudah Wafaa F. , Babateen Abrar M. , Ghabashi Mai A. , Obeidat Ahmad A. , Al Yacoub Azzam N. , Alazzeh Awfa Y. , Azzeh Firas S.
Published: January 2024

Weight loss is a significant health problem among patients with head and neck cancer (HNC) that is attributable primarily to the tumor or tumor therapy. Critical weight loss (CWL) is defined as the unintentional loss of ≥5% of weight. Therefore, this study’s goal was to investigate and determine the possible factors influencing CWL among patients with HNC who have received radiotherapy or concurrent chemoradiotherapy (CCRT). We conducted a retrospective analysis of 175 patients who received radiotherapy or CCRT as either their primary, adjuvant, or combined treatment at the Oncology Center in King Abdullah Medical City. All patients were ≥18 years of age and diagnosed with HNC with no metastasis. The study results showed that 107 patients (61%) had CWL, while 68 (39%) did not. The following factors were significantly predictive of CWL with a multivariate regression analysis: pretreatment BMI (AOR = 1.1, 95% CI = 1.02–1.17), oral cavity cancer (AOR = 10.36, 95% CI = 1.13–94.55), and male sex (AOR = 3.15, 95% CI = 1.39–7.11). In conclusion, weight loss is highly prevalent among HNC patients during treatment. Accordingly, pretreatment BMI, cancer in the oral cavity, and being male can be considered predictive factors for CWL.
Influence of the La0.2Sr0.7Ti0.95Ni0.05O3 (LSTN) Synthesis Method on SOFC Anode Performance
Authors: Dahan Moran , Fadeev Ludmila , Hayun Hagay , Gozin Michael , Gelbstein Yaniv , Rosen Brian A.
Published: January 2024

Solid oxide fuel cells are characterized by a high efficiency for converting chemical energy into electricity and fuel flexibility. This research work focuses on developing durable and efficient anodes for solid oxide fuel cells (SOFCs) based on exsolving nickel from the perovskite structure. A-site-deficient La- and Ni-doped strontium titanates (La0.2Sr0.7Ti0.95Ni0.05O3−δ, LSTN) were synthesized using four different techniques and mixed with Ce0.8Gd0.2O2−δ (GDC) to form the SOFC anode. The synthesis routes of interest for comparison included solid-state, sol-gel, hydrothermal, and co-precipitation methods. LSTN powders were characterized via XRD, SEM, TPR, BET and XPS. In situ XRD during reduction was measured and the reduced powders were analyzed using TEM. The impact of synthesis route on SOFC performance was investigated. All samples were highly durable when kept at 0.5 V for 48 h at 800 °C with H2 fuel. Interestingly, the best performance was observed for the cell with the LSTN anode prepared via co-precipitation, while the conventional solid-state synthesis method only achieved the second-best results.
TGFβ and Hippo Signaling Pathways Coordinate to Promote Acinar to Ductal Metaplasia in Human Pancreas
Authors: Nipper Michael , Xu Yi , Liu Jun , Yin Xue , Liu Zhijie , Ye Zhengqing , Zhang Jianmin , Chen Yidong , Wang Pei
Published: January 2024

Background & Aims: Acinar-to-ductal metaplasia (ADM) serves as a precursor event in the development of pancreatic ductal adenocarcinoma (PDAC) upon constitutive environmental and genetical stress. While the role of ADM in PDAC progression has been established, the molecular mechanisms underlying human ADM remain elusive. We previously demonstrated the induction of ADM in human acinar cells through the transforming growth factor beta (TGFβ) signaling pathway. We aim to investigate the interaction between TGFβ and Hippo pathways in mediating ADM. Methods: RNA-sequencing was conducted on sorted normal primary human acinar, ductal, and AD (acinar cells that have undergone ADM) cells. ATAC-seq analysis was utilized to reveal the chromatin accessibility in these three cell types. ChIP-Seq of YAP1, SMAD4, and H3K27ac was performed to identify the gene targets of YAP1 and SMAD4. The role of YAP1/TAZ in ADM-driven cell proliferation, as well as in oncogenic KRAS driven proliferation, was assessed using sphere formation assay. Results: AD cells have a unique transcription profile, with upregulated genes in open chromatin states in acinar cells. YAP1 and SMAD4 co-occupy the loci of ADM-related genes, including PROM1, HES1, and MMP7, co-regulating biological functions such as cell adhesion, cell migration, and inflammation. Overexpression of YAP1/TAZ promoted acinar cell proliferation but still required the TGFβ pathway. YAP1/TAZ were also crucial for TGFβ-induced sphere formation and were necessary for KRAS-induced proliferation. Conclusions: Our study reveals the intricate transition between acinar and AD states in human pancreatic tissues. It unveils the complex interaction between the Hippo and TGF-β pathways during ADM, highlighting the pivotal role of YAP1/TAZ and SMAD4 in PDAC initiation.
The Multifaceted Role of Cofilin in Neurodegeneration and Stroke: Insights into Pathogenesis and Targeting as a Therapy
Authors: Shehjar Faheem , Almarghalani Daniyah A. , Mahajan Reetika , Hasan Syed A.-M. , Shah Zahoor A.
Published: January 2024

This comprehensive review explores the complex role of cofilin, an actin-binding protein, across various neurodegenerative diseases (Alzheimer’s, Parkinson’s, schizophrenia, amyotrophic lateral sclerosis (ALS), Huntington’s) and stroke. Cofilin is an essential protein in cytoskeletal dynamics, and any dysregulation could lead to potentially serious complications. Cofilin’s involvement is underscored by its impact on pathological hallmarks like Aβ plaques and α-synuclein aggregates, triggering synaptic dysfunction, dendritic spine loss, and impaired neuronal plasticity, leading to cognitive decline. In Parkinson’s disease, cofilin collaborates with α-synuclein, exacerbating neurotoxicity and impairing mitochondrial and axonal function. ALS and frontotemporal dementia showcase cofilin’s association with genetic factors like C9ORF72, affecting actin dynamics and contributing to neurotoxicity. Huntington’s disease brings cofilin into focus by impairing microglial migration and influencing synaptic plasticity through AMPA receptor regulation. Alzheimer’s, Parkinson’s, and schizophrenia exhibit 14-3-3 proteins in cofilin dysregulation as a shared pathological mechanism. In the case of stroke, cofilin takes center stage, mediating neurotoxicity and neuronal cell death. Notably, there is a potential overlap in the pathologies and involvement of cofilin in various diseases. In this context, referencing cofilin dysfunction could provide valuable insights into the common pathologies associated with the aforementioned conditions. Moreover, this review explores promising therapeutic interventions, including cofilin inhibitors and gene therapy, demonstrating efficacy in preclinical models. Challenges in inhibitor development, brain delivery, tissue/cell specificity, and long-term safety are acknowledged, emphasizing the need for precision drug therapy. The call to action involves collaborative research, biomarker identification, and advancing translational efforts. Cofilin emerges as a pivotal player, offering potential as a therapeutic target. However, unraveling its complexities requires concerted multidisciplinary efforts for nuanced and effective interventions across the intricate landscape of neurodegenerative diseases and stroke, presenting a hopeful avenue for improved patient care.
Room Temperature Corrosion Behavior of Selective Laser Melting (SLM)-Processed Ni-Fe Superalloy (Inconel 718) in 3.5% NaCl Solution at Different pH Conditions: Role of Microstructures
Authors: Thuneman Thomas , Raja Krishnan S. , Charit Indrajit
Published: January 2024

Inconel 718 (UNS N07718) is a nickel-base superalloy containing iron that is used at cryogenic temperatures (arctic pipe components) and at high temperatures (gas turbines). This alloy is also used in off-shore oil drilling due to its high overall strength and resistance to corrosion. Inconel 718 components are created by a selective laser melting (SLM) additive manufacturing route and result in isotropic fine-grained microstructures with metastable phases (such as Laves phases) that are not usually present in conventional manufacturing processes. In this work, SLM Inconel 718 alloy specimens were investigated in four different conditions: (1) As-manufactured (AS-AM), (2) Additively manufactured and hot isostatically pressed (AM-HIP), (3) As-manufactured and heat-treated (solution annealing followed by two-step aging), and 4) AM-HIP and heat-treated. Localized corrosion behavior was evaluated at room temperature in a 3.5% NaCl solution at three different pH conditions (pH 1.25, 6.25, and 12.25). Electrochemical tests, including linear polarization, cyclic polarization, potentiostatic conditioning, electrochemical impedance spectroscopy, and Mott–Schottky analyses, were used to compare the corrosion behaviors of the SLM specimens with that of the conventionally wrought IN718 samples. The results showed that the additively manufactured specimens showed better corrosion resistance than the wrought material in the acidic chloride solution, and the AM-HIP specimens exhibited superior corrosion resistance to the as-manufactured ones. Hot isostatic pressing resulted in the visible elimination of the dendritic structure, indicating compositional homogeneity as well as a significant decrease in porosity. In addition, the deleterious secondary phases, such as Laves and δ phases, were not observed in the microstructure of the HIPed samples. The AM-HIP material showed the highest corrosion resistance in all the pH conditions. The two-step aging treatment, in general, resulted in the deterioration of corrosion resistance, which could be attributed to the formation of γ′ and γ″ precipitates that increased the cathodic reaction catalytic activities. In the additively manufactured samples, the presence of the Laves phase was more detrimental to corrosion resistance than any other phases and MC carbide and grain boundary δ phase increased the susceptibility to corrosion in wrought materials.
Anderson–Fabry Disease: Red Flags for Early Diagnosis of Cardiac Involvement
Authors: Iorio Annamaria , Lucà Fabiana , Pozzi Andrea , Rao Carmelo Massimiliano , Chimenti Cristina , Di Fusco Stefania Angela , Rossini Roberta , Caretta Giorgio , Cornara Stefano , Giubilato Simona , Di Matteo Irene , Di Nora Concetta , Pilleri Anna , Gelsomino Sandro , Ceravolo Roberto , Riccio Carmine , Grimaldi Massimo , Colivicchi Furio , Oliva Fabrizio , Gulizia Michele Massimo ,   the Cardiac Rare Diseases Working Group Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO)
Published: January 2024

Anderson–Fabry disease (AFD) is a lysosome storage disorder resulting from an X-linked inheritance of a mutation in the galactosidase A (GLA) gene encoding for the enzyme alpha-galactosidase A (α-GAL A). This mutation results in a deficiency or absence of α-GAL A activity, with a progressive intracellular deposition of glycosphingolipids leading to organ dysfunction and failure. Cardiac damage starts early in life, often occurring sub-clinically before overt cardiac symptoms. Left ventricular hypertrophy represents a common cardiac manifestation, albeit conduction system impairment, arrhythmias, and valvular abnormalities may also characterize AFD. Even in consideration of pleiotropic manifestation, diagnosis is often challenging. Thus, knowledge of cardiac and extracardiac diagnostic “red flags” is needed to guide a timely diagnosis. Indeed, considering its systemic involvement, a multidisciplinary approach may be helpful in discerning AFD-related cardiac disease. Beyond clinical pearls, a practical approach to assist clinicians in diagnosing AFD includes optimal management of biochemical tests, genetic tests, and cardiac biopsy. We extensively reviewed the current literature on AFD cardiomyopathy, focusing on cardiac “red flags” that may represent key diagnostic tools to establish a timely diagnosis. Furthermore, clinical findings to identify patients at higher risk of sudden death are also highlighted.
Quantitative Analysis of Retinal Perfusion in Patients with Frontotemporal Dementia Using Optical Coherence Tomography Angiography
Authors: Esser Eliane Luisa , Lahme Larissa , Dierse Sebastian , Diener Raphael , Eter Nicole , Wiendl Heinz , Duning Thomas , Pawlowski Matthias , Krämer Julia , Alnawaiseh Maged
Published: January 2024

Background: Optical coherence tomography angiography (OCT-A) provides detailed visualization of the perfusion of the vascular network of the eye. While in other forms of dementia, such as Alzheimer’s disease and mild cognitive impairment, reduced retinal perfusion was frequently reported, data of patients with frontotemporal dementia (FTD) are lacking. Objective: Retinal and optic nerve head perfusion was evaluated in patients with FTD with OCT-A. Quantitative OCT-A metrics were analyzed and correlated with clinical markers and vascular cerebral lesions in FTD patients. Methods: OCT-A was performed in 18 eyes of 18 patients with FTD and 18 eyes of 18 healthy participants using RTVue XR Avanti with AngioVue. In addition, patients underwent a detailed ophthalmological, neurological, and neuropsychological examination, cerebral magnetic resonance imaging (MRI), and lumbar puncture. Results: The flow density in the optic nerve head (ONH) and in the superficial capillary plexus (SCP) of the macula of patients was significantly lower compared to that of healthy controls (p < 0.001). Similarly, the VD in the deep capillary plexus (DCP) of the macula of patients was significantly lower compared to that of healthy controls (p < 0.001). There was no significant correlation between the flow density data, white matter lesions in brain MRI, cognitive deficits, and cerebrospinal fluid markers of dementia. Conclusions: Patients with FTD showed a reduced flow density in the ONH, and in the superficial and deep retinal capillary plexus of the macula, when compared with that of healthy controls. Quantitative analyses of retinal perfusion using OCT-A may therefore help in the diagnosis and monitoring of FTD. Larger and longitudinal studies are necessary to evaluate if OCT-A is a suitable biomarker for patients with FTD.
Best Practices in Nuclear Imaging for the Diagnosis of Transthyretin Amyloid Cardiomyopathy (ATTR-CM) in KSA: The Eagle Eyes of Local Experts
Authors: Alqarni Abdullah , Aljizeeri Ahmed , Bakhsh Aquib Mohammadidrees , El-Zeftawy Hossam Ahmed Maher , Farghaly Hussein R. , Alqadhi Mukhtar Ahmed M. , Algarni Mushref , Asiri Zain Mohammed , Osman Ahmed , Haddadin Haya , Alayary Islam , Al-Mallah Mouaz H.
Published: January 2024

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a complex and serious form of heart failure caused by the accumulation of transthyretin amyloid protein in the heart muscle. Variable symptoms of ATTR-CM can lead to a delayed diagnosis. Recognizing the diagnostic indicators is crucial to promptly detect this condition. A targeted literature review was conducted to examine the latest international consensus recommendations on a comprehensive diagnosis of ATTR-CM. Additionally, a panel consisting of nuclear medicine expert consultants (n = 10) and nuclear imaging technicians (n = 2) convened virtually from the Kingdom of Saudi Arabia (KSA) to formulate best practices for ATTR-CM diagnosis. The panel reached a consensus on a standard diagnostic pathway for ATTR-CM, which commences by evaluating the presence of clinical red flags and initiating a cardiac workup to assess the patient’s echocardiogram. Cardiac magnetic resonance imaging may be needed, in uncertain cases. When there is a high suspicion of ATTR-CM, patients undergo nuclear scintigraphy and hematologic tests to rule out primary or light-chain amyloidosis. The expert panel emphasized that implementing best practices will support healthcare professionals in KSA to improve their ability to detect and diagnose ATTR-CM more accurately and promptly. Diagnosing ATTR-CM accurately and early can reduce morbidity and mortality rates through appropriate treatment.
Nuclear Abnormalities in LMNA p.(Glu2Lys) Variant Segregating with LMNA-Associated Cardiocutaneous Progeria Syndrome
Authors: Wilke Matheus V. M. B. , Wick Myra , Schwab Tanya L. , Starosta Rodrigo Tzovenos , Clark Karl J. , Connolly Heidi M. , Klee Eric W.
Published: January 2024

The LMNA gene encodes lamin A and lamin C, which play important roles in nuclear organization. Pathogenic variants in LMNA cause laminopathies, a group of disorders with diverse phenotypes. There are two main groups of disease-causing variants: missense variants affecting dimerization and intermolecular interactions, and heterozygous substitutions activating cryptic splice sites. These variants lead to different disorders, such as dilated cardiomyopathy and Hutchinson–Gilford progeria (HGP). Among these, the phenotypic terms for LMNA-associated cardiocutaneous progeria syndrome (LCPS), which does not alter lamin A processing and has an older age of onset, have been described. Here, we present the workup of an LMNA variant of uncertain significance, NM_170707.2 c. 4G>A, p.(Glu2Lys), in a 36-year-old female with severe calcific aortic stenosis, a calcified mitral valve, premature aging, and a family history of similar symptoms. Due to the uncertainty of in silico predictions for this variant, an assessment of nuclear morphology was performed using the immunocytochemistry of stable cell lines to indicate whether the p.(Glu2Lys) had a similar pathogenic mechanism as a previously described pathogenic variant associated with LCPS, p.Asp300Gly. Indirect immunofluorescence analysis of nuclei from stable cell lines showed abnormal morphology, including lobulation and occasional ringed nuclei. Relative to the controls, p.Glu2Lys and p.Asp300Gly nuclei had significantly (p < 0.001) smaller average nuclear areas than controls (mean = 0.10 units, SD = 0.06 for p.Glu2Lys; and mean = 0.09 units, SD = 0.05 for p.Asp300Gly versus mean = 0.12, SD = 0.05 for WT). After functional studies and segregation studies, this variant was upgraded to likely pathogenic. In summary, our findings suggest that p.Glu2Lys impacts nuclear morphology in a manner comparable to what was observed in p.Asp300Gly cells, indicating that the variant is the likely cause of the LCPS segregating within this family.
Conserved Role of Heterotrimeric G Proteins in Plant Defense and Cell Death Progression
Authors: Karimian Parastoo , Trusov Yuri , Botella Jose Ramon
Published: January 2024

Programmed cell death (PCD) is a critical process in plant immunity, enabling the targeted elimination of infected cells to prevent the spread of pathogens. The tight regulation of PCD within plant cells is well-documented; however, specific mechanisms remain elusive or controversial. Heterotrimeric G proteins are multifunctional signaling elements consisting of three distinct subunits, Gα, Gβ, and Gγ. In Arabidopsis, the Gβγ dimer serves as a positive regulator of plant defense. Conversely, in species such as rice, maize, cotton, and tomato, mutants deficient in Gβ exhibit constitutively active defense responses, suggesting a contrasting negative role for Gβ in defense mechanisms within these plants. Using a transient overexpression approach in addition to knockout mutants, we observed that Gβγ enhanced cell death progression and elevated the accumulation of reactive oxygen species in a similar manner across Arabidopsis, tomato, and Nicotiana benthamiana, suggesting a conserved G protein role in PCD regulation among diverse plant species. The enhancement of PCD progression was cooperatively regulated by Gβγ and one Gα, XLG2. We hypothesize that G proteins participate in two distinct mechanisms regulating the initiation and progression of PCD in plants. We speculate that G proteins may act as guardees, the absence of which triggers PCD. However, in Arabidopsis, this G protein guarding mechanism appears to have been lost in the course of evolution.