bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene correlation network analysis to identify regulatory factors in sciatic nerve injury
Authors: Li Liuxun , Du Xiaokang , Ling Haiqian , Li Yuhang , Wu Xuemin , Jin Anmin , Yang Meiling
Published: October 2021

Background

Sciatic nerve injury (SNI), which frequently occurs under the traumatic hip and hip fracture dislocation, induces serious complications such as motor and sensory loss, muscle atrophy, or even disabling. The present work aimed to determine the regulating factors and gene network related to the SNI pathology.

Methods

Sciatic nerve injury dataset GSE18803 with 24 samples was divided into adult group and neonate group. Weighted gene co-expression network analysis (WGCNA) was carried out to identify modules associated with SNI in the two groups. Moreover, differentially expressed genes (DEGs) were determined from every group, separately. Subsequently, co-expression network and protein–protein interaction (PPI) network were overlapped to identify hub genes, while functional enrichment and Reactome analysis were used for a comprehensive analysis of potential pathways. GSE30165 was used as the test set for investigating the hub gene involvement within SNI. Gene set enrichment analysis (GSEA) was performed separately using difference between samples and gene expression level as phenotype label to further prove SNI-related signaling pathways. In addition, immune infiltration analysis was accomplished by CIBERSORT. Finally, Drug–Gene Interaction database (DGIdb) was employed for predicting the possible therapeutic agents.

Results

14 SNI status modules and 97 DEGs were identified in adult group, while 15 modules and 21 DEGs in neonate group. A total of 12 hub genes was overlapping from co-expression and PPI network. After the results from both test and training sets were overlapped, we verified that the ten real hub genes showed remarkably up-regulation within SNI. According to functional enrichment of hub genes, the above genes participated in the immune effector process, inflammatory responses, the antigen processing and presentation, and the phagocytosis. GSEA also supported that gene sets with the highest significance were mostly related to the cytokine–cytokine receptor interaction. Analysis of hub genes possible related signaling pathways using gene expression level as phenotype label revealed an enrichment involved in Lysosome, Chemokine signaling pathway, and Neurotrophin signaling pathway. Immune infiltration analysis showed that Macrophages M2 and Regulatory T cells may participate in the development of SNI. At last, 25 drugs were screened from DGIdb to improve SNI treatment.

Conclusions

The gene expression network is determined in the present work based on the related regulating factors within SNI, which sheds more light on SNI pathology and offers the possible biomarkers and therapeutic targets in subsequent research.
What are the significant factors affecting pain in patients with Hartofilakidis type Ι developmental dysplasia of the hip?
Authors: Gu Yange , Jin Wenshu , Zhang Han , Shi Zhiwei , Yue Yaohui , Yan Zhaolong , Zhao Zhang , Li Shufeng , Yan Xinfeng
Published: October 2021

Objective

To explore the influencing factors of age at onset of pain and severe pain in patients with Hartofilakidis type I developmental dysplasia of the hip (DDH).

Methods

A retrospective study of 83 patients with DDH treated at our hospital from January 2017 to June 2021 was conducted. The age at onset of pain, patients’ demographic data, and radiographic parameters were collected. Multiple linear regression was used to determine the influencing factors of age at onset of pain. Cox regression analysis was used to determine the influencing factors of severe pain attacks.

Results

According to the results of multiple linear regression analysis, when the distance between the medial femoral head and the ilioischial line increased by one millimetre, the age at onset of pain decreased by 1.7 years (β = − 1.738, 95% CI − 1.914–[− 1.561], p < 0.001). When the sharp angle increases by one degree, the age at onset of pain decreases by 0.3 years (β = − 0.334, 95% CI − 0.496–[− 0.171], p < 0.001). According to the results of the Cox regression analysis, for each additional degree of the lateral centre-edge angle (LCEA), the probability of severe pain was reduced by 5% (Exp [β]: = 0.947, 95% CI 0.898–0.999, p = 0.044). For each additional millimetre in the distance between the medial femoral head and the ilioischial line, the likelihood of severe pain increased by 2.4 times (Exp [β]: 2.417, 95% CI 1.653–3.533, p < 0.001).

Conclusion

Larger distances between the medial femoral head and the ilioischial line and sharp angle can lead to an earlier age at onset of pain in patients with DDH. Small LCEA and excessive distance between the medial femoral head and the ilioischial line are risk factors for severe pain.
Preoperative ultrasound to map the three-dimensional anatomical distribution of the lateral femoral cutaneous nerve in direct anterior approach for total hip arthroplasty
Authors: Zhang Yu , Yao Yao , Wang Yexian , Zhuang Zaikai , Shen Ying , Jiang Qing , Chen Dongyang
Published: October 2021

Background

The postoperative complaints of hypoesthesia or a burning sensation due to lateral femoral cutaneous nerve (LFCN) injury in patients are not yet solved. The present study aimed to identify the three-dimensional (3D) distribution of LFCN using preoperative ultrasound and evaluate the rate of injury in direct anterior approach for total hip arthroplasty.

Methods

A total of 59 patients (28 males and 31 females, age 69.0 ± 4.6 years, BMI 24.7 ± 3.0 kg/m2) were randomly allocated to the ultrasound group and 58 patients (28 males and 30 females, age 68.5 ± 4.5 years, BMI 24.8 ± 2.8 kg/m2) were in the control group. Surgeons received the data of 3D distribution of LFCN only in the ultrasound group before surgery with respect to the direction, the depth on the skin, and the length to tensor fasciae latae (TFL). The anatomical characteristics of LFCN in the surgical region were summarized. At 1 and 3 months of post surgery, the rate of LFCN injury and abnormal sensitive area was evaluated in both groups.

Results

There was a significant consistency in gender, age and BMI of these two groups (P > 0.05). Based on the data from the ultrasound group, over 90% of patients had one or two branches of LFCN. LFCN always courses in the fascia layer, the depth ranged from 6.8 ± 2.6 (3.0–12.0) mm to 11.1 ± 3.4 (4.0–17.0) mm and depended on the thickness of the subcutaneous fat, and length was 3.3 ± 4.6 (− 5.0–10.0) mm at proximal part and − 2.7 ± 4.7 (− 10.0–8.0) at distal end to the medial edge of TFL. Both the rate of LFCN injury and abnormal sensory area in the ultrasound group was significantly lower than those in the control group (3.4% vs. 25.9%, P = 0.001, at 1 month; 3.4% vs. 22.4%, P = 0.005, at 3 months).

Conclusions

LFCN mostly courses along the medial border of TFL in the fascia layer. The 3D distribution of LFCN using preoperative ultrasound mapping could help the surgeons to evaluate the risk of injury preoperatively and decrease the rate of injury during the operation. However, some branch injuries, especially for the fan type LFCN, could not be avoided.
Instability of the posterior pelvic ring: introduction of innovative implants
Authors: Grüneweller Niklas , Wähnert Dirk , Vordemvenne Thomas
Published: October 2021

Background

Increasing numbers of posterior pelvic ring fractures, especially in elderly patients, demonstrate the need for soft tissue protecting surgical techniques. Standard of care is iliosacral screw osteosynthesis. This type of osteosynthesis has its limitations especially in patients with reduced bone properties. Therefore, the development of new and straightforward surgical techniques and implant designs is favorable.

Methods

Introducing this modular system for the posterior pelvic ring, known complications of iliosacral screw osteosynthesis, such as implant loosening and malpositioning may be reduced, due to innovative mechanical characteristics.

Results

The shown cases demonstrate the potential benefits of the system with a wide range of treatment options due to its modularity.

Conclusion

The modular implant system presented here can significantly facilitate and improve the stabilization of posterior pelvic ring instabilities.
Analysis of bronchial and vascular patterns in left upper lobes to explore the genesis of mediastinal lingular artery and its influence on pulmonary anatomical variation
Authors: Gao Chuan , Xu Wen-zheng , Li Zhi-hua , Chen Liang
Published: October 2021

Background

For thoracic surgeons, three-dimensional computed tomography bronchography and angiography (3-DCTBA) is a convenient way to analyze pulmonary variations before segmentectomy. Mediastinal lingular artery (MLA) is one of the representative variations.

Methods

The 3-DCTBA data of left upper lobe (LUL) were collected from patients who underwent pulmonary surgery from January 2018 to December 2019. We reviewed the patterns of bronchi and pulmonary vessels and grouped them according to different classifications.

Results

Among all the 404 cases of 3-DCTBA, mediastinal lingular artery (MLA) was found in 107 cases (26.49%). The patterns of B3 and the vein in left upper division (LUD) are distinct between mediastinal (M-type) group and interlobar (IL-type) group. The patterns of bronchi and veins in lingular division, as well as the pattern of pulmonary artery in LUD, have no differences between M-type and IL-type groups.

Conclusions

Mediastinal lingular artery is speculated to originate from the variation of B3, and the MLA independently influences the venous pattern in LUD in turn.
Novel microwave surgical instrument for use in various lung resection situations
Authors: Kamigaichi Atsushi , Mimura Takeshi , Yamashita Yoshinori
Published: October 2021

A novel surgical energy device with high sealing ability using microwave technology has been developed. This novel microwave surgical instrument (MSI) is capable of sealing and dissecting a vessel ≤ 5 mm in diameter. The high sealing ability of the MSI enables fine dissection of the lung parenchyma by a scissor-type blade. This device is particularly useful in situations wherein the use of an automatic suturing instrument is difficult. Here, we describe the dissection of the lung parenchyma using this device in three patients (cases 1–3). This device was used for wedge resection of a tumor located close to the pulmonary hilum, for subsegmentectomy, and for dividing incomplete interlobar fissure (cases 1–3, respectively). In all the cases, the postoperative course was uneventful. This MSI is effective for resection of the lung parenchyma, allowing fine tissue dissection and excellent tissue sealing. This technique could assist surgeons in various lung resection cases.
NMPA-approved traditional Chinese medicine-Pingwei Pill: new indication for colistin recovery against MCR-positive bacteria infection
Authors: Sheng Qiushuang , Du Runbao , Ma Cunhui , Zhou Yonglin , Shen Xue , Hou Xiaoning , Xu Lei , Li Li , Deng Xuming , Wang Jianfeng
Published: October 2021

Background

The wide spread of plasmid-mediated colistin resistance by mobile colistin resistance (MCR) in Enterobacteriaceae severely limits the clinical application of colistin as a last-line drug against bacterial infection. The identification of colistin potentiator from natural plants or their compound preparation as antibiotic adjuncts is a new promising strategy to meet this challenge.

Methods

Herein, the synergistic activity, as well as the potential mechanism, of Pingwei pill plus antibiotics against MCR-positive Gram-negative pathogens was examined using checkerboard assay, time-killing curves, combined disk test, western blot assay, and microscope analysis. Additionally, the Salmonella sp. HYM2 infection models of mouse and chick were employed to examine the in vivo efficacy of Pingwei pill in combination with colistin against bacteria infection. Finally, network pharmacology and molecular docking assay were used to predicate other actions of Pingwei pill for Salmonella infection.

Results

Our results revealed that Pingwei Pill synergistically potentiated the antibacterial activity of colistin against MCR-1-positive bacteria by accelerating the damage and permeability of the bacterial outer membrane with an FIC (Fractional Inhibitory Concentration) index less than 0.5. The treatment of Pingwei Pill neither inhibited bacterial growth nor affected MCR production. Notably, Pingwei Pill in combination with colistin significantly prolonged the median survival in mouse and chick models of infection using the Salmonella sp. strain HYM2, decreased bacteria burden and organ index of infected animal, alleviated pathological damage of cecum, which suggest that Pingwei Pill recovered the therapeutic performance of colistin for MCR-1- positive Salmonella infection in mice and the naturally infected host chick. Pharmacological network topological analysis, molecular docking, bacterial adhesion, and invasion pathway verification assays were performed to identify the other molecular mechanisms of Pingwei Pill as a colistin potentiator against Gram-negative bacteria infection.

Conclusion

Taken together, NMPA (National Medical Products Administration)-approved Pingwei Pill is a promising adjuvant with colistin for MCR-positive bacterial infection with a shortened R&D (research and development) cycle and affordable R&D cost and risk.
Resilience of health systems in conflict affected governorates of Iraq, 2014–2018
Authors: Ibrahim Shaimaa , Al-Dahir Sara , Al Mulla Taha , Lami Faris , Hossain S. M. Moazzem , Baqui Abdullah , Burnham Gilbert
Published: October 2021

Objectives

The objective of this study was to assess the resilience of health systems in four governorates affected by conflict from 2014 to 2018, and to convey recommendations.

Methods

Health managers from Al Anbar, Ninawa, Salah al-Din, and Kirkuk governorates discussed resilience factors of Primary Health Care services affected by the 2014–2017 ISIS insurgency in focus groups, and general discussions. Additional information was gathered from key informants and a UNICEF health facility survey. Three specific aspects were examined: (1) meeting health needs in the immediate crisis response, (2) adaptation of services, (3) restructuring and recovery measures. Data from a MoH/UNICEF national health facility survey in 2017 were analyzed for functionality.

Results

There were many common themes across the four governorates, with local variations. (1) Absorption The shock to the public sector health services by the ISIS invasion caught health services in the four governorates unprepared, with limited abilities to continue to provide services. Private pharmacies and private clinics in some places withstood the initial shock better than the public sector. (2) Adaptation After the initial shock, many health facilities adapted by focusing on urgent needs for injury and communicable disease care. In most locations, maternal, neonatal, and child health (MNCH) preventive and promotive PHC services stopped. Ill persons would sometimes consult health workers in their houses at night for security reasons. (3) Restructuring or transformative activities In most areas, health services recovery was continuing in 2020. Some heavily damaged facilities are still functioning, but below pre-crisis level. Rebuilding lost community trust in the public sector is proving difficult.

Conclusion

Health services generally had little preparation for and limited resilience to the ISIS influx. Governorates are still restructuring services after the liberation from ISIS in 2017. Disaster planning was identified by all participants as a missing component, as everyone anticipated future similar emergencies.
The roles of GTPase-activating proteins in regulated cell death and tumor immunity
Authors: He Hua , Huang Jingjing , Wu Sufang , Jiang Shiyao , Liang Lu , Liu Yueying , Liu Wenbing , Xie Li , Tao Yongguang , Jiang Yiqun , Cong Li
Published: October 2021

GTPase-activating protein (GAP) is a negative regulator of GTPase protein that is thought to promote the conversion of the active GTPase-GTP form to the GTPase-GDP form. Based on its ability to regulate GTPase proteins and other domains, GAPs are directly or indirectly involved in various cell requirement processes. We reviewed the existing evidence of GAPs regulating regulated cell death (RCD), mainly apoptosis and autophagy, as well as some novel RCDs, with particular attention to their association in diseases, especially cancer. We also considered that GAPs could affect tumor immunity and attempted to link GAPs, RCD and tumor immunity. A deeper understanding of the GAPs for regulating these processes could lead to the discovery of new therapeutic targets to avoid pathologic cell loss or to mediate cancer cell death.
Helicopter emergency medical services missions to islands and the mainland during a 3-year period in Denmark: a population-based study on patient and sociodemographic characteristics, comorbidity, and use of healthcare services
Authors: Møller Thea Palsgaard , Ersbøll Annette Kjær , Kjærulff Thora Majlund , Bihrmann Kristine , Alstrup Karen , Knudsen Lars , Hansen Troels Martin , Berlac Peter Anthony , Lippert Freddy , Barfod Charlotte
Published: October 2021

Background

The Danish Helicopter Emergency Medical Services (HEMS) is part of the Danish Emergency Medical Services System serving 5.7 million citizens with 1% living on islands not connected to the mainland by road. HEMS is dispatched based on pre-defined criteria including severity and urgency, and moreover to islands for less urgent cases, when rapid transport to further care is needed. The study aim was to characterize patient and sociodemographic factors, comorbidity and use of healthcare services for patients with HEMS missions to islands versus mainland.

Methods

Descriptive study of data from the HEMS database in a three-year period from 1 October 2014 to 30 September 2017. All missions in which a patient was either treated on scene or transported by HEMS were included.

Results

Of 5776 included HEMS missions, 1023 (17.7%) were island missions. In total, 90.2% of island missions resulted in patient transport by HEMS compared with 62.1% of missions to the mainland. Disease severity was serious or life-threatening in 34.7% of missions to islands compared with 65.1% of missions to mainland and less interventions were performed by HEMS on island missions. The disease pattern differed with more “Other diseases” registered on islands compared with the mainland where cardiovascular diseases and trauma were the leading causes of contact. Patients from islands were older than patients from the mainland. Sociodemographic characteristics varied between inhabiting island patients and mainland patients: more island patients lived alone, less were employed, more were retired, and more had low income. In addition, residing island patients had to a higher extend severe comorbidity and more contacts to general practitioners and hospitals compared with the mainland patients.

Conclusions

HEMS missions to islands count for 17.7% of HEMS missions and 90.2% of island missions result in patient transport. The island patients encountered by HEMS are less severely diseased or injured and interventions are less frequently performed. Residing island patients are older than mainland patients and have lower socioeconomic position, more comorbidities and a higher use of health care services. Whether these socio-economic differences result in longer hospital stay or higher mortality is still to be investigated.
A retrospective survey study of paramedic students’ exposure to SARS-CoV-2, participation in the COVID-19 pandemic response, and health-related quality of life
Authors: Häikiö Kristin , Andersen Jeanette V. , Bakkerud Morten , Christiansen Carl R. , Rand Kim , Staff Trine
Published: October 2021

Background

Healthcare workers have reported increased anxiety while working in hospitals during the COVID-19 pandemic, and the role of healthcare students in a health crisis has been discussed among clinicians and researchers. The simultaneous international shortage of personal protection equipment (PPE) during the first wave of the pandemic potentially exposed healthcare workers and students to the virus during their work and clinical training. Our aim was therefore to evaluate the extent to which paramedic students in Oslo, Norway, were exposed to the SARS-CoV-2 virus and were involved in voluntary and/or paid healthcare-related work. An evaluation was also made of the students’ COVID-19-related symptoms and of their health-related quality of life (HRQoL) during the first wave of the pandemic.

Methods

Paramedic students (n = 155) at Oslo Metropolitan University, Norway, were invited to complete an online survey five months after the first cases of COVID-19 were detected. The university was situated in the epicenter of the pandemic in Norway. The responses were analyzed using descriptive statistics, independent sample t-tests, and linear regression analysis.

Results

Of the 109 respondents (70.3%), 40 worked in patient-related healthcare work. Of those, seven (17.5%) students experienced insufficient supplies of PPE, six (15.0%) participated in aerosol-generating procedures without adequate PPE, and nine (22.5%) experienced insufficient time to don PPE. Seventy-five (70.1%) students experienced no COVID-19-related symptoms, and no students tested positive for COVID-19. HRQoL was scored 0.92 (sd 0.12), which was significantly higher than for the general population before the pandemic (p = 0.002). Students continued with their education and participated in a variety of pandemic-related emergency tasks during the first wave of the pandemic.

Conclusions

Paramedic students were valuable contributors to the national pandemic response. Despite potential exposure to SARS-CoV-2 in unpredictable emergency settings with limited supplies of personal protection equipment, no students tested positive for COVID-19. Their health-related quality of life remained high. Students’ participation and utilization in similar health crises should be considered in future health crises.
Protocol: A multi-modal, physician-centered intervention to improve guideline-concordant prostate cancer imaging
Authors: Makarov Danil V. , Ciprut Shannon , Kelly Matthew , Walter Dawn , Shedlin Michele G. , Braithwaite Ronald Scott , Tenner Craig T. , Gold Heather T. , Zeliadt Steven , Sherman Scott E.
Published: October 2021

Background

Almost half of Veterans with localized prostate cancer receive inappropriate, wasteful staging imaging. Our team has explored the barriers and facilitators of guideline-concordant prostate cancer imaging and found that (1) patients with newly diagnosed prostate cancer have little concern for radiographic staging but rather focus on treatment and (2) physicians trust imaging guidelines but are apt to follow their own intuition, fear medico-legal consequences, and succumb to influence from imaging-avid colleagues. We used a theory-based approach to design a multi-level intervention strategy to promote guideline-concordant imaging to stage incident prostate cancer.

Methods

We designed the Prostate Cancer Imaging Stewardship (PCIS) intervention: a multi-site, stepped wedge, cluster-randomized trial to determine the effect of a physician-focused behavioral intervention on Veterans Health Administration (VHA) prostate cancer imaging use. The multi-level intervention, developed according to the Theoretical Domains Framework (TDF) and Behavior Change Wheel, combines traditional physician behavior change methods with novel methods of communication and data collection. The intervention consists of three components: (1) a system of audit and feedback to clinicians informing individual clinicians and their sites about how their behavior compares to their peers’ and to published guidelines, (2) a program of academic detailing with the goal to educate providers about prostate cancer imaging, and (3) a CPRS Clinical Order Check for potentially guideline-discordant imaging orders. The intervention will be introduced to 10 participating geographically distributed study sites.

Discussion

This study is a significant contribution to implementation science, providing VHA an opportunity to ensure delivery of high-quality care at the lowest cost using a theory-based approach. The study is ongoing. Preliminary data collection and recruitment have started; analysis has yet to be performed.

Trial registration

CliniclTrials.gov NCT03445559. Prospectively registered on February 26, 2018
Differential enrichment of H3K9me3 at annotated satellite DNA repeats in human cell lines and during fetal development in mouse
Authors: Vojvoda Zeljko Tanja , Ugarković Đurđica , Pezer Željka
Published: October 2021

Background

Trimethylation of histone H3 on lysine 9 (H3K9me3) at satellite DNA sequences has been primarily studied at (peri)centromeric regions, where its level shows differences associated with various processes such as development and malignant transformation. However, the dynamics of H3K9me3 at distal satellite DNA repeats has not been thoroughly investigated.

Results

We exploit the sets of publicly available data derived from chromatin immunoprecipitation combined with massively parallel DNA sequencing (ChIP-Seq), produced by the The Encyclopedia of DNA Elements (ENCODE) project, to analyze H3K9me3 at assembled satellite DNA repeats in genomes of human cell lines and during mouse fetal development. We show that annotated satellite elements are generally enriched for H3K9me3, but its level in cancer cell lines is on average lower than in normal cell lines. We find 407 satellite DNA instances with differential H3K9me3 enrichment between cancer and normal cells including a large 115-kb cluster of GSATII elements on chromosome 12. Differentially enriched regions are not limited to satellite DNA instances, but instead encompass a wider region of flanking sequences. We found no correlation between the levels of H3K9me3 and noncoding RNA at corresponding satellite DNA loci. The analysis of data derived from multiple tissues identified 864 instances of satellite DNA sequences in the mouse reference genome that are differentially enriched between fetal developmental stages.

Conclusions

Our study reveals significant differences in H3K9me3 level at a subset of satellite repeats between biological states and as such contributes to understanding of the role of satellite DNA repeats in epigenetic regulation during development and carcinogenesis.
Targeting CDC7 potentiates ATR-CHK1 signaling inhibition through induction of DNA replication stress in liver cancer
Authors: Guo Yuchen , Wang Jun , Benedict Bente , Yang Chen , van Gemert Frank , Ma Xuhui , Gao Dongmei , Wang Hui , Zhang Shu , Lieftink Cor , Beijersbergen Roderick L. , te Riele Hein , Qiao Xiaohang , Gao Qiang , Sun Chong , Qin Wenxin , Bernards René , Wang Cun
Published: October 2021

Background

Liver cancer is one of the most commonly diagnosed cancers and the fourth leading cause of cancer-related death worldwide. Broad-spectrum kinase inhibitors like sorafenib and lenvatinib provide only modest survival benefit to patients with hepatocellular carcinoma (HCC). This study aims to identify novel therapeutic strategies for HCC patients.

Methods

Integrated bioinformatics analyses and a non-biased CRISPR loss of function genetic screen were performed to identify potential therapeutic targets for HCC cells. Whole-transcriptome sequencing (RNA-Seq) and time-lapse live imaging were performed to explore the mechanisms of the synergy between CDC7 inhibition and ATR or CHK1 inhibitors in HCC cells. Multiple in vitro and in vivo assays were used to validate the synergistic effects.

Results

Through integrated bioinformatics analyses using the Cancer Dependency Map and the TCGA database, we identified ATR-CHK1 signaling as a therapeutic target for liver cancer. Pharmacological inhibition of ATR or CHK1 leads to robust proliferation inhibition in liver cancer cells having a high basal level of replication stress. For liver cancer cells that are resistant to ATR or CHK1 inhibition, treatment with CDC7 inhibitors induces strong DNA replication stress and consequently such drugs show striking synergy with ATR or CHK1 inhibitors. The synergy between ATR-CHK1 inhibition and CDC7 inhibition probably derives from abnormalities in mitosis inducing mitotic catastrophe.

Conclusions

Our data highlights the potential of targeting ATR-CHK1 signaling, either alone or in combination with CDC7 inhibition, for the treatment of liver cancer.
Dose-response effect of prebiotic ingestion (β-glucans isolated from Saccharomyces cerevisiae) in diabetic rats with periodontal disease
Authors: Azzi Diana Vilela , de Jesus Pereira Andressa Naira , de Oliveira Silva Viviam , de Carvalho Foureaux Renata , Lima Andressa Ribeiro Veiga , Barducci Robson Sfaciotti , Albuquerque Adriana Silva , Reis Gabriel Lasmar , de Oliveira Raphael Ricon , Andrade Eric Francelino , Zangeronimo Márcio Gilberto , Chalfun-Júnior Antonio , Pereira Luciano José
Published: October 2021

Background

Periodontal disease is one of the most frequent comorbidities in diabetic patients and can contribute to poor blood glucose control.

Objective

To evaluate the effects of ingesting different doses of beta-glucans (BG) isolated from Saccharomyces cerevisiae on alveolar bone loss (ABL) and inflammatory/metabolic parameters in normal and diabetic rats with ligature-induced periodontal disease (PD).

Design

Sixty male rats were assigned into two groups: non-diabetic or diabetic (i.p. 70 mg/kg streptozotocin) with PD. Then, groups were subdivided into five subgroups according BG doses: 0 mg/Kg; 10 mg/Kg; 20 mg/Kg; 40 mg/Kg or 80 mg/Kg. Animals received BG for 28 days and ligatures were placed on lower first molars during the last 14 days.

Results

ABL of diabetic and non-diabetic animals receiving BG 40 mg/kg (1.33 ± 0.03 mm and 0.77 ± 0.07 mm, respectively) and 80 mg/kg (1.26 ± 0.07 mm and 0.78 ± 0.05 mm, respectively) doses was lower (p < 0.05) in comparison to respective controls (1.59 ± 0.11 mm and 0.90 mm ±0.08). COX-2 (Control: 1.66 ± 0.12; 40 mg/kg: 1.13 ± 0.07; 80 mg/kg: 0.92 ± 0.18) and RANKL expressions (Control: 1.74 ± 0.34; 40 mg/kg: 1.03 ± 0.29 ;80 mg/kg: 0.75 ± 0.21), together with the RANKL/OPG ratio (Control: 1.17 ± 0.08; 40 mg/kg: 0.67 ± 0.09; 80 mg/kg: 0.63 ± 0.28) were attenuated above the same dose (p < 0.05). BG did not influence (p > 0.05) metabolic parameters in non-diabetic rats. In diabetic animals, doses above 40 mg/kg reduced IL-1β (Control: 387 ± 66; 40 mg/kg: 309 ± 27; 80 mg/kg: 300 ± 14) and TNF-α (Control: 229 ± 19; 40 mg/kg: 128 ± 53; 80 mg/kg: 71 ± 25), blood glucose levels (Control: 402 ± 49; 40 mg/kg: 334 ± 32; 80 mg/kg: 287 ± 56), total cholesterol (Control: 124 ± 8; 40 mg/kg: 120 ± 10; 80 mg/kg: 108 ± 9), LDL-c + VLDL-c (Control: 106 ± 8; 40 mg/kg: 103 ± 10; 80 mg/kg: 87 ± 10) and triacylglycerols (Control: 508 ± 90; 40 mg/kg: 301 ± 40; 80 mg/kg: 208 ± 61), whereas increased HDL-c (Control: 18 ± 0.5; 40 mg/kg: 19 ± 1; 80 mg/kg: 21 ± 1) (p < 0.05). Optimal dose needed to reduce ABL was higher in diabetic animals with PD.

Conclusions

BG ingestion reduced ABL and improved inflammatory profile in a dose-dependent manner. Best effects were achieved with doses above 40 mg/kg.
RETRACTED ARTICLE: The best drug supplement for obesity treatment: a systematic review and network meta-analysis
Authors: Salari Nader , Jafari Samira , Darvishi Niloofar , Valipour Elahe , Mohammadi Masoud , Mansouri Kamran , Shohaimi Shamarina
Published: October 2021

Background

Obesity is a complex disease with an increasing prevalence worldwide. There are different weight-management options for obesity treatment, including dietary control, exercise, surgery, and medication. Medications are always associated with different responses from different people. More safety and efficacy of drugs with fewer side effects are valuable for any clinical condition. In this systematic review and network meta-analysis, different anti-obesity drugs are compared to identify the most effective drug.

Methods

All relevant studies were extracted by searching national and international databases of SID, MagIran, ProQuest, PubMed, Science Direct, Scopus, Web of Science (WoS), and Google Scholar without time limit until October 2020. Finally, the meta-analysis was performed with the 11 remaining studies containing 14 different drug supplements. The standardized mean difference (SMD) was calculated at a 95% confidence interval (CI) to evaluate the effects of each treatment group compared with placebo. A random-effect model was used to evaluate the effect of individual studies on the final result. Heterogeneity and incompatibility of the network were assessed by Cochran’s Q and Higgins I2, and the Net Heat chart, respectively. Data analysis was performed using R software.

Results

Our results showed that there were significant mean effects in people intervened with Phentermine 15.0 mg + Topiramate 92.0 mg, Phentermine 7.5 mg + Topiramate 46.0 mg, Pramlintide, Naltrexone + Bupropion 32, and Liraglutide, with SMD effects size = − 9.1, − 7.4, − 6.5, − 5.9, − 5.35, respectively.

Conclusion

This study was performed to compare the effect of different drugs used for weight loss in obese patients. The most effective drugs for weight loss were phentermine and topiramate, pramlintide, naltrexone, bupropion, and liraglutide compared to placebo treatment, respectively. This study provides new insights into anti-obesity drugs and hopes to shed new light on future research to manage and treat obesity.
Fatal anaphylaxis due to peanut exposure from oral intercourse
Authors: McKibbin Lundy R. , Siu Sidney Kin-Hung , Roberts Hannah T. , Shkrum Michael , Jeimy Samira
Published: October 2021

Background

Intimacy-related allergic reactions, including anaphylaxis, are under-reported due to social stigma, lack of awareness, and misdiagnosis. The differential diagnosis for intimacy-related anaphylaxis is extensive and includes systemic human seminal plasma allergy, exercise-induced anaphylaxis, asthma exacerbation, latex allergy, and transference of food or drug allergens through saliva or seminal fluid.

Case presentation

Two adolescents met on a popular dating phone application. One individual had a long-standing history of asthma and peanut allergy. Although they never kissed, the male with peanut allergy received fellatio, while the other male had eaten peanut butter before they met. During fellatio, the peanut allergic male developed respiratory symptoms, used his bronchodilator, and collapsed. He remained unconscious despite aggressive interventions by emergency personnel called to the site. The clinical history and autopsy results suggested anaphylaxis to peanut allergen exposure from the intimate exposure as the cause of death.

Discussion and conclusions

To date, nearly all reported cases of intimacy-related anaphylaxis involve symptomatic women. This is the first report of intimacy-related anaphylaxis involving men who have sex with men and the first report of potential allergen transfer from oral mucosa to a patient receiving fellatio. Based on the paucity of published cases, death from intimacy-related anaphylaxis is exceedingly rare. Post-mortem analysis is inherently difficult, as an elevated tryptase level has myriad potential causes; nevertheless, the authors suggest that intimacy-related anaphylaxis due to peanut allergy is the most likely diagnosis. With increasing popularity of relationship applications, especially amongst stigmatized populations, this case highlights the importance of allergy awareness and patient education to decrease risk, particularly in the adolescent population, who are already at increased risk of severe anaphylaxis. Especially amongst those participating in intimate activities, disclosure of one’s allergies warrants discussion, as the outcome can be fatal. Our case demonstrates the crucial need for increased advocacy in food allergy, education around intimacy-related anaphylaxis, and the importance of allergy awareness and prevention across all populations.
Inferior vena cava thrombosis during extracorporeal membrane oxygenation: a case report and review of the literature
Authors: Chen YouLian , Chen HuaiSheng , Liu XueYan , Hong ChengYing , Zhang HuaDong
Published: October 2021

Background

Extracorporeal membrane oxygenation (ECMO) is an effective cardiopulmonary support therapy, which can provide temporary cardiopulmonary support for critically ill patients whose condition cannot be reversed by conventional therapy. However, there are many complications in the use of ECMO, such as bleeding, thrombosis, and so on. Among them, inferior vena cava (IVC) thrombosis which can cause pulmonary embolism is a rare complication, which may be life-threatening.

Case presentation

A 75-year-old female patient (Han Chinese ethnicity) with acute heart failure due to acute myocardial infarction in our department was retrospectively analyzed. After regular treatment was unsuccessful, she was treated with venoarterial ECMO (VA-ECMO). After her condition improved, she was withdrawn from ECMO and experienced a complication of IVC thrombosis. Enoxaparin was given immediately for 1 mg/kg every 12 hours hypodermic injection. The thrombus disappeared after anticoagulant therapy. She was discharged on the 60th day. Her level of consciousness returned to normal without residual central nervous system-related complications.

Conclusions

IVC thrombosis is one of the possible serious complications in the process of ECMO therapy. Prevention of thrombosis and optimization of the anticoagulant regimen are the main preventive measures. Anticoagulant therapy is still the main treatment of IVC thrombosis in the process of ECMO therapy. Other interventional strategies need to accumulate clinical experience.
Cerebellar degeneration in primary Sjögren syndrome: a case report
Authors: Chuah Seow Lin , Jobli Ahmad Tirmizi , Wan Sharifah Aishah , Teh Cheng Lay
Published: October 2021

Background

Cerebellar degeneration is a rare and severe presentation of primary Sjögren syndrome. There are few case reports of cerebellar degeneration associated with different autoimmune diseases, especially with systemic lupus erythematosus and neuro-Behcet’s disease. There are only six patients reported worldwide to be affected by cerebellar atrophy associated with primary Sjögren syndrome. In this report, we describe a patient with primary Sjögren syndrome who presented with ataxia due to cerebellar degeneration.

Case presentation

We report the case of a 37-year-old Chinese woman with primary Sjögren syndrome who presented with ataxia over 3 months associated with tremor of the limbs. Magnetic resonance imaging of the brain revealed bilateral cerebellar atrophy. Based on the presence of cerebellar signs with magnetic resonance imaging brain findings, she was diagnosed as cerebellar degeneration secondary to primary Sjögren syndrome. She was treated with methylprednisolone, hydroxychloroquine, and two cycles of monthly intravenous cyclophosphamide. Subsequently, she refused further treatment, and her neurological symptoms remained the same upon the last clinic review. Primary cerebellar degeneration is rarely associated with primary Sjögren syndrome. The pathogenesis of the neurological manifestations in primary Sjögren syndrome is unclear. Treatment involves corticosteroids and immunosuppressive agents with no consensus of a specific therapy for the management of primary Sjögren syndrome with central nervous system involvement.

Conclusions

Cerebellar degeneration is a rare presentation of primary Sjögren syndrome. Early diagnosis and treatment of this condition is needed to ensure a good outcome.
Noncanonical Wnt5a signaling regulates tendon stem/progenitor cells senescence
Authors: Chen Minhao , Li Yingjuan , Xiao Longfei , Dai Guangchun , Lu Panpan , Rui Yunfeng
Published: October 2021

Background

The structural and functional properties of tendon decline with age, and these changes contribute to tendon disorder. Tendon stem/progenitor cells (TSPCs) play a vital role in tendon repair, regeneration and homeostasis maintaining. Although studies have demonstrated that tendon aging is closely associated with the altered TSPCs function on senescence, the cellular and molecular mechanisms of TSPCs senescence remain largely unknown. This study was designed to investigate the role of Wnt5a in TSPCs senescence.

Methods

TSPCs were isolated from 2-month-old and 20-month-old male C57BL/6 mice. The expression of Wnt5a was determined by RNA sequencing, qRT-PCR and western blotting. TSPCs were then treated with Wnt5a shRNA or recombinant Wnt5a or AG490 or IFN-γ or Ror2-siRNA. Western blotting, β-gal staining, qRT-PCR, immunofluorescence staining and cell cycle analysis were used for confirming the role of Wnt5a in TSPCs senescence.

Results

We found a canonical to noncanonical Wnt signaling shift due to enhanced expression of Wnt5a in aged TSPCs. Functionally, we demonstrated that inhibition of Wnt5a attenuated TSPCs senescence, age-related cell polarity and the senescence-associated secretory phenotype (SASP) expression in aged TSPCs. Mechanistically, the JAK–STAT signaling pathway was activated in aged TSPCs, while Wnt5a knockdown inhibited the JAK–STAT signaling pathway, suggesting that Wnt5a modulates TSPCs senescence via JAK–STAT signaling pathway. Moreover, knockdown of Ror2 inhibited Wnt5a-induced activation of the JAK–STAT signaling pathway, which indicates that Wnt5a potentiates JAK–STAT signaling pathway through Ror2, and Ror2 acts as the functional receptor of Wnt5a in TSPCs senescence.

Conclusion

Our results demonstrate a critical role of noncanonical Wnt5a signaling in TSPCs senescence, and Wnt5a could be an attractive therapeutic target for antagonizing tendon aging.
In search of sex-related mediators of affective illness
Authors: Sikes-Keilp Christopher , Rubinow David R.
Published: October 2021

Sex differences in the rates of affective disorders have been recognized for decades. Studies of physiologic sex-related differences in animals and humans, however, have generally yielded little in terms of explaining these differences. Furthermore, the significance of these findings is difficult to interpret given the dynamic, integrative, and highly context-dependent nature of human physiology. In this article, we provide an overview of the current literature on sex differences as they relate to mood disorders, organizing existing findings into five levels at which sex differences conceivably influence physiology relevant to affective states. These levels include the following: brain structure, network connectivity, signal transduction, transcription/translation, and epigenesis. We then evaluate the importance and limitations of this body of work, as well as offer perspectives on the future of research into sex differences. In creating this overview, we attempt to bring perspective to a body of research that is complex, poorly synthesized, and far from complete, as well as provide a theoretical framework for thinking about the role that sex differences ultimately play in affective regulation. Despite the overall gaps regarding both the underlying pathogenesis of affective illness and the role of sex-related factors in the development of affective disorders, it is evident that sex should be considered as an important contributor to alterations in neural function giving rise to susceptibility to and expression of depression.
Classifying natural products from plants, fungi or bacteria using the COCONUT database and machine learning
Authors: Capecchi Alice , Reymond Jean-Louis
Published: October 2021

Natural products (NPs) represent one of the most important resources for discovering new drugs. Here we asked whether NP origin can be assigned from their molecular structure in a subset of 60,171 NPs in the recently reported Collection of Open Natural Products (COCONUT) database assigned to plants, fungi, or bacteria. Visualizing this subset in an interactive tree-map (TMAP) calculated using MAP4 (MinHashed atom pair fingerprint) clustered NPs according to their assigned origin (https://tm.gdb.tools/map4/coconut_tmap/), and a support vector machine (SVM) trained with MAP4 correctly assigned the origin for 94% of plant, 89% of fungal, and 89% of bacterial NPs in this subset. An online tool based on an SVM trained with the entire subset correctly assigned the origin of further NPs with similar performance (https://np-svm-map4.gdb.tools/). Origin information might be useful when searching for biosynthetic genes of NPs isolated from plants but produced by endophytic microorganisms.
Two fungal flavonoid-specific glucosidases/rutinosidases for rutin hydrolysis and rutinoside synthesis under homogeneous and heterogeneous reaction conditions
Authors: Kotik Michael , Javůrková Hana , Brodsky Katerina , Pelantová Helena
Published: October 2021

The glycosidases within GH5-23 cleave the glycosidic bond of β-glucosylated or rutinosylated flavonoids. Moreover, by virtue of their transglycosylation activity, glycoconjugates with glucosyl and rutinosyl moieties are accessible. Here we report the biochemical characterization and biotechnological assessment of two heterologously expressed members of GH5-23—McGlc fromMucor circinelloidesandPcGlc fromPenicillium chrysogenum. Both enzymes exhibited the highest hydrolytic activities with quercetin-3-β-O-glucopyranoside, whereas lower specificity constants were determined with the rutinosides narcissin, rutin and hesperidin. High stabilities against thermal, ethanol and dimethyl sulfoxide-induced inactivation, a very limited secondary hydrolysis of the formed transglycosylation products, and no detectable product inhibition were additional features appropriate for biotechnological applications. The enzymes were compared in their efficiencies to hydrolyze rutin and to synthesize 2-phenylethyl rutinoside under homogeneous and heterogeneous reaction conditions using high rutin concentrations of 100 and 300 mM. Highest transglycosylation efficiencies were achieved with fully dissolved rutin in reaction mixtures containing 25% dimethyl sulfoxide. Molecular docking and multiple sequence alignments suggest that the hydrophobic environment of aromatic residues within the + 1 subsite of GH5-23 glycosidases is very important for the binding of flavonoid glucosides and rutinosides.
Existence uniqueness of mild solutions for ψ-Caputo fractional stochastic evolution equations driven by fBm
Authors: Yang Min
Published: October 2021

In this paper, we investigate the existence uniqueness of mild solutions for a class of ψ-Caputo fractional stochastic evolution equations with varying-time delay driven by fBm, which seems to be the first theoretical result of the ψ-Caputo fractional stochastic evolution equations. Alternative conditions to guarantee the existence uniqueness of mild solutions are obtained using fractional calculus, stochastic analysis, fixed point technique, and noncompact measure method. Moreover, an example is presented to illustrate the effectiveness and feasibility of the obtained abstract results.
Elliptic problem driven by different types of nonlinearities
Authors: Choudhuri Debajyoti , Repovš Dušan D.
Published: October 2021

In this paper we establish the existence and multiplicity of nontrivial solutions to the following problem: $$\begin{aligned} \begin{aligned} (-\Delta )^{\frac{1}{2}}u+u+\bigl(\ln \vert \cdot \vert * \vert u \vert ^{2}\bigr)&=f(u)+\mu \vert u \vert ^{- \gamma -1}u,\quad \text{in }\mathbb{R}, \end{aligned} \end{aligned}$$

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, f is a function with a certain type of growth. We prove the existence of a nontrivial solution at a certain mountain pass level and another ground state solution when the nonlinearity f is of exponential critical growth.