bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 in kidney transplantation-implications for immunosuppression and vaccination
Authors: Kodali Lavanya , Budhiraja Pooja , Gea-Banacloche Juan
Published: November 2022

COVID-19 pandemic continues to challenge the transplant community, given increased morbidity and mortality associated with the disease and poor response to prevention measures such as vaccination. Transplant recipients have a diminished response to both mRNA and vector-based vaccines compared to dialysis and the general population. The currently available assays to measure response to vaccination includes commercially available antibody assays for anti-Spike Ab, or anti- Receptor Binding Domain Ab. Positive antibody testing on the assays does not always correlate with neutralizing antibodies unless the antibody levels are high. Vaccinations help with boosting polyfunctional CD4+ T cell response, which continues to improve with subsequent booster doses. Ongoing efforts to improve vaccine response by using additional booster doses and heterologous vaccine combinations are underway. There is improved antibody response in moderate responders; however, the ones with poor response to initial vaccination doses, continue to have a poor response to sequential boosters. Factors associated with poor vaccine response include diabetes, older age, specific immunosuppressants such as belatacept, and high dose mycophenolate. In poor responders, a decrease in immunosuppression can increase response to vaccination. COVID infection or vaccination has not been associated with an increased risk of rejection. Pre- and Post-exposure monoclonal antibodies are available to provide further protection against COVID infection, especially in poor vaccine responders. However, the efficacy is challenged by the emergence of new viral strains. A recently approved bivalent vaccine offers better protection against the Omicron variant.
Facultative symbionts are potential agents of symbiont-mediated RNAi in aphids
Authors: Li Tong , Wei Yongjun , Zhao Chenchen , Li Shaojian , Gao Suxia , Zhang Yuanchen , Wu Yuqing , Lu Chuantao
Published: November 2022

Aphids are major crop pests, and they can be controlled through the application of the promising RNA interference (RNAi) techniques. However, chemical synthesis yield of dsRNA for RNAi is low and costly. Another sustainable aphid pest control strategy takes advantage of symbiont-mediated RNAi (SMR), which can generate dsRNA by engineered microbes. Aphid host the obligate endosymbiont Buchnera aphidicola and various facultative symbionts that not only have a wide host range but are also vertically and horizontally transmitted. Thus, we described the potential of facultative symbionts in aphid pest control by SMR. We summarized the community and host range of these facultative symbionts, and then reviewed their probable horizontal transmitted routes and ecological functions. Moreover, recent advances in the cultivation and genetic engineering of aphid facultative symbionts were discussed. In addition, current legislation of dsRNA-based pest control strategies and their safety assessments were reviewed.
Physical, chemical, and biological control of black rot of brassicaceae vegetables: A review
Authors: Liu Zeci , Wang Huiping , Wang Jie , Lv Jian , Xie Bojie , Luo Shilei , Wang Shuya , Zhang Bo , Li Zhaozhuang , Yue Zhibin , Yu Jihua
Published: November 2022

As one of the important sources of human nutrition, Brassicaceae vegetables are widely grown worldwide. Black rot caused by Xanthomonas campestris pv. campestris (Xcc) seriously affects the quality and yield of Brassicaceae vegetables. Therefore, it is important to study control methods of Xcc for Brassicaceae vegetable production. This paper reviews the physical, chemical, and biological control methods of Xcc in Brassicaceae vegetables developed in recent years, and the underlying mechanisms of control methods are also discussed. Based on our current knowledge, future research directions for Xcc control are also proposed. This review also provides a reference basis for the control of Xcc in the field cultivation of Brassicaceae vegetables.
Identification of two novel neutralizing nanobodies against swine hepatitis E virus
Authors: Chen Yiyang , Wang Xueting , Zhang Meimei , Li Jinyao , Gao Xueyan , Nan Yuchen , Zhao Qin , Zhou En-Min , Liu Baoyuan
Published: November 2022

Hepatitis E virus (HEV) is thought to be a zoonotic pathogen that causes serious economic loss and threatens human health. However, there is a lack of efficient antiviral strategies. As a more promising tool for antiviral therapy, nanobodies (also named single-domain antibodies, sdAbs) exhibit higher specificity and affinity than traditional antibodies. In this study, nanobody anti-genotype four HEV open reading frame 2 (ORF2) was screened using phage display technology, and two nanobodies (nb14 and nb53) with high affinity were prokaryotically expressed. They were identified to block HEV ORF2 virus like particle (VLP) sp239 (aa 368–606) absorbing HepG2 cells in vitro. With the previously built animal model, the detection indicators of fecal shedding, viremia, seroconversion, alanine aminotransferase (ALT) levels, and liver lesions showed that nb14 could completely protect rabbits from swine HEV infection, and nb53 partially blocked swine HEV infection in rabbits. Collectively, these results revealed that nb14, with its anti-HEV neutralizing activity, may be developed as an antiviral drug for HEV.
Characterization and identification of a novel chromosomal class C β-lactamase, LAQ-1, and comparative genomic analysis of a multidrug resistance plasmid in Lelliottia amnigena P13
Authors: Li Anqi , Yan Chunxia , Zhang Lei , Liu Shuang , Feng Chunlin , Zhang Linhua , Dong Fubo , Sheng Xiusheng , Wang Lan , Zhang Yanfang , Lu Junwan , Xu Jiefeng , Zheng Lin , Bao Qiyu , Cheng Cong , Huang Dawei
Published: November 2022

Introduction

Lelliottia amnigena, a bacterium usually isolated from natural environments, may cause human infections and has been suggested to be naturally resistant to second- and third-generation cephalosporins.

Methods

In this study, we determined the whole-genome sequence of an isolate, L. Amnigena P13, isolated from animal farm sewage. On the basis of genome sequence analysis, susceptibility testing, molecular cloning, and enzyme kinetic parameter analysis, we identified a novel chromosome-encoded AmpC β-lactamase, LAQ-1.

Results and Discussion

blaLAQ-1 is resistant to penicillin G, ampicillin, and several first- to fourth-generation cephalosporins, such as cefazolin, cefoxitin and cefepime. The MIC levels of some β-lactams, such as cefoxitin, cefepime, aztreonam and cefazolin, for the recombinant clone (pUCP24-blaLAQ-1/DH5α) increased by approximately 4- to 64-fold compared with those of the control strain (pUCP24/DH5α). The kinetic properties of LAQ-1, with the highest catalytic activity observed toward piperacillin, were basically the same as those of typical class C β-lactamases, and avibactam had a strong inhibitory effect on its hydrolytic activity. The genetic background of blaLAQ-1 was relatively conserved, and no mobile genetic element (MGE) was found around it. The plasmid pP13-67 of L. amnigena P13 harbored 12 resistance genes [qnrS1, aph(6)-Id, aadA2, sul1, sul2,blaTEM-1, qacEΔ1, dfrA12, tetA and floR] related to different mobile genetic elements within an ~22 kb multidrug resistance region. The multidrug resistance region shared the highest nucleotide sequence similarities with those of the chromosomes or plasmids of different bacterial species, indicating the possibility of horizontal transfer of these resistance genes among different bacterial species.
Dysphagia assessment in ischemic stroke after mechanical thrombectomy: When and how?
Authors: Lapa Sriramya , Neuhaus Elisabeth , Harborth Elena , Neef Vanessa , Steinmetz Helmuth , Foerch Christian , Reitz Sarah Christina
Published: November 2022

Background

Dysphagia is a frequent symptom in acute ischemic stroke (AIS). Endovascular treatment (EVT) has become the standard of care for acute stroke secondary to large vessel occlusion. Although standardized guidelines for poststroke dysphagia (PSD) management exist, they do not account for this setting in which patients receive EVT under general anesthesia. Therefore, the aim of this study was to evaluate PSD prevalence and severity, as well as an appropriate time point for the PSD evaluation, in patients undergoing EVT under general anesthesia (GA).

Methods

We prospectively included 54 AIS patients undergoing EVT under GA. Fiberoptic Endoscopic Evaluation of Swallowing (FEES) was performed within 24 h post-extubation in all patients. Patients presenting significant PSD received a second FEES-assessment to determine the course of dysphagia deficits over time. Dysphagia severity was rated according the Fiberoptic Dysphagia Severity Scale (FEDSS).

Results

At first FEES (FEES 1) assessment, performed in the median 13 h (IQR 5–17) post-extubation, 49/54 patients (90.7%) with dysphagia were observed with a median FEDSS of 4 (IQR 3–6). Severe dysphagia requiring tube feeding was identified in 28/54 (51.9%) subjects, whereas in 21 (38.9%) patients early oral diet with certain food restrictions could be initiated. In the follow up FEES examination conducted in the median 72 h (IQR 70–97 h) after initial FEES 34/49 (69.4%) patients still presented PSD. Age (p = 0.030) and ventilation time (p = 0.035) were significantly associated with the presence of PSD at the second FEES evaluation. Significant improvement of dysphagia frequency (p = 0.006) and dysphagia severity (p = 0.001) could be detected between the first and second dysphagia assessment.

Conclusions

PSD is a frequent finding both immediately within 24 h after extubation, as well as in the short-term course. In contrast to common clinical practice, to delay evaluation of swallowing for at least 24 h post-extubation, we recommend a timely assessment of swallowing function after extubation, as 50% of patients were safe to begin oral intake. Given the high amount of severe dysphagic symptoms, we strongly recommend application of instrumental swallowing diagnostics due to its higher sensitivity, when compared to clinical swallowing examination. Furthermore, advanced age, as well as prolonged intubation, were identified as significant predictors for delayed recovery of swallowing function.
Newborn screening and gene therapy in SMA: Challenges related to vaccinations
Authors: Kotulska Katarzyna , Jozwiak Sergiusz , Jedrzejowska Maria , Gos Monika , Ogrodnik Magdalena , Wysocki Jacek , Czajka Hanna , Kuchar Ernest
Published: November 2022

Spinal muscular atrophy (SMA) affects one in 7,500–10,000 newborns. Before the era of disease-modifying therapies, it used to be the major genetic cause of mortality in infants. Currently, there are three therapies approved for SMA, including two molecules modifying the splicing of the SMN2 gene and one gene therapy providing a healthy copy of the SMN gene with a viral vector. The best effects of any of these therapies are achieved when the treatment is administered in the presymptomatic stage of the disease, therefore newborn screening programs are being introduced in many countries. Patients identified in newborn screening might be eligible for gene therapy. However, gene therapy and the associated administration of steroids in newborns might interfere with the vaccination schedule, which includes live immunization against tuberculosis in some countries. The timing of gene therapy in patients who received live vaccinations has not yet been addressed neither in the clinical trials nor in the existing international guidelines. The Polish Vaccinology Association has developed the first recommendations for gene therapy administration in newborns who received live vaccination against tuberculosis. Their statement was implemented in the current guidelines for Polish SMA patients identified in the newborn screening program and might be helpful for medical professionals in other countries where live vaccine against tuberculosis is still in routine use in newborns.
Integrated transcriptomic and metabolomic profiling reveals dysregulation of purine metabolism during the acute phase of spinal cord injury in rats
Authors: Zeng Zhong , Li Mei , Jiang Zhanfeng , Lan Yuanxiang , Chen Lei , Chen Yanjun , Li Hailiang , Hui Jianwen , Zhang Lijian , Hu Xvlei , Xia Hechun
Published: November 2022

Introduction

Spinal cord injury (SCI) results in drastic dysregulation of microenvironmental metabolism during the acute phase, which greatly affects neural recovery. A better insight into the potential molecular pathways of metabolic dysregulation by multi-omics analysis could help to reveal targets that promote nerve repair and regeneration in the future.

Materials and methods

We established the SCI model and rats were randomly divided into two groups: the acute-phase SCI (ASCI) group (n = 14, 3 days post-SCI) and the sham group with day-matched periods (n = 14, without SCI). In each group, rats were sacrificed at 3 days post-surgery for histology study (n = 3), metabolome sequencing (n = 5), transcriptome sequencing (n = 3), and quantitative real-time polymerase chain reaction (n = 3). The motor function of rats was evaluated by double-blind Basso, Beattie, and Bresnahan (BBB) Locomotor Scores at 0, 1, 2, 3 days post-SCI in an open field area. Then the transcriptomic and metabolomic data were integrated in SCI model of rat to reveal the underlying molecular pathways of microenvironmental metabolic dysregulation.

Results

The histology of the microenvironment was significantly altered in ASCI and the locomotor function was significantly reduced in rats. Metabolomics analysis showed that 360 metabolites were highly altered during the acute phase of SCI, of which 310 were up-regulated and 50 were down-regulated, and bioinformatics analysis revealed that these differential metabolites were mainly enriched in arginine and proline metabolism, D-glutamine and D-glutamate metabolism, purine metabolism, biosynthesis of unsaturated fatty acids. Transcriptomics results showed that 5,963 genes were clearly altered, of which 2,848 genes were up-regulated and 3,115 genes were down-regulated, and these differentially expressed genes were mainly involved in response to stimulus, metabolic process, immune system process. Surprisingly, the Integrative analysis revealed significant dysregulation of purine metabolism at both transcriptome and metabolome levels in the acute phase of SCI, with 48 differential genes and 16 differential metabolites involved. Further analysis indicated that dysregulation of purine metabolism could seriously affect the energy metabolism of the injured microenvironment and increase oxidative stress as well as other responses detrimental to nerve repair and regeneration.

Discussion

On the whole, we have for the first time combined transcriptomics and metabolomics to systematically analyze the potential molecular pathways of metabolic dysregulation in the acute phase of SCI, which will contribute to broaden our understanding of the sophisticated molecular mechanisms of SCI, in parallel with serving as a foundation for future studies of neural repair and regeneration after SCI.
Impact of oral nutrition supplementation on outcomes of esophageal cancer patients treated with chemotherapy: A retrospective cohort study with propensity score matching
Authors: Li Xuemei , Dai Tingting , Rao Zhiyong , Hu Wen
Published: November 2022

Objective

There is a lack of evidence regarding the outcomes of oral nutrition supplementation (ONS) in patients with esophageal cancer (EC) who received chemotherapy treatment. The aim of this study was to perform a retrospective cohort study by comparing an adequate ONS group with a control group.

Materials and methods

The study was performed in the Oncology Department of West China Hospital of Sichuan University. Patients at nutritional risk were identified from March 2016 to June 2019, and divided into an ONS group and a control group. To control for potential confounding variables, the propensity score method with matching was carried out. The main outcomes were length of stay (LOS) and hospitalization cost. Secondary outcomes included the incidence of pulmonary infection and myelosuppression.

Results

Out of 5,316 hospitalizations, a one-to-one matched sample was created (N = 229). The pathological tumor, node, metastasis (pTNM) stage of patients ranged from II to IV. A total of 69 patients received ONS, and 160 patients did not receive ONS. The incidence of myelosuppression in the ONS group and the control group was 4.3 vs. 17.4% (P = 0.014), respectively. However, ONS was associated with a 2 days increase in LOS, from 7 to 9 days (P < 0.000) and a hospitalization cost increase of $731, from $1134 to $1865 (P = 0.005). No statistical differences were observed in the incidence of pulmonary infection between the two groups. Further subgroup analysis based on body mass index (BMI) showed that at BMI ≤ 18.5 kg/m2, the incidence of myelosuppression in the ONS group was lower than that in the control group (3.0 vs. 20.8%, P = 0.022). At BMI > 18.5 kg/m2, no statistical differences were observed in the incidence of myelosuppression between the two groups.

Conclusion

Although ONS increases hospitalization cost and LOS, it may be associated with reduced myelosuppression incidence, especially for patients with a BMI ≤ 18.5 kg/m2.
Effects of preoperative carbohydrate loading on recovery after elective surgery: A systematic review and Bayesian network meta-analysis of randomized controlled trials
Authors: Tong Enyu , Chen Yiming , Ren Yanli , Zhou Yuanyuan , Di Chunhong , Zhou Ying , Shao Shihan , Qiu Shuting , Hong Yu , Yang Lei , Tan Xiaohua
Published: November 2022

Background

Preoperative carbohydrate loading is an important element of the enhanced recovery after surgery (ERAS) paradigm in adult patients undergoing elective surgery. However, preoperative carbohydrate loading remains controversial in terms of improvement in postoperative outcomes and safety. We conducted a Bayesian network meta-analysis to evaluate the effects and safety of different doses of preoperative carbohydrates administrated in adult patients after elective surgery.

Methods

MEDLINE (PubMed), Web of Science, EMBASE, EBSCO, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure (CNKI) were searched to identify eligible trials until 16 September 2022. Outcomes included postoperative insulin resistance, residual gastric volume (RGV) during the surgery, insulin sensitivity, fasting plasma glucose (FPG), fasting serum insulin (Fin) level, the serum levels of C-reactive protein (CRP), postoperative scores of pain, patients’ satisfaction, thirst, hunger, anxiety, nausea and vomit, fatigue, and weakness within the first 24 h after surgery and the occurrences of postoperative infection. The effect sizes were estimated using posterior mean difference (continuous variables) or odds ratios (dichotomous variables) and 95 credible intervals (CrIs) with the change from baseline in a Bayesian network meta-analysis with random effect.

Results

Fifty-eight articles (N = 4936 patients) fulfilled the eligibility criteria and were included in the meta-analysis. Both preoperative oral low-dose carbohydrate loading (MD: –3.25, 95% CrI: –5.27 to –1.24) and oral high-dose carbohydrate loading (MD: –2.57, 95% CrI: –4.33 to –0.78) were associated with postoperative insulin resistance compared to placebo/water. When trials at high risk of bias were excluded, association with insulin resistance was found for oral low-dose carbohydrate loading compared with placebo/water (MD: –1.29, 95%CrI: –2.26 to –0.27) and overnight fasting (MD: –1.17, 95%CrI: –1.88 to –0.43). So, there was large uncertainty for all estimates vs. control groups. In terms of safety, oral low-dose carbohydrate administration was associated with the occurrences of postoperative infection compared with fasting by 0.42 (95%Crl: 0.20–0.81). In the other outcomes, there was no significant difference between the carbohydrate and control groups.

Conclusion

Although preoperative carbohydrate loading was associated with postoperative insulin resistance and the occurrences of postoperative infection, there is no evidence that preoperative carbohydrate administration alleviates patients’ discomfort.

Systematic review registration

[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022312944].
Safety profile of tyrosine kinase inhibitors used in non-small-cell lung cancer: An analysis from the Italian pharmacovigilance database
Authors: Barbieri Maria Antonietta , Sorbara Emanuela Elisa , Cicala Giuseppe , Santoro Vincenza , Cutroneo Paola Maria , Franchina Tindara , Santarpia Mariacarmela , Silvestris Nicola , Spina Edoardo
Published: November 2022

Introduction

Non-small cell lung cancer (NSCLC) is often caused by molecular alterations that can be detected by predictive biomarkers including mutations or amplifications of several genes. Several tyrosine kinase inhibitors (TKIs) have been approved in Europe by the European Medicines Agency (EMA) for NSCLC. The aim of this study was to analyze the onset of adverse drug reactions (ADRs) related to TKIs in NSCLC through a spontaneous reporting system (SRS) database.

Methods

All ADR reports having as suspected drug afatinib (AFT), alectinib (ALEC), brigatinib (BRG), ceritinib (CER), crizotinib (CRIZ), erlotinib (ERL), gefitinib (GEF), lorlatinib (LORL), nintedanib (NTB), and osimertinib (OSI) recorded into the Report Reazioni Avverse dei Medicinali (RAM) system database for national data and into the Italian SRS database for Sicilian data and collected from 2006 to 2021 have been evaluated. A descriptive analysis of basal demographic and drug-related characteristics was performed. A case-by-case methodology was conducted paying particular attention to all serious ADR reports collected in Sicily, focusing on type of seriousness, age, sex, concomitant drugs, and comorbidities.

Results

Of the 3,048 Italian reports, most of ADRs were related to ERL (n = 1,448), followed by AFT (n = 435) and GEF (n = 366). ADR reports were slightly more frequent in females (52.2%) and in the age group >65 years (53.0%). A higher number of cases were related to skin disorders (n = 1,766; 57.9%), followed by gastrointestinal disorders (n = 1,024; 33.6%), general disorders and administration site conditions (n = 536; 17.6%), and infections (n = 483; 15.8%). The case-by-case assessment of Sicilian ADRs showed that 33 cases were serious (12.5%) and mainly involved ERL (n = 17; 51.5%), occurring in males with a higher onset of respiratory diseases (30.3%) such as respiratory failure, interstitial lung disease and dyspnea.

Discussion

The analysis of spontaneous ADR reports of TKIs confirmed, in general, well-known risks, which often include skin, gastrointestinal, general, liver, and respiratory diseases as well as infections. However, more attention should be paid to the occurrence of serious life-threatening ADRs including respiratory failure, interstitial lung disease, and cardiogenic shock, especially in young patients.
Renal insufficiency predicts worse prognosis in newly diagnosed IgD multiple myeloma patients
Authors: Yan Ge , Li Huangmin , Zhang Yiding , Xia Chenyan , Wang Mengxiao , Jia Yu , Shang Jin , Zhao Zhanzheng
Published: November 2022

Objective

IgD multiple myeloma (MM) is a rare type of MM, accounting for about 1%–2% of all MMs. IgD MM always causes kidney damage and even leads to renal failure, which is the most common complication. This study aimed to explore the risk factors of renal damage and prognosis of IgD MM patients.

Design

From March 2018 to November 2021, 85 patients with IgD MM diagnosed for the first time at the First Affiliated Hospital of Zhengzhou University were included in this study. We collected information on clinical features and laboratory examinations. Patients were divided into the renal impairment (RI) (47/85) and non-renal impairment (no-RI) (38/85) groups. Binary logistic regression was used to explore risk factors of renal damage. The Chi-square test was used to analyze the difference in chemotherapy effect between the two groups. We also analyzed whether early dialysis was beneficial to acute renal failure (RF) in IgD MM patients. Finally, Kaplan-Meier was used to compare the survival of the two groups.

Results

In IgD MM, 55.3% of patients had renal damage as a complication, of which up to 59.6% presented with acute renal failure as the first manifestation. Serum β2-microglobulin (β2-MG) was an independent risk factor for renal damage in IgD MM (p = 0.002), but cytogenetic analysis suggested that it had no effect on patients’ renal damage. There was also no significant difference in the effect of chemotherapy between the two groups (p = 0.255). In patients with acute renal failure, there was no significant difference between dialysis and no dialysis groups in the proportion of patients with improved renal function after treatment. The median overall survival (OS) of the RI group was significantly shorter than that of the no-RI group (p = 0.042). In the RI group, the median OS was 29 months, and in the no-RI group, the median OS was > 40 months.

Conclusion

Elevated serum β2-MG is an independent risk factor for renal damage. Compared with the no-RI group, patients in the RI group had poorer prognosis and shorter median OS. For patients with acute renal failure as the first manifestation, the treatment of primary disease is more meaningful than dialysis.
The efficacy and safety of Apatinib in the treatment of advanced non-small cell lung cancer: A retrospective trial
Authors: Wang Jijin , Huang Di , Yang Wenjing , Song Qingxu , Jia Yibin , Chen Pengxiang , Cheng Yufeng
Published: November 2022

Background

As a potent inhibitor of the vascular endothelial growth factor (VEGF) signaling pathway, Apatinib has been used in antitumor treatment for some time. The study aimed to research the therapeutic effects and toxicity of Apatinib in the treatment of advanced non-small cell lung cancer (NSCLC).

Methods

We retrospectively analyzed 128 NSCLC patients treated with Apatinib in Qilu Hospital of Shandong University. Response Evaluation Criteria in Solid Tumors (RECIST) criteria was adopted to evaluate the treatment effect, and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was conducted to determine the Adverse Events (AEs). Cox proportional hazard model and Kaplan-Meier function were applied to evaluate the progression-free survival (PFS) and overall survival (OS).

Results

Among 128 NSCLC patients, partial response (PR) were observed in 15 patients, stable disease (SD) in 66 patients and progressive disease (PD) in 47 patients. The objective response rate (ORR) and disease control rate (DCR) accounted for 11.7% and 63.3% respectively. The median PFS (mPFS) and median OS (mOS) were 4.4 months and 17.2 months. Common side effects of Apatinib were hypertension (n=48), proteinuria (n=35), and hand-foot syndrome (HFS) (n=30), all of the side effects were controllable. No significant difference was observed in efficacy and AEs between the higher dose group (Apatinib>500mg/d) and the lower dose group (Apatinib=500mg/d).

Conclusions

The study suggested that Apatinib with a lower dose (=500mg/d) has good efficacy and safety in the treatment of advanced NSCLC after first-line chemotherapy.
The initial experience of MRI-guided precision prone breast irradiation with daily adaptive planning in treating early stage breast cancer patients
Authors: Ng John , Pennell Ryan , Formenti Silvia C.
Published: November 2022

Background

A major challenge in breast radiotherapy is accurately targeting the surgical cavity volume. Application of the emerging MRI-guided radiotherapy (MRgRT) technique in breast radiotherapy may enable more accurate targeting and potentially reduce side effects associated with treatment.

Purpose

To study the feasibility of delivering MRI-guided partial breast radiotherapy or Precision Prone Irradiation (PPI) to treat DCIS and early stage breast cancer patients.

Materials and methods

Eleven patients with diagnosed DCIS or early stage breast cancer treated with lumpectomy underwent CT-based and MRI-based simulations and treatment planning in the prone position. MRI-guided radiotherapy was utilized to deliver partial breast irradiation. A customized adaptive plan was created for each delivered radiotherapy fraction and the cumulative doses to the target volumes and nearby organs at risk were determined. The CT-based and the MRI-guided radiotherapy plans were compared with respect to target volumes, target volume coverage, and dose to nearby organs.

Results

All patients receiving PPI successfully completed their treatments as planned. Clinical target volume (CTV) and planning target volume (PTV) dose coverage and organs-at-risk (OAR) dose constraints were met in all fractions planned and delivered and the MRI-guided clinical target volumes were smaller when compared to those of the CT-based partial breast radiotherapy plans for these eleven patients.

Conclusions

MRI-guided partial breast radiotherapy as a breast radiotherapy technology is feasible and is a potential high clinical impact application of MRgRT. PPI has the potential to improve the therapeutic index of breast radiotherapy by more accurately delivering radiation dose to the cavity target and decreasing toxicities associated with radiation to the surrounding normal tissues. Prospective clinical data and further technical refinements of this novel technology may broaden its clinical implementation.
Hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta gene as a tumour suppressor in stomach adenocarcinoma
Authors: Li Yun , Xiong Jian-Bo , Jie Zhi-Gang , Xiong Hui
Published: November 2022

Background

Stomach adenocarcinoma (STAD) is the most common type of gastric cancer. In this study, the functions and potential mechanisms of hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB) in STAD were explored.

Methods

Different bioinformatics analyses were performed to confirm HADHB expression in STAD. HADHB expression in STAD tissues and cells was also evaluated using western blot, qRT-PCR, and immunohistochemistry. Further, the viability, proliferation, colony formation, cell cycle determination, migration, and wound healing capacity were assessed, and the effects of HADHB on tumour growth, cell apoptosis, and proliferation in nude mice were determined. The upstream effector of HADHB was examined using bioinformatics analysis and dual luciferase reporter assay. GSEA was also employed for pathway enrichment analysis and the expression of Hippo-YAP pathway-related proteins was detected.

Results

The expression of HADHB was found to be low in STAD tissues and cells. The upregulation of HADHB distinctly repressed the viability, proliferation, colony formation, cell cycle progression, migration, invasion, and wound healing of HGC27 cells, while knockdown of HADHB led to opposite effects. HADHB upregulation impeded tumour growth and cell proliferation, and enhanced apoptosis in nude mice. KLF4, whose expression was low in STAD, was identified as an upstream regulator of HADHB. KLF4 upregulation abolished the HADHB knockdown-induced tumour promoting effects in AGS cells. Further, HADHB regulates the Hippo-YAP pathway, which was validated using a pathway rescue assay. Low expression of KLF4 led to HADHB downregulation in STAD.

Conclusion

HADHB might function as a tumour suppressor gene in STAD by regulation the Hippo-YAP pathway.
Deep learning magnetic resonance imaging predicts platinum sensitivity in patients with epithelial ovarian cancer
Authors: Lei Ruilin , Yu Yunfang , Li Qingjian , Yao Qinyue , Wang Jin , Gao Ming , Wu Zhuo , Ren Wei , Tan Yujie , Zhang Bingzhong , Chen Liliang , Lin Zhongqiu , Yao Herui
Published: November 2022

Objective

The aim of the study is to develop and validate a deep learning model to predict the platinum sensitivity of patients with epithelial ovarian cancer (EOC) based on contrast-enhanced magnetic resonance imaging (MRI).

Methods

In this retrospective study, 93 patients with EOC who received platinum-based chemotherapy (≥4 cycles) and debulking surgery at the Sun Yat-sen Memorial Hospital from January 2011 to January 2020 were enrolled and randomly assigned to the training and validation cohorts (2:1). Two different models were built based on either the primary tumor or whole volume of the abdomen as the volume of interest (VOI) within the same cohorts, and then a pre-trained convolutional neural network Med3D (Resnet 10 version) was transferred to automatically extract 1,024 features from two MRI sequences (CE-T1WI and T2WI) of each patient to predict platinum sensitivity. The performance of the two models was compared.

Results

A total of 93 women (mean age, 50.5 years ± 10.5 [standard deviation]) were evaluated (62 in the training cohort and 31 in the validation cohort). The AUCs of the whole abdomen model were 0.97 and 0.98 for the training and validation cohorts, respectively, which was better than the primary tumor model (AUCs of 0.88 and 0.81 in the training and validation cohorts, respectively). In k-fold cross-validation and stratified analysis, the whole abdomen model maintained a stable performance, and the decision function value generated by the model was a prognostic indicator that successfully discriminates high- and low-risk recurrence patients.

Conclusion

The non-manually segmented whole-abdomen deep learning model based on MRI exhibited satisfactory predictive performance for platinum sensitivity and may assist gynecologists in making optimal treatment decisions.
Fetal mesenchymal hamartoma of the liver: A case report and literature review
Authors: Liu Xin , Tian Sha , Zhu Zhenchuang , Peng Fei , Yuan Qiang , Duan Xufei , Yan Xueqiang
Published: November 2022

This paper reports the diagnosis and treatment process of a case of fetal mesenchymal hamartoma of the liver (MHL), and reviews the previous literature reports. At 38+2 weeks of gestation, prenatal ultrasound found a well bound mixed solid and cystic mass, which was located at the lower edge of the right lobe of the liver and in front of the right kidney of the fetus, but the source and nature of the mass were not clear by ultrasound. Due to the approaching due date, the fetus showed no other abnormal symptoms, and no special treatment was given with the consent of the family members. A female fetus was delivered weighing 3,520 g at 39 weeks. An exploratory laparotomy was performed on the eighth day after delivery. During the operation, it was found that the tumor originated from the fifth, sixth and seventh hepatic segment and the corresponding hepatic segments were removed. Recovery was uneventful and the infant was discharged on the 6th day after surgery. Follow-up at 2 years showed a thriving young girl, and there was no tumor recurrence.
Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents
Authors: Yang Chao , Xia An-Jie , Du Cheng-Hao , Hu Ming-Xing , Gong You-Ling , Tian Rong , Jiang Xin , Xie Yong-Mei
Published: November 2022

7-Ethyl-10-hydroxycamptothecin (SN38), a highly potent metabolite of irinotecan, has an anticancer efficacy 100–1000 folds more than irinotecan in vitro. However, the clinical application of SN38 has been limited due to the very narrow therapeutic window and poor water solubility. Herein, we report the SN38-glucose conjugates (Glu-SN38) that can target cancer cells due to their selective uptake via glucose transporters, which are overexpressed in most cancers. The in vitro antiproliferative activities against human cancer cell lines and normal cells of Glu-SN38 were investigated. One of the conjugates named 5b showed high potency and selectivity against human colorectal cancer cell line HCT116. Furthermore, 5b remarkably inhibited the growth of HCT116 in vivo. These results suggested that 5b could be a promising drug candidate for treating colorectal cancer.
Erythromycin attenuates oxidative stress-induced cellular senescence via the PI3K-mTOR signaling pathway in chronic obstructive pulmonary disease
Authors: Xiaofei Yi , Tingting Li , Xuan Wei , Zhiyi He
Published: November 2022

Background and Purpose: Chronic obstructive pulmonary disease (COPD) is proposed to hasten lung aging. Erythromycin protects against oxidative stress and inflammatory responses. However, the potential anti-senescence effect of erythromycin remains disclosed. In the present study, we investigated whether erythromycin influenced oxidative stress-induced cellular senescence and investigated its related mechanisms.

Methods: A cigarrete smoke (CS) -induced emphysema mouse model and a H2O2-induced premature senescence model in human bronchial epithelial cell line (BEAS-2B) were established. Senescence-related markers (P53, P21 and SA-β-Gal activity), and levels of oxidative stress biomarkers (MDA, SOD and ROS) were measured. Additionally, cells were pretreated with rapamycin (mTOR inhibitor) or erythromycin, and the expression levels of components of the PI3K-mTOR signaling pathway were measured in BEAS-2B cells.

Results: Exposed to H2O2, increased SA-β-gal activity was observed in BEAS-2B cells suggesting premature senescence. Erythromycin inhibited the expression of P53 and P21 in the CS-induced emphysema mouse model. MDA levels significantly increased and SOD levels decreased in the CS-exposed mice and H2O2-induced BEAS-2B cells. Rapamycin and erythromycin significantly suppressed the expression of P53 and P21. Additionally, rapamycin and erythromycin inhibited the PI3K-mTOR signaling pathway.

Conclusion: Our findings suggest that erythromycin ameliorates oxidative stress-induced cellular senescence via the PI3K-mTOR signaling pathway. Hence, we establish a theoretical foundation for the clinical application of erythromycin for COPD prevention and treatment.
Postbiotic muramyl dipeptide alleviates colitis via activating autophagy in intestinal epithelial cells
Authors: You Yaying , Xiao Yongtao , Lu Ying , Du Jun , Cai Hui , Cai Wei , Yan Weihui
Published: November 2022

The pathogenesis of IBD is complicated and still unclear. Nucleotide-binding oligomerization domain 2 (NOD2) plays a significant role in regulating gut inflammation under the activation of muramyl dipeptide (MDP), which is used as a postbiotic. The study aimed to investigate the effect of MDP on the intestinal barrier in colitis and the mechanism involved. In this study, C57BL/6 mice were challenged with dextran sodium sulfate (DSS) for establishing a colitis model with the pre-treatment of MDP in vivo. Intestinal permeability was reflected by detecting the serum concentration of 4 kDa Fluorescein Isothiocyanate-Dextran. The expression of inflammation, barrier-related proteins, and autophagy was tested by Western Blotting. Proliferation and apoptosis in intestinal epithelial cells were detected by immunohistochemistry. Caco-2 cells were exposed to lipopolysaccharide for imitating inflammation in vitro. The findings showed that administration of MDP ameliorated losses of body weight loss, gross injury, and histology score of the colon in the DSS-induced colitis mice. MDP significantly ameliorated the condition of gut permeability, and promoted intestinal barrier repair by increasing the expression of Zonula occludens-1 and E-cadherin. Meanwhile, MDP promoted proliferation and reduced apoptosis of intestinal epithelial cells. In the experiment group treated with MDP, LC3 was upregulated, and p62 was downregulated, respectively. These results suggested that MDP stimulation attenuates intestinal inflammation both in vivo and in vitro. Potentially, MDP reduced the intestinal barrier damage by regulating autophagy in intestinal epithelial cells. Future trials investigating the effects of MDP-based postbiotics on IBD may be promising.
Metals-triggered compound CDPDP exhibits anti-arthritic behavior by downregulating the inflammatory cytokines, and modulating the oxidative storm in mice models with extensive ADMET, docking and simulation studies
Authors: Hassan Syed Shams ul , Abbas Syed Qamar , Muhammad Ishaq , Wu Jia-Jia , Yan Shi-Kai , Ali Fawad , Majid Muhammad , Jin Hui-Zi , Bungau Simona
Published: November 2022

Triggering through abiotic stress, including chemical triggers like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metal Nickel on actinobacteria Streptomyces sp. SH-1327 to obtain a stress-derived compound was firstly investigated. A new compound cyclo-(D)-Pro-(D)-Phe (CDPDP) was triggered from the actinobacteria strain SH-1327 with the addition of nickel ions 1 mM. The stress compound was further evaluated for its anti-oxidant, analgesic, and anti-inflammatory activity against rheumatoid arthritis through in-vitro and in-vivo assays in albino mice. A remarkable in-vitro anti-oxidant potential of CDPDP was recorded with the IC50 value of 30.06 ± 5.11 μg/ml in DPPH, IC50 of 18.98 ± 2.91 against NO free radicals, the IC50 value of 27.15 ± 3.12 against scavenging ability and IC50 value of 28.40 ± 3.14 μg/ml for iron chelation capacity. Downregulation of pro-inflammatory mediators (NO and MDA), suppressed levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-Iβ) and upregulation of expressions of anti-oxidant enzymes (GSH, catalase, and GST) unveiled its anti-inflammatory potential. CDPDP was analyzed in human chondrocyte cell line CHON-001 and the results demonstrated that CDPDP significantly increased cell survival, and inhibited apoptosis of IL-1β treated chondrocytes and IL-1β induced matrix degrading markers. In addition, to evaluate the mitochondrial fitness of CHON-001 cells, CDPDP significantly upregulated pgc1-α, the master regulator of mitochondrial biogenesis, indicating that CDPDP provides protective effects in CHON-001 cells. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile of the CDPDP showed that CDPDP is safe in cases of hepatotoxicity, cardiotoxicity, and cytochrome inhibition. Furthermore, docking results showed good binding of CDPDP with IL-6–17.4 kcal/mol, and the simulation studies proved the stability between ligand and protein. Therefore, the findings of the current study prospect CDPDP as a potent anti-oxidant and a plausible anti-arthritic agent with a strong pharmacokinetic and pharmacological profile.
Assessing amino acid solubility of black soldier fly larvae meal in Atlantic salmon (Salmo salar) in vivo and in vitro
Authors: Radhakrishnan Gopika , Silva Marta S. , Lock Erik-Jan , Belghit Ikram , Philip Antony Jesu Prabhu
Published: November 2022

In vitro and in vivo methods were used to evaluate amino acids solubility of black soldier fly (BSF) larvae meal and two experimental diets (reference and test diets) for Atlantic salmon. The current study used in vitro method such as pH stat to compare and standardise the salmon extracted enzyme (SE), and commercial enzyme (CE) based on their hydrolytic capacity on a purified protein substrate. Further, an in vitro amino acid solubility of feed ingredients and diets were measured using the standardised enzyme volume from SE and CE. Results showed that SE and CE exhibit similar protein hydrolytic capacity upon standardisation on purified substrates. However, when using the two-stage hydrolysis (acidic and alkaline steps), significantly higher amino acid solubility was observed with CE except for glycine, and proline which were equally solubilised by both SE, and CE. No significant difference was observed between reference and test diet using the SE except for tyrosine, valine, leucine, and phenylalanine, which were significantly higher solubilised in reference diet than test diet. Whereas higher solubility of valine, isoleucine, aspartic acid, and glutamic acid was observed in test diet using CE than SE. Similarly, the solubility of valine, isoleucine, and glutamic acid were higher in BSF larvae meal when CE was used. The in vivo true protein digestibility of BSF larvae meal was 99%, and 81% for the test diet containing BSF larvae meal. The results demonstrated a positive correlation (r = 0.91; p < 0.01) between salmon and commercial enzymes but overall, no significant correlation was observed for amino acid solubility between in vivo and in vitro. However, there was a strong positive correlation for protein solubility using SE (r = 0.98) than CE (r = 0.74) with the in vivo true protein digestibility. The efficiency of SE, and CE can be compared, and standardised based on DH%, and hence correlates better with the in vivo protein digestibility but not with amino acid solubilities.
The inflammatory response, a mixed blessing for muscle homeostasis and plasticity
Authors: Bouredji Zineb , Argaw Anteneh , Frenette Jérôme
Published: November 2022

Skeletal muscle makes up almost half the body weight of heathy individuals and is involved in several vital functions, including breathing, thermogenesis, metabolism, and locomotion. Skeletal muscle exhibits enormous plasticity with its capacity to adapt to stimuli such as changes in mechanical loading, nutritional interventions, or environmental factors (oxidative stress, inflammation, and endocrine changes). Satellite cells and timely recruited inflammatory cells are key actors in muscle homeostasis, injury, and repair processes. Conversely, uncontrolled recruitment of inflammatory cells or chronic inflammatory processes leads to muscle atrophy, fibrosis and, ultimately, impairment of muscle function. Muscle atrophy and loss of function are reported to occur either in physiological situations such as aging, cast immobilization, and prolonged bed rest, as well as in many pathological situations, including cancers, muscular dystrophies, and several other chronic illnesses. In this review, we highlight recent discoveries with respect to the molecular mechanisms leading to muscle atrophy caused by modified mechanical loading, aging, and diseases. We also summarize current perspectives suggesting that the inflammatory process in muscle homeostasis and repair is a double-edged sword. Lastly, we review recent therapeutic approaches for treating muscle wasting disorders, with a focus on the RANK/RANKL/OPG pathway and its involvement in muscle inflammation, protection and regeneration processes.