bluuebunny/crossref_metadata_2025 huggingface dataset:
Letter to the Editor: An ultra-sensitive assay using cell-free DNA fragmentomics for multi-cancer early detection
Authors: Bao Hua , Wang Zheng , Ma Xiaoji , Guo Wei , Zhang Xiangyu , Tang Wanxiangfu , Chen Xin , Wang Xinyu , Chen Yikuan , Mo Shaobo , Liang Naixin , Ma Qianli , Wu Shuyu , Xu Xiuxiu , Chang Shuang , Wei Yulin , Zhang Xian , Bao Hairong , Liu Rui , Yang Shanshan , Jiang Ya , Wu Xue , Li Yaqi , Zhang Long , Tan Fengwei , Xue Qi , Liu Fangqi , Cai Sanjun , Gao Shugeng , Peng Junjie , Zhou Jian , Shao Yang
Published: June 2022

Early detection can benefit cancer patients with more effective treatments and better prognosis, but existing early screening tests are limited, especially for multi-cancer detection. This study investigated the most prevalent and lethal cancer types, including primary liver cancer (PLC), colorectal adenocarcinoma (CRC), and lung adenocarcinoma (LUAD). Leveraging the emerging cell-free DNA (cfDNA) fragmentomics, we developed a robust machine learning model for multi-cancer early detection. 1,214 participants, including 381 PLC, 298 CRC, 292 LUAD patients, and 243 healthy volunteers, were enrolled. The majority of patients (N = 971) were at early stages (stage 0, N = 34; stage I, N = 799). The participants were randomly divided into a training cohort and a test cohort in a 1:1 ratio while maintaining the ratio for the major histology subtypes. An ensemble stacked machine learning approach was developed using multiple plasma cfDNA fragmentomic features. The model was trained solely in the training cohort and then evaluated in the test cohort. Our model showed an Area Under the Curve (AUC) of 0.983 for differentiating cancer patients from healthy individuals. At 95.0% specificity, the sensitivity of detecting all cancer reached 95.5%, while 100%, 94.6%, and 90.4% for PLC, CRC, and LUAD, individually. The cancer origin model demonstrated an overall 93.1% accuracy for predicting cancer origin in the test cohort (97.4%, 94.3%, and 85.6% for PLC, CRC, and LUAD, respectively). Our model sensitivity is consistently high for early-stage and small-size tumors. Furthermore, its detection and origin classification power remained superior when reducing sequencing depth to 1× (cancer detection: ≥ 91.5% sensitivity at 95.0% specificity; cancer origin: ≥ 91.6% accuracy). In conclusion, we have incorporated plasma cfDNA fragmentomics into the ensemble stacked model and established an ultrasensitive assay for multi-cancer early detection, shedding light on developing cancer early screening in clinical practice.
A novel inhalable quercetin-alginate nanogel as a promising therapy for acute lung injury
Authors: Chen Yi-Bing , Zhang Ya-Bin , Wang Yu-Le , Kaur Prabhleen , Yang Bo-Guang , Zhu Yan , Ye Lei , Cui Yuan-Lu
Published: June 2022

Background

Acute lung injury (ALI), a severe health-threatening disease, has a risk of causing chronic pulmonary fibrosis. Informative and powerful evidence suggests that inflammation and oxidative stress play a central role in the pathogenesis of ALI. Quercetin is well recognized for its excellent antioxidant and anti-inflammatory properties, which showed great potential for ALI treatment. However, the application of quercetin is often hindered by its low solubility and bioavailability. Therefore, to overcome these challenges, an inhalable quercetin-alginate nanogel (QU-Nanogel) was fabricated, and by this special “material-drug” structure, the solubility and bioavailability of quercetin were significantly enhanced, which could further increase the activity of quercetin and provide a promising therapy for ALI.

Results

QU-Nanogel is a novel alginate and quercetin based “material-drug” structural inhalable nanogel, in which quercetin was stabilized by hydrogen bonding to obtain a “co-construct” water-soluble nanogel system, showing antioxidant and anti-inflammatory properties. QU-Nanogel has an even distribution in size of less than 100 nm and good biocompatibility, which shows a stronger protective and antioxidant effect in vitro. Tissue distribution results provided evidence that the QU-Nanogel by ultrasonic aerosol inhalation is a feasible approach to targeted pulmonary drug delivery. Moreover, QU-Nanogel was remarkably reversed ALI rats by relieving oxidative stress damage and acting the down-regulation effects of mRNA and protein expression of inflammation cytokines via ultrasonic aerosol inhalation administration.

Conclusions

In the ALI rat model, this novel nanogel showed an excellent therapeutic effect by ultrasonic aerosol inhalation administration by protecting and reducing pulmonary inflammation, thereby preventing subsequent pulmonary fibrosis. This work demonstrates that this inhalable QU-Nanogel may function as a promising drug delivery strategy in treating ALI.

Graphical Abstract
Development and validation of a PCR-free nucleic acid testing method for RNA viruses based on linear molecular beacon probes
Authors: Du Fuyu , Zhang Weijie , Yao Huimin , Xia Yuqiong , Zhang Xianghan , Yang Peng , Ning Pengbo
Published: June 2022

Background

RNA viruses periodically trigger pandemics of severe human diseases, frequently causing enormous economic losses. Here, a nucleic acid extraction-free and amplification-free RNA virus testing probe was proposed for the sensitive and simple detection of classical swine fever virus (CSFV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on a double-stranded molecular beacon method. This RNA virus probe contains two base sequences—a recognition strand that binds to the specific domain of CSFV N2 or SARS-CoV-2 N, with a fluorophore (FAM) labeled at the 5′ end, and a complementary strand (CSFV-Probe B or SARS-CoV-2-Probe B), combined with a quencher (BHQ2) labeled at the 3′ end.

Results

Using linear molecular beacon probe technology, the detection limit of the RNA virus probe corresponding to CSFV and SARS-CoV-2 were as low as 0.28 nM and 0.24 nM, respectively. After CSFV E2 and SARS-CoV-2 N genes were transfected into corresponding host cells, the monitoring of RNA virus probes showed that fluorescence signals were dramatically enhanced in a concentration- and time-dependent manner. These results were supported by those of quantitative (qRT-PCR) and visualization (confocal microscopy) analyses. Furthermore, CSF-positive swine samples and simulated SARS-CoV-2 infected mouse samples were used to demonstrate their applicability for different distributions of viral nucleic acids in series tissues.

Conclusions

The proposed RNA virus probe could be used as a PCR-free, cost-effective, and rapid point-of-care (POC) diagnostic platform for target RNA virus detection, holding great potential for the convenient monitoring of different RNA viruses for early mass virus screening.

Graphical Abstract
Reciprocal regulation of NRF2 by autophagy and ubiquitin–proteasome modulates vascular endothelial injury induced by copper oxide nanoparticles
Authors: Li Na , Du Hang , Mao Lejiao , Xu Ge , Zhang Mengling , Fan Yinzhen , Dong Xiaomei , Zheng Lijun , Wang Bin , Qin Xia , Jiang Xuejun , Chen Chengzhi , Zou Zhen , Zhang Jun
Published: June 2022

NRF2 is the key antioxidant molecule to maintain redox homeostasis, however the intrinsic mechanisms of NRF2 activation in the context of nanoparticles (NPs) exposure remain unclear. In this study, we revealed that copper oxide NPs (CuONPs) exposure activated NRF2 pathway in vascular endothelial cells.NRF2knockout remarkably aggravated oxidative stress, which were remarkably mitigated by ROS scavenger. We also demonstrated that KEAP1 (the negative regulator of NRF2) was not primarily involved in NRF2 activation in thatKEAP1knockdown did not significantly affect CuONPs-induced NRF2 activation. Notably, we demonstrated that autophagy promoted NRF2 activation as evidenced by thatATG5knockout or autophagy inhibitors significantly blocked NRF2 pathway. Mechanically, CuONPs disturbed ubiquitin–proteasome pathway and consequently inhibited the proteasome-dependent degradation of NRF2. However, autophagy deficiency reciprocally promoted proteasome activity, leading to the acceleration of degradation of NRF2 via ubiquitin–proteasome pathway. In addition, the notion that the reciprocal regulation of NRF2 by autophagy and ubiquitin–proteasome was further proven in a CuONPs pulmonary exposure mice model. Together, this study uncovers a novel regulatory mechanism of NRF2 activation by protein degradation machineries in response to CuONPs exposure, which opens a novel intriguing scenario to uncover therapeutic strategies against NPs-induced vascular injury and disease.

Graphical Abstract
Association of single nucleotide polymorphisms (SNPs) with gastric cancer susceptibility and prognosis in population in Wuwei, Gansu, China
Authors: Fan Ping , Zhang Zhiyi , Lu Linzhi , Guo Xingcai , Hao Zhicheng , Wang Xinghua , Ye Yancheng
Published: June 2022

Background

Gastric cancer (GC) is the sixth most common cancer. China is one of the most frequent GC occurred countries, and Wuwei, Gansu, is one of the highest incidence area in China. Possible biomarkers of GC susceptibility and prognosis among the population in Wuwei are urgently needed.

Methods

All participants in this study were recruited from the Wuwei Cancer Hospital in Gansu, including 303 patients diagnosed with GC and 200 non-cancer controls. DNA was extracted for further single nucleotide polymorphisms (SNP) genotyping. All SNPs were firstly screened by additive logistic regression model then selected SNPs were subjected to univariate Cox regression analysis and multivariate Cox regression analysis for their associations with GC occurrence.

Results

The results showed that 31 SNPs were significantly related to the incidence of GC in Wuwei, Gansu, China. Genotype rs4823921 was significantly related to the overall survival of GC patients and AC/AA genotype of rs4823921 polymorphism was significantly associated with an increased risk of GC in Wuwei population.

Conclusions

Thirty-one SNPs were significantly related to the incidence of GC in Wuwei and rs4823921 genotype AC/AA was significantly associated with poor prognosis of GC patients in Wuwei, Gansu.
Diagnostic potential of a circulating miRNA model associated with therapeutic effect in heart failure
Authors: Qian Lu , Zhao Qian , Yu Ping , Lü Jinhui , Guo Yuefan , Gong Xin , Ding Yuanyuan , Yu Shanshan , Fan Lieying , Fan Huimin , Zhang Yuzhen , Liu Zhongmin , Sheng Hongzhuan , Yu Zuoren
Published: June 2022

Heart failure (HF), as the leading cause of death, is continuing to increase along with the aging of the general population all over the world. Identification of diagnostic biomarkers for early detection of HF is considered as the most effective way to reduce the risk and mortality. Herein, we collected plasma samples from HF patients (n = 40) before and after medical therapy to determine the change of circulating miRNAs through a quantitative real-time PCR (QRT-PCR)-based miRNA screening analysis. miR-30a-5p and miR-654-5p were identified as the most significantly changed miRNAs in the plasma of patients upon treatment. In consistence, miR-30a-5p showed upregulation and miR-654-5p showed downregulation in the circulation of 30 HF patients, compared to 15 normal controls in the training phase, from which a two-circulating miRNA model was developed for HF diagnosis. Next, we performed the model validation using an independent cohort including 50 HF patients and 30 controls. As high as 98.75% of sensitivity and 95.00% of specificity were achieved. A comparison between the miRNA model and NT-pro BNP in diagnostic accuracy of HF indicated an upward trend of the miRNA model. Moreover, change of the two miRNAs was further verified in association with the therapeutic effect of HF patients, in which miR-30a-5p showed decrease while miR-654-5p showed increase in the plasma of patients after LVAD implantation. In conclusion, the current study not only identified circulating miR-654-5p for the first time as a novel biomarker of HF, but also developed a novel 2-circulating miRNA model with promising potentials for diagnosis and prognosis of HF patients, and in association with therapeutic effects as well.
Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats
Authors: Zhao Yu-Ting , Deng Jie , Liu He-Ming , Wei Jia-You , Fan Hai-Ting , Liu Meng , Xu Ting , Chen Ting-Feng , He Jing-Yi , Sun Wei-Ming , Jia Tao-Yu , Zhang Xue-Qin , Xin Wen-Jun
Published: June 2022

Background

The adaption of brain region is fundamental to the development and maintenance of nervous system disorders. The prelimbic cortex (PrL) participates in the affective components of the pain sensation. However, whether and how the adaptation of PrL contributes to the comorbidity of neuropathic pain and depression are unknown.

Methods

Using resting-state functional magnetic resonance imaging (rs-fMRI), genetic knockdown or overexpression, we systematically investigated the activity of PrL region in the pathogenesis of neuropathic pain/depression comorbid using the combined approaches of immunohistochemistry, electrophysiology, and behavior.

Results

The activity of PrL and the excitability of pyramidal neurons were decreased, and the osteoclastic tartrate-resistant acid phosphatase 5 (Acp5) expression in PrL neurons was upregulated following the acquisition of spared nerve injury (SNI)-induced comorbidity. Genetic knockdown of Acp5 in pyramidal neurons, but not parvalbumin (PV) neurons or somatostatin (SST) neurons, attenuated the decrease of spike number, depression-like behavior and mechanical allodynia in comorbidity rats. Overexpression of Acp5 in PrL pyramidal neurons decreased the spike number and induced the comorbid-like behavior in naïve rats. Moreover, the expression of interleukin-6 (IL-6), phosphorylated STAT3 (p-STAT3) and acetylated histone H3 (Ac-H3) were significantly increased following the acquisition of comorbidity in rats. Increased binding of STAT3 to the Acp5 gene promoter and the interaction between STAT3 and p300 enhanced acetylation of histone H3 and facilitated the transcription of Acp5 in PrL in the modeled rodents. Inhibition of IL-6/STAT3 pathway prevented the Acp5 upregulation and attenuated the comorbid-like behaviors in rats.

Conclusions

These data suggest that the adaptation of PrL mediated by IL-6/STAT3/Acp5 pathway contributed to the comorbidity of neuropathic pain/depression induced by SNI.
Professionalism, stigma, and willingness to provide patient-centered safe abortion counseling and care: a mixed methods study of Ethiopian midwives
Authors: Fekadu Addisu , Berhe Aster , Belgu Belete , Yimer Ibrahim , Tesfaye Yeshitila , Holcombe Sarah Jane , Burrowes Sahai
Published: June 2022

Background

Midwives are a large proportion of Ethiopia’s health care workforce, and their attitudes and practices shape the quality of reproductive health care, including safe abortion care (SAC) services. This study examines how midwives’ conceptions of their professional roles and views on women who have abortions relate to their willingness to provide respectful SAC.

Methods

This study uses a cross-sectional, mixed methods design to conduct a regionally representative survey of midwives in Ethiopia’s five largest regions (Oromia; Amhara; Southern Nations, Nationalities, and Peoples [SNNP]; Tigray; and Addis Ababa) with a multistage, cluster sampling design (n = 944). The study reports survey-weighted population estimates and the results of multivariate logistic regression analyzing factors associated with midwives’ willingness to provide SAC. Survey data were triangulated with results from seven focus group discussions (FGDs) held with midwives in the five study regions. Deductive and inductive codes were used to thematically analyze these data.

Results

The study surveyed 960 respondents. An estimated half of midwives believed that providing SAC was a professional duty. Slightly more than half were willing to provide SAC. A belief in right of refusal was common: two-thirds of respondents said that midwives should be able to refuse SAC provision on moral or religious grounds. Modifiable factors positively associated with willingness to provide SAC were SAC training (AOR 4.02; 95% CI 2.60, 6.20), agreeing that SAC refusal risked women’s lives (AOR 1.69; 95% CI 1.20, 2.37), and viewing SAC provision as a professional duty (AOR 1.72; 95% CI 1.23, 2.39). In line with survey findings, a substantial number of FGD participants stated they had the right to refuse SAC. Responses to client scenarios revealed “directive counseling” to be common: many midwives indicated that they would actively attempt to persuade clients to act as they (the midwives) thought was best, rather than support clients in making their own decisions.

Conclusion

Findings suggest a need for new guidelines to clarify procedures surrounding conscientious objection and refusal to provide SAC, as well as initiatives to equip midwives to provide rights-based, patient-centered counseling and avoid directive counseling.
Signs of a turning tide in social norms and attitudes toward abortion in Ethiopia: Findings from a qualitative study in four regions
Authors: O’Connell Kathryn A. , Kebede Addisalem T. , Menna Bereket M. , Woldetensay Mengistu T. , Fischer Sara E. , Samandari Ghazaleh , Kassaw Jemal K.
Published: June 2022

Background

Despite the 2005 expansion in abortion legal indications in Ethiopia, which provided for abortions in cases of rape, incest, or fetal impairment and other circumstances, nearly half of abortions occurred outside health facilities in 2014. The purpose of this study is to explore and understand the social barriers women face in seeking and obtaining quality safe abortion care, as a means to generate evidence that could be used to improve access to and quality of abortion services.

Methods

Thirty-two focus group discussions with both men and women were held in four different regions of Ethiopia: Addis Ababa; Amhara; Oromia; and the Southern Nations, Nationalities, and Peoples’ Region. The study team recruited participants (n = 193) aged 18–55 in each region using a purposive sample with snowball recruitment techniques. We conducted discussions in Amharic or Afaan Oromo using a semi-structured guide and transcribed and translated them into English for analysis. We used deductive coding and analysis to categorize findings into emergent themes around stigma, barriers, and the changing nature of attitudes around abortion.

Results

Despite changes in abortion law, findings show that women with unwanted pregnancies and those seeking abortions are still heavily stigmatized and sanctioned in a number of communities across Ethiopia. Abortion was deemed unacceptable in most cases, though respondents were more tolerant in cases of risk to the mother’s life and of rape. We saw promising indications that changes are taking place in Ethiopian society’s view of abortion, and several participants indicated progress toward a more supportive environment overall for women seeking abortion care. Still, this progress may be limited by variable knowledge of abortion laws and tightly held gender-based social norms, particularly in rural areas. Most participants noted the importance of education and outreach to improve abortion attitudes and norms.

Conclusion

Policymakers should create further awareness in Ethiopia on the availability of quality abortion services in public health facilities and the indications for legal abortion. Such efforts should be based on principles of gender equality, as a means of ensuring enduring changes for women’s reproductive choice throughout the country.
If fear of infertility restricts contraception use, what do we know about this fear? An examination in rural Ethiopia
Authors: Sedlander Erica , Yilma Hagere , Emaway Dessalew , Rimal Rajiv N.
Published: June 2022

Background

Ethiopia has made great progress toward reducing unmet need for family planning and increasing contraception use over the last decade. However, almost one-quarter of women still have an unmet need. The primary reason for non-use is “method-related health concerns” and, within this broad category, the belief that using contraception will cause infertility is common. This belief extends beyond Ethiopia to low-, middle-, and high-income countries across the world. The objective of this paper is to examine associations with the belief that contraception use causes infertility and to subsequently suggest potential strategies to address this misperception.

Methods

We collected data from women of reproductive age (between 15 and 49 years old) in 115 rural districts of Ethiopia (n = 706). Our main outcome variable was the belief that contraception causes infertility. We analyzed data, both individual-level factors and interpersonal factors, using nested logistic regression models.

Results

Almost half of women in our sample (48.2%) believed that contraceptive use causes infertility. In the final model that included factors from both levels, self-efficacy to use contraception (AOR = 0.81, p < 0.05), visiting a health center and speaking to a provider about family planning in the last 12 months (AOR = 0.78, p < 0.05), and husband support of contraception (AOR = 0.77, p < 0.01) were associated with a reduction in the odds of believing that contraception causes infertility. The belief that infertility will result in abandonment from one’s husband (AOR = 3.06, p < 0.001) was associated with an increase in the odds of holding the belief that contraception causes infertility. A home visit in the last 12 months from a health worker who discussed family planning was not associated with the belief that contraceptive use causes infertility.

Conclusions

Given that this belief is both salient and positively associated with other fears such as abandonment from one’s husband, it is critical for family planning programs to address it. Communication campaigns or interventions that address this misperception among couples may diminish this belief, thereby increasing contraception use and reducing unmet need in rural Ethiopia.
Generation and characterization of genome-modified chondrocyte-like cells from the zebra finch cell line immortalized by c-MYC expression
Authors: Jung Kyung Min , Kim Young Min , Yoo Eunhui , Han Jae Yong
Published: June 2022

Background

Due to their cost effectiveness, ease of use, and unlimited supply, immortalized cell lines are used in place of primary cells for a wide range of research purposes, including gene function studies, CRISPR-based gene editing, drug metabolism tests, and vaccine or therapeutic protein production. Although immortalized cell lines have been established for a range of animal species, there is still a need to develop such cell lines for wild species. The zebra finch, which is used widely as a model species to study the neurobiological basis of human speech disorders, has been employed in several functional studies involving gene knockdown or the introduction of exogenous transgenes in vivo; however, the lack of an immortalized zebra finch cell line has hampered precise genome editing studies.

Results

Here, we established an immortalized cell line by a single genetic event, expression of the c-MYC oncogene, in zebra finch embryonic fibroblasts and examined its potential suitability for gene targeting investigations. Retroviral vector-mediated transduction of c-MYC was used to immortalize zebra finch primary fibroblasts; the transformed cells proliferated stably over several passages, resulting in the expression of chondrocyte-specific genes. The transfection efficiency of the immortalized cells was much higher than that of the primary cells. Targeted knockout of the SOX9 gene, which plays a role in the differentiation of mesenchymal progenitor cells into chondrocytes, was conducted in vitro and both apoptosis and decreased expression levels of chondrogenic marker genes were observed in edited cells.

Conclusions

The c-MYC induced immortalized chondrocyte-like cell line described here broadens the available options for establishing zebra finch cell lines, paves the way for in-depth biological researches, and provides convenient approaches for biotechnology studies, particularly genomic modification research.
Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α
Authors: Leng Qingyang , Zhou Jianhua , Li Chang , Xu Yanhong , Liu Lu , Zhu Yi , Yang Ying , Zhang Hongli , Li Xiaohua
Published: June 2022

Background

Promoting the browning of white adipose tissue (WAT) is a promising approach for the treatment of obesity and related comorbidities because it increases energy expenditure. In this study, we investigated whether Dihydromyricetin (DHM), a flavonoid component, could ameliorate diet-induced obesity through promoting the browning of WAT.

Methods

Male C57BL/6 J mice were received a high-fat diet (HFD) to induce obesity and subsequently were treated with DHM (100 mg/kg/day) or vehicle for 4 weeks. The effects of DHM on weight reduction and metabolic phenotype improvement were observed in the mice. The expression of genes and protein involved in browning of WAT were assessed in inguinal WAT (iWAT) of the mice. Then, the effect of DHM on the inducing browning program was verified in adipocytes differentiated from stromal vascular fraction (SVF) cells of mouse iWAT. Finally, the mechanism by which DHM improves the browning of WAT was explored using RNA-seq and luciferase reporter assay.

Results

We find that DHM reduces body weight, decreases WAT mass, improves glucose and lipid metabolic disorders, and ameliorates hepatic steatosis in diet-induced obese (DIO) mice. Further studies show that DHM induces WAT browning, which is manifested by increased expression of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and enhanced mitochondrial activity in iWAT and primary adipocytes. In addition, we also find that DHM enhances interferon regulatory factor 4 (IRF4) expression, which is a key transcriptional regulator of PGC-1α.

Conclusion

Our findings identify that DHM prevents obesity by inducing the browning of WAT through the upregulation of IRF4/PGC-1α, which may have potential therapeutic implications for the treatment of obesity.
Influence of surface treatment and curing mode of resin composite cements on fibroblast behavior
Authors: Rohr Nadja , Baumann Celina , Märtin Sabrina , Zitzmann Nicola U.
Published: June 2022

Background

Human gingival fibroblast (HGF-1) cells in the connective tissue provide an effective barrier between the alveolar bone and the oral environment. Cement margins of restorations with intrasulcular preparation or cemented implant restorations are in contact with HGF cells. However, it is unknown to what extend the cement surface finish affects the behavior of HGF cells. The purpose of this study was to compare the behavior of HGF-1 cells in contact with two different resin composite cements with three different surface treatments after light-curing and autopolymerization, respectively.

Methods

Disks of one adhesive (Multilink Automix, Ivoclar Vivadent [MLA]) and one self-adhesive (RelyX Unicem 2 Automix, 3 M [RUN]) resin composite cement were either light-cured or autopolymerized. Specimen surfaces were prepared with the oxygen inhibition layer intact, polished with P2500-grit silicon carbide paper or treated with a scaler. Cells were cultivated on the specimens for 24 h. Viability assay was performed, and cell morphology was examined with scanning electron microscopy. Additionally, roughness parameters of the specimen were analyzed with a 3D laser scanning microscope. Three-way ANOVA was applied to determine the effect of cement material, curing mode and surface treatment (a = 0.05).

Results

Overall, cement material (p = 0.031), curing mode (p = 0.001), and surface treatment (p < 0.001) significantly affected relative cell viability of HGF. The autopolymerized specimen with the oxygen inhibition layer left intact displayed the lowest relative cell viability (MLA 25.7%, RUN 46.6%). Removal of the oxygen inhibition layer with a scaler increased cell viability but also resulted in higher surface roughness values.

Conclusions

HGF cell viability is affected by the surface treatment and the curing mode. The oxygen inhibition layer is an inhibitory factor for the viability of HGF cells. Autopolymerization enhances the cytotoxic potential of the oxygen inhibition layer.
A novel in situ passive heating method for evaluating whole-tree responses to daytime warming in remote environments
Authors: Werkmeister Georgina A. , Galbraith David , Docherty Emma , Borges Camilla Silva , da Rocha Jairo Matos , da Silva Paulo Alves , Marimon Beatriz Schwantes , Marimon-Junior Ben Hur , Phillips Oliver L. , Gloor Emanuel
Published: June 2022

Background

Many significant ecosystems, including important non-forest woody ecosystems such as the Cerrado (Brazilian savannah), are under threat from climate change, yet our understanding of how increasing temperatures will impact native vegetation remains limited. Temperature manipulation experiments are important tools for investigating such impacts, but are often constrained by access to power supply and limited to low-stature species, juvenile individuals, or heating of target organs, perhaps not fully revealing how entire or mature individuals and ecosystems will react to higher temperatures.

Results

We present a novel, modified open top chamber design for in situ passive heating of whole individuals up to 2.5 m tall (but easily expandable) in remote field environments with strong solar irradiance. We built multiple whole-tree heating structures (WTHSs) in an area of Cerrado around native woody species Davilla elliptica and Erythroxylum suberosum to test the design and its effects on air temperature and humidity, while also studying the physiological responses of E. suberosum to short-term heating. The WTHSs raised internal air temperature by approximately 2.5 °C above ambient during the daytime. This increased to 3.4 °C between 09:00 and 17:00 local time when thermal impact was greatest, and during which time mean internal temperatures corresponded closely with maximum ambient temperatures. Heating was consistent over time and across WTHSs of variable size and shape, and they had minimal effect on humidity. E. suberosum showed no detectable response of photosynthesis or respiration to short-term experimental heating, but some indication of acclimation to natural temperature changes.

Conclusions

Our WTHSs produced a consistent and reproducible level of daytime heating in line with mid-range climate predictions for the Cerrado biome by the end of the century. The whole-tree in situ passive heating design is flexible, low-cost, simple to build using commonly available materials, and minimises negative impacts associated with passive chambers. It could be employed to investigate the high temperature responses of many understudied species in a range of complex non-forest environments with sufficient solar irradiance, providing new and important insights into the possible impacts of our changing climate.
A model for genuineness detection in genetically and phenotypically similar maize variety seeds based on hyperspectral imaging and machine learning
Authors: Tu Keling , Wen Shaozhe , Cheng Ying , Xu Yanan , Pan Tong , Hou Haonan , Gu Riliang , Wang Jianhua , Wang Fengge , Sun Qun
Published: June 2022

Background

Variety genuineness and purity are essential indices of maize seed quality that affect yield. However, detection methods for variety genuineness are time-consuming, expensive, require extensive training, or destroy the seeds in the process. Here, we present an accurate, high-throughput, cost-effective, and non-destructive method for screening variety genuineness that uses seed phenotype data with machine learning to distinguish between genetically and phenotypically similar seed varieties. Specifically, we obtained image data of seed morphology and hyperspectral reflectance for Jingke 968 and nine other closely-related varieties (non-Jingke 968). We then compared the robustness of three common machine learning algorithms in distinguishing these varieties based on the phenotypic imaging data.

Results

Our results showed that hyperspectral imaging (HSI) combined with a multilayer perceptron (MLP) or support vector machine (SVM) model could distinguish Jingke 968 from varieties that differed by as few as two loci, with a 99% or higher accuracy, while machine vision imaging provided  ~ 90% accuracy. Through model validation and updating with varieties not included in the training data, we developed a genuineness detection model for Jingke 968 that effectively discriminated between genetically similar and distant varieties.

Conclusions

This strategy has potential for wide adoption in large-scale variety genuineness detection operations for internal quality control or governmental regulatory agencies, or for accelerating the breeding of new varieties. Besides, it could easily be extended to other target varieties and other crops.
Efficacy and safety of radiotherapy plus anti-PD1 versus transcatheter arterial chemoembolization plus sorafenib for advanced hepatocellular carcinoma: a real-world study
Authors: Li Jian-Xu , Deng Wen-Xiang , Huang Shi-Ting , Lin Xiao-Feng , Long Mei-Ying , Zhang Jie , Su Ting-Shi , Li Li-Qing , Pang Ya-Dan , Liang Chun-Feng , Zhou Hong-Mei , Lu Hai-Yan , Liang Shi-Xiong , Xiang Bang-De
Published: June 2022

Background

The combination of transcatheter arterial chemoembolization (TACE) plus sorafenib prolonged progression-free survival (PFS) and overall survival (OS) than sorafenib or TACE monotherapy for patients with hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of radiotherapy (RT) plus monoclonal antibody against programmed cell death 1 (anti-PD1) versus TACE plus sorafenib for patients with advanced HCC.

Methods

Patients with advanced HCC who treated with RT plus anti-PD1 and TACE plus sorafenib were enrolled. Objective response rate (ORR), PFS, disease control rate (DCR) and OS were calculated to assess the antitumor response and the treatment-related adverse events to the safety.

Results

Between January 2018 to March 2021, 37 patients underwent RT plus anti-PD1 and 41 patients underwent TACE plus sorafenib. The baseline characteristics between the two groups were comparable. The ORR and DCR were significantly higher in the RT + PD1 group than the TACE plus sorafenib group according to RECIST 1.1 (54.05% vs. 12.20%, P < 0.001; 70.27% vs. 46.37%, P = 0.041; respectively) and according to mRECIST (56.76% vs. 31.71%, P = 0.039; 70.27% vs. 46.37%, P = 0.041; respectively). RT plus anti-PD1 provided significantly better PFS (HR, 0.51; 95% CI 0.30–0.86; P = 0.017) than TACE plus sorafenib. Moreover, patients with RT plus anti-PD1 had significantly higher 3-, 6-, and 9-month OS rates than those with TACE plus sorafenib(97.3% vs. 92.30%, P < 0.001; 91.89% vs. 68.60%, P < 0.001; 75.5% vs. 60.60%, P < 0.001; respectively). The median OS was more favorable 17.4 months for the RT + PD1 group and 11.9 months for the TACE plus sorafenib group. No treatment-related death was observed. Grade 3 or more treatment-related adverse events (TRAEs) occurred significantly less in patients in the RT + PD1 group than the TACE plus sorafenib group (29.7% vs. 75.6%, P < 0.001), and all TRAEs were manageable.

Conclusions

In this real-world study, RT plus anti-PD1 showed significantly promising efficacy and manageable safety than TACE plus sorafenib in patients with advanced HCC. Toxicities were manageable, with no unexpected safety signals. The study provides evidence on a new therapeutic method in the treatment of advanced HCC.
Variation in patterns and volumes of injuries admitted to a level one trauma center during lockdown for COVID-19
Authors: Ower Cornelia , Stock Kerstin , Kaiser Peter , Ulmer Hanno , Arora Rohit , Haselbacher Matthias
Published: June 2022

Introduction

Due to the global COVID-19 pandemic, a ban on sports outside one’s home and a prohibition on travel between communities were imposed in spring 2020 in Tyrol, Austria. The aim of this study was to evaluate the impact of these restrictions on a level one trauma center. The objective was to identify the most common injury patterns to ensure targeted prevention in times of an ongoing pandemic.

Material and methods

Patients who presented themselves to our trauma center between weeks 7 and 22 in 2020 were retrospectively compared to a mean of the patients of the three previous years (2017–2019). The evaluated variables were the number of patients, age, gender, country of residence, place of accident, time of treatment, injured body region and anatomical structure, number of surgical intervention and severely injured patients.

Results

Comparing the mean count of treated patients per week in 2020 of the pre-lockdown period (n = 804.6) with the lockdown period (n = 201.8) a decrease in admissions by 69.7% could be observed. The admission incidence was 9.9 times higher in previous years than in 2020 during the lockdown period. Among the injuries treated during the lockdown the largest increase in relative numbers was in home injuries, head or face injuries and superficial or penetrating injuries. There was a decrease of seriously injured patients as well as patients that needed surgery during the lockdown compared to previous years.

Conclusions

We observed a significant change in the pattern and volume of injuries during a strict lockdown. Intervention programs to reduce the risk of home injuries should be introduced. Furthermore, in order to save resources during a pandemic, specific guidelines on patient management and treatment should be established for the respective medical specialties.

Trial registration: 1157/2020, 10.12.2020.
Allogenic perinatal tissue for musculoskeletal regenerative medicine applications: a systematic review protocol
Authors: Aratikatla Adarsh , Maffulli Nicola , Rodriguez Hugo C. , Gupta Manu , Potty Anish G. , El-Amin Saadiq F. , Gupta Ashim
Published: June 2022

Background

Musculoskeletal ailments impact the lives of millions of people, and at times necessitate surgery followed by physiotherapy, drug treatments, or immobilization. Regenerative musculoskeletal medicine has undergone enormous progress over the last few decades. Sources of tissues used for regenerative medicine purposes can be grouped into autologous or allogenic. Although autologous sources are promising, there is a wide range of limitations with the treatment, including the lack of randomized controlled studies for orthopaedic conditions, donor site morbidity, and highly variable outcomes for patients. Allogenic sources bypass some of these shortcomings and are a promising source for orthopaedic regenerative medicine applications.

Methods

A systematic search will be performed using PubMed, Elsevier, ScienceDirect, and Google Scholar databases for articles published in English before May 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and guidelines will be used. Studies will be eligible if they apply to acute and chronic orthopaedic musculoskeletal complications or animal or human disease models. Publications must include the use of MSCs and/or tissue obtained from amniotic/chorionic membrane, amniotic fluid, umbilical cord, and/or umbilical cord-derived Wharton’s jelly as an intervention. Placebos, noninjury models, acute injury models, non-injury models, and gold standard treatments will be compared. The study selection will be performed by two independent reviewers using a dedicated reference management software. Data synthesis and meta-analysis will be performed separately for preclinical and clinical studies.

Discussion

The results will be published in relevant peer-reviewed scientific journals. Investigators will present results at national or international conferences.

Trial registration: The Protocol will be registered on PROSPERO international prospective register of systematic reviews prior to commencement.
Magnetically controlled growing rods in the management of early onset scoliosis: a systematic review
Authors: Migliorini Filippo , Chiu Wai On , Scrofani Raffaele , Chiu Wai Kwong , Baroncini Alice , Iaconetta Giorgio , Maffulli Nicola
Published: June 2022

Background

Early onset scoliosis (EOS) presents in patients younger than 10 years. Magnetically controlled growing rods (MCGR) were developed as an outpatient distraction system for EOS, allowing to avoid multiple surgeries. This systematic review investigated the efficacy and feasibility of MCGR in EOS.

Methods

This systematic review was conducted according to the PRISMA guidelines. PubMed, Google scholar, Embase, and Scopus were accessed in May 2022. All the clinical trials which investigate the role of MCGR for early onset scoliosis were accessed. Only studies reporting data in patients younger than 10 years with a preoperative Cobb Angle greater than 40° were eligible. The following data was extracted at baseline and at last follow-up: mean kyphosis angle, overall mean Cobb angle, mean T1–S1 length. Data from complication were also collected.

Results

Data from 23 clinical studies (504 patients) were included in the present study. 56% (282 of 504) were females. The average length of the follow-up was 28.9 ± 16.0 months. The mean age of the patients was 8.7 ± 1.9 years old. The mean BMI was 17.7 ± 7.6 kg/m2. The mean kyphosis angle had reduced by the last follow-up (P = 0.04), as did the overall mean Cobb angle (P < 0.0001), while the overall T1–S1 length increased (P = 0.0002). Implant-associated complications, followed by spinal alignment failure, wound healing ailments, pulmonary complications, progressive trunk stiffness, persistent back pain, and fracture.

Conclusion

The management of EOS remains challenging. The current evidence indicates that MCGR may be effective to distract the spine and model the curve in EOS.
Factors influencing severity of recurrent malaria in a conflict-affected state of South Sudan: an unmatched case-control study
Authors: Idris Israel Oluwaseyidayo , Ayeni Gabriel Omoniyi , Iyamu Ihoghosa Osamuyi , Sina-Odunsi Ayomide Busayo , Adebisi Yusuff Adebayo , Obwoya Justin Geno
Published: June 2022

Background

The burden of malaria remains the highest in sub-Saharan Africa and South Sudan is not an exception. The country has borne the brunt of years of chronic warfare and remains endemic of malaria, with increasing mortality and morbidity. Limited data still exists on factors influencing the recurrence of severe malaria, especially in emergency contexts such as South Sudan, affected by various conflicts and humanitarian situations. This study therefore aimed to investigate factors influencing severity of occurrence malaria in selected primary healthcare centres in South Sudan. This would assist and guide in malaria prevention, treatment, and eradication efforts.

Methods

We conducted an unmatched case-control study using routinely collected clinic data for individuals aged 1 year and above who received a diagnosis of severe malaria at 3 primary healthcare centres (PHCC); Malual Bab PHCC, Matangai PHCC and Malek PHCC between September 15, 2019 to December 15, 2019 in South Sudan. Patient characteristics were analyzed using simple descriptive statistics. Inferential statistics were also conducted to identify the associated factors influencing recurrence of severe malaria. All analyses were conducted using R Version 3.6.2.

Results

A total of 289 recurrent malaria cases were included in this study. More than half of the participants were female. Overall, the prevalence of severe recurrent malaria was 66.1% (191) while 74.4% (215) did not complete malaria treatment. Among those who did not complete malaria treatment, 76.7% (165) had severe recurrent malaria, while among those who completed malaria treatment 35.1% (26) had severe recurrent malaria (p < 0.001). There is a significant association between marital status (OR 0.33, 95% CI 0.19–0.56, p < 0.001), employment status (OR 0.35, 95% CI 0.14–0.87, p = 0.024), the use of preventive measures (OR 3.82, 95% CI 1.81–8.43, p < 0.001) and nutrition status (OR 0.22, 95% CI 0.13–0.37, p < 0.001). When adjusted for employment, marital status, nutritional and prevention measures in turns using Mantel–Haenszel test of association, this effect remained statistically significant.

Conclusions

Our study showed that there is a high prevalence of severe recurrent malaria in South Sudan and that a significant relationship exists between severe recurrent malaria and antimalarial treatment dosage completion influenced by certain personal and social factors such as marital status, employment status, the use of preventive measures and nutrition status. Findings from our study would be useful for effective response to control and prevent malaria in endemic areas of South Sudan.
Translational landscape of glioblastoma immunotherapy for physicians: guiding clinical practice with basic scientific evidence
Authors: Kreatsoulas Daniel , Bolyard Chelsea , Wu Bill X. , Cam Hakan , Giglio Pierre , Li Zihai
Published: June 2022

Despite recent advances in cancer therapeutics, glioblastoma (GBM) remains one of the most difficult cancers to treat in both the primary and recurrent settings. GBM presents a unique therapeutic challenge given the immune-privileged environment of the brain and the aggressive nature of the disease. Furthermore, it can change phenotypes throughout the course of disease—switching between mesenchymal, neural, and classic gene signatures, each with specific markers and mechanisms of resistance. Recent advancements in the field of immunotherapy—which utilizes strategies to reenergize or alter the immune system to target cancer—have shown striking results in patients with many types of malignancy. Immune checkpoint inhibitors, adoptive cellular therapy, cellular and peptide vaccines, and other technologies provide clinicians with a vast array of tools to design highly individualized treatment and potential for combination strategies. There are currently over 80 active clinical trials evaluating immunotherapies for GBM, often in combination with standard secondary treatment options including re-resection and anti-angiogenic agents, such as bevacizumab. This review will provide a clinically focused overview of the immune environment present in GBM, which is frequently immunosuppressive and characterized by M2 macrophages, T cell exhaustion, enhanced transforming growth factor-β signaling, and others. We will also outline existing immunotherapeutic strategies, with a special focus on immune checkpoint inhibitors, chimeric antigen receptor therapy, and dendritic cell vaccines. Finally, we will summarize key discoveries in the field and discuss currently active clinical trials, including combination strategies, burgeoning technology like nucleic acid and nanoparticle therapy, and novel anticancer vaccines. This review aims to provide the most updated summary of the field of immunotherapy for GBM and offer both historical perspective and future directions to help inform clinical practice.