bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness and cost-effectiveness of MicroShunt implantation versus standard trabeculectomy for open-angle glaucoma (a SIGHT study): study protocol of a multicentre randomised controlled trial
Authors: Scheres Lotte M. J. , van den Biggelaar Frank J. H. M. , Winkens Bjorn , Kujovic-Aleksov Stefani , Müskens Rogier P. H. M. , de Waard Peter W. T. , de Crom Ronald M. P. C. , Ernest Paul J. G. , Pijl Benjamin J. , Ramdas Wishal D. , van Rijn Laurentius J. , Tan Annelie , Dirksen Carmen D. , Beckers Henny J. M.
Published: January 2023

Background

Trabeculectomy is the “gold standard” initial surgical procedure for open-angle glaucoma worldwide. During the last decade, the introduction of less invasive procedures, including new bleb-forming surgery such as the MicroShunt, has altered the approach of glaucoma management. At present, there is insufficient evidence comparing the effectiveness between these procedures nor versus trabeculectomy. Furthermore, there is no data available on patient impact and cost-effectiveness. This study aims to address this gap in evidence and establish whether MicroShunt implantation is non-inferior compared to trabeculectomy with regard to effectiveness and whether it is cost-effective.

Methods

A multicentre, non-inferiority, randomised controlled trial (RCT) studying open-angle glaucoma with an indication for surgery will be conducted. Patients with previous ocular surgery except for phacoemulsification are excluded, as are patients with ocular comorbidity compromising the visual field or requiring a combined procedure. After informed consent is obtained, patients will be randomly allocated to the intervention, a PRESERFLO™ MicroShunt implantation, or the control group, trabeculectomy, using block randomisation (blocks of 2, 4 or 6 patients). In total, 124 patients will be randomised in a 1:1 ratio, stratified by centre. The primary endpoint will be intraocular pressure (IOP) one year after surgery. Secondary outcomes include IOP-lowering medication use, treatment failure, visual acuity, visual field progression, additional interventions, adverse events, patient-reported outcome measures (PROMs), and cost-effectiveness. Study outcomes will be measured up to 12 months postoperatively.

Discussion

This study protocol describes the design of a multicentre non-inferiority randomised controlled trial. To this date, cost-effectiveness studies evaluating the MicroShunt have not been undertaken. This multicentre RCT will provide more insight into whether MicroShunt implantation is non-inferior compared to standard trabeculectomy regarding postoperative IOP and whether MicroShunt implantation is cost-effective.

Trial registration

ClinicalTrials.gov, Identifier: NCT03931564, Registered 30 April 2019.
Mycobacterium infection secondary to exogenous lipoid pneumonia caused by nasal drops: a case report and literature review
Authors: Wang Huihong , Lu Shan , Li Hequan , Wang Yuehong
Published: January 2023

Background

Exogenous lipoid pneumonia (ELP) is a rare disease and its diagnosis is often mistaken or delayed. Secondary infection with rapidly growing non-tuberculous mycobacteria is a rare complication of lipoid pneumonia.

Case presentation

A 38-year-old man presented with fever, cough, sputum, chest tightness, and shortness of breath. He had a 2-year history of allergic rhinitis and used liquid paraffin-containing menthol nasal drops daily. A chest CT scan showed multiple patchy ground glass opacities with blurred borders in both lungs, which were located in the inner pulmonary field and distributed along the bronchi. His ambient air PO2 was 63 mmHg. The patient was diagnosed with ELP by CT-guided lung biopsy. The nasal drops were discontinued, and systemic glucocorticoids were administered. During treatment, the pulmonary lesions deteriorated, and bronchoalveolar lavage was performed during bronchoscopy. Additionally, Mycobacterium abscessus was detected in the lavage fluid. Upon detection of a secondary M. abscessus infection, glucocorticoids were gradually discontinued, and anti-M. abscessus treatment was implemented. The patient’s symptoms rapidly ameliorated. After 11 months of anti-M. abscessus treatment, a repeat CT scan showed clear regression of the lung lesions.

Conclusion

Routine microbiological examination of samples, including sputum or alveolar lavage fluid, is necessary for patients with diagnosed or suspected ELP.
Analysis of the curative effect of cervical spondylotic radiculopathy with osseous foraminal stenosis using ultrasonic osteotome in anterior cervical surgery
Authors: Liu Junlin , Kong Qingquan , Feng Pin , Zhang Bin , Ma Junsong , Hu Yuan
Published: January 2023

Purpose

To explore the clinical efficacy and operation points of cervical radiculopathy with osseous foraminal stenosis treated with ultrasonic osteotome in anterior cervical surgery.

Methods

From January 2018 to June 2021，a retrospective analysis of 23 patients with cervical radiculopathy with bony foraminal stenosis during this period was retrospectively analyzed. Anterior Cervical Discectomy and Fusion (ACDF) was used for all cases in this group. Intraoperative use of ultrasonic osteotome to decompress the nerve in the intervertebral foramina. The operation time, intraoperative blood loss and complication rate were recorded in this group of patients. Interbody fusion was evaluated using Brantigan criteria. The IC-PACS imaging system was used to measure the intervertebral foramen area (IFA) before and after surgery to evaluate the range of decompression. The VAS (Visual Analogue Scale, VAS) score and NDI (Neck Disability Index, NDI) score before and after surgery were recorded to evaluate the clinical efficacy.

Results

All enrolled patients were followed up regularly for 1 year or more. The mean operative time was 61.5 ± 8.0 minutes. The average intraoperative blood loss was 88.3 ± 12.8 ml, and the average hospital stay was 8.1 ± 1.7d. Twenty one cases of successful fusion were followed up 1 year after operation, and the fusion rate was 91.3%. IFA expanded from 25.1 ± 4.0 mm2 before operation to 57.9 ± 3.4 mm2 at 1 year after operation, and the difference was statistically significant (P < 0.001). The VAS score and NDI score of patients 3 days after surgery, 3 months after surgery, and 1 year after surgery were significantly lower than those before surgery (P < 0.001). There was 1 case of dysphagia and 1 case of Cage subsidence after operation, and the complication rate was 8.6%.

Conclusion

Anterior cervical surgery using ultrasonic osteotome in the treatment of cervical radiculopathy with bony foraminal stenosis has reliable clinical efficacy and high safety, and is worthy of clinical promotion.
Association of hospital volume with perioperative and oncological outcomes of robot-assisted laparoscopic radical prostatectomy: a retrospective multicenter cohort study
Authors: Tatenuma Tomoyuki , Ebara Shin , Kawase Makoto , Sasaki Takeshi , Ikehata Yoshinori , Nakayama Akinori , Toide Masahiro , Yoneda Tatsuaki , Sakaguchi Kazushige , Teishima Jun , Inoue Takahiro , Kitamura Hiroshi , Saito Kazutaka , Koga Fumitaka , Urakami Shinji , Koie Takuya , Makiyama Kazuhide
Published: January 2023

Background

This retrospective multicenter cohort study investigated the association of hospital volume with perioperative and oncological outcomes in patients treated with robot-assisted radical prostatectomy (RARP).

Methods

We collected the clinical data of patients who underwent RARP at eight institutions in Japan between September 2012 and August 2021. The patients were divided into two groups based on the treatment site—high- and non-high-volume hospitals. We defined a high-volume hospital as one where RARP was performed for more than 100 cases per year.

Results

After excluding patients who received neoadjuvant therapy, a total of 2753 patients were included in this study. In the high-volume hospital group, console time and estimated blood loss were significantly (p < 0.001) lower than that of the non-high-volume hospital group. However, the continence rate at 3 months after RARP, positive surgical margins, and prostate-specific antigen (PSA)-relapse-free survival showed no significant differences between the two groups. Furthermore, the console time was significantly shorter after 100 cases in the non-high-volume hospital group but not in the high-volume hospital group.

Conclusions

A higher hospital volume was significantly associated with shorter console time and less estimated blood loss. However, oncological outcomes and early continence recovery appear to be comparable regardless of the hospital volume in Japan.
Biochemical characterization and insights into the potency of the acidic Aspergillus niger NRC114 purified α-galactosidase in removing raffinose family oligosaccharides from soymilk yogurt
Authors: Othman Abdelmageed M. , Elshafei Ali M. , Elsayed Maysa A. , Ibrahim Gamil E. , Hassan Mohamed M. , Mehanna Nayra S.
Published: January 2023

Background

Because humans lack α-galactosidase, foods containing certain oligosaccharides from the raffinose family, such as soybeans and other legumes, may disrupt digestion and cause flatulence.

Results

Aspergillus niger NRC114 α-galactosidase was purified using protein precipitation, gel filtration, and ion exchange chromatography steps, which resulted in a 123-fold purification. The purified enzyme was found to be 64 kDa using the SDS-PAGE approach. The optimum pH and temperature of the purified α-galactosidase were detected at pH 3.5 and 60 ºC, respectively. The pure enzyme exhibited potent acidic pH stability at pH 3.0 and pH 4.0 for 2 h, and it retained its full activity at 50 ºC and 60 ºC for 120 min and 90 min, respectively. The enzyme was activated using 2.5 mM of K+, Mg2+, Co2+, or Zn2+ by 14%, 23%, 28%, and 11%, respectively. The Km and Vmax values of the purified enzyme were calculated to be 0.401 µM and 14.65 μmol min−1, respectively. The soymilk yogurt showed an increase in its total phenolic content and total flavonoids after enzyme treatment, as well as several volatile compounds that were detected and identified using GC–MS analysis. HPLC analysis clarified the enzymatic action in the hydrolysis of raffinose family oligosaccharides.

Conclusion

The findings of this study indicate the importance of A. niger NRC114 α-galactosidase enzyme for future studies, especially its applications in a variety of biological fields.
How do carbohydrate quality indices influence on bone mass density in postmenopausal women? A case–control study
Authors: Nouri Mehran , Mahmoodi Marzieh , Shateri Zainab , Ghadiri Marzieh , Rajabzadeh-Dehkordi Milad , Vali Mohebat , Gargari Bahram Pourghassem
Published: January 2023

Background

Carbohydrates are the primary energy source in Asian countries, including Iran. An emerging method can be used to measure the quality of carbohydrates, including the carbohydrate quality index (CQI), which includes a variety of components. Low-carbohydrate diet score (LCDS) has been proposed as a new method of scoring micronutrient intake that could provide a reasonable explanation for the link between diet and the risk of chronic diseases.

Objective

This study aimed to investigate the relationship between CQI, LCDS, glycemic index (GI), glycemic load (GL), insulin load (IL), and insulin index (II) with bone mass density (BMD) in postmenopausal women.

Method

In this case–control study, 131 postmenopausal women with osteoporosis/osteopenia and 131 healthy postmenopausal women aged 45–65 participated. The dual-energy X-ray absorptiometry (DEXA) method measured the BMD of the lumbar vertebrae and femoral neck. A validated semi-quantitative food frequency questionnaire was used to assess dietary intake. Logistic regression were used to evaluate the relation between GI, GL, II, IL, CQI, and LCDS with BMD.

Results

Diets with higher GI increased the risk of osteopenia and osteoporosis, but LCDS and CQI decreased the risk of osteopenia and osteoporosis.

Conclusion

These findings suggest that a higher intake of fruits and vegetables and receiving various dietary vitamins, minerals, and antioxidant compounds may be a useful way to prevent osteopenia in Iranian women.
The role of consumer choice in out-of-pocket spending on health
Authors: Nübler Laura , Busse Reinhard , Siegel Martin
Published: January 2023

Background

Analyses of out-of-pocket healthcare spending often suffer from an inability to distinguish necessary from optional spending in the data without making further assumptions. We propose a two-dimensional rating of the spending categories often available in household budget survey data where we consider the requirement to pay for necessary healthcare as one dimension and the incentive to pay extra for additional services, higher quality options or more convenience as a second dimension to assess the distortionary potential of higher spending for additional healthcare or higher quality options.

Methods

We use three waves of a large German Household Budget Survey and decompose the Kakwani-index of total out-of-pocket healthcare spending into contributions of the eleven spending categories available in our data, across which user charge regulations vary considerably. We compute and decompose Kakwani-indexes for the different spending categories to compare the degrees of regressiveness across them.

Results

The results suggest that categories with higher incentives for additional spending exhibit smaller contributions to the overall regressive effect of total out-of-pocket spending than categories where spending is presumably mostly on necessary and effective care.

Conclusions

Assessing the consumer choice potential of different spending categories is important because extra spending among the better-off may outweigh necessary spending in aggregate expenditure data, and may also hint at potential inequalities in the quality of provided healthcare.
A novel method for the translation and cross-cultural adaptation of health-related quality of life patient-reported outcome measurements
Authors: Teig Catherine J. P. , Bond Malcolm J. , Grotle Margreth , Kjøllesdal Møyfrid , Saga Susan , Cvancarova Milada S. , Ellström Engh Marie A. , Martini Angelita
Published: January 2023

Background

This paper presents a novel methodology for translation and cross-cultural adaptation of health-related quality-of-life patient-reported outcome measures, incorporating the Delphi method. Specifically, we describe the process of translating the Pelvic Floor Distress Inventory-20 and Pelvic Floor Impact Questionnaire-7 from English to Norwegian using this method.

Methods

The multistep translation method combined the European Organization for Research and Treatment of Cancer Quality of Life guidelines, an Expert Panel review, and the Delphi method. It comprised two independent forward- and back-translations. While the bilingual pelvic floor Expert Panel ensured rigorous cross-checking and effective cross-cultural adaptation, the addition of the Delphi method (comprising the attributes of anonymity, controlled feedback, and statistical group response) further established consensus on translated items.

Outcomes

The application of the Delphi method in the Expert Panel phase proved adequate in producing comprehensible intermediate Norwegian versions ready for pilot testing. The Expert Panel reviewed the comments made by patients completing the instruments and offered advice to allow final translated versions to be produced and tested for measurement properties. This iterative approach, internal logic, and anonymity between rounds improved the evaluations that the panel members provided, which in turn enhanced the final translated Patient Reported Outcome Measures (PROMs).

Conclusions

To our knowledge, this work represents the first demonstration of the application of an Expert Panel review incorporating a Delphi method to assess health-related quality-of-life instruments. The controlled feedback approach, iterative nature, internal logic, and anonymity of the Delphi consensus method appeared to ensure a good cross-cultural adaptation of these PROMs.
SLERT, as a novel biomarker, orchestrates endometrial cancer metastasis via regulation of BDNF/TRKB signaling
Authors: Tian Jun , Cheng Hailing , Wang Ning , Wang Chenhui
Published: January 2023

Background

Recent evidence suggests that the box H/ACA small nucleolar RNA (snoRNA)-ended long noncoding RNA (lncRNA), SLERT, plays a critical role in gene regulation. However, its role in cancer remains undetermined. Herein, we explored its implication in human endometrial cancer (EC).

Methods

EC plasma and tissue samples were collected for the detection of SLERT expression using qRT-PCR method. The functional investigation was tested by CCK-8 and transwell assays. Luciferase reporter, RNA pull-down, and immunoprecipitation (RIP) assays were used to determine the regulatory network involved in SLERT. The in vivo effect of SLERT was tested by caudal vein lung metastasis model.

Results

Stable knockdown of SLERT significantly inhibited EC cell (KLE and AN3CA) migration and invasion, while it did not affect cell viability. SLERT induced epithelial-mesenchymal transition (EMT) via elevating N-cadherin and Vimentin and downregulating E-cadherin. Further investigation showed that SLERT directly binds to METTL3, increasing the m6A levels of BDNF mRNA; then, the m6A sites were read by IGF2BP1, enhancing BDNF mRNA stability, followed by the activation of BDNF/TRKB signaling, an inducer of EMT. The animal model showed that overexpression of SLERT increased EC cell lung metastasis, and this effect was effectively blocked by BDNF silencing or treatment with TRKB inhibitor k252a. Clinically, EC patients have high levels of SLERT both in tissue or plasma, which might be used as a biomarker of diagnosis and prognosis.

Conclusion

Our findings, for the first time, uncover the metastasis-promoting effect of SLERT in EC via in vitro and in vivo evidence, providing a potential therapeutic target for metastatic EC treatment.
Jak2/STAT6/c-Myc pathway is vital to the pathogenicity of Philadelphia-positive acute lymphoblastic leukemia caused by P190BCR-ABL
Authors: Qin Run , Wang Teng , He Wei , Wei Wei , Liu Suotian , Gao Miao , Huang Zhenglan
Published: January 2023

Background

The Philadelphia chromosome encodes the BCR-ABL fusion protein, which has two primary subtypes, P210 and P190. P210 and P190 cause Philadelphia-positive chronic myeloid leukemia (Ph+ CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), respectively. The Ph+ ALL is more malignant than Ph+ CML in disease phenotype and progression. This implies the key pathogenic molecules and regulatory mechanisms caused by BCR-ABL in two types of leukemia are different. It is reported that STAT6 was significantly activated only in P190 transformed cells. However, the potential role and the mechanism of STAT6 activation in Ph+ ALL and its activation mechanism by P190 are still unknown.

Methods

The protein and mRNA levels of STAT6, c-Myc, and other molecules were measured by western blot and quantitative real-time PCR. The STAT6 inhibitor AS1517499 was used to specifically inhibit p-STAT6. The effect of p-STAT6 inhibition on Ph+ CML and Ph+ ALL cells was identified by CCK-8 and FCM assay. Dual luciferase reporter and ChIP assay were performed to confirm the direct binding between STAT6 and c-Myc. The impact of STAT6 inhibition on tumor progression was detected in Ph+ CML and Ph+ ALL mouse models.

Results

Our results demonstrated that P210 induced CML-like disease, and P190 caused the more malignant ALL-like disease in mouse models. STAT6 was activated in P190 cell lines but not in P210 cell lines. Inhibition of STAT6 suppressed the malignancy of Ph+ ALL in vitro and in vivo, whereas it had little effect on Ph+ CML. We confirmed that p-STAT6 regulated the transcription of c-Myc, and STAT6 was phosphorylated by p-Jak2 in P190 cell lines, which accounted for the discrepant expression of p-STAT6 in P190 and P210 cell lines. STAT6 inhibition synergized with imatinib in Ph+ ALL cells.

Conclusions

Our study suggests that STAT6 activation plays an essential role in the development of Ph+ ALL and may be a potential therapeutic target in Ph+ ALL.
c-MYC mediates the crosstalk between breast cancer cells and tumor microenvironment
Authors: Gao Fang-yan , Li Xin-tong , Xu Kun , Wang Run-tian , Guan Xiao-xiang
Published: January 2023

The MYC oncogenic family is dysregulated in diverse tumors which is generally linked to the poor prognosis of tumors. The members in MYC family are transcription factors which are responsible for the regulation of various genes expression. Among them, c-MYC is closely related to the progression of tumors. Furthermore, c-MYC aberrations is tightly associated with the prevalence of breast cancer. Tumor microenvironment (TME) is composed of many different types of cellular and non-cellular factors, mainly including cancer-associated fibroblasts, tumor-associated macrophages, vascular endothelial cells, myeloid-derived suppressor cells and immune cells, all of which can affect the diagnosis, prognosis, and therapeutic efficacy of breast cancer. Importantly, the biological processes occurred in TME, such as angiogenesis, immune evasion, invasion, migration, and the recruition of stromal and tumor-infiltrating cells are under the modulation of c-MYC. These findings indicated that c-MYC serves as a critical regulator of TME. Here, we aimed to summarize and review the relevant research, thus to clarify c-MYC is a key mediator between breast cancer cells and TME.
Bafilomycin A1 inhibits SARS-CoV-2 infection in a human lung xenograft mouse model
Authors: Zhang Cuiling , Wei Bingjie , Liu Zirui , Yao Wei , Li Yiquan , Lu Jing , Ge Chenchen , Yu Xiaoyang , Li Dapeng , Zhu Yilong , Shang Chao , Jin Ningyi , Li Xiao
Published: January 2023

Coronavirus disease 2019 is a global pandemic caused by SARS-CoV-2. The emergence of its variant strains has posed a considerable challenge to clinical treatment. Therefore, drugs capable of inhibiting SARS-CoV-2 infection, regardless of virus variations, are in urgently need. Our results showed that the endosomal acidification inhibitor, Bafilomycin A1 (Baf-A1), had an inhibitory effect on the viral RNA synthesis of SARS-CoV-2, and its Beta and Delta variants at the concentration of 500 nM. Moreover, the human lung xenograft mouse model was used to investigate the anti-SARS-CoV-2 effect of Baf-A1. It was found that Baf-A1 significantly inhibited SARS-CoV-2 replication in the human lung xenografts by in situ hybridization and RT-PCR assays. Histopathological examination showed that Baf-A1 alleviated SARS-CoV-2-induced diffuse inflammatory infiltration of granulocytes and macrophages and alveolar endothelial cell death in human lung xenografts. In addition, immunohistochemistry analysis indicated that Baf-A1 decreased inflammatory exudation and infiltration in SARS-CoV-2-infected human lung xenografts. Therefore, Baf-A1 may be a candidate drug for SARS-CoV-2 treatment.
Novel insights into the somatic proteome of Strongyloides stercoralis infective third-stage larvae
Authors: Dishnica Klevia , Piubelli Chiara , Manfredi Marcello , Kondaveeti Ravi Teja , Longoni Silvia Stefania , Degani Monica , Buonfrate Dora , Giorgetti Alejandro , Tiberti Natalia
Published: January 2023

Background

Strongyloidiasis is a neglected tropical disease affecting an estimated 600 million people, particularly in resource-limited settings. The infection can persist lifelong due to unusual auto-infective cycle of Strongyloides stercoralis. The lack of a diagnostic gold standard and limited knowledge of the mechanisms underpinning this chronic infection are key issues in disease management. To date, only a few proteomics studies have been conducted to elucidate the molecular mechanisms associated with Strongyloides parasitism or to highlight novel immunological markers, with the result that our knowledge of S. stercoralis proteome remains limited. This study aims at expanding the characterization of S. stercoralis infective larvae (iL3) in order to further explore the mechanisms of parasitism and to highlight possible novel targets for serodiagnosis.

Methods

iL3 obtained from an infected subject were analysed by high-throughput tandem mass spectrometry. To achieve a more comprehensive characterization of the iL3 proteome we analysed the experimental dataset using an automatic search strategy combined with manual annotation, which included gene ontology (GO) analysis, InterPro annotation, assessment of the homology with Homo sapiens and other pathogens of clinical importance and B-cell epitope prediction.

Results

Our pipeline identified 430 S. stercoralis proteins, 187 (43%) of which were uncharacterized. Oxidoreductases and peptidases were amongst the most represented protein categories, as highlighted by molecular function GO analyses, while membrane and mitochondrial proteins were the most represented cellular component GO categories. A high proportion of proteins bearing the CAP, SCP or thioredoxin domain or belonging to cysteine-rich secretory, transthyretin-like or peptidase protein families were also identified. Additionally, we highlighted nine proteins displaying low homology with H. sapiens or other related pathogens and bearing amino acid sequences with immunogenic properties.

Conclusions

Our comprehensive description and annotation of the S. stercoralis iL3 proteome contribute to expanding the ‘omics characterization of this parasite and provide experimental evidence on the most represented proteins associated with S. stercoralis parasitism, as inferred from genomic and transcriptomic data. Moreover, novel candidate immunogenic proteins to be evaluated as novel serological diagnostic markers are highlighted.

Graphical Abstract
E2F1 combined with LINC01004 super-enhancer to promote hepatocellular carcinoma cell proliferation and metastasis
Authors: Li Jingxuan , Wang Jiying , Wang Yanping , Zhao Xueyan , Su Tao
Published: January 2023

Introduction

Super-enhancer-associated lncRNAs play important roles in the occurrence and development of malignant tumors, including hepatocellular carcinoma (HCC).

Objectives

The current work aimed to identify and characterize super-enhancer-associated lncRNAs in the pathogenesis of HCC.

Methods

H3K27ac ChIP-seq data from HepG2 cell line and two HCC tissues were used to identify super-enhancer-associated lncRNAs in HCC. JQ-1 treatment and CRISPR-dCas9 system were performed to confirm super-enhancer activity. Quantitative real-time PCR (qPCR), ChIP-qPCR, and dual-luciferase reporter system assay demonstrated the regulation of E2F1 on super-enhancer. Functional loss experiment was used to identify the function of LINC01004.

Results

In this study, we identified and characterized LINC01004, a novel super-enhancer-associated lncRNA, as a crucial oncogene in HCC. LINC01004 was upregulated in liver cancer tissues and was associated with poor patient prognosis. Moreover, LINC01004 promoted cell proliferation and metastasis of HCC. The binding of E2F1 to the super-enhancer could promote the transcription of LINC01004, while the inhibition of super-enhancer activity decreased LINC01004 expression.

Conclusion

This finding might provide mechanistic insights into the molecular mechanisms underlying hepatocarcinogenesis and the biological function of super-enhancer. LINC01004 can serve as a potential therapeutic target for HCC patient.

Graphical abstract
The Bakarwals of Jammu and Kashmir and their changing marriage rituals
Authors: Dar Sajad Ahmad
Published: January 2023

The Bakarwals of Jammu and Kashmir are a nomadic pastoral group, notified as a Scheduled Tribe (ST), under the Jammu and Kashmir Scheduled Tribes Act, 1991. Ensuing from ethnographic fieldwork conducted with the Bakarwals in the Jammu and Kashmir region, this paper argues that the traditional marriage practices of the Bakarwals have transformed in the contemporary times with respect to the various processes associated with globalization and the increasing access to the new facilities of mobility. The cultural transactions resulting as a part of liberalization and globalization have led the Bakarwals to associate with modern traditions, rituals and customs, which are essentially non-Bakarwal patterns of life. This paper highlights the new patterns and meanings adopted by the Bakarwals of Kashmir as a mode of their new existence. The exposure to new variants of contemporary culture and shrinking pastures have made many Bakarwals to give up their traditional occupation of rearing livestock —an occupation once seen as sacred. Many of the Bakarwals have started practising agricultural farming, while few have started working as labourers and others have started taking “modern” occupations like driving. In marriages too, the Bakarwals are seen to follow the traditions and rituals followed by the non-Bakarwal groups. The Bakarwals used to have their own traditions, customs and rituals in marriages which were not seen in other non-Bakarwal groups. However, in contemporary times, the Bakarwals are avoiding these ancestral traditions, rituals and customs. This paper is an attempt to document the changes in the marriage practices and rituals, which were once cherished by the Bakarwals but now seem on the verge of extinction.
Variants of a putative baseplate wedge protein extend the host range of Pseudomonas phage K8
Authors: Sun Li , You Jiajia , Li Donghang , Zhang Zhiqiang , Qin Xuying , Pang Wenjing , Li Peize , Han Qingzhu , Li Yueying , Huang Zhiwei , Zhang Xixi , Gong Mengxin , Yang Hongjiang
Published: January 2023

Background

Narrow host range is a major limitation for phage applications, but phages can evolve expanded host range through adaptations in the receptor-binding proteins.

Results

Here, we report that Pseudomonas phage K8 can evolve broader host range and higher killing efficiency at the cost of virion stability. Phage K8 host range mutant K8-T239A carries a mutant version of the putative baseplate wedge protein GP075, termed GP075m. While phage K8 adsorbs to hosts via the O-specific antigen of bacterial LPS, phage K8-T239A uses GP075m to also bind the bacterial core oligosaccharide, enabling infection of bacterial strains resistant to K8 infection due to modified O-specific antigens. This mutation in GP075 also alters inter-protein interactions among phage proteins, and reduces the stability of phage particles to environmental stressors like heat, acidity, and alkalinity. We find that a variety of mutations in gp075 are widespread in K8 populations, and that the gp075-like genes are widely distributed among the domains of life.

Conclusion

Our data show that a typical life history tradeoff occurs between the stability and the host range in the evolution of phage K8. Reservoirs of viral gene variants may be widely present in phage communities, allowing phages to rapidly adapt to any emerging environmental stressors.
Frequency and accuracy of intraoperative bone margin sampling for T4a cancers of the head and neck at the QEII Health Sciences Centre: A retrospective chart review
Authors: Lamport Anna-Claire , MacKay Colin A. , Bullock Martin J. , Taylor S. Mark , Trites Jonathan R. , Corsten Martin , Rigby Matthew H.
Published: January 2023

Background

Stage T4a cancers are associated with a 5-year survival of 21.6–59.0%. Adequate resection of these tumors is a critical factor in maximizing survival. Tumors invading bone pose a unique challenge to intraoperative bone margin assessment. Due to processing limitations, there had been no formal standardized protocol for intraoperative bone sampling at the QEII Health Sciences Centre. These resections often involve extensive reconstruction, making salvage surgery difficult if positive margins are detected post-surgically. The purpose of this study was to assess the accuracy and frequency of intraoperative bone margin assessment during the study period and to determine survival and recurrence rates associated with positive final bone margins.

Methods

A retrospective chart review was conducted including patients with stage T4a head and neck cancer involving bone that underwent primary surgical resection in Nova Scotia between 2009 and 2019. Eligible patients were identified through the Cancer Care Nova Scotia registry. Exclusion criteria included patients with stage T4a tumors involving bone that did not receive primary surgical treatment with curative intent and patients with stage T4a tumors that did not invade bone.

Results

Of 67 patients included, 50 were amenable to intraoperative bone margin sampling while 18 had intraoperative sampling. Four patients had positive intraoperative margins and one had final positive bone margins. The incidence of final bone margin positivity was 7.5%. Median survival following surgery was 4.56 years for patients with final negative bone margins (n = 62) and 3.98 years for patients with positive final bone margins (n = 5). All patients with final positive bone margins received adjuvant radiation therapy. Of patients with negative final bone margins, 16.1% received no adjuvant therapy, 61.3% received adjuvant radiation therapy and 21.0% received adjuvant chemoradiation therapy.

Conclusion

Intraoperative bone margin sampling occurred in 26.8% of all cases and 36.0% of amenable cases. Median survival of patients with positive final bone margins was 0.58 years lower than those with negative final bone margins, although this difference did not reach statistical significance. This will provide baseline data for comparison of the standardized intraoperative bone margin sampling protocol implemented at the QEII Health Sciences Centre.

Graphical Abstract
Gamification of e-learning in higher education: a systematic literature review
Authors: Khaldi Amina , Bouzidi Rokia , Nader Fahima
Published: January 2023

In recent years, university teaching methods have evolved and almost all higher education institutions use e-learning platforms to deliver courses and learning activities. However, these digital learning environments present significant dropout and low completion rates. This is primarily due to the lack of student motivation and engagement. Gamification which can be defined as the application of game design elements in non-game activities has been used to address the issue of learner distraction and stimulate students’ involvement in the course. However, choosing the right combination of game elements remains a challenge for gamification designers and practitioners due to the lack of proven design approaches, and there is no one-size-fits-all approach that works regardless of the gamification context. Therefore, our study focused on providing a comprehensive overview of the current state of gamification in online learning in higher education that can serve as a resource for gamification practitioners when designing gamified systems. In this paper, we aimed to systematically explore the different game elements and gamification theory that have been used in empirical studies; establish different ways in which these game elements have been combined and provide a review of the state-of-the-art of approaches proposed in the literature for gamifying e-learning systems in higher education. A systematic search of databases was conducted to select articles related to gamification in digital higher education for this review, namely, Scopus and Google Scholar databases. We included studies that consider the definition of gamification as the application of game design elements in non-game activities, designed for online higher education. We excluded papers that use the term of gamification to refer to game-based learning, serious games, games, video games, and those that consider face-to-face learning environments. We found that PBL elements (points, badges, and leaderboards), levels, and feedback and are the most commonly used elements for gamifying e-learning systems in higher education. We also observed the increasing use of deeper elements like challenges and storytelling. Furthermore, we noticed that of 39 primary studies, only nine studies were underpinned by motivational theories, and only two other studies used theoretical gamification frameworks proposed in the literature to build their e-learning systems. Finally, our classification of gamification approaches reveals the trend towards customization and personalization in gamification and highlights the lack of studies on content gamification compared to structural gamification.
Early cessation of breastfeeding and the associated factors among mothers with children aged 2 to 3 years in rural Southern Ethiopia: a community-based cross-sectional study
Authors: Temesgen Kidus , Andarge Eshetu , Fikadu Teshale , Bekele Muluken , Chisha Yilma , Esubalew Habtamu , Toma Temesgen Mohammed
Published: January 2023

Background

Breast milk is the first natural food for babies. It has nutritional, immunological, developmental, psychological, societal and environmental advantages. Failing to feed children for twenty-four months has so many negative consequences to children. Though studies have well documented the duration of breast feeding in the first six months, the proportion of women completing the recommended duration and factors associated with it has not been well investigated in rural places of Ethiopia. Therefore, this study aims to fill this gap in evidence among mothers with children aged 2 to 3 years in Arba Minch Health and Demographic Surveillance Site in 2021 E.C.

Methods

A community-based cross-sectional study was conducted in all kebeles of the surveillance site by employing multi-stage sampling technique. Descriptive statistics was done to summarize findings and binary logistics regression model was used to identify factors significantly associated with early breast-feeding cessation respectively. OR with its 95% CI was obtained to quantify the degree of association between explanatory variables and early breastfeeding cessation.

Result

The proportion of early cessations of breast feeding was 29.30% (25.02, 33.64%). Being from a household with no fathers ‘education or primary education [AOR=0.22; 95%CI (0.07, 0.74)] and [AOR=0.30; 95%CI (0.12, 0.76)], farmer mothers [AOR=6.40; 95%CI: (1.38, 29.74)], birth interval of less than 2 years [AOR=2.07; 95%CI: (1.03, 4.16)], and with mothers’ one or two to three antenatal care visits [AOR = 2.73; 95%CI: (1.27,5.88)] were factors significantly associated with early cessations of breast feeding.

Conclusion and recommendation

The proportion of early cessations of breast feeding was high. Father’s education, being farmer, birth interval and ante natal care visit were significant factors. Health education about proper breast feeding practice and improving ante natal care attendance might improve premature cessation of breast feeding among women.
Enzalutamide induced non-ischemic cardiomyopathy. A case report and review of literature on anti-androgen therapy-related cardiovascular events
Authors: Kumar Aswini , Reddy Aswanth , Sekar Arjun
Published: January 2023

Prostate cancer has a very high prevalence among elder men, and this could potentially increase as longevity in many parts of the world is increasing. Early stages of prostate cancer can have surgical options, but the more advanced stages require some form of anti-androgen therapy. There are novel anti-androgen agents that were recently approved. Cardiovascular toxicity has been reported with some of these drugs. This is a novel report of likely cardiovascular toxicity due to Enzalutamide, which typically has a safer cardiovascular profile than Abiraterone.

We describe a 72-year-old male with repeated recurrence of prostate cancer with metastasis. The second time it recurred was within 2 years of the 1st recurrence and was treated with Enzalutamide.

However, within 2 weeks he developed systolic congestive heart failure that improved with stopping the drug and medical optimization.

Literature review shows that Abiraterone has more cardiovascular side effects than Enzalutamide which more commonly causes hypertension. The timeline in our case suggests Enzalutamide causing congestive heart failure which is a novel finding. This finding warrants further research regarding the safety profile of novel anti-androgen therapy. This includes risk stratification for potential cardiovascular adverse events and risk/benefit analysis prior to initiating therapy. Data on cumulative dose accumulation and risks can also be an area of future research.
Prevalence of autism spectrum disorder among children referred to special needs clinic in Giza
Authors: Meguid Nagwa A. , Nashaat Neveen Hassan , Ghannoum Heba , Hashem Heba Saher , Hussein Gina , El-Saied Amal
Published: January 2023

Background

Little is known about the prevalence of autism spectrum disorder (ASD) among the population with disability in Egypt. Furthermore, the increasing prevalence of ASD and the variability of the ASD manifestations and severity highlight the importance of investigating the ASD comorbidities.

Aim of work

This analysis was to compare the prevalence of autism with that of other disabilities among children visiting the clinic for special needs and to explore possible comorbid disorders in this sample of Egyptian ASD participants.

Methods

The study included individuals who visited the clinic for special needs in Giza, affiliated to the National Research Centre, for nearly 4 years (2019 to 2022). They were subjected to full clinical evaluation. Autistic children were further subjected to scales for confirming diagnosis and severity evaluation.

Results

The results revealed that a total of 3555 individuals were referred to the clinic. The percentage of children who were diagnosed as having ASD was 22.5% (N = 803; age: 4.5 ± 2.4 years). The most common associated comorbidities with ASD were language and intellectual deficits (80.25%, 58.7%). Hearing impairment was the least common (0.75%). The scores of the childhood autism rating scale were higher in the groups with the comorbid disorders (p = 0.03 or < 0.0001).

Conclusion

The prevalence of ASD among children with disability varied from other countries. Comorbid disorders have led to increasing the severity of ASD. We emphasize that accurate and early diagnosis of autism is the key for proper management of cases.
Follistatin Forms a Stable Complex With Inhibin A That Does Not Interfere With Activin A Antagonism
Authors: Kappes Emily C , Kattamuri Chandramohan , Czepnik Magdalena , Yarawsky Alexander E , Brûlé Emilie , Wang Ying , Ongaro Luisina , Herr Andrew B , Walton Kelly L , Bernard Daniel J , Thompson Thomas B
Published: January 2023

Inhibins are transforming growth factor-β family heterodimers that suppress follicle-stimulating hormone (FSH) secretion by antagonizing activin class ligands. Inhibins share a common β chain with activin ligands. Follistatin is another activin antagonist, known to bind the common β chain of both activins and inhibins. In this study, we characterized the antagonist-antagonist complex of inhibin A and follistatin to determine if their interaction impacted activin A antagonism. We isolated the inhibin A:follistatin 288 complex, showing that it forms in a 1:1 stoichiometric ratio, different from previously reported homodimeric ligand:follistatin complexes, which bind in a 1:2 ratio. Small angle X-ray scattering coupled with modeling provided a low-resolution structure of inhibin A in complex with follistatin 288. Inhibin binds follistatin via the shared activin β chain, leaving the α chain free and flexible. The inhibin A:follistatin 288 complex was also shown to bind heparin with lower affinity than follistatin 288 alone or in complex with activin A. Characterizing the inhibin A:follistatin 288 complex in an activin-responsive luciferase assay and by surface plasmon resonance indicated that the inhibitor complex readily dissociated upon binding type II receptor activin receptor type IIb, allowing both antagonists to inhibit activin signaling. Additionally, injection of the complex in ovariectomized female mice did not alter inhibin A suppression of FSH. Taken together, this study shows that while follistatin binds to inhibin A with a substochiometric ratio relative to the activin homodimer, the complex can dissociate readily, allowing both proteins to effectively antagonize activin signaling.
Beyond Expression: Role of Phosphorylated Residues of EZH2 in Lineage Plasticity in Prostate Cancer
Authors: Nouruzi Shaghayegh , Tabrizian Nakisa , Zoubeidi Amina
Published: January 2023

Despite the development of effective targeted therapies and a significant understanding of carcinogenesis and cancer progression, treatment resistance is a major obstacle in achieving durable long-term control in many types of cancers. Emerging evidence supports that nongenetic mechanisms could play an underappreciated role in therapy resistance. These mechanisms include phenotypic plasticity, which is recognized as a hallmark of cancer and translates to epigenetic and transcriptional control of gene expression. Alterations in the expression and activity of the epigenetic modifier enhancer of zeste homolog 2 (EZH2) support prostate cancer lineage plasticity and progression. EZH2 expression and activity is elevated in castration-resistant prostate cancer treated with androgen receptor pathway inhibitors and in treatment-resistant prostate cancer. Moreover, 17 known residues of EZH2 are phosphorylated on by multiple kinases that modulate its activity, localization, stability, and polycomb repressive complex (PRC2) assembly. In this review, we explore the contribution of EZH2 phosphorylation in regulating canonical PRC2 in a methylation-dependent manner as an epigenetic repressor and in a noncanonical manner independent of PRC2 as a transcription activator. Apart from the contribution of EZH2 phosphorylation at serine 21, threonine 350, and threonine 311 in prostate cancer progression and treatment resistance, we discuss how other EZH2 phosphorylated residues with unknown functions could contribute to prostate cancer based on their upstream regulators and potential therapeutic utility.
An interview with Christopher Wright
Authors: Zenner Helen L.
Published: January 2023

Christopher Wright is Professor of Cell and Developmental Biology and the director of the Program in Developmental Biology at Vanderbilt University. His lab works on pancreas organogenesis and how it relates to disease, using techniques spanning from single-cell technology through to high-resolution imaging. Chris was awarded the 2022 Society for Developmental Biology (SDB) Victor Hamburger Outstanding Educator Prize and we talked about what winning this award means to him, as well as discussing his career and his hopes for the future of developmental biology.
Embracing the diversity of model systems to deconstruct the basis of regeneration and tissue repair
Authors: Amiel Aldine R. , Tsai Stephanie L. , Wehner Daniel
Published: January 2023

The eighth EMBO conference in the series ‘The Molecular and Cellular Basis of Regeneration and Tissue Repair’ took place in Barcelona (Spain) in September 2022. A total of 173 researchers from across the globe shared their latest advances in deciphering the molecular and cellular basis of wound healing, tissue repair and regeneration, as well as their implications for future clinical applications. The conference showcased an ever-expanding diversity of model organisms used to identify mechanisms that promote regeneration. Over 25 species were discussed, ranging from invertebrates to humans. Here, we provide an overview of the exciting topics presented at the conference, highlighting novel discoveries in regeneration and perspectives for regenerative medicine.