bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender differences in changes in alcohol consumption achieved by free provision of non-alcoholic beverages: a secondary analysis of a randomized controlled trial
Authors: Dobashi Shohei , Kawaida Kyoko , Saito Go , Owaki Yukiko , Yoshimoto Hisashi
Published: January 2024

Background

We recently demonstrated that a 12-week intervention consisting of the provision of free non-alcoholic beverages reduced alcohol consumption in excessive drinkers for 8 weeks after the intervention. However, gender differences in this effect were not explored. Thus, this secondary analysis investigated gender differences in the influence of non-alcoholic beverage provision on alcohol consumption.

Methods

Individuals who frequently drank excessively (at least 40 g/day in men and 20 g/day in women) and who were not diagnosed with alcoholism were recruited. Participants were randomized into the intervention or control group by simple randomization using a random number table. In the intervention group, free non-alcoholic beverages were provided once every 4 weeks for 12 weeks (three times in total). The consumption of alcoholic and non-alcoholic beverages was calculated based on a drinking diary submitted with the previous 4 weeks’ of data. In this study, we compared the longitudinal changes in alcohol consumption between genders in both groups.

Results

The provision of non-alcoholic beverages significantly reduced alcohol consumption in both genders; however, significant differences in alcohol consumption between the control and intervention groups were observed only in men. The average alcohol consumption during the intervention fell below the level associated with a high risk of non-communicable diseases in men (32.7 g/day), but not in women (24.8 g/day). Correlation coefficient analysis showed that replacing alcoholic beverages with the provided non-alcoholic beverages resulted in different drinking patterns according to gender. The percent changes in the consumption of alcoholic and non-alcoholic beverages relative to baseline levels did not differ between genders.

Conclusions

Our results suggest that the provision of non-alcoholic beverages reduced alcohol consumption irrespective of gender. Of note, providing non-alcoholic beverages might be particularly useful for reducing high-risk alcohol consumption in male excessive drinkers.

Trial registration

UMIN UMIN000047949. Registered 4 June 2022.
Alamandine attenuates ovariectomy-induced osteoporosis by promoting osteogenic differentiation via AMPK/eNOS axis
Authors: Luo Wanxin , Yao Chen , Sun Jie , Zhang Bo , Chen Hao , Miao Jin , Zhang Yafeng
Published: January 2024

Background

Alamandine is a newly characterized peptide of renin angiotensin system. Our study aims to investigate the osteo-preservative effects of alamandine, explore underlying mechanism and bring a potential preventive strategy for postmenopausal osteoporosis in the future.

Methods

An ovariectomy (OVX)-induced rat osteoporosis model was established for in vivo experiments. Micro-computed tomography and three-point bending test were used to evaluate bone strength. Histological femur slices were processed for immunohistochemistry (IHC). Bone turnover markers and nitric oxide (NO) concentrations in serum were determined with enzyme-linked immunosorbent assay (ELISA). The mouse embryo osteoblast precursor (MC3T3-E1) cells were used for in vitro experiments. The cell viability was analysed with a Cell Counting Kit‑8. We performed Alizarin Red S staining and alkaline phosphatase (ALP) activity assay to observe the differentiation status of osteoblasts. Western blotting was adopted to detect the expression of osteogenesis related proteins and AMP-activated protein kinase/endothelial nitric oxide synthase (AMPK/eNOS) in osteoblasts. DAF-FM diacetate was used for semi-quantitation of intracellular NO.

Results

In OVX rats, alamandine alleviated osteoporosis and maintained bone strength. The IHC showed alamandine increased osteocalcin and collagen type I α1 (COL1A1) expression. The ELISA revealed alamandine decreased bone turnover markers and restored NO level in serum. In MC3T3-E1 cells, alamandine promoted osteogenic differentiation. Western blotting demonstrated that alamandine upregulated the expression of osteopontin, Runt-related transcription factor 2 and COL1A1. The intracellular NO was also raised by alamandine. Additionally, the activation of AMPK/eNOS axis mediated the effects of alamandine on MC3T3-E1 cells and bone tissue. PD123319 and dorsomorphin could repress the regulating effect of alamandine on bone metabolism.

Conclusion

Alamandine attenuates ovariectomy-induced osteoporosis by promoting osteogenic differentiation via AMPK/eNOS axis.
A novel starch-active lytic polysaccharide monooxygenase discovered with bioinformatics screening and its application in textile desizing
Authors: Zhang Meijuan , Fu Xiaoping , Gu Rongrong , Zhao Bohua , Zhao Xingya , Song Hui , Zheng Hongchen , Xu Jianyong , Bai Wenqin
Published: January 2024

Background

Lytic polysaccharide monooxygenases (LPMOs) catalyzing the oxidative cleavage of different types of polysaccharides have potential to be used in various industries. However, AA13 family LPMOs which specifically catalyze starch substrates have relatively less members than AA9 and AA10 families to limit their application range. Amylase has been used in enzymatic desizing treatment of cotton fabric for semicentury which urgently need for new assistant enzymes to improve reaction efficiency and reduce cost so as to promote their application in the textile industry.

Results

A total of 380 unannotated new genes which probably encode AA13 family LPMOs were discovered by the Hidden Markov model scanning in this study. Ten of them have been successfully heterologous overexpressed. AlLPMO13 with the highest activity has been purified and determined its optimum pH and temperature as pH 5.0 and 50 °C. It also showed various oxidative activities on different substrates (modified corn starch > amylose > amylopectin > corn starch). The results of enzymatic textile desizing application showed that the best combination of amylase (5 g/L), AlLPMO13 (5 mg/L), and H2O2 (3 g/L) made the desizing level and the capillary effects increased by 3 grades and more than 20%, respectively, compared with the results treated by only amylase.

Conclusion

The Hidden Markov model constructed basing on 34 AA13 family LPMOs was proved to be a valid bioinformatics tool for discovering novel starch-active LPMOs. The novel enzyme AlLPMO13 has strong development potential in the enzymatic textile industry both concerning on economy and on application effect.
Exploring Jordanian children and parents’ awareness, behavior, and perception of pediatric oral health
Authors: Hammouri Eman Hussein , Mustafa Asem Thabit , Jaradat Taghreed Falah , Ghozlan Moa’th Mohammad , Bani Salman Mahmoud Yaseen , Ersheidat Ala’ Ahmad , Nawasra Israa Mohammad
Published: January 2024

Background

To evaluate children’s and parents’ practice and attitude toward oral hygiene and their knowledge about oral hygiene.

Methods

This cross-sectional questionnaire-based study was conducted on randomly selected children who were seen in the Pediatric dentistry clinic in different Royal Medical Services hospitals. A modified questionnaire was used to gather information from the child or parents to gather the child’s demographic data and evaluate the children’s and parents’ practice and attitude toward oral hygiene, their knowledge about oral hygiene, information about the parent and family, and oral examination, the questionnaire questions' reliability and validity were assessed by test–retest and Cronbach's Alpha test.

Results

Three hundred seventy four patients were included, and the average age was 5.06 ± 3.58 SD years. Children’s and parents’ practice toward oral hygiene was inadequate where the majority (83.3%) brush their teeth occasionally, change their toothbrushes infrequently, apply toothpaste inappropriately, and less than half (47.2%) clean their tongue after teeth brushing. A significant number (73%) of candidates were aware that oral health has a significant role in their general health and can prevent dental problems. Participants agreed that maintaining a healthy mouth is an individual responsibility. The majority of participants came from large family size (the average family members 6.1 ± 1.7 SD) who live below the poverty line.

Conclusion

Our study demonstrated that awareness of oral health status in children below the age of 12 was poor. Although their oral knowledge was good their attitude and behavior were inadequate. These findings urge the need for expanded, well-organized, preventive educational programs that include school’s syllabus, house visits, and hospitals for parents and children alike.
What works in radiology education for medical students: a systematic review and meta-analysis
Authors: Wade Stuart W.T. , Velan Gary M. , Tedla Nicodemus , Briggs Nancy , Moscova Michelle
Published: January 2024

Background

Medical imaging related knowledge and skills are widely used in clinical practice. However, radiology teaching methods and resultant knowledge among medical students and junior doctors is variable. A systematic review and meta-analysis was performed to compare the impact of different components of radiology teaching methods (active versus passive teaching, eLearning versus traditional face-to-face teaching) on radiology knowledge / skills of medical students.

Methods

PubMed and Scopus databases were searched for articles published in English over a 15-year period ending in June 2021 quantitatively comparing the effectiveness of undergraduate medical radiology education programs regarding acquisition of knowledge and/or skills. Study quality was appraised by the Medical Education Research Study Quality Instrument (MERSQI) scoring and analyses performed to assess for risk of bias. A random effects meta-analysis was performed to pool weighted effect sizes across studies and I2statistics quantified heterogeneity. A meta-regression analysis was performed to assess for sources of heterogeneity.

Results

From 3,052 articles, 40 articles involving 6,242 medical students met inclusion criteria. Median MERSQI score of the included articles was 13 out of 18 possible with moderate degree of heterogeneity (I2 = 93.42%). Thematic analysis suggests trends toward synergisms between radiology and anatomy teaching, active learning producing superior knowledge gains compared with passive learning and eLearning producing equivalent learning gains to face-to-face teaching. No significant differences were detected in the effectiveness of methods of radiology education. However, when considered with the thematic analysis, eLearning is at least equivalent to traditional face-to-face teaching and could be synergistic.

Conclusions

Studies of educational interventions are inherently heterogeneous and contextual, typically tailored to specific groups of students. Thus, we could not draw definitive conclusion about effectiveness of the various radiology education interventions based on the currently available data. Better standardisation in the design and implementation of radiology educational interventions and design of radiology education research are needed to understand aspects of educational design and delivery that are optimal for learning.

Trial registration

Prospero registration number CRD42022298607.
Toward sleep health as a focus of physical therapy practice: one lecture can positively impact sleep knowledge and beliefs in entry-level students
Authors: Siengsukon Catherine F. , Glaser Allison , Nelson Eryen
Published: January 2024

Background

Challenges to integrating health promotion including sleep health into entry-level physical therapist curricula include lack of faculty expertise, time, and support. A lecture provided by a content expert may mitigate such challenges. The purpose of this study was to determine if a sleep education session impacts Doctor of Physical Therapy students’ knowledge and beliefs about sleep.

Methods

Faculty shared the opportunity to participate in the study 1–3 days prior to the remotely-provided lecture including sleep health assessment and interventions. The survey included demographics, a sleep health knowledge question, 11 questions on “What I think about sleep as a professional”, and the 20-item Sleep Beliefs Scale. McNemar’s and paired sample t-tests determined change in knowledge and beliefs.

Results

209 individuals (70% female, 86% Caucasian, 25.5 ± 3.4 years old) completed the pre-lecture survey, and 137 individuals completed the post-lecture survey. There was an increase in knowledge about sleep health (p < .001) and change in Sleep Beliefs Scales score (p < .001).

Conclusions

A single remotely provided sleep education session increased DPT students’ knowledge and changed their beliefs about sleep. Future studies should determine if these positive beliefs about sleep translate into clinical practice and enhance patient outcomes.
Coverage of education and training of traumatic brain injury-induced growth hormone deficiency in US residency and fellowship programs: a cross-sectional study
Authors: Cárdenas Javier , Kelepouris Nicky , Adiga Radhika , Yuen Kevin C. J.
Published: January 2024

Background

Hypopituitarism, including growth hormone deficiency (GHD), is a common sequela of traumatic brain injury (TBI). This study explored the coverage of education and training of TBI-induced hypopituitarism in general and GHD in particular, in postgraduate program curricula to identify knowledge gaps and opportunities.

Methods

An online survey and qualitative interviews (focus groups) were conducted among endocrinology, neurology, and physiatry postgraduate program directors in the United States (US). The study received an IRB exemption.

Results

A total of 419 fellowship and residency programs were invited to participate; 60 program directors completed the survey and 11 of these participated in the focus groups. About half of the respondents considered TBI-induced hypopituitarism important or fairly important to include in the curriculum, and nearly two-thirds considered it an appropriate training component. Neurology program directors considered education regarding hypopituitarism following TBI less important and relevant for their curricula compared with endocrinology and physiatry program directors. About half (53%) of the programs responded that they included TBI-induced pituitary disorders in their curricula. About two-thirds (68%) of endocrinology programs, compared with only one-quarter (25%) of neurology programs, covered TBI-induced pituitary disorders. Respondents identified multiple barriers to expanding hypopituitarism following TBI in the curriculum, including the rarity of condition and lack of time/room in the curriculum. Respondents reported that consensus clinical guidelines and the availability of more data on TBI-induced hypopituitarism, including GHD, would greatly impact the development of educational curricula on this topic.

Conclusions

To improve the management of TBI-induced hypopituitarism, education and training should be expanded in US fellowship and residency programs to prepare trainees to effectively screen, diagnose, and treat TBI-induced hypopituitarism, including GHD.
Hospital governance accountability structure: a scoping review
Authors: Jalilvand Mohammad Ali , Raeisi Ahmad Reza , Shaarbafchizadeh Nasrin
Published: January 2024

Introduction

Hospitals, as complex organizations with clinical, financial, and social functions, face different barriers to providing high-quality and safe services at reasonable costs. Various initiatives have been carried out in hospital governance to improve quality, safety, and accountability. This research aims to identify the structures and dimensions that make hospital governance accountable.

Methods

The research used Arksey and O'Malley's scoping review framework to examine the research literature on hospital governance structure and accountability. The literature review included PubMed, Web of Science, Embase, Scopus ProQuest, Google search engine, and Google Scholar databases from 2010 to 2023. Data were analyzed using the content analysis method.

Results

Excluding unrelated and duplicate sources, 40 articles and reports were included in the study. The studies were reviewed and analyzed based on organizational type, type of source, year of publication, objectives, and key findings. Accountable governance features were extracted from the selected articles and reports. The four main themes include inclusive governance, commitment to accountability, planning for accountability, and autonomous governance. Thirteen subthemes were extracted from the study literature.

Conclusion

Various initiatives have been implemented regarding the reform of the governance structure of public hospitals in different countries. Many of these reforms aim to improve financial and clinical accountability. The study results could be used to identify the structures and dimensions that make hospital governance accountable.
Patient level barriers to accessing TB care services during the COVID-19 pandemic in Uganda, a mixed methods study
Authors: Bbuye Mudarshiru , Muyanja Stella Zawedde , Sekitoleko Isaac , Padalkar Roma , Robertson Nicole , Helwig Madeline , Hopkinson Dennis , Siddharthan Trishul , Jackson Peter
Published: January 2024

Introduction

Lockdown measure has been utilized widely to mitigate COVID-19 pandemic transmission and recently during the 2022 Sudan Ebola Virus Disease outbreak in Uganda. These have setback effects on the continuity of essential health services such as tuberculosis (TB) care, reversing progress made in the fight against tuberculosis (TB) over the past decade. We set out to understand patient-reported barriers to accessing TB care services during the COVID-19 pandemic in Uganda.

Methods

Mixed methods study involving review of medical records of TB patients who received TB care from January to September 2020. We used quantitative and qualitative methods including phone questionnaires and in-depth interviews. We carried out descriptive statistics, a chi-square test and conducted a thematic analysis.

Results

We carried out phone interviews with 672 participants. The majority (60%) were male and with an average of 35 years (SD:11). A significantly higher proportion of patients reported a barrier to TB care access during the COVID-19 lockdown than pre-lockdown (79.9% vs. 68.1% p = 0.027). We carried out in-depth interviews with 28 participants (54% (15/28): male). Barriers experienced by these participants included lack of a means of transport to reach the health facility, lack of money to pay the transport fares, long distances to the facility, fear of COVID-19 infection, stigma due to overlap between TB and COVID-19 symptoms, and few health care workers available during the lockdown period.

Conclusion

Lockdown measures instituted to mitigate the transmission of COVID1-19 affected access to TB care services in Uganda. Uganda is at risk of future emerging and re-emerging diseases of epidemic potential. Therefore, there should be measures to ensure the continuity of essential services such as tuberculosis care during the implementation of future epidemic response interventions such as a lockdown.
Phylogenetically evolutionary analysis provides insights into the genetic diversity and adaptive evolution of porcine deltacoronavirus
Authors: Guo Zhenhua , Lu Qingxia , Jin Qianyue , Li Peng , Xing Guangxu , Zhang Gaiping
Published: January 2024

Background

Porcine deltacoronavirus (PDCoV) is one of the emerging swine enteric coronaviruses (SECoVs), which has been widely prevalent in the North America and Asia. In addition to causing severe diarrhea in piglets, PDCoV also shows the potential to infect diverse host species, including calves, chickens, turkey poults, and humans. However, the clinical pathogenicity and genetic evolution of PDCoV is still not fully understood.

Results

Here, we recorded an outbreak of a novel recombinant PDCoV strain (CHN-HeN06-2022) in a large nursery fattening pig farm. Genomic analysis showed that the CHN-HeN06-2022 strain shared 98.3-98.7% sequence identities with the Chinese and American reference strains. To clarify the evolutionary relationships, phylogenetic analysis was performed using the PDCoV genome sequences available in the GenBank database. Based on genetic distance and geographical distribution, the phylogenetic tree clearly showed that all the PDCoV sequences could be divided into lineage 1 and lineage 2, which were further classified into sublineage 1.1 (Chinese strains), 1.2 (the North American strains), 2.1 (the Southeast Asian strains), and 2.2 (Chinese strains). Corresponding to the evolutionary tree, we found that, compared to lineage 1, lineage 2 strains usually contain a continuous 6-nt deletion in Nsp2 and a 9-nt deletion in Nsp3, respectively. Furthermore, recombination analysis suggested that the CHN-HeN06-2022 occurred segments exchange crossed Nsp2 and Nsp3 region between sublineage 1.1 and sublineage 2.1. Combined with previously reported recombinant strains, the highest recombination frequency occurred in Nsp2, Nsp3, and S gene. Additionally, we identified a total of 14 amino acid sites under positive selection in spike protein, most of which are located in the regions related with the viral attachment, receptor binding, and membrane fusion.

Conclusions

Taken together, our studies provide novel insights into the genetic diversity and adaptive evolution of PDCoV. It would be helpful to the development of vaccine and potential antiviral agent.
Chestnut tannin extract modulates growth performance and fatty acid composition in finishing Tan lambs by regulating blood antioxidant capacity, rumen fermentation, and biohydrogenation
Authors: Gao Changpeng , Qi Mingjiang , Zhou Yuxiang
Published: January 2024

Tannins as plant extracts have emerged as promising and potential alternatives for antibiotics in modern livestock cultivation systems. This study investigates the effect of dietary chestnut tannin extract (CTE) in finishing Tan lambs. Twenty-seven male Tan lambs were randomly divided into three groups: (1) control group (CON; basal diet); (2) low-dose CTE group (LCTE; basal diet + 2 g/kg CTE, dry matter [DM] basis); (3) high-dose CTE group (HCTE; basal diet + 4 g/kg CTE, DM basis). The HCTE group exhibited markedly higher average daily gain (ADG) and DM intake than CON (P < 0.01). The ruminal total volatile fatty acid concentration increased linearly with increasing CTE supplementation (P < 0.01), while the opposite trend was observed for butyrate molar proportion (P < 0.01). Upon increasing CTE dosage, plasma glucose, high-density lipoprotein cholesterol, glutathione peroxidase, and superoxide dismutase content increased linearly (P < 0.05), whereas low-density lipoprotein cholesterol and urea nitrogen decreased linearly or quadratically (P < 0.05), respectively. A linear increase was also observed in ruminal t6 C18:1 and t9, c12 C18:2 proportions (P < 0.01), and plasma C18:2n-6 and n-6 polyunsaturated fatty acids proportions with increased CTE supplementation (P < 0.01). In the longissimus dorsi muscle, the atherogenic index decreased linearly (P < 0.05), while c11 C18:1 and C20:5n-3 increased linearly (P < 0.05). Moreover, c9, t11 conjugated linoleic acids proportion increased in subcutaneous fat with CTE supplementation (P < 0.01). In conclusion, Dietary CTE enhances the ADG of finishing Tan lambs in a dose-dependent manner, modulates plasma metabolites and antioxidant capacity, and improves rumen fermentation and body fatty acid composition. These results provide a reference for the rational application of CTE in ruminant production.
Identification of a new gene signature for prognostic evaluation in cervical cancer: based on cuproptosis-associated angiogenesis and multi-omics analysis
Authors: Kang Jiawen , Jiang Jingwen , Xiang Xiaoqing , Zhang Yong , Tang Jie , Li Lesai
Published: January 2024

Patients with recurrent or metastatic cervical cancer are in urgent need of novel prognosis assessment or treatment approaches. In this study, a novel prognostic gene signature was discovered by utilizing cuproptosis-related angiogenesis (CuRA) gene scores obtained through weighted gene co-expression network analysis (WGCNA) of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. To enhance its reliability, the gene signature was refined by integrating supplementary clinical variables and subjected to cross-validation. Meanwhile, the activation of the VEGF pathway was inferred from an analysis of cell-to-cell communication, based on the expression of ligands and receptors in cell transcriptomic datasets. High-CuRA patients had less infiltration of CD8 + T cells and reduced expression of most of immune checkpoint genes, which indicated greater difficulty in immunotherapy. Lower IC50 values of imatinib, pazopanib, and sorafenib in the high-CuRA group revealed the potential value of these drugs. Finally, we verified an independent prognostic gene SFT2D1 was highly expressed in cervical cancer and positively correlated with the microvascular density. Knockdown of SFT2D1 significantly inhibited ability of the proliferation, migration, and invasive in cervical cancer cells. CuRA gene signature provided valuable insights into the prediction of prognosis and immune microenvironment of cervical cancer, which could help develop new strategies for individualized precision therapy for cervical cancer patients.
DNA mismatch repair system regulates the expression of PD-L1 through DNMTs in cervical cancer
Authors: Guo Fan , Lu Ruijiao , Kong Weina , Anwar Miyessar , Feng Yangchun
Published: January 2024

Background

Cervical cancer (CC) is a potential clinical application of PD-1/PD-L1 inhibitor. We aimed to study the mechanism of DNA mismatch repair (MMR) system regulating the expression of PD-L1 in CC through DNA methyltransferase (DNMTs).

Methods

We collected pathological specimens from 118 cases of CC to analyze the relationship between PD-L1 expression and DNMTs in different MMR states. RNA interference (RNAi) technique was used to simulate the formation of CC cell line with MMR deficiency (dMMR) state, and subcutaneous tumor formation experiment was carried out in nude mice to verify the relationship between PD-L1 expression and DNMTs in MMR state.

Results

The PD-L1 positive rate in 118 cases of CC was 58.47%, while the microsatellite instability (MSI) status accounted for 5.93%. There was a significant difference in the expression of PD-L1 between patients within the dMMR and MMR proficient (pMMR) groups (χ2 = 21.405, P < 0.001). Subcutaneous inoculation after infection of Siha cells led to successful tumorigenesis in nude mice, accompanied by a significant increase in the level of PD-L1 expression in the mouse tumors, while the expression level of MLH1 and MSH2 protein decreased significantly. We also found that PD-L1 expression was closely related to the expression of DNMTs.

Conclusion

PD-L1 is universal expressed on the surface of CC cells, dMMR status enhances the expression of PD-L1 on the surface of CC cells, dMMR states of CC are related to the demethylation status of the PD-L1 gene promoter region.
Advancement in nanomaterials for environmental pollutants remediation: a systematic review on bibliometrics analysis, material types, synthesis pathways, and related mechanisms
Authors: Asghar Nosheen , Hussain Alamdar , Nguyen Duc Anh , Ali Salar , Hussain Ishtiaque , Junejo Aurangzeb , Ali Attarad
Published: January 2024

Environmental pollution is a major issue that requires effective solutions. Nanomaterials (NMs) have emerged as promising candidates for pollution remediation due to their unique properties. This review paper provides a systematic analysis of the potential of NMs for environmental pollution remediation compared to conventional techniques. It elaborates on several aspects, including conventional and advanced techniques for removing pollutants, classification of NMs (organic, inorganic, and composite base). The efficiency of NMs in remediation of pollutants depends on their dispersion and retention, with each type of NM having different advantages and disadvantages. Various synthesis pathways for NMs, including traditional synthesis (chemical and physical) and biological synthesis pathways, mechanisms of reaction for pollutants removal using NMs, such as adsorption, filtration, disinfection, photocatalysis, and oxidation, also are evaluated. Additionally, this review presents suggestions for future investigation strategies to improve the efficacy of NMs in environmental remediation. The research so far provides strong evidence that NMs could effectively remove contaminants and may be valuable assets for various industrial purposes. However, further research and development are necessary to fully realize this potential, such as exploring new synthesis pathways and improving the dispersion and retention of NMs in the environment. Furthermore, there is a need to compare the efficacy of different types of NMs for remediating specific pollutants. Overall, this review highlights the immense potential of NMs for mitigating environmental pollutants and calls for more research in this direction.

Graphical Abstract
Claudin-18.2 mediated interaction of gastric Cancer cells and Cancer-associated fibroblasts drives tumor progression
Authors: Liu Shengde , Zhang Zizhen , Jiang Lei , Zhang Miao , Zhang Cheng , Shen Lin
Published: January 2024

Background

Claudin-18.2 (CLDN18.2) has emerged as an alluring therapeutic target against gastrointestinal tumors in recent years. However, a thorough understanding of its regulatory mechanism in gastric cancer remains elusive.

Methods

We presented a comprehensive study comprising 185 gastric cancer patients, which included 112 cases with high CLDN18.2 expression and 73 cases with low CLDN18.2 expression as determined by immunohistochemistry. After overdressed CLDN18.2 in AGS and NUGC4 cell lines, we elucidated the functions of CLDN18.2 in connecting gastric cancer cells and cancer-associated fibroblasts (CAFs) through an in vitro adhesion models and in vivo lung colonization models. The molecular mechanism underlying CLDN18.2-mediated interaction between gastric cancer cells and CAFs was identified through RNA sequencing and protein-proximity labeling techniques in vivo.

Results

In our own cohort, a correlation was observed between high levels of CLDN18.2 expression and advanced cancer stage, poor prognosis, and heightened infiltration of CAFs. We elucidated a pivotal role of CLDN18.2 in mediating adhesion between gastric cancer cells and CAFs, which leads to the adhesion of cancer cells to stroma tissue and facilitates the clustering of cancer cells and CAFs into embolus, enhancing gastric cancer’s metastatic progression and the risk of embolic death. Mechanistically, it was discovered that CAFs can activate adhesion and metastasis-related signaling pathways in CLDN18.2-positive gastric cancer cells. Furthermore, using an in vivo protein-proximity labeling approach, we identified S100 calcium binding protein A4 (S100A4) as a distinctive marker of CAFs that interacts with CLDN18.2 to enhance gastric cancer progression.

Conclusions

Our findings illuminated the role of the CLDN18.2-mediated interaction between cancer cells and CAFs in promoting gastric cancer progression and embolism, thereby providing insight into potential therapeutic avenues for CLDN18.2 positive cancers.
Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis
Authors: Liu Xin Tracy , Huang Yu , Liu Da , Jiang Yingxin Celia , Zhao Min , Chung Long Hoa , Han Xingxing Daisy , Zhao Yinan , Chen Jinbiao , Coleman Paul , Ting Ka Ka , Tran Collin , Su Yingying , Dennis Claude Vincent , Bhatnagar Atul , Liu Ken , Don Anthony Simon , Vadas Mathew Alexander , Gorrell Mark Douglas , Zhang Shubiao , Murray Michael , Kavurma Mary Meltem , McCaughan Geoffrey William , Gamble Jennifer Ruth , Qi Yanfei
Published: January 2024

Background

Hepatocellular carcinoma (HCC) remains a leading life-threatening health challenge worldwide, with pressing needs for novel therapeutic strategies. Sphingosine kinase 1 (SphK1), a well-established pro-cancer enzyme, is aberrantly overexpressed in a multitude of malignancies, including HCC. Our previous research has shown that genetic ablation of Sphk1 mitigates HCC progression in mice. Therefore, the development of PF-543, a highly selective SphK1 inhibitor, opens a new avenue for HCC treatment. However, the anti-cancer efficacy of PF-543 has not yet been investigated in primary cancer models in vivo, thereby limiting its further translation.

Methods

Building upon the identification of the active form of SphK1 as a viable therapeutic target in human HCC specimens, we assessed the capacity of PF-543 in suppressing tumor progression using a diethylnitrosamine-induced mouse model of primary HCC. We further delineated its underlying mechanisms in both HCC and endothelial cells. Key findings were validated in Sphk1 knockout mice and lentiviral-mediated SphK1 knockdown cells.

Results

SphK1 activity was found to be elevated in human HCC tissues. Administration of PF-543 effectively abrogated hepatic SphK1 activity and significantly suppressed HCC progression in diethylnitrosamine-treated mice. The primary mechanism of action was through the inhibition of tumor neovascularization, as PF-543 disrupted endothelial cell angiogenesis even in a pro-angiogenic milieu. Mechanistically, PF-543 induced proteasomal degradation of the critical glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, thus restricting the energy supply essential for tumor angiogenesis. These effects of PF-543 could be reversed upon S1P supplementation in an S1P receptor-dependent manner.

Conclusions

This study provides the first in vivo evidence supporting the potential of PF-543 as an effective anti-HCC agent. It also uncovers previously undescribed links between the pro-cancer, pro-angiogenic and pro-glycolytic roles of the SphK1/S1P/S1P receptor axis. Importantly, unlike conventional anti-HCC drugs that target individual pro-angiogenic drivers, PF-543 impairs the PFKFB3-dictated glycolytic energy engine that fuels tumor angiogenesis, representing a novel and potentially safer therapeutic strategy for HCC.
The effects of reproductive variables on child mortality in Ethiopia: evidence from demographic and health surveys from 2000 to 2016
Authors: Debere Hailu Refera , Adjiwanou Visseho
Published: January 2024

Background

Child mortality is a crucial indicator reflecting a country's health and socioeconomic status. Despite significant global improvements in reducing early childhood deaths, Southern Asia and sub-Saharan Africa still bear the highest burden of newborn mortality. Ethiopia is one of five countries that account for half of new-born deaths worldwide.

Methods

This study examined the relationship between specific reproductive factors and under-five mortality in Ethiopia. A discrete-time survival model was applied to analyze data collected from four Ethiopian Demographic and Health Surveys (EDHS) conducted between 2000 and 2016. The study focused on investigating the individual and combined effects of three factors: preceding birth interval, maternal age at childbirth, and birth order, on child mortality.

Results

The study found that lengthening the preceding birth interval to 18–23, 24–35, 36–47, or 48+ months reduced the risk of under-five deaths by 30%, 46%, 56%, and 60% respectively, compared to very short birth intervals (less than 18 months). Giving birth between the ages 20–34 and 35+ reduced the risk by 34% and 8% respectively, compared to giving birth below the age of 20. The risk of under-five death was higher for a 7th-born child by 17% compared to a 2nd or 3rd-born child. The combined effect analysis showed that higher birth order at a young maternal age increased the risk. In comparison, lower birth order in older maternal age groups was associated with higher risk. Lastly, very short birth intervals posed a greater risk for children with higher birth orders.

Conclusion

Not only does one reproductive health variable negatively affect child survival, but their combination has the strongest effect. It is therefore recommended that policies in Ethiopia should address short birth intervals, young age of childbearing, and order of birth through an integrated strategy.
Impact of ACE I gene insertion/deletion, A-240T polymorphisms and the renin–angiotensin–aldosterone system on COVID-19 disease
Authors: Zobel Christian M. , Kuhn Hartmut , Schreiner Maximilian , Wenzel Werner , Wendtland Jasper , Goekeri Cengiz , Scheit Lorenz , Oltmanns Klaas , Rauschning Dominic , Grossegesse Marica , Hofmann Natalie , Wirtz Hubert , Spethmann Sebastian ,   BwKrhs-Covid-Research-Group, Baumgarten Ullrich , Wageloehner Tobias , Neumann Nino , Mueller Annette , Mueller Rico , Krueger Jan Philip , Borchert Alena , Weinreich Felix , Keidel Franziska , Koch Maria , Schüßler Meike
Published: January 2024

Background

The coronavirus disease 2019 (COVID-19) pandemic is driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to an enormous burden on patient morbidity and mortality. The renin–angiotensin–aldosterone system (RAAS) plays a significant role in various pulmonary diseases. Since SARS-CoV-2 utilizes the angiotensin-converting enzyme (ACE)2 receptor to exert its virulence and pathogenicity, the RAAS is of particular importance in COVID 19.

Methods

Our preliminary study investigates retrospectively the influence of selected ACE-polymorphisms (I/D location at intron 16 in the B-coding sequence (rs4646994) and A-240T (rs 4291) at the A-promoter) as well as ACE1 and ACE2 serum levels on disease severity and the inflammatory response in inpatients and outpatients with COVID-19.

Results

Our study included 96 outpatients and 88 inpatients (65.9% male, mean age 60 years) with COVID-19 from April to December 2020 in four locations in Germany. Of the hospitalized patients, 88.6% participants were moderately ill (n = 78, 64% male, median age 60 years), and 11.4% participants were severely ill or deceased (n = 10, 90% male, median age 71 years). We found no polymorphism-related difference in disease, in age distribution, time to hospitalization and time of hospitalization for the inpatient group. ACE1 serum levels were significantly increased in the DD compared to the II polymorphism and in the TT compared to the AA polymorphism. There was no significant difference in ACE 1 serum levels l between moderately ill and severely ill patients. However, participants requiring oxygen supplementation had significantly elevated ACE1 levels compared to participants not requiring oxygen, with no difference in ACE2 levels whereas females had significantly higher ACE2 levels.

Conclusions

Although there were no differences in the distribution of ACE polymorphisms in disease severity, we found increased proinflammatory regulation of the RAAS in patients with oxygen demand and increased serum ACE2 levels in women, indicating a possible enhanced anti-inflammatory immune response.

Clinical trial registration: PreBiSeCov: German Clinical Trials Register, DRKS-ID: DRKS00021591, Registered on 27th April 2020.
HTLV-1 reverse transcriptase homology model provides structural basis for sensitivity to existing nucleoside/nucleotide reverse transcriptase inhibitors
Authors: Tardiota Nicolas , Jaberolansar Noushin , Lackenby Julia A. , Chappell Keith J. , O’Donnell Jake S.
Published: January 2024

The human T-lymphotropic virus type 1 (HTLV-1) infects millions of people globally and is endemic to various resource-limited regions. Infections persist for life and are associated with increased susceptibility to opportunistic infections and severe diseases including adult T cell leukemia/lymphoma and HTLV-1-associated myelopathy-tropical spastic paraparesis. No HTLV-1-specific anti-retrovirals have been developed and it is unclear whether existing anti-retrovirals developed for treatment of human immunodeficiency virus (HIV) have efficacy against HTLV-1. To understand the structural basis for therapeutic binding, homology modelling and machine learning were used to develop a structural model of the HTLV-1 reverse transcriptase. With this, molecular docking experiments using a panel of FDA-approved inhibitors of viral reverse transcriptases to assess their capacity for binding, and in turn, inhibition. Importantly, nucleoside/nucleotide reverse transcriptase inhibitor but not non-nucleoside reverse transcriptase inhibitors were predicted to bind the HTLV-1 reverse transcriptase, with similar affinity to HIV-1 reverse transcriptase. By strengthening the rationale for clinical testing of therapies such as tenofovir alafenamide, zidovudine, lamivudine, and azvudine for treatment of HTLV-1, this study has demonstrated the power of in silico structural biology approaches in drug design and therapeutic testing.
Neuronal and glial vulnerability of the suprachiasmatic nucleus in tauopathies: evidence from human studies and animal models
Authors: Son Gowoon , Neylan Thomas C. , Grinberg Lea T.
Published: January 2024

Tauopathies, a group of neurodegenerative diseases that includes Alzheimer’s disease, commonly lead to disturbances in sleep-wake patterns and circadian rhythm disorders. The circadian rhythm, a recurring 24-hour cycle governing human biological activity, is regulated by the hypothalamic suprachiasmatic nucleus (SCN) and endogenous transcriptional-translational feedback loops. Surprisingly, little attention has been given to investigating tauopathy-driven neuropathology in the SCN and the repercussions of SCN and circadian gene dysfunction in the human brain affected by tauopathies. This review aims to provide an overview of the current literature on the vulnerability of the SCN in tauopathies in humans. Emphasis is placed on elucidating the neuronal and glial changes contributing to the widespread disruption of the molecular circadian clock. Furthermore, this review identifies areas of knowledge requiring further investigation.
Granulomatous myocarditis arising from intravesical Bacillus Calmette–Guérin therapy leading to death diagnosed by postmortem examination: a case report
Authors: Geetha Saroja D. , Chavarria Hector D. , Abdelwahed Mohammed , Kataria Nidhi , Bijol Vanesa , Das Kasturi
Published: January 2024

Background

Intravesical Bacillus Calmette–Guérin (BCG) is used as a standard adjuvant therapy for non-muscle invasive urothelial cancer. Most patients tolerate the treatment well, with mild side effects. Systemic complications are extremely rare, occur due to BCG dissemination and are associated with immunocompromised state and urothelial breach.

Case presentation

We present a case of a 78-year-old male, a former smoker, with history of non-muscle invasive urothelial carcinoma status post partial resection followed by intravesical BCG therapy. An autopsy was performed due to the sudden nature of his death. Autopsy showed multiple necrotizing granulomas in the brain, atrium, ventricles, lungs, kidneys, and urinary bladder. Stains for acid-fast bacilli and fungi were negative. In addition, bilateral lungs showed evidence of bronchopneumonia secondary to cytomegalovirus.

Conclusion

Granulomatous myocarditis arising from BCG therapy is extremely rare. Our patient with urothelial cancer treated with BCG developed multiorgan granulomas, most likely due to a hypersensitivity reaction to intravesical BCG. Arrhythmia induced by granulomatous myocarditis was the cause of his death. Although there have been few cases of systemic BCG-osis causing fatal sepsis leading to death, a cardiac cause of death is unique.
Sex differences in a mouse model of diet-induced obesity: the role of the gut microbiome
Authors: Stapleton Saluda , Welch Grace , DiBerardo Lindsay , Freeman Linnea R
Published: January 2024

Background

Recent decades have seen an exponential rise in global obesity prevalence, with rates nearly doubling in a span of 40 years. A comprehensive knowledge base regarding the systemic effects of obesity is required to create new preventative and therapeutic agents effective at combating the current obesity epidemic. Previous studies of diet-induced obesity utilizing mouse models have demonstrated a difference in bodyweight gain by sex. In such studies, female mice gained significantly less weight than male mice when given the same high fat (HF) diet, indicating a resistance to diet-induced obesity. Research has also shown sex differences in gut microbiome composition between males and females, indicated to be in part a result of sex hormones. Understanding metabolic differences between sexes could assist in the development of new measures for obesity prevention and treatment. This study aimed to characterize sex differences in weight gain, plasma lipid profiles, fecal microbiota composition, and fecal short chain fatty acid levels. We hypothesized a role for the gut microbiome in these sex differences that would be normalized following microbiome depletion.

Methods

A mouse model was used to study these effects. Mice were divided into treatment groups by sex, diet, and presence/absence of an antibiotic cocktail to deplete genera in the gut microbiome. We hypothesized that sex differences would be present both in bodyweight gain and systemic measures of obesity, including hormone and circulating free fatty acid levels.

Results

We determined statistically significant differences for sex and/or treatment for the outcome measures. We confirm previous findings in which male mice gained significantly more weight than female mice fed the same high fat diet. However, sex differences persisted following antibiotic administration for microbiome depletion.

Conclusions

We conclude that sex differences in the gut microbiome may contribute to sex differences in obesity, but they do not explain all of the differences.
Multivariate time series collaborative compression for monitoring systems in securing cloud-based digital twin
Authors: Miao Zicong , Li Weize , Pan Xiaodong
Published: January 2024

With the booming of cloud-based digital twin systems, monitoring key performance indicators has become crucial for ensuring system security and reliability. Due to the massive amount of monitoring data generated, data compression is necessary to save data transmission bandwidth and storage space. Although the existing research has proposed compression methods for multivariate time series (MTS), it is still a challenge to guarantee the correlation between data when compressing the MTS. This paper proposes an MTS Collaborative Compression (MTSCC) method based on the two-step compression scheme. First, shape-based clustering is implemented to group the MTS. Afterward, the compressed sensing is optimized to achieve collaborative compression of grouped data. Based on a real-world MTS dataset, the experimental results show that the proposed MTSCC can effectively preserve the complex temporal correlation between indicators while achieving efficient data compression, and the root mean squared error of correlation between the reconstructed and original data is only 0.0489 in the case of 30% compression ratio. Besides, it is verified that using the reconstructed data in the production environment has almost the same performance as using the original data.