bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric Invasive Pneumococcal Disease (IPD) in Yogyakarta, Indonesia: A Case Series
Authors: Arguni Eggi , Wijaya Conroy Surya , Indrawanti Ratni , Safitri Laksono Ida , Ishiwada Naruhiko
Published: June 2022

Given the fact that invasive pneumococcal disease (IPD) has a high clinical burden, particularly among children in developing countries, data on its occurrence and clinical profile in Indonesia is still insufficient. We presented 3 cases of IPD in children who were admitted to Dr. Sardjito General Hospital, Yogyakarta, Indonesia between 2016 and 2019. While our first 2 patients had milder course of disease, our third patient who presented with meningoencephalitis had poor outcome. Risk factors shown in our cases were young age and malignancy history. Multiple antibiotic resistance was observed in our isolates. The fact that none of our patients have received pneumococcal vaccination marks the necessity of this vaccine especially for at-risk children.
The Missiological Challenge of the Anonymous Missionary in the Nordic Context
Authors: Kääriäinen Jukka
Published: June 2022

At the intersection of international development and Christian mission, are we in an era of the “anonymous missionary”? Karl Rahner proposed the “anonymous Christian” for understanding the religious other. Analogously, can a secular development professional, employed by a Christian mission agency, be considered an “anonymous missionary”? Can a professional hold a personal, secular identity while publicly representing an employer’s Christian identity? Is such hybrid identity missiologically tenable? In this article, I will constructively critique this growing trend, highlight its missiological incoherencies, identify the missiological challenges it poses, and underscore the indispensable role of missionary faith and spirituality.
Use of Bayes factors to evaluate the effects of host genetics, litter and cage on the rabbit cecal microbiota
Authors: Velasco-Galilea María , Piles Miriam , Ramayo-Caldas Yuliaxis , Varona Luis , Sánchez Juan Pablo
Published: June 2022

Background

The rabbit cecum hosts and interacts with a complex microbial ecosystem that contributes to the variation of traits of economic interest. Although the influence of host genetics on microbial diversity and specific microbial taxa has been studied in several species (e.g., humans, pigs, or cattle), it has not been investigated in rabbits. Using a Bayes factor approach, the aim of this study was to dissect the effects of host genetics, litter and cage on 984 microbial traits that are representative of the rabbit microbiota.

Results

Analysis of 16S rDNA sequences of cecal microbiota from 425 rabbits resulted in the relative abundances of 29 genera, 951 operational taxonomic units (OTU), and four microbial alpha-diversity indices. Each of these microbial traits was adjusted with mixed linear and zero-inflated Poisson (ZIP) models, which all included additive genetic, litter and cage effects, and body weight at weaning and batch as systematic factors. The marginal posterior distributions of the model parameters were estimated using MCMC Bayesian procedures. The deviance information criterion (DIC) was used for model comparison regarding the statistical distribution of the data (normal or ZIP), and the Bayes factor was computed as a measure of the strength of evidence in favor of the host genetics, litter, and cage effects on microbial traits. According to DIC, all microbial traits were better adjusted with the linear model except for the OTU present in less than 10% of the animals, and for 25 of the 43 OTU with a frequency between 10 and 25%. On a global scale, the Bayes factor revealed substantial evidence in favor of the genetic control of the number of observed OTU and Shannon indices. At the taxon-specific level, significant proportions of the OTU and relative abundances of genera were influenced by additive genetic, litter, and cage effects. Several members of the genera Bacteroides and Parabacteroides were strongly influenced by the host genetics and nursing environment, whereas the family S24-7 and the genus Ruminococcus were strongly influenced by cage effects.

Conclusions

This study demonstrates that host genetics shapes the overall rabbit cecal microbial diversity and that a significant proportion of the taxa is influenced either by host genetics or environmental factors, such as litter and/or cage.
Comparative genomics analysis and virulence-related factors in novel Aliarcobacter faecis and Aliarcobacter lanthieri species identified as potential opportunistic pathogens
Authors: Chuan Jiacheng , Belov Anatoly , Cloutier Michel , Li Xiang , Khan Izhar U. H. , Chen Wen
Published: June 2022

Background

Emerging pathogenic bacteria are an increasing threat to public health. Two recently described species of the genus Aliarcobacter, A. faecis and A. lanthieri, isolated from human or livestock feces, are closely related to Aliarcobacter zoonotic pathogens (A. cryaerophilus, A. skirrowii, and A. butzleri). In this study, comparative genomics analysis was carried out to examine the virulence-related, including virulence, antibiotic, and toxin (VAT) factors in the reference strains of A. faecis and A. lanthieri that may enable them to become potentially opportunistic zoonotic pathogens.

Results

Our results showed that the genomes of the reference strains of both species have flagella genes (flaA, flaB, flgG, flhA, flhB, fliI, fliP, motA and cheY1) as motility and export apparatus, as well as genes encoding the Twin-arginine translocation (Tat) (tatA, tatB and tatC), type II (pulE and pulF) and III (fliF, fliN and ylqH) secretory pathways, allowing them to secrete proteins into the periplasm and host cells. Invasion and immune evasion genes (ciaB, iamA, mviN, pldA, irgA and fur2) are found in both species, while adherence genes (cadF and cj1349) are only found in A. lanthieri. Acid (clpB), heat (clpA and clpB), osmotic (mviN), and low-iron (irgA and fur2) stress resistance genes were observed in both species, although urease genes were not found in them. In addition, arcB, gyrA and gyrB were found in both species, mutations of which may mediate the resistance to quaternary ammonium compounds (QACs). Furthermore, 11 VAT genes including six virulence (cadF, ciaB, irgA, mviN, pldA, and tlyA), two antibiotic resistance [tet(O) and tet(W)] and three cytolethal distending toxin (cdtA, cdtB, and cdtC) genes were validated with the PCR assays. A. lanthieri tested positive for all 11 VAT genes. By contrast, A. faecis showed positive for ten genes except for cdtB because no PCR assay for this gene was available for this species.

Conclusions

The identification of the virulence, antibiotic-resistance, and toxin genes in the genomes of A. faecis and A. lanthieri reference strains through comparative genomics analysis and PCR assays highlighted the potential zoonotic pathogenicity of these two species. However, it is necessary to extend this study to include more clinical and environmental strains to explore inter-species and strain-level genetic variations in virulence-related genes and assess their potential to be opportunistic pathogens for animals and humans.
A cross-sectional study describing peripheral neuropathy in patients with symptoms of gastroparesis: associations with etiology, gastrointestinal symptoms, and gastric emptying
Authors: Moors Victoria J. , Graveran Kathleen D. , Shahsavari Dariush , Parkman Henry P.
Published: June 2022

Background

Peripheral neuropathy (PN) is present in diabetic gastroparesis but is not described in idiopathic gastroparesis.

Aims

(1) Determine prevalence of PN in idiopathic gastroparesis; (2) assess if patients with symptoms of gastroparesis and PN differ in gastric emptying and symptoms, both gastrointestinal and psychosocial, from patients without PN (nPN); (3) compare this relationship to that in other etiological groups.

Methods

250 patients with symptoms of gastroparesis underwent gastric emptying scintigraphy and answered questionnaires including severity of gastroparesis symptoms using the Gastroparesis Cardinal Symptom Index (GCSI) and presence of peripheral neuropathy using the Neuropathy Total Symptom Score-6 (NTSS-6).

Results

PN, defined by NTSS-6 > 6, was present in 70/250 (28%) patients: 22/148 (15%) idiopathic, 33/61 (54%) diabetic, and 11/32 (34%) postsurgical (p < 0.01). Among 148 patients with symptoms of idiopathic gastroparesis, defined as non-diabetic, non-postsurgical, and not caused by a known disorder such as Parkinson’s or connective tissue disease, symptoms of gastroparesis were more severe in PN than nPN: bloating (4.05 ± 1.17 vs. 2.99 ± 1.61, p < 0.01), abdominal distension (3.86 ± 1.49 vs. 2.45 ± 1.68, p < 0.01), and upper abdominal pain (3.64 ± 1.22 vs. 2.71 ± 1.78, p = 0.03). Ninety-nine idiopathic patients underwent gastric emptying scintigraphy: 7/43 (16%) patients with delayed gastric emptying and 9/56 (16%) patients with normal gastric emptying had PN. Among patients with idiopathic gastroparesis, abdominal distension (4.43 ± 0.53 vs. 2.89 ± 1.68, p = 0.01) was more severe in PN than nPN. The association of PN and worse gastrointestinal symptoms was not as apparent in patients with symptoms of diabetic or postsurgical gastroparesis.

Conclusions

PN was present in 70/250 (28%) of patients with symptoms of gastroparesis and was present to a lesser extent in idiopathic than diabetic gastroparesis. The presence of PN in IG was associated with more severe gastroparetic symptoms than in nPN. Screening for PN may help identify a gastroparesis cohort with peripheral neuropathy who are more symptomatic.
Feasibility of screening for critical congenital heart disease using pulse oximetry in Indonesia
Authors: Murni Indah K. , Wibowo Tunjung , Arafuri Nadya , Oktaria Vicka , Dinarti Lucia K. , Panditatwa Dicky , Patmasari Linda , Noormanto Noormanto , Nugroho Sasmito
Published: June 2022

Background

Screening of critical congenital heart disease (CCHD) using pulse oximetry is a routine procedure in many countries, but not in Indonesia. This study aimed to evaluate the feasibility of implementing CCHD screening with pulse oximetry for newborns in Yogyakarta, Indonesia.

Methods

A cross-sectional study was conducted at four hospitals in Yogyakarta, Indonesia. Newborns aged 24–48 hours who met the inclusion criteria were screened on the right hand and left or right foot using a pulse oximeter. Positive results were indicated by: either (1) SpO2 level < 90% in one extremity, (2) SpO2 level of 90–94% in both right hand and either foot on three measurements conducted 1 hour apart, or (3) a saturation difference > 3% between the upper and lower extremity on three measurements conducted 1 hour apart. Positive findings were confirmed by echocardiography.

Results

Of 1452 newborns eligible for screening, 10 had positive results and were referred for echocardiographic evaluation. Of those, 8 (6 per 1000 live birth, 8/1452) had CCHD. Barriers found during screening processes were associated with hospital procedures, equipment, healthcare personnel, and condition of the newborn.

Conclusion

Pulse oximetry screening might be feasible to be implemented within the routine newborn care setting for CCHD in Indonesia. In order to successfully implement pulse oximetry screening to identify CCHD in Indonesia, the barriers will need to be addressed.
Speaking COVID-19: supporting COVID-19 communication and engagement efforts with people from culturally and linguistically diverse communities
Authors: Seale Holly , Harris-Roxas Ben , Heywood Anita , Abdi Ikram , Mahimbo Abela , Chauhan Ashfaq , Woodland Lisa
Published: June 2022

Background

Since the emergence of COVID-19, issues have been raised regarding the approach used to engage with Culturally and Linguistically Diverse (CaLD) communities during this public health crisis. This study aimed to understand the factors impacting communication and engagement efforts during the COVID-19 pandemic from the perspective of crucial CaLD community stakeholders and opinion leaders.

Methods

Forty-six semi-structured telephone interviews were undertaken with key stakeholders who have an active role (established before the pandemic) in delivering services and other social support to CaLD communities in Australia.

Results

Seven key themes emerged: (1) the digital divide and how to connect with people; (2) information voids being filled by international material; (3) Differentiating established with new and emerging communities’ needs; (4) speaking COVID-19; (5) ineffectiveness of direct translations of English language resources; (6) coordination is needed to avoid duplication and address gaps and (7) recognising the improvements in governments’ approach.

Conclusion

Alliances must be set up that can be activated in the future to reduce issues around resource development, translation, and dissemination of messages to minimise gaps in the response. Financial assistance must be provided in a timely way to community organisations to support the development and dissemination of culturally appropriate communication materials.
Evaluation the association of facet tropism in multi-sports athletes with cervical disc hernia
Authors: Eroglu Ali , Eroglu Ahmet
Published: June 2022

Background

Facet tropism (FT) can be defined as the angular difference between the orientation of the right and left facet joints in axial or sagittal planes. Most studies discuss about the relationship with lumbar disc hernia and facet joint angle. However, little is known about the association of facet tropism with disc herniation in the cervical spine in multisports athletes. In this study, We aimed to investigate the relationship between cervical facet tropism and disc hernia in athletes of different branches between the ages of 20–40 from the cervical MR images of the cases.

Methods

This is a retrospective study performed on athletes who applied our hospital between January 2014–2019 with neck pain and have MR imaging of the cervical spine. Cervical MR images of the patients were evaluated by an experienced radiologist from the hospital system database and archives. 79 cases (52 men and 27 women) were included in the study.

Results

No statistically significant difference was found between the facet joint angles of both groups at all levels (p˃0.05). Only left C6-7 disc angles of CDH group were measured as 92.99° ± 10.770 (620–1130) and 88.58° ± 7.65° (67°-110°) for the normal group and this difference was found statistically significant (p = 0.007).

Conclusion

In this study, we did not predict that cervical facet tropism may be a factor associated with cervical disc hernia in young athletes with CDH.
Biomechanical effects of an oblique lumbar interbody fusion combined with posterior augmentation: a finite element analysis
Authors: Huang Shengjia , Min Shaoxiong , Wang Suwei , Jin Anmin
Published: June 2022

Background

Oblique lateral interbody fusion (OLIF) is widely used to treat lumbar degenerative disc disease. This study aimed to evaluate the biomechanical stability of OLIF, OLIF including posterior pedicle screw and rod (PSR), and OLIF including cortical screw and rod (CSR) instrumentation through finite element analysis.

Methods

A complete L2-L5 finite element model of the lumbar spine was constructed. Surgical models of OLIF, such as stand-alone, OLIF combined with PSR, and OLIF combined with CSR were created in the L3-L4 surgical segments. Range of motion (ROM), end plate stress, and internal fixation peak stress were compared between different models under the same loading conditions.

Results

Compared to the intact model, ROM was reduced in the OLIF model under all loading conditions. The surgical models in order of increasing ROM were PSR, CSR, and stand-alone; however, the difference in ROM between BPS and CSR was less than 0.4° and was not significant under any loading conditions. The stand-alone model had the highest stress on the superior L4 vertebral body endplate under all loading conditions, whereas the end plate stress was relatively low in the BPS and CSR models. The CSR model had the highest internal fixation stress, concentrated primarily at the end of the screw.

Conclusions

OLIF alone significantly reduces ROM but does not provide sufficient stability. Addition of posterior PSR or CSR internal fixation instrumentation to OLIF surgery can significantly improve biomechanical stability of the segment undergoing surgery.
Risk assessment of the work-related musculoskeletal disorders based on individual characteristics using path analysis models
Authors: Darvishi Ebrahim , Ghasemi Fakhradin , Sadeghi Fateme , Abedi Kamaladdin , Rahmati Somaye , Sadeghzade Ghazale
Published: June 2022

Background

This study aimed to assess the risk of work-related musculoskeletal disorders (WMSDs) using the path analysis models.

Methods

This study was carried out on 350 office employees with good general health. All variables were collected using a questionnaire. Personality traits and mental workload of employees were evaluated using the NEO Personality Inventory and the NASA-task load index software, respectively. The individual and personality traits were used as predictor variables, and mental workload (MWL) and body posture scores as mediating variables of the musculoskeletal discomforts. The role of predictor and mediating variables on discomforts was explained based on the path analysis models.

Results

The impact coefficient of MWL and posture on WMSDs was significant. The coefficient of the direct effect of body mass index (BMI) and gender on musculoskeletal disorders was significant and positive and the women have reported a higher rate of discomforts. The strongest positive impact of personality traits on MWL and posture was conscientiousness, followed by neuroticism and agreeableness. In return, the strongest negative impact was extroversion, followed by openness. The strongest positive impact of individual factors on MWL and posture was BMI, followed by work experience.

Conclusion

Gender, BMI, neuroticism, extraversion, and conscientiousness can be strong predictors for musculoskeletal discomforts which can mediate the impact of body posture and mental workload (mediating factors) on musculoskeletal discomfort. Therefore, personality and individual traits can be strong alarming and indicators for risk identification and preventing musculoskeletal disorders when choosing people for a job or task.
Effect of parental attitudes on the practice and medicalization of female genital mutilation: a secondary analysis of Egypt Health Issues Survey, 2015
Authors: Aziz Mirette , Elgibaly Omaima , Ibrahim Fatma Elzahraa
Published: June 2022

Background

Despite the observed decrease in female genital mutilation (FGM) prevalence, it is increasingly being medicalized. We examined the attitudes of both parents towards the FGM practice in Egypt, and highlighted the effect of fathers’ decision making and attitudes towards FGM and violence on FGM practice and medicalization.

Methods

This study is a secondary analysis of Egypt Health Issues Survey (EHIS), 2015. The 2015 EHIS involved a systematic random selection of a subsample of 614 Shiakhas/villages out of the 884 shiakhas/villages that had been chosen as Primary Sampling Units in the 2014 EDHS. Descriptive statistics of the study sample and parents’ attitudes was performed. Three indices were created describing; mothers’ and fathers’ attitudes towards FGM, decision making and rejecting violence against women. Bivariate and multivariable analyses were conducted to identify predictors of FGM practice and medicalization.

Results

A considerable proportion of EHIS girls; 16.4% were circumcised and 36% of girls were expected to be circumcised. More than two thirds of circumcised girls were circumcised by a physician; namely 67% and 13.5% by nurses. The majority of mothers (88.4%) and fathers (84.8%) believed that FGM practice should continue. They believed that FGM is a religious obligation (72.3% of mothers and 73% of fathers). Parents believed that husbands prefer a circumcised wife (81.1% and 82.5% of mothers and fathers respectively). Being in the poorest wealth quintile (OR = 4.2, p < 0.001) and living in rural Upper Egypt (OR = 4.55, p < 0.001) were the predictors of FGM practice, while medicalization was more likely among the rich and educated parents. Parents’ attitudes supporting FGM was significantly associated with its practice (OR = 1.97, p < 0.001, for mothers and OR = 1.27, p < 0.001, for fathers). Rejecting violence against women was associated with less likelihood of practicing FGM (OR = 0.89, p < 0.05) and more likelihood of its medicalization (OR = 1.25, p < 0.01).

Conclusion

More attention should be paid to enforce the laws against FGM practice by health care providers. Raising the community awareness on girls’ human rights and elimination of FGM practice which is a severe form of violence against women and gender inequality in sexual rights should be prioritized with targeting men in FGM programs.
Light regulates the degradation of the regulatory protein VE-1 in the fungus Neurospora crassa
Authors: Gil-Sánchez María del Mar , Cea-Sánchez Sara , Luque Eva M. , Cánovas David , Corrochano Luis M.
Published: June 2022

Background

Fungi use light as an environmental signal to regulate developmental transitions that are key aspects of their biological cycles and that are also relevant for their dispersal and infectivity as plant or animal pathogens. In addition, light regulates the accumulation of photoprotective pigments, like carotenoids, and other secondary metabolites. Most fungal light responses occur after changes in gene transcription and we describe here a novel effect of light in the regulation of degradation of VE-1, a key component of the velvet complex, in the model fungus Neurospora crassa. The velvet complex is a fungal-specific protein complex that coordinates fungal development, secondary metabolism, and light regulation by interacting with other regulators and photoreceptors and modifying gene expression.

Results

We have characterized the role of VE-1 during conidiation in N. crassa. In vegetative mycelia, VE-1 is localized in the cytoplasm and nuclei and is required for light-dependent transcription but does not interact with the photoreceptor and transcription factor WC-1. VE-1 is more stable in light than in darkness during asexual development (conidiation). We have shown that this light effect requires the blue-light photoreceptor WC-1. We have characterized the role of the proteasome, the COP9 signalosome (CSN), and the adaptor component of cullin-RING ubiquitin ligases, FWD-1, in the degradation of VE-1.

Conclusions

We propose that this new effect of light allows the fungal cell to adapt quickly to changes in light exposure by promoting the accumulation of VE-1 for the regulation of genes that participate in the biosynthesis of photoprotective pigments.
Differential proteomics of placentas reveals metabolic disturbance and oxidative damage participate yak spontaneous miscarriage during late pregnancy
Authors: Pei Jie , Zhao Shoubao , Yin Mancai , Wu Fude , Li Jiye , Zhang Guomo , Wu Xiaoyun , Bao Pengjia , Xiong Lin , Song Weiru , Ba Yang , Yan Ping , Song Rende , Guo Xian
Published: June 2022

Background

High spontaneous miscarriage rate in yak, especially during late pregnancy, have caused a great economic loss to herdsmen living in the Qinghai-Tibet plateau. However, the mechanism underlying spontaneous miscarriage is still poorly understood. In the present study, placenta protein markers were identified to elucidate the pathological reasons for yak spontaneous miscarriage through isobaric tags for relative and absolute quantification (iTRAQ) proteomic technology and bioinformatic approaches.

Results

Subsequently, a total of 415 differentially expressed proteins (DEPs) were identified between aborted and normal placentas. The up-regulated DEPs in the aborted placentas were significantly associated with “spinocerebellar ataxia”, “sphingolipid signalling”, “relaxin signalling”, “protein export”, “protein digestion and absorption” and “aldosterone synthesis and secretion” pathway. While the down-regulated DEPs in the aborted placentas mainly participated in “valine, leucine and isoleucine degradation”, “PPAR signalling”, “peroxisome”, “oxidative phosphorylation”, “galactose metabolism”, “fatty acid degradation”, “cysteine and methionine metabolism” and “citrate cycle” pathway.

Conclusions

The results implied that the identified DEPs could be considered as placental protein markers for yak miscarriage during late pregnancy, and biomacromolecule metabolic abnormality and oxidative damage might be responsible for the high spontaneous miscarriage rate in yak. These findings provide an important theoretical basis for deciphering the pathologic mechanism of late spontaneous miscarriage in yak.
Comprehensive genetic testing improves the clinical diagnosis and medical management of pediatric patients with isolated hearing loss
Authors: Xiang Jiale , Jin Yuan , Song Nana , Chen Sen , Shen Jiankun , Xie Wen , Sun Xiangzhong , Peng Zhiyu , Sun Yu
Published: June 2022

Purpose

Genetic testing is widely used in diagnosing genetic hearing loss in patients. Other than providing genetic etiology, the benefits of genetic testing in pediatric patients with hearing loss are less investigated.

Methods

From 2018–2020, pediatric patients who initially presented isolated hearing loss were enrolled. Comprehensive genetic testing, including GJB2/SLC26A4 multiplex amplicon sequencing, STRC/OTOA copy number variation analysis, and exome sequencing, were hierarchically offered. Clinical follow-up and examinations were performed.

Results

A total of 80 pediatric patients who initially presented isolated hearing loss were considered as nonsyndromic hearing loss and enrolled in this study. The definitive diagnosis yield was 66% (53/80) and the likely diagnosis yield was 8% (6/80) through comprehensive genetic testing. With the aid of genetic testing and further clinical follow-up and examinations, the clinical diagnoses and medical management were altered in eleven patients (19%, 11/59); five were syndromic hearing loss; six were nonsyndromic hearing loss mimics.

Conclusion

Syndromic hearing loss and nonsyndromic hearing loss mimics are common in pediatric patients who initially present with isolated hearing loss. The comprehensive genetic testing provides not only a high diagnostic yield but also valuable information for clinicians to uncover subclinical or pre-symptomatic phenotypes, which allows early diagnosis of SHL, and leads to precise genetic counseling and changes the medical management.
Oxidoreduction potential controlling for increasing the fermentability of enzymatically hydrolyzed steam-exploded corn stover for butanol production
Authors: Xia Menglei , Wang Di , Xia Yiming , Shi Haijiao , Tian Zhongyu , Zheng Yu , Wang Min
Published: June 2022

Background

Lignocellulosic biomass is recognized as an effective potential substrate for biobutanol production. Though many pretreatment and detoxification methods have been set up, the fermentability of detoxicated lignocellulosic substrate is still far lower than that of starchy feedstocks. On the other hand, the number of recent efforts on rational metabolic engineering approaches to increase butanol production inClostridiumstrains is also quite limited, demonstrating the physiological complexity of solventogenic clostridia. In fact, the strain performance is greatly impacted by process control. developing efficient process control strategies could be a feasible solution to this problem.

Results

In this study, oxidoreduction potential (ORP) controlling was applied to increase the fermentability of enzymatically hydrolyzed steam-exploded corn stover (SECS) for butanol production. When ORP of detoxicated SECS was controlled at − 350 mV, the period of fermentation was shortened by 6 h with an increase of 27.5% in the total solvent (to 18.1 g/L) and 34.2% in butanol (to 10.2 g/L) respectively. Silico modeling revealed that the fluxes of NADPH, NADH and ATP strongly differed between the different scenarios. Quantitative analysis showed that intracellular concentrations of ATP, NADPH/NADP+, and NADH/NAD+were increased by 25.1%, 81.8%, and 62.5%. ORP controlling also resulted in a 2.1-fold increase in butyraldehyde dehydrogenase, a 1.2-fold increase in butanol dehydrogenase and 29% increase in the cell integrity.

Conclusion

ORP control strategy effectively changed the intracellular metabolic spectrum and significantly improvedClostridiumcell growth and butanol production. The working mechanism can be summarized into three aspects: First, Glycolysis and TCA circulation pathways were strengthened through key nodes such as pyruvate carboxylase [EC: 6.4.1.1], which provided sufficient NADH and NADPH for the cell. Second, sufficient ATP was provided to avoid “acid crash”. Third, the key enzymes activities regulating butanol biosynthesis and cell membrane integrity were improved.
SHTXTHHly, an extracellular secretion platform for the preparation of bioactive peptides and proteins in Escherichia coli
Authors: Zhu Wen , Wang Yang , Lv Liangyin , Wang Hui , Shi Wenqiang , Liu Zexin , Yang Wei , Zhu Jianwei , Lu Huili
Published: June 2022

Background

In previous work, we developed an E. coli extracellular secretion platform XTHHly based on the hemolysin A secretion system. It can produce bioactive peptides with simple purification procedures. However, the wider application of this platform is limited by poor secretion efficiency.

Results

In this study, we first discovered a positive correlation between the isoelectric point (pI) value of the target protein and the secretion level of the XTHHly system. Given the extremely high secretion level of S tag, we fused it at the N-terminus and created a novel SHTXTHHly system. The SHTXTHHly system significantly increased the secretion levels of antimicrobial peptides (PEW300, LL37, and Aurein 1.2) with full bioactivities, suggesting its excellent capacity for secretory production of bioactive peptides. Furthermore, RGDS, IL-15, and alcohol dehydrogenase were successfully secreted, and their bioactivities were largely maintained in the fusion proteins, indicating the potential applications of the novel system for the rapid determination of protein bioactivities. Finally, using the SHTXTHHly system, we produced the monomeric Fc, which showed a high affinity for Fcγ Receptor I and mediated the antibody-dependent immunological effects of immune cells, demonstrating its potential applications in immunotherapies.

Conclusions

The SHTXTHHly system described here facilitates the secretory production of various types of proteins in E. coli. In comparison to previously reported expression systems, our work enlightens an efficient and cost-effective way to evaluate the bioactivities of target proteins or produce them.

Graphical abstract
Health effects and cost-effectiveness of a multilevel physical activity intervention in low-income older adults; results from the PEP4PA cluster randomized controlled trial
Authors: Crist Katie , Full Kelsie M. , Linke Sarah , Tuz-Zahra Fatima , Bolling Khalisa , Lewars Brittany , Liu Chenyu , Shi Yuyan , Rosenberg Dori , Jankowska Marta , Benmarhnia Tarik , Natarajan Loki
Published: June 2022

Background

Older adults are the least active population in the U.S. Low-income communities have fewer physical activity (PA) resources, contributing to less PA and increased chronic disease risk. This study assessed the effect of the multilevel, peer-led, Peer Empowerment Program 4 Physical Activity (PEP4PA) on moderate-to-vigorous PA (MVPA) and health outcomes, over 2 years of follow up.

Methods

In a cluster-randomized controlled trial, 12 senior or community centers serving low-income older adults were assigned to a PA intervention (n = 6) or usual programming (n = 6) condition. PEP4PA included self-monitoring, health coaching, group walks, social support, and community advocacy to improve walking conditions. The primary outcome was daily minutes of MVPA (7-day accelerometer). Secondary outcomes included Perceived Quality of Life (PQoL), 6-Minute Walk Test (6-MWT), blood pressure (BP), and depressive symptoms at baseline, 6, 12, 18 and 24 months. Mixed effects regression models estimated the effects on outcomes between groups over time and included random effects for repeated measures and center clustering. Effect modification by sex and income status was assessed. We calculated the incremental cost per daily minute of MVPA gained in the intervention group relative to the control group to assess cost effectiveness.

Results

We enrolled 476 older adults (50 + years). Participants were on average 71 years old, 76% female, 60% low income, and 38% identified as racial or ethnic minorities. Compared to the control group, intervention participants sustained roughly a 10 min/day increase in MVPA from baseline at all time points and increased mean PQoL scores from unsatisfied at baseline to satisfied at 12, 18 and 24 months. Males and higher-income groups had greater improvements in MVPA. No significant effects were observed for 6-MWT or depressive symptoms, and BP results were mixed. The incremental cost per minute MVPA gained per person was $0.25, $0.09, $0.06, and $0.05 at 6, 12, 18 and 24 months, respectively.

Conclusions

PEP4PA achieved increases in MVPA and PQoL in low-income older adults, over 2 years of follow up. The peer-led, community-based intervention provides a sustainable and cost-effective model to improve health behaviors in underserved, aging populations.

Trial registration

ClinicalTrials.gov (NCT02405325) March 20, 2015.
Role of exosomes in the pathogenesis, diagnosis, and treatment of central nervous system diseases
Authors: Fan Yishu , Chen Zhuohui , Zhang Mengqi
Published: June 2022

Central nervous system (CNS) diseases, such as multiple sclerosis, Alzheimer's disease (AD), and Parkinson’s disease (PD), affect millions of people around the world. Great efforts were put in disease related research, but few breakthroughs have been made in the diagnostic and therapeutic approaches. Exosomes are cell-derived extracellular vesicles containing diverse biologically active molecules secreted by their cell of origin. These contents, including nucleic acids, proteins, lipids, amino acids, and metabolites, can be transferred between different cells, tissues, or organs, regulating various intercellular cross-organ communications and normal and pathogenic processes. Considering that cellular environment and cell state strongly impact the content and uptake efficiency of exosomes, their detection in biological fluids and content composition analysis potentially offer a multicomponent diagnostic readout of several human diseases. Recently, studies have found that aberrant secretion and content of exosomes are closely related to the pathogenesis of CNS diseases. Besides, loading natural cargoes, exosomes can deliver drugs cross the blood brain barrier, making them emerging candidates of biomarkers and therapeutics for CNS diseases. In this review, we summarize and discuss the advanced research progress of exosomes in the pathological processes of several CNS diseases in regarding with neuroinflammation, CNS repair, and pathological protein aggregation. Moreover, we propose the therapeutic strategies of applying exosomes to the diagnosis, early detection, and treatment of CNS diseases.
Targeted BRD4 protein degradation by dBET1 ameliorates acute ischemic brain injury and improves functional outcomes associated with reduced neuroinflammation and oxidative stress and preservation of blood–brain barrier integrity
Authors: Liu Lei , Yang Changjun , Lavayen Bianca P. , Tishko Ryland J. , Larochelle Jonathan , Candelario-Jalil Eduardo
Published: June 2022

Bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra-terminal domain (BET) protein family, plays a crucial role in regulating inflammation and oxidative stress that are tightly related to stroke development and progression. Consequently, BRD4 blockade has attracted increasing interest for associated neurological diseases, including stroke. dBET1 is a novel and effective BRD4 degrader through the proteolysis-targeting chimera (PROTAC) strategy. We hypothesized that dBET1 protects against brain damage and neurological deficits in a transient focal ischemic stroke mouse model by reducing inflammation and oxidative stress and preserving the blood–brain barrier (BBB) integrity. Post-ischemic dBET1 treatment starting 4 h after stroke onset significantly ameliorated severe neurological deficits and reduced infarct volume 48 h after stroke. dBET1 markedly reduced inflammation and oxidative stress after stroke, indicated by multiple pro-inflammatory cytokines and chemokines including IL-1β, IL-6, TNF-α, CCL2, CXCL1 and CXCL10, and oxidative damage markers 4-hydroxynonenal (4-HNE) and gp91phoxand antioxidative proteins SOD2 and GPx1. Meanwhile, stroke-induced BBB disruption, increased MMP-9 levels, neutrophil infiltration, and increased ICAM-1 were significantly attenuated by dBET1 treatment. Post-ischemic dBET1 administration also attenuated ischemia-induced reactive gliosis in microglia and astrocytes. Overall, these findings demonstrate that BRD4 degradation by dBET1 improves acute stroke outcomes, which is associated with reduced neuroinflammation and oxidative stress and preservation of BBB integrity. This study identifies a novel role of BET proteins in the mechanisms resulting in ischemic brain damage, which can be leveraged to develop novel therapies.
Duck hepatitis A virus type 1 mediates cell cycle arrest in the S phase
Authors: Liu Yuanzhi , Li Yanglin , Wang Mingshu , Cheng Anchun , Ou Xumin , Mao Sai , Sun Di , Wu Ying , Yang Qiao , Jia Renyong , Tian Bin , Zhang Shaqiu , Zhu Dekang , Chen Shun , Liu Mafeng , Zhao Xinxin , Huang Juan , Gao Qun , Yu Yanling , Zhang Ling
Published: June 2022

Background

Duck hepatitis A virus type 1 (DHAV-1) is one of the most serious pathogens endangering the duck industry. However, there are few studies on the regulation of the cell cycle by DHAV-1.

Methods

In this study, flow cytometry was applied to analyze the effect of DHAV-1 infection on the cell cycle of duck embryo fibroblasts (DEFs). Subsequently, we analyzed the effects of cell cycle phases on DHAV-1 replication by real-time reverse transcriptase quantitative PCR (real-time RT-qPCR).

Results

Flow cytometry data analysis found that DEFs in the S phase increased by 25.85% and 54.21% at 24 h and 48 h after DHAV-1 infection, respectively. The levels of viral RNA detected by real-time RT-qPCR were higher in the DEFs with synchronization in the S phase or G0/G1 phase than in the control group. However, there was no difference in viral copy number between the G2/M phase arrest and control groups. In addition, non-structural protein 3D of DHAV-1 significantly increased cells in the S phase, indicating that 3D protein is one of the reasons for the cell cycle arrest in the S phase.

Conclusions

In summary, DHAV-1 infection induces the cell cycle arrest of DEFs in the S phase. Both S phase and G0/G1 phase synchronization facilitate the replication of DHAV-1, and 3D protein is one of the reasons for the S phase arrest.
Cerebrospinal fluid osmolality cannot predict development or surgical outcome of idiopathic normal pressure hydrocephalus
Authors: Oernbo Eva Kjer , Steffensen Annette Buur , Gredal Hanne , Poulsen Helle Harding , Rostgaard Nina , Rasmussen Cecilie Holm , Møller-Nissen Marlene , Simonsen Anja Hviid , Hasselbalch Steen Gregers , Juhler Marianne , MacAulay Nanna
Published: June 2022

Background

The etiology of idiopathic normal pressure hydrocephalus (iNPH) is currently unknown. With no visible obstructions, altered cerebrospinal fluid (CSF) dynamics may explain the accumulation of ventricular fluid. We hypothesized that elevated osmolality in the CSF of iNPH patients could potentiate formation of ventricular fluid and thereby cause the disease progression and/or predict the surgical outcome. To address this hypothesis, we determined the lumbar and ventricular CSF osmolality of iNPH patients at different disease stages and compared with lumbar CSF samples obtained from control subjects.

Methods

The osmolality of CSF was determined on a total of 35 iNPH patients at diagnosis and at the subsequent treatment with shunt surgery (n = 20) and compared with the CSF osmolality from 20 control subjects. Simultaneously collected lumbar and ventricular CSF samples from experimental pigs were used to evaluate the compatibility between CSF from different compartments.

Results

We found no evidence of increased osmolality in the CSF of iNPH patients upon diagnosis or at the time of shunt treatment months after the diagnosis, compared with control individuals. CSF tapped from the lumbar space could be used as a read-out for ventricular CSF osmolality, as these were similar in both the patient group and in experimental pigs. We further observed no correlation between the CSF osmolality in iNPH patients and their responsiveness to shunt surgeries.

Conclusions

The osmolality of lumbar CSF is a reliable reflection of the ventricular CSF osmolality, and is not elevated in iNPH patients. iNPH therefore does not appear to arise as a function of osmotic imbalances in the CSF system and CSF osmolality cannot serve as a biomarker for iNPH or as a predictive tool for shunt responsiveness.
EBF1-mediated up-regulation of lncRNA FGD5-AS1 facilitates osteosarcoma progression by regulating miR-124-3p/G3BP2 axis as a ceRNA
Authors: Shuang Ou , Zhou Jianmin , Cai Zijun , Liao Longteng , Wang Yuehua , Wang Wenyu , Xu Meng
Published: June 2022

Background

As a skeletal malignancy, osteosarcoma has high incidence among primary malignant bone tumors. With increasing researches on molecules which mediate cancer progression, molecular mechanism has gradually become the pivot of osteosarcoma research and treatment.

Aim

Our study aimed at investigating the function of G3BP stress granule assembly factor 2 (G3BP2), which is an oncogene for breast cancer (BC) and prostate cancer but remains unknown in osteosarcoma cells.

Methods

Related gene expression was confirmed by RT-qPCR. Functional assays including immunofluorescence (IF), colony formation, transferase-mediated dUTP nick-end labeling (TUNEL) as well as transwell assays were utilized to test the cell biological process caused by the genes. Meanwhile, RNA pull-down assay, along with luciferase reporter and RNA immunoprecipitation (RIP) assays, was utilized to detect the interaction G3BP2, miR-124-3p and FGD5 antisense RNA 1 (FGD5-AS1) may exert on the regulation of osteosarcoma cells.

Results

G3BP2 was with high expression in osteosarcoma cells, and it aggravated the malignant cell behaviors in osteosarcoma. Additionally, miR-124-3p was verified to negatively regulate G3BP2 expression in osteosarcoma cells. Moreover, lncRNA FGD5-AS1 was predicted and testified to be the sponge of miR-124-3p and modulated G3BP2 expression positively. Subsequently, FGA5-AS1 accelerated osteosarcoma cell proliferation through up-regulating G3BP2. Furthermore, we identified EBF transcription factor 1 (EBF1) as the transcription factor for FGA5-AS1, and EBF1 served as a tumor facilitator in osteosarcoma cells.

Conclusion

EBF1 induced-FGA5-AS1 aggravated osteosarcoma cell malignancy by targeting miR-124-3p and G3BP2.
The role of NURR1 in metabolic abnormalities of Parkinson’s disease
Authors: Al-Nusaif Murad , Yang Yuting , Li Song , Cheng Cheng , Le Weidong
Published: June 2022

A constant metabolism and energy supply are crucial to all organs, particularly the brain. Age-dependent neurodegenerative diseases, such as Parkinson’s disease (PD), are associated with alterations in cellular metabolism. These changes have been recognized as a novel hot topic that may provide new insights to help identify risk in the pre-symptomatic phase of the disease, understand disease pathogenesis, track disease progression, and determine critical endpoints. Nuclear receptor-related factor 1 (NURR1), an orphan member of the nuclear receptor superfamily of transcription factors, is a major risk factor in the pathogenesis of PD, and changes in NURR1 expression can have a detrimental effect on cellular metabolism. In this review, we discuss recent evidence that suggests a vital role of NURR1 in dopaminergic (DAergic) neuron development and the pathogenesis of PD. The association between NURR1 and cellular metabolic abnormalities and its implications for PD therapy have been further highlighted.
Molecular cytogenetic characterization of a de novo derivative chromosome X with an unbalanced t(X;9) translocation in a fetus and literature review
Authors: Wu Qiong , Kong Hui , Shen Yanyan , Chen Jing
Published: June 2022

Partial trisomy 9p is one of the most frequent autosome anomalies in newborn infants featured by craniofacial dysmorphism, intellectual disability and psychomotor growth. Female patients carrying monosomy Xq usually show mild symptoms due to skewed X-chromosome inactivation (XCI). Unbalanced translocation between chromosome X and chromosome 9 is rare in prenatal diagnosis. The skewed inactivation of abnormal X would spread into the extra segment of chromosome 9 presented in the der(X) leading to mild phenotypes. We reported on a fetus with high risk of trisomy 9p(13.32 Mb 9p23-p24.3 duplication)suggested by noninvasive prenatal testing (NIPT), the fetus was normal by ultrasonography. G-banding with trypsin-giemsa (GTG), copy number variations sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were carried out to delineate the nature of rearrangement. Final karyotype of the fetus was identified as 46,X,der(X)t(X;9)(q27;p23)dn. An unbalanced X-autosome translocation with a deletion of Xqter-q27.2 and a duplication of 9pter-p23 led to mild phenotypes with no obvious alteration by prenatal ultrasonography, or obvious pathological alterations after pregnancy termination.