bluuebunny/crossref_metadata_2025 huggingface dataset:
Personal factors associated with carpal tunnel syndrome (CTS): a case-control study
Authors: Al Shahrani Eman , Al Shahrani Abeer , Al-Maflehi Nassr
Published: December 2021

Background

Carpal tunnel syndrome (CTS) is one of the most common nerve entrapments in the upper limb. In Saudi Arabia, few studies have investigated CTS in the general population. This study aimed to determine the association between personal factors and CTS.

Methods

A case-control study involved adults aged 18 and above. Cases were recruited from electrophysiology lab records as consecutive case series, while controls were individuals who were free of CTS symptoms according to the Boston Carpal Tunnel Questionnaire (BCTQ). The electronic medical records of participants were reviewed to obtain age, height, weight, medical conditions, and mobile numbers. Cases and controls were contacted via phone to complete a questionnaire that was designed based on previous literature. We used multivariate binary logistic regression to identify the personal factors significantly associated with CTS.

Results

A total of 95 cases and 190 controls were included. Most of the participants were female (84.2%) and Saudi (93%). Most of cases were above 45 years of age (73.7%), while 84.7% were 45 year – old or younger among the control group. Stratified logistic regression showed that performance of household chores was significantly associated with CTS. While physical exercise associated with decreased odds of CTS.

Conclusions

This study adds to the body of evidence on personal factors associated with CTS. However, the degree of differences in the age structure of the cases compared with the controls suggest that there is a considerable potential for residual confounding affecting the results.

Trial registration number

Not applicable.
Evaluation of the efficacy and safety of conventional and biportal endoscopic decompressive laminectomy in patients with lumbar spinal stenosis (ENDO-B trial): a protocol for a prospective, randomized, assessor-blind, multicenter trial
Authors: Park Hyun-Jin , Park Sang-Min , Song Kwang-Sup , Kim Ho-Joong , Park Si-Young , Kang Taewook , Kang Min-Seok , Heo Dong-Hwa , Park Choon-Keun , Lee Dong-Geun , Hwang Jin-Sub , Jang Jae-Won , Kim Jun-Young , Kim Jin-Sung , Lee Hong-Jae , Yoon Joon-Hyeok , Park Chang-Won , You Ki-Han
Published: December 2021

Background

Recent studies on biportal endoscopic spine surgery in patients with lumbar spinal stenosis have reported good clinical results. However, these studies have been limited by the small sample sizes and use of a retrospective study design. Therefore, we aim to compare the efficacy and safety of biportal endoscopic decompressive laminectomy with those of conventional decompressive laminectomy in a multicenter, prospective, randomized controlled trial.

Methods

This study will include 120 patients (60 per group, aged 20–80 years) with 1- or 2-level lumbar spinal stenosis, who will be recruited from six hospitals. The study will be conducted from July 2021 to December 2024. The primary outcome (Oswestry Disability Index at 12 months after surgery) will be evaluated through a modified intention-to-treat method. The secondary outcomes will include the following: visual analog scale score for low back and lower extremity radiating pain, EuroQol 5-dimensions score, surgery satisfaction, walking time, postoperative return to daily life period, postoperative surgical scars, and some surgery-related variables. Radiographic outcomes will be analyzed using magnetic resonance imaging or computed tomography. All outcomes will be evaluated before the surgery and at 2 weeks, 3 months, 6 months, and 12 months postoperatively. This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines for reporting of clinical trial protocols.

Discussion

It is hypothesized that the efficacy and safety of biportal endoscopic and conventional decompressive laminectomy will be comparable in patients with lumbar spinal stenosis. The results of this trial will provide a high level of evidence for the efficacy and safety of the biportal endoscopic technique in patients with lumbar spinal stenosis and facilitate the development of clinical practice guidelines. Furthermore, the results of this study may indicate the feasibility of the biportal endoscopic technique for other types of spinal surgery.

Trial registration

The ENDO-B trial is registered at Clinical Research Information Service (CRIS, cris.nih.go.kr) (KCT0006057; April 52,021).
Comparison between microendoscopic laminectomy and open posterior decompression surgery for single-level lumbar spinal stenosis: a multicenter retrospective cohort study
Authors: Ohtomo Nozomu , Nakamoto Hideki , Miyahara Junya , Yoshida Yuichi , Nakarai Hiroyuki , Tozawa Keiichiro , Fukushima Masayoshi , Kato So , Doi Toru , Taniguchi Yuki , Matsubayashi Yoshitaka , Higashikawa Akiro , Takeshita Yujiro , Kawamura Naohiro , Inanami Hirohiko , Tanaka Sakae , Oshima Yasushi
Published: December 2021

Background

Microendoscopic laminectomy (MEL), in which a 16-mm tubular retractor with an internal scope is used, has shown excellent surgical results for patients with lumbar spinal canal stenosis. However, no reports have directly compared MEL with open laminectomy. This study aimed to elucidate patient-reported outcomes (PROs) and perioperative complications in patients undergoing MEL versus open laminectomy.

Methods

This is a multicenter retrospective cohort study of prospectively registered patients who underwent lumbar spinal surgery at one of the six high-volume spine centers between April 2017 and September 2018. A total of 258 patients who underwent single posterior lumbar decompression at L4/L5 were enrolled in the study. With regard to demographic data, we prospectively used chart sheets to evaluate the diagnosis, operative procedure, operation time, estimated blood loss, and complications. The follow-up period was 1-year. PROs included a numerical rating scale (NRS) for lower back pain and leg pain, the Oswestry Disability Index (ODI), EuroQol 5 Dimension (EQ-5D), and patient satisfaction with the treatment.

Results

Of the 258 patients enrolled, 252 (97%) completed the 1-year follow-up. Of the 252, 130 underwent MEL (MEL group) and 122 underwent open decompression (open group). The MEL group required a significantly shorter operating time and sustained lesser intraoperative blood loss compared with the open group. The MEL group showed shorter length of postoperative hospitalization than the open group. The overall complication rate was similar (8.2% in the MEL group versus 7.7% in the open group), and the revision rate did not significantly differ. As for PROs, both preoperative and postoperative values did not significantly differ between the two groups. However, the satisfaction rate was higher in the MEL group (74%) than in the open group (53%) (p = 0.02).

Conclusions

MEL required a significantly shorter operating time and resulted in lesser intraoperative blood loss compared with laminectomy. Postoperative PROs and complication rates were not significantly different between the procedures, although MEL demonstrated a better satisfaction rate.
Protease inhibitor concentrations in the saliva of individuals experiencing oral dryness
Authors: Yamamoto Kenkichi , Hiraishi Makiko , Haneoka Mai , Fujinaka Hidetake , Yano Yoshitaka
Published: December 2021

Background

Oral dryness is a common symptom that may interfere with swallowing, chewing, and taste. The most common reason for oral dryness is hyposalivation. Some individuals experiencing oral dryness do not have hyposalivation, however, and the reverse is also true. Here, we focused on healthy individuals with a lower salivary flow rate and evaluated the relationship between the perception of oral dryness and salivary parameters to clarify the cause underlying the perception of oral dryness.

Methods

A total of 59 participants were divided into 2 groups with a lower or higher salivary flow rate according to the median salivary flow rate. In participants with a lower salivary flow rate, we assessed salivary bacterial counts, protease activities, protein concentrations, oral parameters, and the subjective perception of oral dryness.

Results

Protease activities and concentrations of protease inhibitors such as cystatin-D and cystatin-SA in the saliva of participants experiencing oral dryness were significantly higher and lower, respectively, than in those not experiencing oral dryness, even though no difference in the salivary flow rate was detected. Salivary cystatin-D and cystatin-SA concentrations correlated negatively with salivary protease activities.

Conclusions

The composition of salivary protease inhibitors and increased protease activities affect the subjective perception of oral dryness.
Palliative care provider attitudes toward existential distress and treatment with psychedelic-assisted therapies
Authors: Niles Halsey , Fogg Colleen , Kelmendi Ben , Lazenby Mark
Published: December 2021

Background

Existential distress is a significant source of suffering for patients facing life-threatening illness. Psychedelic-Assisted Therapies (PAT) are novel treatments that have shown promise in treating existential distress, but openness to providing PAT may be limited by stigma surrounding psychedelics and the paucity of education regarding their medical use. How PAT might be integrated into existing treatments for existential distress within palliative care remains underexplored.

Methods

The present study aimed to elucidate the attitudes of palliative care clinicians regarding treatments for existential distress, including PAT. We recruited palliative care physicians, advanced practice nurses, and spiritual and psychological care providers from multiple US sites using purposive and snowball sampling methods. Attitudes toward PAT were unknown prior to study involvement. Semi-structured interviews targeted at current approaches to existential distress and attitudes toward PAT were analyzed for thematic content.

Results

Nineteen respondents (seven physicians, four advanced practice nurses, four chaplains, three social workers, and one psychologist) were interviewed. Identified themes were 1) Existential distress is a common experience that is frequently insufficiently treated within the current treatment framework; 2) Palliative care providers ultimately see existential distress as a psychosocial-spiritual problem that evades medicalized approaches; 3) Palliative care providers believe PAT hold promise for treating existential distress but that a stronger evidence base is needed; 4) Because PAT do not currently fit existing models of existential distress treatment, barriers remain.

Conclusions

PAT is seen as a potentially powerful tool to treat refractory existential distress. Larger clinical trials and educational outreach are needed to clarify treatment targets and address safety concerns. Further work to adapt PAT to palliative care settings should emphasize collaboration with spiritual care as well as mental health providers and seek to address unresolved concerns about equitable access.
The distribution of reproductive risk factors disclosed the heterogeneity of receptor-defined breast cancer subtypes among Tanzanian women
Authors: Rweyemamu Linus P. , Akan Gokce , Adolf Ismael C. , Magorosa Erick P. , Mosha Innocent J. , Dharsee Nazima , Namkinga Lucy A. , Lyantagaye Sylvester L. , Nateri Abdolrahman S. , Atalar Fatmahan
Published: December 2021

Background

Recent epidemiological studies suggest that reproductive factors are associated with breast cancer (BC) molecular subtypes. However, these associations have not been thoroughly studied in the African populations. The present study aimed to investigate the prevalence of BC molecular subtypes and assess their association with reproductive factors in Tanzanian BC patients.

Methods

This hospital-based case-only cross-sectional study consisted of 263 histologically confirmed BC patients in Tanzania. Clinico-pathological data, socio-demographic characteristics, anthropometric measurements, and reproductive risk factors were examined using the Chi-square test and one-way ANOVA. The association among reproductive factors and BC molecular subtypes was analyzed using multinomial logistic regression. The heterogeneity of the associations was assessed using the Wald test.

Results

We found evident subtype heterogeneity for reproductive factors. We observed that post-menopausal status was more prevalent in luminal-A subtype, while compared to luminal-A subtype, luminal-B and HER-2 enriched subtypes were less likely to be found in post-menopausal women (OR: 0.21, 95%CI 0.10–0.41,p = 0.001; OR: 0.39, 95%CI 0.17–0.89,p = 0.026, respectively). Also, the luminal-B subtype was more likely to be diagnosed in patients aged ≤ 40 years than the luminal-A subtype (OR: 2.80, 95%CI 1.46–5.32,p = 0.002). Women who had their first full-term pregnancy at < 30 years were more likely to be of luminal-B (OR: 2.71, 95%CI 1.18–4.17,p = 0.018), and triple-negative (OR: 2.28, 95%CI 1.02–4.07,p = 0.044) subtypes relative to luminal-A subtype. Furthermore, we observed that breastfeeding might have reduced odds of developing luminal-A, luminal-B and triple-negative subtypes. Women who never breastfed were more likely to be diagnosed with luminal-B and triple-negative subtypes when compared to luminal-A subtype (OR: 0.46, 95%CI 0.22–0.95,p = 0.035; OR: 0.41, 95%CI 0.20–0.85,p = 0.017, respectively).

.

Conclusion

Our results are the first data reporting reproductive factors heterogeneity among BC molecular subtypes in Tanzania. Our findings suggest that breast-feeding may reduce the likelihood of developing luminal-A, luminal-B, and triple-negative subtypes. Meanwhile, the first full-term pregnancy after 30 years of age could increase the chance of developing luminal-A subtype, a highly prevalent subtype in Tanzania. More interventions to promote modifiable risk factors across multiple levels may most successfully reduce BC incidence in Africa.
“Locus minoris resistentiae” and connective tissue weakness in older women: a case report and literature review on pelvic organ prolapse with inguinal bladder hernia
Authors: Esber A. , Kopera A. , Radosa M. P. , Runnebaum I. B. , Mothes H. K. , Mothes A. R.
Published: December 2021

Background

Conditions such as genital prolapse and hernia are known to be related to connective tissue dysfunction. In this report on cases of the rare simultaneous finding of large genital prolapse and post-prolapse repair female inguinal bladder hernia, we aim to contribute to the discussion of a possible clinical definition of connective tissue weakness, for its clinical assessment and preoperative patient counselling.

Case presentation

Three cases of medial third-grade (MIII, Aachen classification) inguinal bladder hernia developing or enlarging after successful stage-IV pelvic organ prolapse (POP) repair at a university pelvic floor centre are presented. All patients were aged ≥ 80 years with long-standing postmenopausal status. One patient was followed for 5 years and two patients were followed for 6 months. In all patients, ultrasound revealed that the hernia sac contained the urinary bladder, which had herniated through the inguinal hernia orifice. A literature search revealed only one case report of direct female inguinal bladder hernia and few investigations of the simultaneous occurrence of POP and hernia in general.

Conclusion

The simultaneous occurrence of inguinal hernia and female POP can lead to bladder herniation following prolapse surgery in the sense of a “locus minoris resistentiae”. Clinical examination for simultaneous signs of connective tissue weakness and counselling prior to pelvic reconstructive surgery could help to increase patients’ compliance with further surgical treatment for hernia.
Expression levels of MCP-1, HGF, and IGF-1 in endometriotic patients compared with non-endometriotic controls
Authors: Heidari Sahel , Kolahdouz-Mohammadi Roya , Khodaverdi Sepideh , Tajik Nader , Delbandi Ali-Akbar
Published: December 2021

Background

To study the concentrations of monocyte chemoattractant protein-1 (MCP-1), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1) in peritoneal fluid (PF) and serum, and to evaluate their expressions by PF and peripheral blood mononuclear cells (PFMCs and PBMCs, respectively), and ectopic and eutopic endometrial stromal cells of patients with endometriosis (EESCs and EuESCs, respectively) compared with controls.

Methods

The concentrations of mentioned cytokines in serum and PF, as well as their expression in PBMCs, PFMCs, EuESCs and EESCs from endometriosis patients and controls were assessed.

Results

The levels of MCP-1, HGF, and IGF-1 in serum and PF in women with endometriosis were significantly higher than the controls (P < 0.05–P < 0.001). Gene expression of MCP-1 and IGF-1 in the PFMCs, PBMCs and EESCs also showed an increased level compared to controls (P < 0.05–P < 0.01). The protein expression of MCP-1 and IGF-1 by PFMCs was statistically higher in endometriotic women (P < 0.05 and P < 0.01, respectively). The gene and protein expression of HGF in PFMCs and its gene expression by EESCs were significantly higher in endometriotic women compared to controls (P < 0.05–P < 0.01).

Conclusions

The higher concentrations of mentioned cytokines in serum and PF and their higher expression by PFMCs and EESCs in endometriosis patients may contribute to the development of endometriosis.
Remote versus on-site proctored exam: comparing student results in a cross-sectional study
Authors: Andreou Vasiliki , Peters Sanne , Eggermont Jan , Wens Johan , Schoenmakers Birgitte
Published: December 2021

Background

The COVID-19 pandemic has profoundly affected assessment practices in medical education necessitating distancing from the traditional classroom. However, safeguarding academic integrity is of particular importance for high-stakes medical exams. We utilised remote proctoring to administer safely and reliably a proficiency-test for admission to the Advanced Master of General Practice (AMGP). We compared exam results of the remote proctored exam group to those of the on-site proctored exam group.

Methods

A cross-sectional design was adopted with candidates applying for admission to the AMGP. We developed and applied a proctoring software operating on three levels to register suspicious events: recording actions, analysing behaviour, and live supervision. We performed a Mann-Whitney U test to compare exam results from the remote proctored to the on-site proctored group. To get more insight into candidates’ perceptions about proctoring, a post-test questionnaire was administered. An exploratory factor analysis was performed to explore quantitative data, while qualitative data were thematically analysed.

Results

In total, 472 (79%) candidates took the proficiency-test using the proctoring software, while 121 (20%) were on-site with live supervision. The results indicated that the proctoring type does not influence exam results. Out of 472 candidates, 304 filled in the post-test questionnaire. Two factors were extracted from the analysis and identified as candidates’ appreciation of proctoring and as emotional distress because of proctoring. Four themes were identified in the thematic analysis providing more insight on candidates’ emotional well-being.

Conclusions

A comparison of exam results revealed that remote proctoring could be a viable solution for administering high-stakes medical exams. With regards to candidates’ educational experience, remote proctoring was met with mixed feelings. Potential privacy issues and increased test anxiety should be taken into consideration when choosing a proctoring protocol. Future research should explore generalizability of these results utilising other proctoring systems in medical education and in other educational settings.
cbpManager: a web application to streamline the integration of clinical and genomic data in cBioPortal to support the Molecular Tumor Board
Authors: Ustjanzew Arsenij , Desuki Alexander , Ritzel Christoph , Dolezilek Alina Corinna , Wagner Daniel-Christoph , Christoph Jan , Unberath Philipp , Kindler Thomas , Faber Jörg , Marini Federico , Panholzer Torsten , Paret Claudia
Published: December 2021

Background

Extensive sequencing of tumor tissues has greatly improved our understanding of cancer biology over the past years. The integration of genomic and clinical data is increasingly used to select personalized therapies in dedicated tumor boards (Molecular Tumor Boards) or to identify patients for basket studies. Genomic alterations and clinical information can be stored, integrated and visualized in the open-access resource cBioPortal for Cancer Genomics. cBioPortal can be run as a local instance enabling storage and analysis of patient data in single institutions, in the respect of data privacy. However, uploading clinical input data and genetic aberrations requires the elaboration of multiple data files and specific data formats, which makes it difficult to integrate this system into clinical practice. To solve this problem, we developed cbpManager.

Results

cbpManager is an R package providing a web-based interactive graphical user interface intended to facilitate the maintenance of mutations data and clinical data, including patient and sample information, as well as timeline data. cbpManager enables a large spectrum of researchers and physicians, regardless of their informatics skills to intuitively create data files ready for upload in cBioPortal for Cancer Genomics on a daily basis or in batch. Due to its modular structure based on R Shiny, further data formats such as copy number and fusion data can be covered in future versions. Further, we provide cbpManager as a containerized solution, enabling a straightforward large-scale deployment in clinical systems and secure access in combination with ShinyProxy. cbpManager is freely available via the Bioconductor project at https://bioconductor.org/packages/cbpManager/ under the AGPL-3 license. It is already used at six University Hospitals in Germany (Mainz, Gießen, Lübeck, Halle, Freiburg, and Marburg).

Conclusion

In summary, our package cbpManager is currently a unique software solution in the workflow with cBioPortal for Cancer Genomics, to assist the user in the interactive generation and management of study files suited for the later upload in cBioPortal.
Defining an enabling environment for those with chronic disease: an integrative review
Authors: Loizeau Valérie , Morvillers Jean-Manuel , Bertrand Dominique Pougheon , Kilpatrick Kelley , Rothan-Tondeur Monique
Published: December 2021

Background

Health policies are currently being implemented to cope with the 37% of those affected by chronic disease and 63% of deaths worldwide. Among the proposals, there is accelerating support for greater autonomy for patients, which incorporates several concepts, including empowerment. To achieve this, develop an environment to increase an individual’s capacity for action seems to be a fundamental step. The aim of this study is to characterize an enabling environment for patients in the context of chronic disease management.

Methods

An integrative review design was applied. Medline, CINAHL, and Web of Science databases were searched to identify relevant literature published between 2009 and 2019. Overall, the review process was guided by the PRISMA 2020 checklist. The Mixed Methods Appraisal Tool for quality evaluation was used.

Results

A total of 40 articles were analyzed, divided into 18 quantitative studies, 11 qualitative studies, two mixed studies, seven expert opinions, one theory and one conference report. The following characteristics defining an enabling environment were taken from the literature relating to those with a chronic condition: Needs assessment-adaptation of responses, supporting “take care”, involvement in support, knowledge improvement, engagement with professionals, use of information and communication technologies, and organization of care. Beyond that, the interactions highlighted between these seven categories characterize an enabling environment.

Conclusion

This review specifies the essential elements of an enabling environment for patients with chronic conditions. It encompasses the partnership between the healthcare professional, such as the advanced practice nurse, and the individual for whom interventions and care strategies must be devised.
X-linked sideroblastic anaemia in a female fetus: a case report and a literature review
Authors: Nzelu Diane , Shangaris Panicos , Story Lisa , Smith Frances , Piyasena Chinthika , Alamelu Jayanthi , Elmakky Amira , Pelidis Maria , Mayhew Rachel , Sankaran Srividhya
Published: December 2021

Background

X-linked sideroblastic anaemia (XLSA) is commonly due to mutations in the ALAS2 gene and predominantly affects hemizygous males. Heterozygous female carriers of the ALAS2 gene mutation are often asymptomatic or only mildly anaemic. XLSA is usually characterized by microcytic erythrocytes (reduced mean corpuscular volume (MCV)) and hypochromia, along with increased red cell distribution width. However, in females with XLSA the characteristic laboratory findings can be dimorphic and present with macrocytic (elevated MCV) in addition to microcytic red cells.

Case presentation

We report a case of fetal anaemia, presenting in the early third trimester of pregnancy, in a female fetus. Ultrasound findings at 29 weeks were of cardiomegaly, prominent umbilical veins, a small rim of ascites, and mean cerebral artery peak systolic velocity (PSV) value above 1.5 Multiples of the Median (MoM). She underwent non-invasive prenatal testing that determined the rhesus genotype of the fetus to be rhesus B negative. No red blood cell antibodies were reported. Other investigations to determine the underlying cause of fetal anaemia included microarray comparative genomic hybridization, serology to exclude congenital infection and a peripheral blood film and fetal bilirubin to detect haemolysis. The maternal grandmother had a history of sideroblastic anaemia diagnosed at the age of 17 years. The mother had mild macrocytic anaemia with haemoglobin of 10.4 g/dl and MCV of 104 fl. The fetal anaemia was successfully treated with two in utero transfusions (IUTs), and delivery occurred via caesarean section at 37 weeks of gestation. The red cell gene sequencing in both the mother and fetus were heterozygous for an ALAS2 mutation causing in utero manifestations of XLSA. The haemoglobin on discharge to the local hospital at five days of age was 19.1 g/dl. Subsequently, the infant became anaemic, requiring regular 3–4 monthly blood transfusions and demonstrating overall normal development. Her anaemia was unresponsive to pyridoxine.

Conclusions

This is one of four cases reporting multiple female members presenting with discordant clinical features of XLSA from being entirely asymptomatic to hydropic in utero. Our report is novel in that there are no previous cases in the literature of anaemia in a female fetus heterozygous for ALAS2 mutation.
High natural PHA production from acetate in Cobetia sp. MC34 and Cobetia marina DSM 4741T and in silico analyses of the genus specific PhaC2 polymerase variant
Authors: Christensen Mikkel , Jablonski Piotr , Altermark Bjørn , Irgum Knut , Hansen Hilde
Published: December 2021

Background

Several members of the bacterial Halomonadacea family are natural producers of polyhydroxyalkanoates (PHA), which are promising materials for use as biodegradable bioplastics. Type-strain species of Cobetia are designated PHA positive, and recent studies have demonstrated relatively high PHA production for a few strains within this genus. Industrially relevant PHA producers may therefore be present among uncharacterized or less explored members. In this study, we characterized PHA production in two marine Cobetia strains. We further analyzed their genomes to elucidate pha genes and metabolic pathways which may facilitate future optimization of PHA production in these strains.

Results

Cobetia sp. MC34 and Cobetia marina DSM 4741T were mesophilic, halotolerant, and produced PHA from four pure substrates. Sodium acetate with- and without co-supplementation of sodium valerate resulted in high PHA production titers, with production of up to 2.5 g poly(3-hydroxybutyrate) (PHB)/L and 2.1 g poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/L in Cobetia sp. MC34, while C. marina DSM 4741T produced 2.4 g PHB/L and 3.7 g PHBV/L. Cobetia marina DSM 4741T also showed production of 2.5 g PHB/L from glycerol. The genome of Cobetia sp. MC34 was sequenced and phylogenetic analyses revealed closest relationship to Cobetia amphilecti. PHA biosynthesis genes were located at separate loci similar to the arrangement in other Halomonadacea. Further genome analyses revealed some differences in acetate- and propanoate metabolism genes between the two strains. Interestingly, only a single PHA polymerase gene (phaC2) was found in Cobetia sp. MC34, in contrast to two copies (phaC1 and phaC2) in C. marina DSM 4741T. In silico analyses based on phaC genes show that the PhaC2 variant is conserved in Cobetia and contains an extended C-terminus with a high isoelectric point and putative DNA-binding domains.

Conclusions

Cobetia sp. MC34 and C. marina DSM 4741T are natural producers of PHB and PHBV from industrially relevant pure substrates including acetate. However, further scale up, optimization of growth conditions, or use of metabolic engineering is required to obtain industrially relevant PHA production titers. The putative role of the Cobetia PhaC2 variant in DNA-binding and the potential implications remains to be addressed by in vitro- or in vivo methods.
Engineering for an HPV 9-valent vaccine candidate using genomic constitutive over-expression and low lipopolysaccharide levels in Escherichia coli cells
Authors: Wang Kaihang , Zhou Lizhi , Chen Tingting , Li Qiong , Li Jiajia , Liu Liqin , Li Yuqian , Sun Jie , Li Tingting , Wang Yingbin , Kong Zhibo , Zheng Qingbing , Zhang Jun , Yu Hai , Gu Ying , Xia Ningshao , Li Shaowei
Published: December 2021

Background

The various advantages associated with the growth properties of Escherichia coli have justified their use in the production of genetically engineered vaccines. However, endotoxin contamination, plasmid vector instability, and the requirement for antibiotic supplementation are frequent bottlenecks in the successful production of recombinant proteins that are safe for industrial-scaled applications. To overcome these drawbacks, we focused on interrupting the expression of several key genes involved in the synthesis of lipopolysaccharide (LPS), an endotoxin frequently responsible for toxicity in recombinant proteins, to eliminate endotoxin contamination and produce better recombinant proteins with E. coli.

Results

Of 8 potential target genes associated with LPS synthesis, we successfully constructed 7 LPS biosynthesis-defective recombinant strains to reduce the production of LPS. The endotoxin residue in the protein products from these modified E. coli strains were about two orders of magnitude lower than that produced by the wild-type strain. Further, we found that 6 loci—lpxM, lpxP, lpxL, eptA, gutQ and kdsD—were suitable for chromosomal integrated expression of HPV L1 protein. We found that a single copy of the expression cassette conferred stable expression during long-term antibiotic-free cultivation as compared with the more variable protein production from plasmid-based expression. In large-scale fermentation, we found that recombinant strains bearing 3 to 5 copies of the expression cassette had 1.5- to 2-fold higher overall expression along with lower endotoxin levels as compared with the parental ER2566 strain. Finally, we engineered and constructed 9 recombinant E. coli strains for the later production of an HPV 9-valent capsid protein with desirable purity, VLP morphology, and antigenicity.

Conclusions

Reengineering the LPS synthesis loci in the E. coli ER2566 strain through chromosomal integration of expression cassettes has potential uses for the production of a 9-valent HPV vaccine candidate, with markedly reduced residual endotoxin levels. Our results offer a new strategy for recombinant E. coli strain construction, engineering, and the development of suitable recombinant protein drugs.
Metabolic syndrome related gene signature predicts the prognosis of patients with pancreatic ductal carcinoma. A novel link between metabolic dysregulation and pancreatic ductal carcinoma
Authors: Cai Weiyang , Bao Wenming , Chen Shengwei , Yang Yan , Li Yanyan
Published: December 2021

Background

Pancreatic cancer is one of the most common malignancies worldwide. In recent years, specific metabolic activities, which involves the development of tumor, caused wide public concern. In this study, we wish to explore the correlation between metabolism and progression of tumor.

Methods

A retrospective analysis including 95 patients with pancreatic ductal adenocarcinoma (PDAC) and PDAC patients from The Cancer Genome Atlas (TCGA), the International Cancer Genome Consortium (ICGC), and The Gene Expression Omnibus (GEO) database were involved in our study. Multivariate Cox regression analysis was used to construct the prognosis model. The potential connection between metabolism and immunity of PDAC was investigated through a weighted gene co-expression network analysis (WGCNA). 22 types of Tumor-infiltrating immune cells (TIICs) between high-risk and low-risk groups were estimated through CIBERSORT. Moreover, the potential immune-related signaling pathways between high-risk and low-risk groups were explored through the gene set enrichment analysis (GSEA). The role of key gene GMPS in developing pancreatic tumor was further investigated through CCK-8, colony-information, and Transwell.

Results

The prognostic value of the MetS factors was analyzed using the Cox regression model, and a clinical MetS-based nomogram was established. Then, we established a metabolism-related signature to predict the prognosis of PDAC patients based on the TCGA databases and was validated in the ICGC database and the GEO database to find the distinct molecular mechanism of MetS genes in PDAC. The result of WGCNA showed that the blue module was associated with risk score, and genes in the blue module were found to be enriched in the immune-related signaling pathway. Furthermore, the result of CIBERSORT demonstrated that proportions of T cells CD8, T cells Regulatory, Tregs NK cells Activated, Dendritic cells Activated, and Mast cells Resting were different between high-risk and low-risk groups. These differences are potential causes of different prognoses of PDAC patients. GSEA and the protein–protein interaction network (PPI) further revealed that our metabolism-related signature was significantly enriched in immune‐related biological processes. Moreover, knockdown of GMPS in PDAC cells suppressed proliferation, migration, and invasion of tumor cells, whereas overexpression of GMPS performed oppositely.

Conclusion

The results shine light on fundamental mechanisms of metabolic genes on PDAC and establish a reliable and referable signature to evaluate the prognosis of PDAC. GMPS was identified as a potential candidate oncogene with in PDAC, which can be a novel biomarker and therapeutic target for PDAC treatment.
A reciprocal feedback of miR-548ac/YB-1/Snail induces EndMT of HUVECs during acidity microenvironment
Authors: Chen Jingyuan , Han Shengbo , Chen Jinhuang , Hu Ping , Zeng Zhu , Hu Yuhang , Xiong Hewei , Ke Zunxiang , Zhang Ya , Xu Fengyu , Zhao Gang
Published: December 2021

Background

Researches indicated the process of Endothelial-Mesenchymal-Transition (EndMT) of vascular endothelial cells (ECs) was critically involved in the progression of tumor. ECs demonstrated functional and phenotypic heterogeneity when located under different microenvironments. The extracellular pH of tumor tissues was acidic compared to that of normal tissues. However, there was still unclear whether the acidic microenvironment affected the EndMT of vascular ECs.

Methods

Human Umbilical Vein Endothelial Cell (HUVECs) was cultured under the normal or acidic medium to evaluate the alteration of morphology, migration, permeability, and EndMT markers. Microarray assay was adopted to analyze the differential expression of miRNAs in the acidity-treated HUVECs. Gain- and loss- of function experiments were performed to evaluate the functional role of miRNA-548ac on acidity-induced EndMT of HUVECs. Luciferase reporter and Chromatin-immunoprecipitation assays were conducted to assess the downstream pathway of miRNA-548ac in acidity-induced EndMT of HUVECs.

Results

Our results showed that HUVECs demonstrated mesenchymal transition under acidic conditions with the increase of migration, permeability, and expression of α-SMA and Vimentin, but the expression of vascular endothelial cadherin (VE-cadherin) and CD31 were reduced. In addition, the acidity-treated HUVECs remarkably facilitated the transmigration of pancreatic cancer cells. The expression of miRNA-548ac was significantly decreased in the acidity-treated HUVECs. Moreover, overexpression of miR-548ac inhibited the EndMT of HUVECs and consequently impeded the transmigration of pancreatic cancer cells. The miR-548ac inhibited the expression of YB-1 by binding to the 3’UTR of its mRNA, and YB-1 promoted the translation of Snail which was a critical regulator of EndMT. What’s more, Snail transcriptionally inhibited the expression of miR-548ac through binding to the promoter of its host gene.

Conclusions

Our data implicated that the acidic microenvironment promoted the EndMT of HUVECs by the miR-548ac/YB-1/Snail axis, which could contribute to the metastasis of pancreatic cancer.
SYT7 acts as an oncogene and a potential therapeutic target and was regulated by ΔNp63α in HNSCC
Authors: Fu You , Tian Guocai , Zhang Zhiyuan , Yang Xiao
Published: December 2021

Background

Head and neck squamous cell carcinoma (HNSCC) are one of the most common types of head and neck cancer, and it is urgent to find effective treatment for advanced patients. Exploring developing and progressing mechanisms of HNSCC could provide a theoretical basis to find new therapeutic targets.

Methods

In our research, we performed a whole-gene expression profile microarray analysis to identify differential expression genes between squamous cell carcinoma cells and ΔNp63 alpha (ΔNp63α) knockdown cells. As a result, an important gene Synaptotagmin VII (SYT7) was screened out.

Results

SYT7 knockdown affected the proliferation, apoptosis and cell cycle of squamous cell carcinoma cells. The rescue experiment in vitro with ΔNp63α and SYT7 double knockdown resulted in partial reversion of ΔNp63α-induced phenotypes. This was also confirmed by experiments in vivo.

Conclusions

Taken together, we found that ΔNp63α could inhibit the occurrence and progression of HNSCC throughout downregulating the expression of SYT7. Therefore, SYT7/ΔNp63α axis could be a potential therapeutic target for clinical treatment of HNSCC.
Platelet-activating factor acetyl hydrolase IB2 dysregulated cell proliferation in ovarian cancer
Authors: He YingYing , He Zhicheng , Zhang Xiaoyu , Liu Shubai
Published: December 2021

Background

Ovarian cancer is the leading cause of death from gynaecologic illnessed worldwide. Platelet-activating factor acetyl hydrolase IB2 (PAF-AH IB2) is an intracellular serine esterase that hydrolyzes platelet-activating factor, a G-protein-like trimer with two catalytic subunits and one regulatory subunit. The regulatory role of PAF-AH IB2 in the oncogenesis of ovarian cancer is not well understood.

Methods

In this study, the TCGA dataset and clinical cancer tissue microarray were utilized to investigate abnormal overexpression of PAF-AH IB2 in ovarian cancer. To investigate the impact on the cell proliferation, migration, and tumorigenicity in vitro, PAF-AH IB2 stable knocking down (KD) ovarian cancer cells were established by ShRNA. The whole transcription profiling, tyrosine kinase profiling and standard cell functional assays were integrated to explore the biological importance and mechanism of PAF-AH IB2 modulated in ovarian cancer.

Results

PAF-AH IB2 was identified significantly overexpression in four subtypes of ovarian cancer. In vitro, PAF-AH IB2 KD significantly inhibited cancer cell proliferation, migration, and tumorigenicity, activated caspases and caused cell cycle arrest, and made the cells more sensitive to PAF. PAF-AH 1B2 KD cells down-regulated several key regulators of the multiple tyrosine kinases-mediated signaling pathway, suggesting a novel interaction network between the growth factor receptors pathway and PAF-AH 1B2 mediated PAF signalling.

Conclusions

These findings revealed a previously undiscovered role for PAF-AH IB2 as a potenial therapy target and essential signaling mediators in ovarian cancer pathogenesis, as well as new possible preventive and therapeutic strategies to inhibit this enzyme in clinical treatment for ovarian cancer.
The use of respondent‑driven sampling to assess febrile illness treatment-seeking behaviours among forest-goers in Cambodia and Vietnam
Authors: Paudel Mahesh , Tesfazghi Kemi , Nguyen Hoa , Phok Sochea , Srinivasan Shwetha , Wheeler Jennifer
Published: December 2021

Background

Countries in the Greater Mekong sub-region (GMS) aim to eliminate all forms of malaria by 2030. In Cambodia and Vietnam, forest-goers are at an increased risk of malaria. Universal access to prompt diagnosis and treatment is a core malaria intervention. This can only be achieved by understanding the healthcare-seeking behaviour among the most vulnerable groups and eliminating barriers to prompt and effective treatment. This study aimed to explore healthcare-seeking behaviours for febrile illness among populations at risk for malaria in Cambodia and Vietnam.

Methods

In 2019, researchers from Population Services International (PSI) conducted a population-based survey of forest-goers in Cambodia and Vietnam using respondent-driven sampling (RDS) In Cambodia two operational districts, Oral and Phnom Srouch in Kampong Speu Province were included in the study. In Vietnam, communes located within 15 km of the forest edge in Binh Phuoc and Gia Lai Provinces were selected. Adults who had spent at least one night per week or four nights per month in the forest over the previous three months were eligible for the study.

Results

Some 75% of forest-goers in Cambodia and 65% in Vietnam sought treatment for illness outside the home. In Cambodia, 39% sought treatment from the private sector, 32% from community health workers, and 24% from public health facilities. In Vietnam, 62% sought care from community facilities, 29.3% from the private sector, and 6.9% went to a public facility. Among forest-goers who sought care, 33% in Cambodia and 52% in Vietnam did so within 24 h.

Conclusions

This study is consistent with others that show that early diagnosis and treatment of malaria remains an obstacle to malaria elimination. This study also demonstrates that there are gaps in timeliness of care seeking among forest-goers. The findings from this study around provider preference and delays in treatment-seeking can be used to strengthen the design and targeting of malaria interventions and social and behaviour change strategies to accelerate malaria elimination in Cambodia and Vietnam.
Haematological response in experimental human Plasmodium falciparum and Plasmodium vivax malaria
Authors: Woolley Stephen D. , Marquart Louise , Woodford John , Chalon Stephan , Moehrle Joerg J. , McCarthy James S. , Barber Bridget E.
Published: December 2021

Background

Malaria-associated anaemia, arising from symptomatic, asymptomatic and submicroscopic infections, is a significant cause of morbidity worldwide. Induced blood stage malaria volunteer infection studies (IBSM-VIS) provide a unique opportunity to evaluate the haematological response to early Plasmodium falciparum and Plasmodium vivax infection.

Methods

This study was an analysis of the haemoglobin, red cell counts, and parasitaemia data from 315 participants enrolled in IBSM-VIS between 2012 and 2019, including 269 participants inoculated with the 3D7 strain of P. falciparum (Pf3D7), 15 with an artemisinin-resistant P. falciparum strain (PfK13) and 46 with P. vivax. Factors associated with the fractional fall in haemoglobin (Hb-FF) were evaluated, and the malaria-attributable erythrocyte loss after accounting for phlebotomy-related losses was estimated. The relative contribution of parasitized erythrocytes to the malaria-attributable erythrocyte loss was also estimated.

Results

The median peak parasitaemia prior to treatment was 10,277 parasites/ml (IQR 3566–27,815), 71,427 parasites/ml [IQR 33,236–180,213], and 34,840 parasites/ml (IQR 13,302–77,064) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. The median Hb-FF was 10.3% (IQR 7.8–13.3), 14.8% (IQR 11.8–15.9) and 11.7% (IQR 8.9–14.5) in those inoculated with Pf3D7, PfK13 and P. vivax, respectively, with the haemoglobin nadir occurring a median 12 (IQR 5–21), 15 (IQR 7–22), and 8 (IQR 7–15) days following inoculation. In participants inoculated with P. falciparum, recrudescence was associated with a greater Hb-FF, while in those with P. vivax, the Hb-FF was associated with a higher pre-treatment parasitaemia and later day of anti-malarial treatment. After accounting for phlebotomy-related blood losses, the estimated Hb-FF was 4.1% (IQR 3.1–5.3), 7.2% (IQR 5.8–7.8), and 4.9% (IQR 3.7–6.1) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Parasitized erythrocytes were estimated to account for 0.015% (IQR 0.006–0.06), 0.128% (IQR 0.068–0.616) and 0.022% (IQR 0.008–0.082) of the malaria-attributable erythrocyte loss in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively.

Conclusion

Early experimental P. falciparum and P. vivax infection resulted in a small but significant fall in haemoglobin despite parasitaemia only just at the level of microscopic detection. Loss of parasitized erythrocytes accounted for < 0.2% of the total malaria-attributable haemoglobin loss.