bluuebunny/crossref_metadata_2025 huggingface dataset:
The Evolution and Role of the Bursal Acromial Reconstruction
Authors: Curtis Daniel M. , Pullen W. Michael , Helenius Kevin , Freehill Michael T.
Published: March 2021

Background:

Massive, irreparable rotator cuff tears (RCTs) remain a challenging clinical problem with numerous described treatment options. Bursal acromial reconstruction (BAR) represents a promising and evolving technique for a subset of patients with irreparable RCTs.

Indications:

BAR is indicated for patients with massive, irreparable RCTs with a primary complaint of pain, well-compensated shoulder function, and minimal radiographic degenerative changes of the glenohumeral joint as an alternative to reverse total shoulder arthroplasty or superior capsular reconstruction.

Technique Description:

Positioning per surgeon preference and diagnostic arthroscopy is performed. Subacromial decompression with a minimal and gentle acromioplasty is performed, followed by assessment of RCT repairability. If the tear is deemed irreparable, acromial measurements in the medial-lateral and anterior-posterior dimensions are obtained. Two pieces of acellular dermal allograft are cut to the acromial dimensions and affixed together using fibrin glue. The reactive side (facing the acromion), medial, and anterior sides of the graft are labeled. Two suture tapes are passed through the corners of the graft and self-locked and run diagonally in a cruciate configuration using an antegrade suture passer. Medial and lateral #2 fiberwire sutures are placed in a luggage-tag configuration. Neviaser (posterior), middle, and anterior acromioclavicular joint portals are created for medial sided suture passage. Medial graft sutures are shuttled through the respective medial portals and the graft is pulled into the subacromial space. The lateral sutures are then removed from percutaneous posterolateral, middle lateral, and anterolateral portals along the acromial edge. Medial sutures are retrieved using a suture grasper subcutaneously on top of the acromion through the percutaneous lateral portals. The sutures are tied through the lateral portals, starting with the medial-lateral sutures, and the knots are buried. Postoperatively, patients are progressed through passive, active-assisted, and active range of motion between weeks 2 and 6 and strengthening is progressed at 6 weeks.

Results:

Clinical results are lacking in the literature, but anecdotal results in our institution have demonstrated promising early outcomes.

Discussion/Conclusion:

BAR represents a promising alternative in the array of surgical options for treatment of irreparable RCTs.
Intraorbital Abscess: A Rare Cause of Orbit Compression
Authors: Ruiz Samuel , Lim Rizal
Published: March 2021

Introduction: Intraorbital abscess is a rare complication of rhinosinusitis that affects most commonly the pediatric population. It is thought to be caused by direct extension or venous spread of infections from contiguous sites and can lead to life-threatening complications, like permanent visual loss and cerebral abscesses. Objectives: Intraorbital abscess is a rare condition that requires prompt diagnosis and treatment to avoid serious complications. Our objectives are to provide an overview of this rare disease process and its management including our successful treatment experience. Case Description: We present a 2 case report of a 13-year-old pediatric male and a 66-year-old male with history of chronic sinusitis who presented with a right intraorbital abscess successfully treated with external drainage with decompression of the orbit. Conclusion: When intraorbital abscess is encountered, a high index of suspicion is needed to allow prompt and accurate diagnosis for this infrequent condition. Timely surgical drainage of the abscess is needed to prevent the development of fatal complications.
Treatment of a BRAF V600E Positive Ameloblastoma in a Pediatric Patient with MEK Inhibitor Monotherapy
Authors: Daws Steven , Chaiyasate Kongkrit , Lehal Arshi
Published: March 2021

Ameloblastomas are uncommon tumors of the odontogenic epithelium standardly treated with radical resection. Recent studies of the genetic landscape of ameloblastoma have revealed the frequent presence of the BRAF V600E mutation, suggesting a possible role for targeted chemotherapy. We present the case of a primary mandibular ameloblastoma found in a 13-year-old female with confirmed BRAF V600E mutation. Prior to invasive surgical intervention she was treated for 8 weeks with the MEK inhibitor trametinib, but her tumor demonstrated little radiographic, clinical, or histologic response. Previous case reports have shown ameloblastoma in adult patients to be responsive to other agents targeting the MAPK pathway. Our observations in the presented case demonstrate the need for further research into the utility of targeted chemotherapy in ameloblastoma treatment.
Genome-wide identification, characterization and expression analysis of BES1 gene family in tomato
Authors: Su Deding , Xiang Wei , Wen Ling , Lu Wang , Shi Yuan , Liu Yudong , Li Zhengguo
Published: March 2021

Background

As the key regulators in BR signaling, BES1 family genes regulate thousands of target genes involved in various development processes. So far, the functions of BES1 family are poorly understood in tomato, and a comprehensive genomic and expressional analysis is worth to conduct for this family.

Results

Here, nine SlBES1 family members were identified in tomato and classified into five groups based on the conserved motif, gene structure and phylogenetic analysis. Synteny among tomato, Arabidopsis, pepper and rice were further analyzed to obtain insights into evolutionary characteristics. Several cis-elements related to hormone, stress and plant development were exhibited in the promoter regions of SlBES1 family genes. Subcellular localization showed seven members localized both in the nucleus and cytoplasm, implying the presence of dephosphorylated and phosphorylated form of these seven proteins, furthermore, five of them possessed transcription activation activity whereas the left two functioned as transcriptional repressors. Another two members, however, neither localized in the nucleus nor had transactivation activity. Besides, SlBES1.8 showed flower-specific expression while other members expressed ubiquitously in all organs. Moreover, SlBES1 genes exhibited variational expression in response to nine principal plant hormones. Notably, the expression levels of SlBES1 genes presented a dominant downregulated trend in response to stresses.

Conclusions

In this study, we systematically analyzed the genomic characterization of SlBES1 family, together with the analyses of protein functional features and expression patterns, our results lay a foundation for the functional research of SlBES1 family.
Predictive value of stress hyperglycemia ratio for the occurrence of acute kidney injury in acute myocardial infarction patients with diabetes
Authors: Gao Side , Liu Qingbo , Chen Hui , Yu Mengyue , Li Hongwei
Published: March 2021

Background

Acute hyperglycemia has been recognized as a robust predictor for occurrence of acute kidney injury (AKI) in nondiabetic patients with acute myocardial infarction (AMI), however, its discriminatory ability for AKI is unclear in diabetic patients after an AMI. Here, we investigated whether stress hyperglycemia ratio (SHR), a novel index with the combined evaluation of acute and chronic glycemic levels, may have a better predictive value of AKI as compared with admission glycemia alone in diabetic patients following AMI.

Methods

SHR was calculated with admission blood glucose (ABG) divided by the glycated hemoglobin-derived estimated average glucose. A total of 1215 diabetic patients with AMI were enrolled and divided according to SHR tertiles. Baseline characteristics and outcomes were compared. The primary endpoint was AKI and secondary endpoints included all-cause death and cardiogenic shock during hospitalization. The logistic regression analysis was performed to identify potential risk factors. Accuracy was defined with area under the curve (AUC) by a receiver-operating characteristic (ROC) curve analysis.

Results

In AMI patients with diabetes, the incidence of AKI (4.4%, 7.8%, 13.0%; p < 0.001), all-cause death (2.7%, 3.6%, 6.4%; p = 0.027) and cardiogenic shock (4.9%, 7.6%, 11.6%; p = 0.002) all increased with the rising tertile levels of SHR. After multivariate adjustment, elevated SHR was significantly associated with an increased risk of AKI (odds ratio 3.18, 95% confidence interval: 1.99–5.09, p < 0.001) while ABG was no longer a risk factor of AKI. The SHR was also strongly related to the AKI risk in subgroups of patients. At ROC analysis, SHR accurately predicted AKI in overall (AUC 0.64) and a risk model consisted of SHR, left ventricular ejection fraction, N-terminal B-type natriuretic peptide, and estimated glomerular filtration rate (eGFR) yielded a superior predictive value (AUC 0.83) for AKI.

Conclusion

The novel index SHR is a better predictor of AKI and in-hospital mortality and morbidity than admission glycemia in AMI patients with diabetes.
SPPB reference values and performance in assessing sarcopenia in community-dwelling Singaporeans – Yishun study
Authors: Lee Shuen Yee , Choo Pei Ling , Pang Benedict Wei Jun , Lau Lay Khoon , Jabbar Khalid Abdul , Seah Wei Ting , Chen Kenneth Kexun , Ng Tze Pin , Wee Shiou-Liang
Published: March 2021

Background

The Short Physical Performance Battery (SPPB) is an established test of physical performance. We provide reference values for SPPB and determine SPPB performance and cut-offs in assessing sarcopenia for Asian community-dwelling older adults.

Methods

Five hundred thirty-eight (57.8% women) community-dwelling adults aged 21–90 years were recruited. SPPB and its subtest scores and timings (8 ft. gait speed (GS), five-times repeated chair sit-to-stand (STS) and balance) were determined. Appendicular lean mass divided by height-squared, muscle strength (handgrip) and physical performance (6 m GS, STS and SPPB) were assessed to define sarcopenia for various Asian criteria. Area under the ROC curve (AUC) was used to assess performance of SPPB and subtests in discriminating sarcopenia in adults aged ≥60 years. Optimal SPPB and GS subtest cut-offs for each sarcopenia criterion were determined by maximizing sensitivity and specificity.

Results

The mean SPPB score was 11.6(SD 1.1) in men and 11.5(SD1.2) in women. Majority of participants(≥50%) aged 21–80 years achieved the maximum SPPB score. SPPB total and subtest scores generally decreased with age (all p < 0.001), but did not differ between sex. Among older adults (≥60 years), SPPB and GS subtest had varied performance in assessing sarcopenia (AUC 0.54–0.64 and 0.51–0.72, respectively), and moderate-to-excellent performance in assessing severe sarcopenia (AUC 0.69–0.98 and 0.75–0.95, respectively), depending on sarcopenia definitions. The optimal cut-offs for discriminating sarcopenia in both sexes were SPPB ≤11points and GS subtest ≤1.0 m/s. The most common optimal cut-offs for discriminating severe sarcopenia according to various definitions were SPPB ≤11points in both sexes, and GS ≤0.9 m/s in men and ≤ 1.0 m/s in women.

Conclusions

Population-specific normative SPPB values are important for use in diagnostic criteria and to interpret results of studies evaluating and establishing appropriate treatment goals. Performance on the SPPB should be reported in terms of the total sum score and registered time to complete the repeated-chair STS and 8-ft walk tests. The performance of GS subtest was comparable to SPPB and could be a useful, simple and accessible screening tool for discriminating severe sarcopenia in community-dwelling older adults.
Labor dystocia and risk of histological chorioamnionitis and funisitis: a study from a single tertiary referral center
Authors: Kyozuka Hyo , Murata Tuyoshi , Fukuda Toma , Suzuki Erina , Yazawa Riho , Yasuda Shun , Kanno Aya , Yamaguchi Akiko , Hashimoto Yuko , Fujimori Keiya
Published: March 2021

Background

Intrauterine inflammation affects short- and long-term neonatal outcomes. Histological chorioamnionitis and funisitis are acute inflammatory responses in the fetal membranes and umbilical cord, respectively. Although labor dystocia includes a potential risk of intrauterine inflammation, the risk of histological chorioamnionitis and funisitis of labor dystocia has not been evaluated yet. This study aimed to examine the association between labor dystocia and risk of histological chorioamnionitis and funisitis.

Methods

In this retrospective cohort study, the cases who underwent histopathological examinations of the placenta and umbilical cord at Fukushima Medical University Hospital, Japan, between 2015 and 2020, were included. From the dataset, the pathological findings of the patients with labor dystocia and spontaneous preterm birth were reviewed. Based on the location of leukocytes, the inflammation in the placenta (histological chorioamnionitis) and umbilical cord (funisitis) was staged as 0–3. Multiple logistic regression analysis was performed to evaluate the risk of histological chorioamnionitis, histological chorioamnionitis stage ≥2, funisitis, and funisitis stage ≥2.

Result

Of 317 women who met the study criteria, 83 and 144 women had labor dystocia and spontaneous preterm birth, respectively, and 90 women were included as controls. Labor dystocia was a risk factor for histological chorioamnionitis (adjusted odds ratio, 6.3; 95% confidential interval, 1.9–20.5), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 6.0; 95% confidence interval, 1.7–21.8), funisitis (adjusted odds ratio, 15.4; 95% confidence interval, 2.3–101.3), and funisitis stage ≥2 (adjusted odds ratio, 18.5; 95% confidence interval, 2.5–134.0). Spontaneous preterm birth was also a risk factor for histological chorioamnionitis (adjusted odds ratio, 3.7; 95% confidence interval, 1.7–7.8), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 3.0; 95% confidence interval, 1.2–7.9), and funisitis (adjusted odds ratio, 6.6; 95% confidence interval, 1.4–30.6). However, the adjusted odds ratio was smaller in spontaneous preterm births than in labor dystocia.

Conclusion

Labor dystocia is a risk factor for severe histological chorioamnionitis and funisitis. Further studies are required to evaluate the effects of histological chorioamnionitis and funisitis on long-term neonatal outcomes.
The application of late amniocentesis: a retrospective study in a tertiary fetal medicine center in China
Authors: Li Yingting , Yan Huanchen , Chen Jingsi , Chen Fei , Jian Wei , Wang Jiayan , Ye Xiaoqing , Li Yufan , Li Nan , Chiu Philip C. N. , Chen Min
Published: March 2021

Background

To assess the indications and complications of late amniocentesis and the advanced genetic test results in a tertiary university fetal medical medicine unit.

Methods

In this retrospective study, women that underwent amniocentesis at 24+ 0 to 39+ 4 weeks, between January 2014 and December 2019, were recruited. Indications, complications, genetic test results, and pregnancy outcomes were reported for each pregnancy and compared with those who underwent the traditional amniocentesis at 16+ 0 to 23+ 6 weeks (control group). Information was retrieved from patient medical records, checked by research staff, and analyzed.

Results

Of the 1287 women (1321 fetuses) included in the late amniocentesis group, late detected sonographic abnormalities (85.5%) were the most common indication. The overall incidence of preterm birth and intrauterine demise after amniocentesis were 2.5 and 1.3%, respectively. Sixty-nine fetuses with aneuploidy (5.3%) and seventy-two fetuses with pathogenic copy number variations (5.5%) were identified by chromosomal microarray analysis. The maximal diagnostic yield (70%) was in the subgroup of fetuses with the abnormal diagnostic test results, followed by abnormal NIPT results (35.7%) and multiple abnormalities (23.8%). And 35.4% of the pregnancies were finally terminated.

Conclusions

Due to the high detection rates of advanced genetic technologies and the safety of the invasive procedure (3.9% vs 4.0%), it is reasonable to recommend late amniocentesis as an effective and reliable method to detect late-onset fetal abnormalities. However, chromosomal microarray and whole-exome sequencing may result in uncertain results like variants of uncertain significance. Comprehensive genetic counseling is necessary.
Effect of policosanol from insect wax on amyloid β-peptide-induced toxicity in a transgenic Caenorhabditis elegans model of Alzheimer’s disease
Authors: Zhang Xin , Ma Chenjing , Sun Long , He Zhao , Feng Ying , Li Xian , Gan Jin , Chen Xiaoming
Published: March 2021

Background

Alzheimer’s disease (AD), an age-related neurodegenerative disorder and a serious public health concern, is mainly caused by β-amyloid (Aβ)-induced toxicity. Currently, a limited number of drugs are effective against AD, and only a few are used for its treatment. According to traditional Chinese medicine, white wax is mainly composed of policosanol, hexacosanol, and octacosanol. Policosanol has been shown to reduce lipid levels in blood and alleviate the symptoms associated with diabetic complications and neurodegenerative disorders, such as Parkinson’s disease and AD. However, the efficacy of policosanol depends on the purity and composition of the preparation, and the therapeutic efficacy of policosanol derived from insect wax (PIW) in AD is unknown.

Methods

Here, we identified the main components of PIW and investigated the effects of PIW on Aβ-induced toxicity and life-span in a transgenic Caenorhabditis elegans model of AD, CL4176. Furthermore, we estimated the expression of amyloid precursor-like protein (apl-1) and the genes involved in various pathways associated with longevity and alleviation of AD-related symptoms in PIW-fed CL4176.

Results

PIW mainly consists of tetracosanol, hexacosanol, octacosanol, and triacontanol; it could decrease the Aβ-induced paralysis rate from 86.87 to 66.97% (P < 0.01) and extend the life-span from 6.2 d to 7.8 d (P < 0.001) in CL4176 worms. Furthermore, PIW downregulated apl-1, a gene known to be associated with the levels of Aβ deposits in C. elegans. Additionally, our results showed that PIW modulated the expression of genes associated with longevity-related pathways such as heat shock response, anti-oxidative stress, and glutamine cysteine synthetase.

Conclusion

Our findings suggest that PIW may be a potential therapeutic agent for the prevention and treatment of AD. However, its effects on murine models and patients with AD need to be explored further.
Transcription initiation of distant core promoters in a large-sized genome of an insect
Authors: Liu Qing , Jiang Feng , Zhang Jie , Li Xiao , Kang Le
Published: March 2021

Background

Core promoters have a substantial influence on various steps of transcription, including initiation, elongation, termination, polyadenylation, and finally, translation. The characterization of core promoters is crucial for exploring the regulatory code of transcription initiation. However, the current understanding of insect core promoters is focused on those of Diptera (especially Drosophila) species with small genome sizes.

Results

Here, we present an analysis of the transcription start sites (TSSs) in the migratory locust, Locusta migratoria, which has a genome size of 6.5 Gb. The genomic differences, including lower precision of transcription initiation and fewer constraints on the distance from transcription factor binding sites or regulatory elements to TSSs, were revealed in locusts compared with Drosophila insects. Furthermore, we found a distinct bimodal log distribution of the distances from the start codons to the core promoters of locust genes. We found stricter constraints on the exon length of mRNA leaders and widespread expression activity of the distant core promoters in locusts compared with fruit flies. We further compared core promoters in seven arthropod species across a broad range of genome sizes to reinforce our results on the emergence of distant core promoters in large-sized genomes.

Conclusions

In summary, our results provide novel insights into the effects of genome size expansion on distant transcription initiation.
Correction to: Graphene-modified CePO4 nanorods effectively treat breast cancer-induced bone metastases and regulate macrophage polarization to improve osteo-inductive ability
Authors: Ge Yu-Wei , Liu Xiao-Liang , Yu De-gang , Zhu Zhen-An , Ke Qin-Fei , Mao Yuan-Qing , Guo Ya-Ping , Zhang Jing-Wei
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Efficacy of the association liver partition and portal vein ligation for staged hepatectomy for the treatment of solitary huge hepatocellular carcinoma: a retrospective single-center study
Authors: Deng Zhenfeng , Jin Zongrui , Qin Yonghui , Wei Mingqi , Wang Jilong , Lu Tingting , Zhang Ling , Zeng Jingjing , Bao Li , Guo Ya , Peng Minhao , Xu Banghao , Wen Zhang
Published: March 2021

Background

The feasibility of association liver partition and portal vein ligation for staged hepatectomy (ALPPS) for solitary huge hepatocellular carcinoma (HCC, maximal diameter ≥ 10 cm) remains uncertain. This study aims to evaluate the safety and the efficacy of ALPPS for patients with solitary huge HCC.

Methods

Twenty patients with solitary huge HCC who received ALPPS during January 2017 and December 2019 were retrospectively analyzed. The oncological characteristics of contemporaneous patients who underwent one-stage resection and transcatheter arterial chemoembolization (TACE) were compared using propensity score matching (PSM).

Results

All patients underwent complete two-staged ALPPS. The median future liver remnant from the ALPPS-I stage to the ALPPS-II stage increased by 64.5% (range = 22.3–221.9%) with a median interval of 18 days (range = 10–54 days). The 90-day mortality rate after the ALPPS-II stage was 5%. The 1- and 3-year overall survival (OS) rates were 70.0% and 57.4%, respectively, whereas the 1- and 3-year progression-free survival (PFS) rates were 60.0% and 43.0%, respectively. In the one-to-one PSM analysis, the long-term survival of patients who received ALPPS was significantly better than those who received TACE (OS, P = 0.007; PFS, P = 0.011) but comparable with those who underwent one-stage resection (OS, P = 0.463; PFS, P = 0.786).

Conclusion

The surgical outcomes of ALPPS were superior to those of TACE and similar to those of one-stage resection. ALPPS is a safe and effective treatment strategy for patients with unresectable solitary huge HCC.
Myeloproliferative neoplasm-driving Calr frameshift promotes the development of pulmonary hypertension in mice
Authors: Minakawa Keiji , Yokokawa Tetsuro , Ueda Koki , Nakajima Osamu , Misaka Tomofumi , Kimishima Yusuke , Wada Kento , Tomita Yusuke , Miura Saori , Sato Yuka , Mimura Kosaku , Sugimoto Koichi , Nakazato Kazuhiko , Nollet Kenneth E. , Ogawa Kazuei , Ikezoe Takayuki , Hashimoto Yuko , Takeishi Yasuchika , Ikeda Kazuhiko
Published: March 2021

Frameshifts in the Calreticulin (CALR) exon 9 provide a recurrent driver mutation of essential thrombocythemia (ET) and primary myelofibrosis among myeloproliferative neoplasms (MPNs). Here, we generated knock-in mice with murine Calr exon 9 mimicking the human CALR mutations, using the CRISPR-Cas9 method. Knock-in mice with del10 [Calrdel10/WT (wild−type) mice] exhibited an ET phenotype with increases of peripheral blood (PB) platelets and leukocytes, and accumulation of megakaryocytes in bone marrow (BM), while those with ins2 (Calrins2/WT mice) showed a slight splenic enlargement. Phosphorylated STAT3 (pSTAT3) was upregulated in BM cells of both knock-in mice. In BM transplantation (BMT) recipients from Calrdel10/WT mice, although PB cell counts were not different from those in BMT recipients from CalrWT/WT mice, Calrdel10/WT BM-derived macrophages exhibited elevations of pSTAT3 and Endothelin-1 levels. Strikingly, BMT recipients from Calrdel10/WT mice developed more severe pulmonary hypertension (PH)—which often arises as a comorbidity in patients with MPNs—than BMT recipients from CalrWT/WT mice, with pulmonary arterial remodeling accompanied by an accumulation of donor-derived macrophages in response to chronic hypoxia. In conclusion, our murine model with the frameshifted murine Calr presented an ET phenotype analogous to human MPNs in molecular mechanisms and cardiovascular complications such as PH.
Feasibility and accuracy of ED frailty identification in older trauma patients: a prospective multi-centre study
Authors: Jarman Heather , Crouch Robert , Baxter Mark , Wang Chao , Peck George , Sivapathasuntharam Dhanupriya , Jennings Cara , Cole Elaine
Published: March 2021

Background

The burden of frailty on older people is identifiable by its adverse effect on mortality, morbidity and long term functional and health outcomes. In patients suffering from a traumatic injury there is increasing evidence that it is frailty rather than age that impacts greatest on these outcomes and that early identification can guide frailty specific care. The aim of this study was to evaluate the feasibility of nurse-led assessment of frailty in older trauma patients in the ED in patients admitted to major trauma centres.

Methods

Patients age 65 years and over attending the Emergency Departments (ED) of five Major Trauma Centres following traumatic injury were enrolled between June 2019 and March 2020. Patients were assessed for frailty whilst in the ED using three different screening tools (Clinical Frailty Scale [CFS], Program of Research to Integrate Services for the Maintenance of Autonomy 7 [PRIMSA7], and the Trauma Specific Frailty Index [TSFI]) to compare feasibility and accuracy. Accuracy was determined by agreement with geriatrician assessment of frailty. The primary outcome was identification of frailty in the ED using three different assessment tools.

Results

We included 372 patients whose median age was 80, 53.8% of whom were female. The most common mechanism of injury was fall from less than 2 m followed by falls greater than 2 m. Completion rates for the tools were variable, 31.9% for TSFI, compared to 93% with PRISMA7 and 98.9% with the CFS. There was substantial agreement when using CFS between nurse defined frailty and geriatrician defined frailty. Agreement was moderate using PRISMA7 and slight using TSFI.

Conclusions

This prospective study has demonstrated that screening for frailty in older major trauma patients within the Emergency Department is feasible and accurate using CFS.

Trial registration

ISRCTN, ISRCTN10671514. Registered 22 October 2019
Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside
Authors:   the International Network Medicine Consortium, Sarno Federica , Benincasa Giuditta , List Markus , Barabasi Albert-Lazlo , Baumbach Jan , Ciardiello Fortunato , Filetti Sebastiano , Glass Kimberly , Loscalzo Joseph , Marchese Cinzia , Maron Bradley A. , Paci Paola , Parini Paolo , Petrillo Enrico , Silverman Edwin K. , Verrienti Antonella , Altucci Lucia , Napoli Claudio
Published: March 2021

Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside.
Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its’ very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of numerous drugs with an increasingly significant role in clinical therapy especially of cancer patients. Here, we provide an overview of clinical epigenetics within the context of network analysis. We illustrate achievements to date and discuss how we can move from traditional medicine into the era of network medicine (NM), where pathway-informed molecular diagnostics will allow treatment selection following the paradigm of precision medicine.
The adipose-derived mesenchymal stem cell secretome promotes hepatic regeneration in miniature pigs after liver ischaemia-reperfusion combined with partial resection
Authors: Jiao Zhihui , Ma Yajun , Zhang Qianzhen , Wang Yue , Liu Tao , Liu Xiaoning , Piao Chenxi , Liu Boyang , Wang Hongbin
Published: March 2021

Background

Hepatic ischaemia-reperfusion injury (HIRI) is inevitable in complicated liver surgery and is a major factor leading to postoperative complications and liver dysfunction. Studies have shown that the paracrine mechanisms of stem cell may be essential to tissue repair and functional improvement after transplantation. However, the role of the adipose-derived mesenchymal stem cell secretome (ASC-secretome) in liver regeneration in large animals remains to be determined.

Methods

Twenty-four miniature pigs were subjected to laparoscopic liver ischaemia-reperfusion combined with partial hepatectomy and divided into the following four groups: the saline group, the DMEM group, the ASC group and the ASC-secretome group. Serum and liver tissue samples were collected before the operation and at 1, 3 and 7 days after the operation, and changes in tissue pathology, serum inflammation, liver function, angiogenesis-related factors and liver tissue regeneration-related genes and proteins were evaluated.

Results

Detailed histological analysis showed that ASCs and the ASC-secretome changed pathological damage to liver tissue after liver ischaemia-reperfusion combined with partial hepatectomy (1 and 3 days: p < 0.01). Compared with the saline and DMEM control groups, the ASC-secretome group had significantly reduced expression levels of ALP (1 and 3 days: p < 0.05), ALT (1 day: p < 0.01; 3 days: p < 0.05) and AST (1 and 3 days: p < 0.01), which promoted the recovery of liver function. Moreover, detection of the expression levels of TNF-α and IL-1β (1 day: p < 0.01; 3 days: p < 0.05), IL-6 (1 and 3 days: p < 0.05) and IL-10 (1 and 3 days: p < 0.01) in serum confirmed that the ASC-secretome had obvious anti-inflammatory effects. In addition, the ASC-secretome increased the expression levels of ANG-1 (3 days: p < 0.01), ANG-2 (3 and 7 days: p < 0.01) and VEGF (1 and 7 days: p < 0.05; 3 days: p < 0.01) and promoted angiogenesis during liver regeneration. Moreover, it promoted the mRNA expression of HGF and Cyclin D1 (1 and 3 days: p < 0.01); increased the levels of p-STAT3 (1 and 3 days: p < 0.01), PCNA and Ki67 (1 and 3 days: p < 0.01; 7 days: p < 0.05); inhibited the negative feedback of SOCS3 (1 and 3 days: p < 0.01); and decreased the mRNA expression of TGF-β (3 days: p < 0.01). The cytokines and growth factors detected in the ASC-secretome included TNF-α, IL-6, IL-1β, ANG-1, ANG-2, VEGF and b-FGF.

Conclusion

The ASC-secretome alleviates the inflammatory response induced by ischaemia-reperfusion combined with partial hepatectomy in miniature pigs and promotes liver regeneration.
Muscle atrophy induced by overexpression of ALAS2 is related to muscle mitochondrial dysfunction
Authors: Peng Yahui , Li Jihong , Luo Dixian , Zhang Shuai , Li Sijia , Wang Dayong , Wang Xidi , Zhang Zhujun , Wang Xue , Sun Changhui , Gao Xu , Hui Yang , He Rongzhang
Published: March 2021

Background

ALAS2 (delta-aminolevulinate synthase 2) is one of the two isoenzymes catalyzing the synthesis of delta-aminolevulinic acid (ALA), which is the first precursor of heme synthesis. ALAS2-overexpressing transgenic mice (Tg mice) showed syndrome of porphyria, a series of diseases related to the heme anabolism deficiency. Tg mice showed an obvious decrease in muscle size. Muscle atrophy results from a decrease in protein synthesis and an increase in protein degradation, which ultimately leads to a decrease in myofiber size due to loss of contractile proteins, organelles, nuclei, and cytoplasm.

Methods

The forelimb muscle grip strength of age-matched ALAS-2 transgenic mice (Tg mice) and wild-type mice (WT mice) were measured with an automated grip strength meter. The activities of serum LDH and CK-MB were measured by Modular DPP. The histology of skeletal muscle (quadriceps femoris and gastrocnemius) was observed by hematoxylin and eosin (HE) staining, immunohistochemistry, and transmission electron microscope. Real-time PCR was used to detect mtDNA content and UCP3 mRNA expression. Evans blue dye staining was used to detect the membrane damage of the muscle fiber. Single skeletal muscle fiber diameter was measured by single-fiber analyses. Muscle adenosine triphosphate (ATP) levels were detected by a luminometric assay with an ATP assay kit.

Results

Compared with WT mice, the strength of forelimb muscle and mass of gastrocnemius were decreased in Tg mice. The activities of serum CK-MB and LDH, the number of central nuclei fibers, and Evans blue positive fibers were more than those in WT mice, while the diameter of single fibers was smaller, which were associated with suppressed expression levels of MHC, myoD1, dystrophin, atrogin1, and MuRF1. Re-expression of eMyHC was only showed in the quadriceps of Tg mice, but not in WT mice. Muscle mitochondria in Tg mice showed dysfunction with descented ATP production and mtDNA content, downregulated UCP3 mRNA expression, and swelling of mitochondria.

Conclusion

ALAS2 overexpressing-transgenic mice (Tg mice) showed muscle dystrophy, which was associated with decreased atrogin-1 and MuRF-1, and closely related to mitochondrial dysfunction.
The inhibitory effects of Staphylococcus aureus on the antibiotic susceptibility and virulence factors of Pseudomonas aeruginosa: A549 cell line model
Authors: Dehbashi Sanaz , Alikhani Mohammad Yousef , Tahmasebi Hamed , Arabestani Mohammad Reza
Published: March 2021

Pseudomonas aeruginosa and Staphylococcus aureus often lead to serious lung infections. This study aimed to investigate the role of S. aureus in the expression of the β-lactamase enzymes and virulence factors of P. aeruginosa in the polymicrobial infections of the respiratory tract. Biofilm and planktonic co-culture of P. aeruginosa and S. aureus were performed in the A549 cell line. Then, antibiotic resistance and virulence factors of P. aeruginosa were examined, and the expression of lasR, lasI, algD, mexR, and KPC genes were determined using qPCR. S.aureus decreased β-lactam resistance but increased resistance to tobramycin in the biofilm condition. Furthermore, S.aureus showed a positive effect on reducing resistance to meropenem, doripenem, and tobramycin (except PA-2). Altough it was demonstrated that S.aureus reduced the viability of P. aeruginosa, particularly in the biofilm state, the pathogenicity of the recovered strains of P.aeruginosa increased. Moreover, the gene expression levels for lasR/I and algD were increased in biofilm conditions. The levels of lasI were more prominent in the virulent strain than the β-lactamase producing strain. Furthermore, the expression of KPC was increased in all strains of P. aeruginosa. According to the findings of this study, S. aureus has an inhibitory effect in polymicrobial infections by suppressing the β-lactamase genes and viability of P. aeruginosa. Also, it cooperates with the biofilm-producing P. aeruginosa strains to increase pathogenicity and resistance to tobramycin.
Left ventricular longitudinal wall fractional shortening accurately predicts longitudinal strain in critically ill patients with septic shock
Authors: Johansson Blixt Patrik , Chew Michelle S. , Åhman Rasmus , de Geer Lina , Blomqwist Lill , Åström Aneq Meriam , Engvall Jan , Andersson Henrik
Published: March 2021

Background

Left ventricular longitudinal strain (LVLS) may be a sensitive indicator of left ventricular (LV) systolic function in patients with sepsis, but is dependent on high image quality and analysis software. Mitral annular plane systolic excursion (MAPSE) and the novel left ventricular longitudinal wall fractional shortening (LV-LWFS) are bedside echocardiographic indicators of LV systolic function that are less dependent on image quality. Both are sparsely investigated in the critically ill population, and may potentially be used as surrogates for LVLS. We assessed if LVLS may be predicted by LV-LWFS and MAPSE in patients with septic shock. We also assessed the repeatability and inter-rater agreement of LVLS, LV-LWFS and MAPSE measurements.

Results

122 TTE studies from 3 echocardiographic data repositories of patients admitted to ICU with septic shock were retrospectively assessed, of which 73 were suitable for LVLS analysis using speckle tracking. The correlations between LVLS vs. LV-LWFS and LVLS vs. MAPSE were 0.89 (p < 0.001) and 0.81 (p < 0.001) with mean squared errors of 5.8% and 9.1%, respectively. Using the generated regression equation, LV-LWFS predicted LVLS with a high degree of accuracy and precision, with bias and limits of agreement of -0.044 ± 4.7% and mean squared prediction error of 5.8%. Interobserver repeatability was good, with high intraclass correlation coefficients (0.96–0.97), small bias and tight limits of agreement (≤ 4.1% for all analyses) between observers for all measurements.

Conclusions

LV-LWFS may be used to estimate LVLS in patients with septic shock. MAPSE also performed well, but was slightly inferior compared to LV-LWFS in estimating LVLS. Feasibility of MAPSE and LV-LWFS was excellent, as was interobserver repeatability.
A time-delay COVID-19 propagation model considering supply chain transmission and hierarchical quarantine rate
Authors: Yang Fangfang , Zhang Zizhen
Published: March 2021

In this manuscript, we investigate a novel Susceptible–Exposed–Infected–Quarantined–Recovered (SEIQR) COVID-19 propagation model with two delays, and we also consider supply chain transmission and hierarchical quarantine rate in this model. Firstly, we analyze the existence of an equilibrium, including a virus-free equilibrium and a virus-existence equilibrium. Then local stability and the occurrence of Hopf bifurcation have been researched by thinking of time delay as the bifurcation parameter. Besides, we calculate direction and stability of the Hopf bifurcation. Finally, we carry out some numerical simulations to prove the validity of theoretical results.
Dietary supplementation of dried plum: a novel strategy to mitigate heat stress in broiler chickens
Authors: Wasti Sanjeev , Sah Nirvay , Singh Amit K. , Lee Chin N. , Jha Rajesh , Mishra Birendra
Published: March 2021

Background

Heat stress is a significant problem in the poultry industry, causing a severe economic loss due to its detrimental effects on chickens’ health and performance. Dried plum (DP) is a good source of minerals, vitamins, antioxidants, and phenolic compounds. Studies have suggested that DP has several health benefits, such as maintaining the body’s redox system, immune status, and calcium hemostasis. Based on the health benefits of DP, we hypothesized that the dietary supplementation of DP would alleviate the detrimental effects of heat stress on broiler chickens.

Results

To test the hypothesis, day-old broiler chicks (n = 72) were randomly allocated to three treatment groups (n = 24/group): no heat stress (NHS), heat stress (HS), and heat stress with dried plum (HS + DP), and reared under standard conditions. The inclusion of 2.5% DP in the feed of the HS + DP group was made during the treatment period, while birds in other groups were provided with a standard finisher diet. After 21 days, birds in the HS and HS + DP groups were exposed to cyclic heat stress conditions (33 °C for 8 h during daytime) for 3 weeks, while those in the NHS group were reared under normal conditions (22–24 °C). Weekly body weight and feed intake were recorded to calculate the average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR). Heat stress significantly decreased the final body weight, ADG, ADFI, and increased FCR compared to the NHS group, whereas dietary supplementation of DP significantly improved these growth performance parameters compared to the HS group. Furthermore, supplementation of DP significantly increased the expression of heat shock protein-related genes (HSF1, HSF3, HSP70, and HSP90), antioxidant-related genes (SOD1, SOD2, GPX1, GPX3, PRDX1, and TXN), tight junction-related genes (CLDN1, and OCLN), and immune-related genes (IL4, MUC2) in the ileum as compared to the HS group. The microbiota analysis showed significant enrichment of Bacillales, Christensenellaceae, Bacillaceae, Peptostreptococcaceae, and Anaerotruncus in heat-stressed birds supplemented with DP as compared to the HS group. Further, DP supplementation also significantly increased the concentration of acetate, propionate, and total VFA in the cecal digesta of the HS + DP group as compared to the HS group.

Conclusion

These findings suggest that DP supplementation effectively improved the growth performances and gut health parameters in the heat-stressed birds. Thus, dried plum can be a potential feed supplement to mitigate heat stress in broiler chickens.
An evaluation of machine learning classifiers for next-generation, continuous-ethogram smart trackers
Authors: Yu Hui , Deng Jian , Nathan Ran , Kröschel Max , Pekarsky Sasha , Li Guozheng , Klaassen Marcel
Published: March 2021

Background

Our understanding of movement patterns and behaviours of wildlife has advanced greatly through the use of improved tracking technologies, including application of accelerometry (ACC) across a wide range of taxa. However, most ACC studies either use intermittent sampling that hinders continuity or continuous data logging relying on tracker retrieval for data downloading which is not applicable for long term study. To allow long-term, fine-scale behavioural research, we evaluated a range of machine learning methods for their suitability for continuous on-board classification of ACC data into behaviour categories prior to data transmission.

Methods

We tested six supervised machine learning methods, including linear discriminant analysis (LDA), decision tree (DT), support vector machine (SVM), artificial neural network (ANN), random forest (RF) and extreme gradient boosting (XGBoost) to classify behaviour using ACC data from three bird species (white stork Ciconia ciconia, griffon vulture Gyps fulvus and common crane Grus grus) and two mammals (dairy cow Bos taurus and roe deer Capreolus capreolus).

Results

Using a range of quality criteria, SVM, ANN, RF and XGBoost performed well in determining behaviour from ACC data and their good performance appeared little affected when greatly reducing the number of input features for model training. On-board runtime and storage-requirement tests showed that notably ANN, RF and XGBoost would make suitable on-board classifiers.

Conclusions

Our identification of using feature reduction in combination with ANN, RF and XGBoost as suitable methods for on-board behavioural classification of continuous ACC data has considerable potential to benefit movement ecology and behavioural research, wildlife conservation and livestock husbandry.
Plant health and its effects on food safety and security in a One Health framework: four case studies
Authors: Rizzo David M. , Lichtveld Maureen , Mazet Jonna A. K. , Togami Eri , Miller Sally A.
Published: March 2021

Although healthy plants are vital to human and animal health, plant health is often overlooked in the One Health literature. Plants provide over 80% of the food consumed by humans and are the primary source of nutrition for livestock. However, plant diseases and pests often threaten the availability and safety of plants for human and animal consumption. Global yield losses of important staple crops can range up to 30% and hundreds of billions of dollars in lost food production. To demonstrate the complex interrelationships between plants and public health, we present four case studies on plant health issues directly tied to food safety and/or security, and how a One Health approach influences the perception and mitigation of these issues. Plant pathogens affect food availability and consequently food security through reductions in yield and plant mortality as shown through the first case study of banana Xanthomonas wilt in East and Central Africa. Case studies 2, 3 and 4 highlight ways in which the safety of plant-based foods can also be compromised. Case study 2 describes the role of mycotoxin-producing plant-colonizing fungi in human and animal disease and examines lessons learned from outbreaks of aflatoxicosis in Kenya. Plants may also serve as vectors of human pathogens as seen in case study 3, with an example of Escherichia coli (E. coli) contamination of lettuce in North America. Finally, case study 4 focuses on the use of pesticides in Suriname, a complex issue intimately tied to food security though protection of crops from diseases and pests, while also a food safety issue through misuse. These cases from around the world in low to high income countries point to the need for interdisciplinary teams to solve complex plant health problems. Through these case studies, we examine challenges and opportunities moving forward for mitigating negative public health consequences and ensuring health equity. Advances in surveillance technology and functional and streamlined workflow, from data collection, analyses, risk assessment, reporting, and information sharing are needed to improve the response to emergence and spread of plant-related pathogens and pests. Our case studies point to the importance of collaboration in responses to plant health issues that may become public health emergencies and the value of the One Health approach in ensuring food safety and food security for the global population.
Application of diffusion tensor imaging in Alzheimer’s disease: quantification of white matter microstructural changes
Authors: Esrael Shereen Magdy Abdel Malak , Hamed Ahmed Mostafa Mohamed , Khedr Eman M. , Soliman Radwa Kamel
Published: March 2021

Background

Alzheimer’s disease (AD) is the most common cause of dementia in the aging population, responsible for 60–70% of all demented cases. Diffusion tensor imaging (DTI) is a very recent technique that allows the mapping of white matter (WM) microstructure changes in neurological disorders. The current study was conducted to compare DTI parameters between AD patients and healthy elderly subjects and to determine whether DTI can act as a potential biomarker for AD.

Results

There were significant differences in Modified Mini-Mental State Examination (MMMSE) and Clinical Dementia Rating (CDR) between the two groups. As regards the DTI parameters, significant differences were found between AD patients versus healthy subjects, in the mean diffusivity (MD) of the splenium [(1.05 ± 0.19) vs. (0.92 ± 0.22) ,P=0.03], the MD of the right uncinate fasciculus [(0.92 ± 0.04) vs. (0.87 ± 0.05),P= 0.01],  and MD of the right arcuate fasciculus (AF) [(0.83 ± 0.04) vs. (0.79 ± 0.04)P=0.01],  as well as the MD of the right and left inferior fronto-occipital fasiculus (IFOF) [(0.89 ± 0.06) vs. (0.83 ± 0.04),P=0.01]. In addition, there were significant differences in the fractional anisotropy (FA) of the right and left cingulum between both groups [(0.45 ± 0.02) vs. (0.47 ± 0.03),P=0.01 and (0.45 ± 0.03) vs. 0.49± 0.04),P=0.01, respectively]. The overall accuracy of the aforementioned parameters ranged between 73 and 81% with the MD of the left cingulum revealing the highest accuracy.

Conclusion

DTI proofed to be a useful tool in differentiating AD patients from healthy subjects. In our study, we found that the splenium, cingulum, IFOF, and the right UF and right AF are the main tracts involved in AD. The left cingulum provided the highest accuracy in differentiating AD from normal subjects.