bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging features of β-catenin-activated hepatocellular adenoma with weak β-catenin activation: A rare case report
Authors: Minamiguchi Kiyoyuki , Marugami Nagaaki , Uchiyama Tomoko , Kusano Hironori , Yasuda Satoshi , Sho Masayuki , Tanaka Toshihiro
Published: November 2022

We report valuable imaging findings in a case of β-catenin-activated hepatocellular adenoma (β-HCA) with weak β-catenin activation. A 40 year-old female presented with a liver tumor in S8 that was incidentally detected on ultrasonography. The tumor showed marked enhancement and early venous drainage into the middle hepatic vein in the arterial phase of contrast-enhanced computed tomography (CT). The tumor revealed slight hypointensity in the hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI). Six months after detection, the tumor had increased in size and a biopsy indicated hepatocellular carcinoma. The tumor was resected and pathologically diagnosed as β-HCA with weak β-catenin activation such as exon 3 S45 mutation and exon 7/8 mutation. Marked enhancement in the arterial phase of CT and MRI is a characteristic finding of β-HCA with weak β-catenin activation. Furthermore, the degree of β-catenin activation might determine the signal intensity of β-HCA in the hepatobiliary phase of EOB-MRI.
Marketisation policies in the neoliberal era: How culture and governance structures affect the introduction of market principles in local care policies
Authors: Och Ralf , Pfau-Effinger Birgit
Published: November 2022

Confronted with the problem of ageing populations since the 1990s, many European welfare states have massively expanded public support for the care of the elderly. This expansion occurred during the neoliberal era in which the marketisation of social services was high on European countries’ political agendas. There are many studies concerned with cross-national differences between national policies regarding the marketisation of care, but little comparative research has been carried out at the local level. This article is innovative in that it explores the role of welfare cultures and local governance structures in local policies regarding the marketisation of long-term care (LTC). We present the findings of a historical comparative case study of four medium-sized cities in Germany for the period 1995–2007. Our empirical study took a multi-level approach to exploring the extent to which the central German state affords local governments operational autonomy for LTC marketization, then analysed the differences in local policies regarding LTC marketisation. According to our findings, German LTC policies are rather centralised and afford local governments operational autonomy towards marketisation only in a few fields. In these fields, local LTC policies differ substantially between eastern and western German cities. We find that differences in the relevant political actors’ main cultural ideas and in local governance structures contribute to this variation, whereas the financial and demographic differences that were analysed do not.
Identification of the Apex of the Medial Longitudinal Arch Break in Progressive Collapsing Foot Disorder
Authors: Weigelt Lizzy , Philpott Matthew , Kelly Gerry , Kasture Sarang P. , Mason Lyndon W. , Molloy Andrew P.
Published: November 2022

Category:

Midfoot/Forefoot

Introduction/Purpose:

Progressive Collapsing Foot Disorder (PCFD) is caused by failure of both dynamic and static structures. The aim of this study was to identify the anatomical location of the medial longitudinal arch break in symptomatic flat foot deformity and analyze its relationship with Meary's angle.

Methods:

We analyzed weight-bearing radiographs of 81 patients [mean age 53.7 years (range, 18-81) with 101 flat feet. The apex of the medial arch break was determined on the lateral foot radiographs as the intersection of the anatomical axis of the talus and the first metatarsal. Therefore, the overall centre of rotation of angulation (CORA) of the medial arch break was documented as the angle at its apex (Meary's angle). Each separate joint angulation was then calculated to determine if the overall CORA was made of separate CORAs. Correlations between the apex location, and the number of apices, with Meary's angle were conducted.

Results:

There was an isolated apex of deformity in 50.4% (51/101) of cases. These were localised at talonavicular joint (TNJ) in 47% (24/51), the naviculocuneiform joint (NCJ) in 52.9% (27/51) and none at the cuneiform-first metatarsal joint (C-1MTJ). The remaining 49.5% (50/101) had combination apices with the primary deformity being at TNJ in 58% (29/50), the NCJ in 40% (20/50), and 2% (1/50) at the C-1MTJ. The mean Meary's angle was -17.9° for isolated and -18° for combination which was not statistically significant (p=0.92). There was no statistical difference in the talonavicular uncoverage angle between the single and combination apices group (p= 0.99).

Conclusion:

The apex of the medial arch break occurs distal to the talonavicular joint in the majority of cases, and thereby the main insertion points of the posterior tibial tendon and spring ligament. In 52.9% (27/51) of cases, the deformity occurs solely distal to the TNJ and in 58% (29/50) cases, it involves joints in addition to the TNJ. These will involve pathology of other structures, including the naviculocuneiform ligament. Surgical strategies in successfully correcting Progressive Collapsing Foot Disorder will therefore need to address joints distal to the TNJ in the majority of cases.
Racial Disparities in Early Adverse Events and Unplanned Readmission after Open Fixation of Below- Knee Fractures
Authors: Xu Amy L. , Raad Micheal , Shafiq Babar , Srikumaran Umasuthan , Aiyer Amiethab A.
Published: November 2022

Category:

Trauma; Ankle; Hindfoot; Other

Introduction/Purpose:

Race-based differences in the surgical management of hip fractures are well-established. Studies assessing these disparities for below-knee fractures have yet to be conducted despite their high volume. Our purpose was to determine whether 1) early postoperative complications and 2) time to surgery for operative fixation of below-knee fractures differ for black versus white patients, and to assess whether disparities exist between fracture subtypes.

Methods:

The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was queried for patients (>=18 years) undergoing open fixation of below-knee fractures between 2010-2019. This yielded 9,172 patients; 1,120 (12%) were black. We collected patient demographics and preoperative risk factors. Primary outcomes were 30-day postoperative complications and time to surgical fixation. Fractures were further subclassified as tibia and/or fibula shaft, isolated malleolar, bi/trimalleolar, and pilon fractures. Nearest-neighbor propensity score matching in a 1:1 ratio was applied to compare outcomes by race. Alpha = 0.05.

Results:

After matching, we identified 1,120 white patients with equal propensity scores as our black patients. Black patients had 1.5 times higher odds (95% confidence interval [CI]: 1.0-2.0) of experiencing any early adverse event when compared with matched white counterparts. Blacks also had 1.9 times higher odds (95% CI: 1.2-3.0) of requiring unplanned readmission within 30 days of operative fixation. Fifty-eight black patients (5.3%) required short-term readmission, compared with 351 white patients (4.5%) - 32 (2.9%) in the matched cohort. The most common reasons for readmission were wound, gastrointestinal, thromboembolic, and recurrent musculoskeletal complications for both races. There were no significant differences by race in time to surgery. Fracture subtype was not associated with postoperative complications or time to surgery in the multivariable analysis.

Conclusion:

Racial disparities in the early postoperative course after open fixation of below-knee fractures exist, with significantly higher rates of early adverse events and unplanned readmission for black versus white patients that persist after propensity matching. These trends may be secondary to a host of community- and hospital-level factors, illustrating the importance of interventions that consider the differences between hip and non-hip fractures and increase resources to vulnerable areas.
The Biomechanical Burden of Orthopaedic Procedures and Musculoskeletal Injuries Sustained by Surgeons: A Systematic Review
Authors: Xu Amy L. , Covarrubias Oscar , Yakkanti Ramakanth , Aiyer Amiethab A.
Published: November 2022

Category:

Other; Trauma

Introduction/Purpose:

Orthopaedic surgeons are at high risk for experiencing work-related musculoskeletal injuries and chronic pain. This is largely due to daily exposure to repetitive large magnitude forces, altered posture from the use of leaded vests, and prolonged standing often in irregular body positions. We sought to synthesize available evidence regarding 1) the biomechanics of orthopaedic surgery and 2) musculoskeletal injuries sustained by orthopaedic surgeons with subsequent treatment and consequences.

Methods:

To conduct this systematic review, we queried four databases (PubMed, Embase, MEDLINE, and Web of Science) for original research studies presenting on the biomechanics of orthopaedic surgery or musculoskeletal injuries sustained by orthopaedic surgeons. Studies were excluded if they were not original research (i.e., reviews) or reported on injuries to patients, non-musculoskeletal injuries, or non-orthopaedic subspecialties. The literature search yielded 3,202 publications, 36 of which were included in the final analysis.

Results:

Eight studies reported on the biomechanics of orthopaedic surgery. Surgeons spent an average 41.6% of time slouched during surgeries. Head and whole spine angles were closest to natural standing position when using a microscope for visualization and with higher surgical field heights. Use of lead aprons resulted in a shifted weight distribution on the forefoot, gain in thoracic kyphosis, and increase in lateral deviation from postural loading. Twenty-eight studies reported on musculoskeletal conditions experienced by orthopaedic surgeons. The overall prevalence of musculoskeletal symptoms or injury involving any body region ranged from 44-97%. Prevalence by body region in decreasing order were as follows: lower back (15.2-89.5%), hip/thigh (4.4- 86.6%), neck (2.4-74%), hand/wrist (10.5-54%), shoulder (7.1-48.5%), elbow (3.1-28.3%), knee/lower leg (7.9-27.4%), and foot/ankle (7-25.7%). Of surgeons with any reported musculoskeletal symptom or injury, 27-65.7% required nonoperative treatment, 3.2- 34.3% required surgery, and 33.3-59.3% indicated that their operative performance was affected.

Conclusion:

The orthopaedic surgeon population experiences a high prevalence of musculoskeletal symptoms and injuries, likely secondary to the biomechanical burdens of tasks required of them during strenuous operations. Ergonomic interventions must be taken within the operating room to reduce this prevalence, increase the physical well-being of orthopaedic surgeons, and reduce the healthcare costs associated with time off work and early retirement as a result of musculoskeletal conditions.
A Preliminary Look at Reasons for Attrition Among Special Educators Teaching Students with Autism Spectrum Disorder
Authors: McFarland-Whisman Jennifer , Whisman Steven , Lockwood Debra
Published: November 2022

Research on teacher retention and attrition suggests that it may be particularly difficult to fill special education positions in rural, economically disadvantaged, high-minority, and urban U.S. schools. Although teacher retention and attrition have received considerable attention in the literature, less is known about the reasons special educators teaching students with autism spectrum disorder (ASD) leave their positions. Using a series of surveys and follow-up phone interviews, the current study sought to provide preliminary information regarding reasons teachers of students with ASD in West Virginia, a predominantly rural, economically disadvantaged state, may leave their positions and identify the supports that may be most influential in assisting them in staying in their positions. Additional directions for research and ways school districts might better support teachers of students with ASD are discussed.
Allogeneic natural killer cell therapy
Authors: Berrien-Elliott Melissa M. , Jacobs Miriam T. , Fehniger Todd A.
Published: November 2022

Interest in adoptive cell therapy for treating cancer is exploding owing to early clinical successes of autologous chimeric antigen receptor (CAR) T lymphocyte therapy. However, limitations using T cells and autologous cell products are apparent as they (1) take weeks to generate, (2) utilize a 1:1 donor-to-patient model, (3) are expensive, and (4) are prone to heterogeneity and manufacturing failures. CAR T cells are also associated with significant toxicities, including cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and prolonged cytopenias. To overcome these issues, natural killer (NK) cells are being explored as an alternative cell source for allogeneic cell therapies. NK cells have an inherent ability to recognize cancers, mediate immune functions of killing and communication, and do not induce graft-versus-host disease, cytokine release syndrome, or immune effector cell–associated neurotoxicity syndrome. NK cells can be obtained from blood or cord blood or be derived from hematopoietic stem and progenitor cells or induced pluripotent stem cells, and can be expanded and cryopreserved for off-the-shelf availability. The first wave of point-of-care NK cell therapies led to the current allogeneic NK cell products being investigated in clinical trials with promising preliminary results. Basic advances in NK cell biology and cellular engineering have led to new translational strategies to block inhibition, enhance and broaden target cell recognition, optimize functional persistence, and provide stealth from patients’ immunity. This review details NK cell biology, as well as NK cell product manufacturing, engineering, and combination therapies explored in the clinic leading to the next generation of potent, off-the-shelf cellular therapies for blood cancers.
Insight into the physiological and pathological roles of the aryl hydrocarbon receptor pathway in glucose homeostasis, insulin resistance, and diabetes development
Authors: Sayed Tahseen S. , Maayah Zaid H. , Zeidan Heba A. , Agouni Abdelali , Korashy Hesham M.
Published: November 2022

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor that mediates the toxicities of several environmental pollutants. Decades of research have been carried out to understand the role of AhR as a novel mechanism for disease development. Its involvement in the pathogenesis of cancer, cardiovascular diseases, rheumatoid arthritis, and systemic lupus erythematosus have long been known. One of the current hot research topics is investigating the role of AhR activation by environmental pollutants on glucose homeostasis and insulin secretion, and hence the pathogenesis of diabetes mellitus. To date, epidemiological studies have suggested that persistent exposure to environmental contaminants such as dioxins, with subsequent AhR activation increases the risk of specific comorbidities such as obesity and diabetes. The importance of AhR signaling in various molecular pathways highlights that the role of this receptor is far beyond just xenobiotic metabolism. The present review aims at providing significant insight into the physiological and pathological role of AhR and its regulated enzymes, such as cytochrome P450 1A1 (CYP1A1) and CYP1B1 in both types of diabetes. It also provides a comprehensive summary of the current findings of recent research studies investigating the role of the AhR/CYP1A1 pathway in insulin secretion and glucose hemostasis in the pancreas, liver, and adipose tissues. This review further highlights the molecular mechanisms involved, such as gluconeogenesis, hypoxia-inducible factor (HIF), oxidative stress, and inflammation.
ALKBH5 in mouse testicular Sertoli cells regulates Cdh2 mRNA translation to maintain blood–testis barrier integrity
Authors: Cai Zhonglin , Zhang Yao , Yang Lin , Ma Chunhui , Fei Yi , Ding Jing , Song Wei , Tong Wei-Min , Niu Yamei , Li Hongjun
Published: November 2022

Background

RNA N6-methyladenosine (m6A) is involved in mammalian spermatogenesis. In both germ cells and Leydig cells, ALKBH5 regulates spermatogenesis and androgen synthesis in an m6A-dependent manner. However, it is unclear whether ALKBH5 plays a role in testicular Sertoli cells, which constitute the blood–testis barrier (BTB) through cell junctions between adjacent Sertoli cells.

Methods

ALKBH5 expression in the testes of humans and mice was detected by immunohistochemical staining and immunofluorescence staining. BTB integrity was evaluated by BTB assay. m6A-seq was performed to screen for BTB-related molecules regulated by ALKBH5. m6A immunoprecipitation–quantitative real-time polymerase chain reaction (qPCR), RNA immunoprecipitation–qPCR, western blot, coimmunoprecipitation, and polysome fractionation–qPCR analyses were performed to explore the mechanisms of ALKBH5 in BTB. Transmission electron microscopy was applied to observe the BTB ultrastructure.

Results

ALKBH5 in Sertoli cells is related to the integrity of the BTB. Subsequently, the m6A level on Cdh2 mRNA, encoding a structural protein N-cadherin in the BTB, was found to be regulated by ALKBH5. IGF2BP1/2/3 complexes and YTHDF1 promoted Cdh2 mRNA translation. In addition, we found that basal endoplasmic specialization, in which N-cadherin is a main structural protein, was severely disordered in the testes of Alkbh5-knockout mice.

Conclusions

Our study revealed that ALKBH5 regulates BTB integrity via basal endoplasmic specialization by affecting Cdh2 mRNA translation.
Phylogenomics, plastome structure and species identification in Mahonia (Berberidaceae)
Authors: Tong Ruchang , Gui Chaoxia , Zhang Yu , Su Na , Hou Xiaoqi , Liu Meng , Yang Zhaoping , Kang Bing , Chang Zhaoyang , Jabbour Florian , Zhao Liang
Published: November 2022

Background

Elucidating the phylogenetic relationships within species-rich genera is essential but challenging, especially when lineages are assumed to have been going through radiation events. Mahonia Nutt. (Berberidaceae) is a genus with cosmopolitan distribution, comprising approximately 100 species, two of which are known as Caulis Mahoniae (M. bealei and M. fortunei) with crucial pharmacological significance in Chinese herbal medicine. Mahonia is a taxonomically challenging genus, and intrageneric phylogenetic relationships still need to be explored using genome data. Universal DNA barcodes and floral morphological attributes have limited discriminatory power in Mahonia.

Results

We sequenced 17 representative plastomes and integrated three published plastome data together to conduct comparative and phylogenetic analyses. We found that Mahonia and Berberis share a large IR expansion (~ 12 kb), which is recognized as a typical character of Berberideae. Repeated sequences are revealed in the species of Mahonia, which are valuable for further population genetic studies. Using a comparative plastome analysis, we determined eight hypervariable regions whose discriminative power is comparable to that of the whole plastid genomes. The incongruence of the ITS and the plastome tree topologies may be ascribed to ancestral hybridization events and/or to incomplete lineage sorting. In addition, we suggest that leaf epidermal characters could help to distinguish closely related species in Mahonia.

Conclusions

We propose an integrative approach combining special barcodes and micromorphological traits to circumscribe Mahonia species. The results cast a new light on the development of an integrative method for accurate species circumscription and provide abundant genetic resources for further research on Mahonia.
Construction and validation of a novel Ferroptosis-related gene signature predictive model in rectal Cancer
Authors: Shi Wei-Kun , Liu Yu-Xin , Qiu Xiao-Yuan , Zhou Jing-Ya , Zhou Jiao-Lin , Lin Guo-Le
Published: November 2022

Background

Rectal cancer (RC) is one of the most common malignant tumors. Ferroptosis is an iron-dependent form of cell death, which plays an important role in various cancers. However, the correlation between ferroptosis-related genes (FRGs) and prognosis in RC remains unclear.

Methods

Gene expression data from The Cancer Genome Atlas Rectum adenocarcinoma (TCGA-READ) and GSE87211 were downloaded. Clustering and functional enrichment were evaluated. A FRGs risk score was established based on the univariate Cox analysis and the Least absolute shrinkage and selection operator (LASSO) analysis. K-M analysis and ROC analysis were conducted to determine prognostic values. qRT-PCR was performed to validate levels of mRNA expression. Multivariate Cox analysis was used to build a prognostic prediction model based on the risk score.

Results

Based on FRGs, RC patients were grouped into two clusters. In the functional enrichment of differentially expressed genes between the two clusters, immune-related pathways dominated. A novel FRGs signature with 14 genes related to the overall survival (OS) of RC was established. qRT-PCR of the 14 genes identified TP63, ISCU, PLIN4, MAP3K5, OXSR, FANCD2 and ATM were overexpressed in RC tissue; HSPB1, MAPK1, ABCC1, PANX1, MAPK9 and ATG7 were underexpressed; TUBE1 had no difference. The high-risk group had a significantly lower OS than the low-risk group (P < 0.001), and ROC curve analysis confirmed the signature’s predictive capacity. Multivariate analysis demonstrated that the risk score and age were independent prognostic factors.

Conclusion

A novel FRGs model can be used to predict the prognosis in RC, as well as to guide individual treatment.
Atrial-His bundle pacing in fulminant myocarditis with ventricular arrhythmia: a case report
Authors: Jiang Limeng , Wang Liangguo , Zhao Chuhuan , Zhou Xi , Hong Xia , Feng Xiafei , Xu Lei , Wu Shengjie , Chung Roy , Huang Weijian , Su Lan
Published: November 2022

Background

Fulminant myocarditis is a clinical syndrome associated with threatening dysrhythmia which temporary pacemaker can be used for life-saving support. As a method of physiological pacing, His bundle pacing (HBP) maintain better cardiac synchronization than traditional right ventricular (RV) pacing.

Case presentation

It’s a severe case of fulminant myocarditis in a 41-year-old patient who presented for recurrent arrhythmias with hemodynamic instability. Temporary His bundle pacing combined with optimal medical therapy and extracorporeal membrane oxygenators (ECMO) supported him through his critical period of hospitalization.

Conclusions

During 1-year follow up, the cardiac function recovery was obvious without any pacing related complications. Echocardiography showed better atrioventricular and intra-ventricular synchronization during HBP in DDD mode. This is the first reported case of temporary His-purkinje conduction system pacing used for severe fulminant myocarditis.
Multivariate analysis of independent determinants of ADL/IADL and quality of life in the elderly
Authors: Beltz Sebastian , Gloystein Simone , Litschko Thomas , Laag Sonja , van den Berg Neeltje
Published: November 2022

Background

This study evaluated the determinants of disability and quality of life in elderly people who participated at the multi-centred RubiN project (Regional ununterbrochen betreut im Netz) in Germany.

Methods

Baseline data of the subjects aged 70 years and older of the RubiN project were used and only subjects with complete data sets were considered for the ensuing analysis (complete case analysis (CCA)).

Disability was examined using the concepts of ADL (activities of daily living) and IADL (instrumental activities of daily living). Subjects exhibiting one or more deficiencies in ADL respectively IADL were considered as ADL respectively IADL disabled. Quality of life was assessed using the WHOQOL-BREF and the WHOQOL-OLD. Applying multivariate analysis, sociodemographic factors, psychosocial characteristics as well as the functional, nutritional and cognitive status were explored as potential determinants of disability and quality of life in the elderly.

Results

One thousand three hundred seventy-five subjects from the RubiN project exhibited data completeness regarding baseline data. ADL and IADL disability were both associated with the respective other construct of disability, sex, a reduced cognitive and functional status as well as domains of the WHOQOL-BREF. Furthermore, ADL disability was related to social participation, while IADL disability was linked to age, education and social support. Sex, ADL and IADL disability, income, social support and social participation as well as the functional status were predictors of the domain ‘Physical Health’ (WHOQOL-BREF). The facet ‘Social Participation’ (WHOQOL-OLD) was affected by both ADL and IADL disability, income, social participation, the nutritional and also the functional status.

Conclusions

Several potential determinants of disability and quality of life were identified and confirmed in this study. Attention should be drawn to prevention schemes as many of these determinants appear to be at least partly modifiable.
Laparoscopic vs. open procedure for intermediate‑ and high‑risk endometrial cancer: a minimum 4-year follow-up analysis
Authors: Zhou Xing , Wei Sitian , Shao Qingchun , Zhang Jun , Zhao Rong , Shi Rui , Zhang Wei , Dong Kejun , Shu Wan , Wang Hongbo
Published: November 2022

Background

The long-term oncologic outcomes after laparoscopic and open procedures for patients with intermediate‑ and high‑risk endometrial cancer (EC) remain unclear. Accordingly, laparoscopy cannot still be recommended as the standard choice for intermediate‑ and high‑risk EC. This retrospective study aimed to assess the perioperative and long-term oncologic outcomes of laparoscopy and open surgery in patients with intermediate- and high‑risk ECs within a minimum 4-year follow-up.

Methods

We included 201 patients who underwent laparoscopic or open procedures for intermediate‑ and high‑risk EC between 2010 and 2017. Between-procedure comparisons of perioperative and oncological outcomes were performed using the independent t-test or Pearson’s chi-squared test and the Kaplan–Meier method, respectively.

Results

Finally, there were 136 intermediate‑ and 65 high‑risk endometrial tumors in the laparoscopic and open groups, respectively. There were no between-group differences in all baseline characteristics. Compared with the open group, the laparoscopic group had a significantly longer mean operating time (p = 0.005) and a lower mean estimated blood loss (EBL) (p = 0.031). There was a higher possibility of postoperative complication in the open group than in the laparoscopic group (p = 0.048). There were no significant between-group differences in pathological outcomes as well as the recurrence-free survival and overall survival rates (p = 0.626 and p = 0.148, respectively).

Conclusions

Among patients with intermediate‑ and high‑risk EC, laparoscopic surgery has an advantage over the open surgery in reducing EBL and the rate of postoperative complications without weakening the oncological control. There were no between-procedure differences in the recurrence-free and overall survival rates.
Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway
Authors: Li Min-yan , Qin Yan-qin , Tian Yan-ge , Li Kang-chen , Oliver Brian G. , Liu Xue-fang , Zhao Peng , Li Jian-sheng
Published: November 2022

Background

Effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) demonstrates positive effects on stable chronic obstructive pulmonary disease (COPD).

Purpose

To investigate the mechanisms of ECC-BYF III on COPD rats from the aspect of airway epithelial cell senescence.

Methods

COPD model rats (Sprague-Dawley rat) were treated with ECC-BYF III for 8 weeks, and the efficacy was evaluated. Cigarette smoke extract (CSE)-induced senescence model of airway epithelial cells was treated with ECC-BYF III, and related enzymes and proteins involved in oxidative stress and mitophagy were detected.

Results

ECC-BYF III markedly rescued pulmonary function and histopathological changes, which might be associated with the amelioration of lung senescence, including the reduction of malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 levels, increase of the level in total superoxide dismutase (T-SOD), and decease in the p21 level in the airways. Furthermore, ECC-BYF III suppressed p16 and p21 expressions and senescence-associated β-galactosidase (SA-β-Gal) in CSE-induced airway epithelial cells. Moreover, ECC-BYF III upregulated mitophagy-related proteins, including the co-localizations of TOM20 and LC3B, PINK1 and PARK2, and improved mitochondrial function by upregulating mitochondrial mitofusin (MFN)2 and reducing dynamin-related protein 1 (DRP1) expression. ECC-BYF III enhanced the activities of T-SOD and GSH-PX by up-regulating NRF2, thus inhibiting oxidative stress. After intervention with NRF2 inhibitor, the regulation effects of ECC-BYF III on oxidative stress, mitophagy and senescence in airway epithelial cells were significantly suppressed.

Conclusions

ECC-BYF III exerts beneficial effects on COPD rats by ameliorating airway epithelial cell senescence, which is mediated by inhibiting oxidative stress and subsequently enhancing mitophagy through the activation of NRF2 signaling.
Surgical sequence in anterior column realignment with posterior osteotomy is important for degree of adult spinal deformity correction: advantages and indications for posterior to anterior sequence
Authors: Kim Sung-Min , Kim Yong-Chan , Kim Ki-Tack , Ha Kee-Yong , Luo Qiang , Li Xiongjie , Park JunBum
Published: November 2022

Background

We hypothesized that posterior osteotomy prior to ACR (Anterior column realignment) through P-A-P surgical sequence would permit a greater correction for deformity corrective surgery than the traditional A-P sequence without posterior osteotomy. This study aimed to determine the impact of the P-A-P sequence on the restoration of lumbar lordosis (LL) compared to the A-P sequence in deformity corrective surgery for adult spinal deformity (ASD) patients and to identify the characteristics of patients who require this sequence. 

Methods

Between 2017 and 2019, 260 ASD patients who had undergone combined corrective surgery were reviewed retrospectively. This study included 178 patients who underwent posterior osteotomy before the ACR (P-A group) and 82 patients who underwent the A-P sequence (A-P group). Sagittal spinopelvic parameters were determined from pre- and postoperative whole-spine radiographs and compared between the groups. To find better indications for the P-A-P sequence, we conducted additional analysis on postoperative outcomes of patients in the A-P group. 

Results

The P-A group showed a significantly higher change in LL (53.7° vs. 44.3°, p < 0.001), C7 sagittal vertical axis (C7 SVA: 197.4 mm vs. 146.1 mm, p = 0.021), segmental lordosis (SL) L2/3 (16.2° vs. 14.4°, p = 0.043), SL L3/4 (16.2° vs. 13.8°, p = 0.004), and SL L4/5 (15.1° vs. 11.3°, p = 0.001) compared to the A-P group. At the final follow-up, pelvic incidence (PI) minus LL mismatch (PI − LL mismatch) was significantly higher in the A-P group (13.4° vs. 2.9°, p < 0.001). Stepwise logistic regression analysis showed that age ≥ 75 years (odds ratio [OR] = 2.151; 95% confidence interval [CI], 1.414–3.272; p < 0.001), severe osteoporosis (OR = 2.824; 95% CI, 1.481–5.381; p = 0.002), rigid lumbar curve with dynamic changes in LL < 10° (OR = 5.150; 95% CI, 2.296–11.548; p < 0.001), and severe facet joint osteoarthritis (OR = 4.513; 95% CI, 1.958–10.402; p < 0.001) were independent risk factors for PI − LL mismatch ≥ 10° after A-P surgery.

Conclusion

P-A-P sequence for deformity corrective surgery in ASD offers greater LL correction than the A-P sequence. Indications for the procedure include patients aged ≥ 75 years, severe osteoporosis, rigid lumbar curve with dynamic change in LL < 10°, or more than four facet joints of Pathria grade 3 in the lumbar region.
Electronic informed consent criteria for research ethics review: a scoping review
Authors: Yusof Mohd Yusmiaidil Putera Mohd , Teo Chin Hai , Ng Chirk Jenn
Published: November 2022

Background

The research shows a growing trend in using an electronic platform to supplement or replace traditional paper-based informed consent processes. Instead of the traditionally written informed consent document, electronic informed consent (eConsent) may be used to assess the research subject’s comprehension of the information presented. By doing so, respect for persons as one of the research ethical principles can be upheld. Furthermore, these electronic methods may reduce potential airborne infection exposures, particularly during the pandemic, thereby adhering to the beneficence and nonmaleficence principle. This scoping review aims to identify the ethics related criteria that have been included in electronic informed consent processes and to synthesize and map these criteria to research ethics principles, in order to identify the gaps, if any, in current electronic informed consent processes.

Methods

The search was performed based on internet search and three main databases: PubMed, SCOPUS and EBSCO. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation guideline was used to report this work.

Results

Of 34 studies that met the inclusion criteria, 242 essential original constructs were collated, and 7 concepts were derived. Digital content showed the highest percentage of collated original constructs (27%, n = 65) followed by accessibility (24%, n = 56), comprehension engagement (18%, n = 43), autonomy (14%, n = 34), confidentiality (11%, n = 25), language (5%, n = 13), and parental consent (1%, n = 2). Twenty-five new items were synthesized for eConsent criteria which may provide guidance for ethical review of research involving eConsent.

Conclusion

The current study adds significant value to the corpus of knowledge in research ethics by providing ethical criteria on electronic informed consent based on evidence-based data. The new synthesized items in the criteria can be readily used as an initial guide by the IRB/REC members during a review process on electronic informed consent and useful to the future preparation of a checklist.
Using the RE-AIM framework to evaluate the implementation of scaling-up the Friendship Bench in Zimbabwe – a quantitative observational study
Authors: Verhey Ruth , Chitiyo Charmaine , Mboweni Sandra , Turner Jean , Murombo Gift , Healey Andy , Chibanda Dixon , Wagenaar Bradley H. , Araya Ricardo
Published: November 2022

Background

This study aimed to evaluate the real-world implementation of the Friendship Bench (FB) – an evidence-based brief psychological intervention delivered by community health workers (CHWs) – three years after its implementation in three city health departments in Zimbabwe. Implementation sites were evaluated according to their current performance using the RE-AIM framework making this one of the first evaluations of a scaled-up evidence-based psychological intervention in sub-Saharan Africa (SSA).

Methods

Using the RE-AIM guide (www.re-aim.org), the authors designed quantitative indicators based on existing FB implementation data. Thirty-six primary health care clinics (PHC) in Harare (n=28), Chitungwiza (n=4) and Gweru (n=4) were included. Among these clinics 20 were large comprehensive health care centers, 7 medium (mostly maternal and child healthcare) and 9 small clinics (basic medical care and acting as referral clinic). Existing data from these clinics, added to additionally collected data through interviews and field observations were used to investigate and compare the performance of the FB across clinics. The focus was on the RE-AIM domains of Reach, Adoption, and Implementation.

Results

Small clinics achieved 34% reach, compared to large (15%) and medium clinics (9%). Adoption was high in all clinic types, ranging from 59% to 71%. Small clinics led the implementation domain with 53%, followed by medium sized clinics 43% and large clinics 40%. Small clinics performed better in all indicators and differences in performance between small and large clinics were significant. Program activity and data quality depends on ongoing support for delivering agents and buy-in from health authorities.

Conclusion

The Friendship Bench program was implemented over three years transitioning from a research-based implementation program to one led locally. The Reach domain showed the largest gap across clinics where larger clinics performed poorly relative to smaller clinics and should be a target for future implementation improvements. Program data needs to be integrated into existing health information systems. Future studies should seek to optimize scale-up and sustainment strategies to maintain effective task-shared psychological interventions in SSA.
Innate immunity, cytokine storm, and inflammatory cell death in COVID-19
Authors: Karki Rajendra , Kanneganti Thirumala-Devi
Published: November 2022

The innate immune system serves as the first line of defense against invading pathogens; however, dysregulated innate immune responses can induce aberrant inflammation that is detrimental to the host. Therefore, careful innate immune regulation is critical during infections. The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in global morbidity and mortality as well as socio-economic stresses. Innate immune sensing of SARS-CoV-2 by multiple host cell pattern recognition receptors leads to the production of various pro-inflammatory cytokines and the induction of inflammatory cell death. These processes can contribute to cytokine storm, tissue damage, and acute respiratory distress syndrome. Here, we discuss the sensing of SARS-CoV-2 to induce innate immune activation and the contribution of this innate immune signaling in the development and severity of COVID-19. In addition, we provide a conceptual framework for innate immunity driving cytokine storm and organ damage in patients with severe COVID-19. A better understanding of the molecular mechanisms regulated by innate immunity is needed for the development of targeted modalities that can improve patient outcomes by mitigating severe disease.
Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination
Authors: Wang Na , Wang Minghui , Jeevaratnam Suren , Rosenberg Cassandra , Ikezu Tadafumi C. , Shue Francis , Doss Sydney V. , Alnobani Alla , Martens Yuka A. , Wren Melissa , Asmann Yan W. , Zhang Bin , Bu Guojun , Liu Chia-Chen
Published: November 2022

Background

Abnormal lipid accumulation has been recognized as a key element of immune dysregulation in microglia whose dysfunction contributes to neurodegenerative diseases. Microglia play essential roles in the clearance of lipid-rich cellular debris upon myelin damage or demyelination, a common pathogenic event in neuronal disorders. Apolipoprotein E (apoE) plays a pivotal role in brain lipid homeostasis; however, the apoE isoform-dependent mechanisms regulating microglial response upon demyelination remain unclear.

Methods

To determine how apoE isoforms impact microglial response to myelin damage, 2-month-old apoE2-, apoE3-, and apoE4-targeted replacement (TR) mice were fed with normal diet (CTL) or 0.2% cuprizone (CPZ) diet for four weeks to induce demyelination in the brain. To examine the effects on subsequent remyelination, the cuprizone diet was switched back to regular chow for an additional two weeks. After treatment, brains were collected and subjected to immunohistochemical and biochemical analyses to assess the myelination status, microglial responses, and their capacity for myelin debris clearance. Bulk RNA sequencing was performed on the corpus callosum (CC) to address the molecular mechanisms underpinning apoE-mediated microglial activation upon demyelination.

Results

We demonstrate dramatic isoform-dependent differences in the activation and function of microglia upon cuprizone-induced demyelination. ApoE2 microglia were hyperactive and more efficient in clearing lipid-rich myelin debris, whereas apoE4 microglia displayed a less activated phenotype with reduced clearance efficiency, compared with apoE3 microglia. Transcriptomic profiling revealed that key molecules known to modulate microglial functions had differential expression patterns in an apoE isoform-dependent manner. Importantly, apoE4 microglia had excessive buildup of lipid droplets, consistent with an impairment in lipid metabolism, whereas apoE2 microglia displayed a superior ability to metabolize myelin enriched lipids. Further, apoE2-TR mice had a greater extent of remyelination; whereas remyelination was compromised in apoE4-TR mice.

Conclusions

Our findings provide critical mechanistic insights into how apoE isoforms differentially regulate microglial function and the maintenance of myelin dynamics, which may inform novel therapeutic avenues for targeting microglial dysfunctions in neurodegenerative diseases.
Effect of combining eight weeks of neuromuscular training with dual cognitive tasks on landing mechanics in futsal players with knee ligament dominance defect: a randomized controlled trial
Authors: Hamoongard Majid , Hadadnezhad Malihe , Abbasi Ali
Published: November 2022

Background

The performing of jump and landing in futsal simultaneous with divided attention is one of the most common mechanisms of non-contact anterior cruciate ligament (ACL) injury. Neuromuscular training has effectively reduced the risk of ACL injury, but the effect of neurocognitive training has received less attention. This study investigated the effect of combining 8 weeks of neuromuscular training with dual cognitive tasks on the landing mechanics of futsal players with knee ligament dominance defects.

Methods

Thirty male futsal players (mean ± SD: age: 21.86 ± 3.27 years) with knee ligament dominance defects were purposefully identified by the tuck jump test and were randomly divided into the intervention and the control group. The intervention group performed dual task (DT) training for three weekly sessions for 8 weeks and 60 min each, while the control group only did activities of daily living. During the drop vertical jump test, 2D landing kinematics in two moments of initial contact (IC) and full flexion (FF) were assessed. Data were analyzed by means of 2 × 2 repeated measures ANOVA followed by post hoc comparison (Bonferroni) at the significance level of (α ≤ 0.05).

Results

A significant improvement was observed in the intervention group compared to the control group for the dynamic knee valgus at IC (F1,28 = 6.33; P = 0.02, ES = 0.31) and FF (F1,28 = 13.47; P = 0.003, ES = 0.49), knee flexion at IC (F1,28 = 20.08; P = 0.001, ES = 0.41) and FF (F1,28 = 13.67; P = 0.001, ES = 0.32), ankle dorsiflexion at IC (F1,28 = 37.17; P = 0.001, ES = 0.72) and FF (F1,28 = 14.52; P = 0.002, ES = 0.50), and trunk flexion at FF (F1,28 = 20.48; P = 0.001, ES = 0.59) angles. Changes in the trunk flexion at IC (F1,28 = 0.54; P = 0.47, ES = 0.03) and trunk lateral flexion at IC (F1,28 = 0.006; P = 0.93, ES = 0.00) and FF (F1,28 = 2.44; P = 0.141, ES = 0.148) angles were not statistically significant.

Conclusions

DT training compared to the control group improved landing mechanics in futsal players with knee ligament dominance defects.

Trial registration: Current Controlled Trials using the IRCT website with ID number IRCT20210602051477N1 prospectively registered on 20/06/2021.
Defb19 regulates the migration of germ cell and is involved in male fertility
Authors: Jin Jing , Li Xiaofeng , Ye Mei , Qiao Feng , Chen Hao , Fok Kin Lam
Published: November 2022

β-defensins are small antimicrobial peptides that play essential roles in male fertility. Although several members of the β-defensin family are preferentially expressed in the testis, their involvement in spermatogenesis remains elusive. In this study, we have characterized the expression and function of Defb19 in mouse testis. Our results showed that Defb19 is expressed in both Sertoli cells and germ cells. Overexpression of Defb19 in the 15P-1 Sertoli cell line decreases the expression of cell junction molecules and promotes the matrix adhesion and migration of Sertoli cells. Recombinant DEFB19 and conditioned medium of Defb19-overexpressed 15P-1 cells promote the migration of GC2-spd spermatocyte cell line. Knockout of Defb19 in mouse by CRISPR/Cas9 resulted in male subfertility with testicular and epididymal atrophy. A marked increase in apoptosis and a significant decrease in the sperm count were observed in the KO mice. Together, our study has uncovered an important role of Defb19 in male fertility by regulating the migration of both the Sertoli cells and the germ cells. Our study has shed new light on the functions of β-defensins in the testis.
Rapid evidence synthesis to enable innovation and adoption in health and social care
Authors: Norman Gill , Wilson Paul , Dumville Jo , Bower Peter , Cullum Nicky
Published: November 2022

Background

The rapid identification and adoption of effective innovations in healthcare is a known challenge. The strongest evidence base for innovations can be provided by evidence synthesis, but this is frequently a lengthy process and even rapid versions of this can be time-consuming and complex. In the UK, the Accelerated Access Review and Academic Health Science Network (AHSN) have provided the impetus to develop a consistently rapid process to support the identification and adoption of high-value innovations in the English NHS.

Methods

The Greater Manchester Applied Research Collaboration (ARC-GM) developed a framework for a rapid evidence synthesis (RES) approach, which is highly integrated within the innovation process of the Greater Manchester AHSN and the associated healthcare and research ecosystem. The RES uses evidence synthesis approaches and draws on the GRADE Evidence to Decision framework to provide rapid assessments of the existing evidence and its relevance to specific decision problems. We implemented this in a real-time context of decision-making around adoption of innovative health technologies.

Results

Key stakeholders in the Greater Manchester decision-making process for healthcare innovations have found that our approach is both timely and flexible; it is valued for its combination of rigour and speed.

Our RES approach rapidly and systematically identifies, appraises and contextualises relevant evidence, which can then be transparently incorporated into decisions about the wider adoption of innovations. The RES also identifies limitations in existing evidence for innovations and this can inform subsequent evaluations. There is substantial interest from other ARCs and AHSNs in implementing a similar process. We are currently exploring methods to make completed RES publicly available. We are also exploring methods to evaluate the impact of using RES as more implementation decisions are made.

Conclusions

The RES framework we have implemented combines transparency and consistency with flexibility and rapidity. It therefore maximises utility in a real-time decision-making context for healthcare innovations.