bluuebunny/crossref_metadata_2025 huggingface dataset:
Attenuated clinical and osteoclastic phenotypes of Paget’s disease of bone linked to the p.Pro392Leu/SQSTM1 mutation by a rare variant in the DOCK6 gene
Authors: Dessay Mariam , Couture Emile , Maaroufi Halim , Fournier Frédéric , Gagnon Edith , Droit Arnaud , Brown Jacques P. , Michou Laëtitia
Published: March 2022

Background

We identified two families with Paget's disease of bone (PDB) linked to the p.Pro392Leu mutation within the SQSTM1 gene displaying a possible digenism. This study aimed at identifying this second genetic variant cosegregating with the p.Pro392Leu mutation and at characterizing its impact on the clinical and cellular phenotypes of PDB.

Methods

Whole exome sequencing was performed in one patient per family and two healthy controls. We compared clinical characteristics of PDB in 14 relatives from the two families. The osteoclastic phenotype was compared in in vitro differentiated osteoclasts from 31 participants carrying the DOCK6 and/or SQSTM1 variants. Tridimensional models of SQSTM1 and DOCK6 proteins were generated to evaluate the impact of these variants on their stability and flexibility. Statistical analyses were performed with Graphpad prism.

Results

Whole-exome sequencing allowed us to identify the p.Val45Ile missense variant in the DOCK6 gene in patients. In both families, the mean age at PDB diagnosis was delayed in pagetic patients carrier of the p.Val45Ile variant alone compared to those carrying the p.Pro392Leu mutation alone (67 vs. 44 years, P = 0.03). Although both p.Val45Ile and p.Pro392Leu variants gave rise to a pagetic phenotype of osteoclast versus healthy controls, the p.Val45Ile variant was found to attenuate the severity of the osteoclastic phenotype of PDB caused by the p.Pro392Leu mutation when both variants were present. The DOCK6 mRNA expression was higher in carriers of the p.Val45Ile variant than in pagetic patients without any mutations and healthy controls. Structural bioinformatics analyses suggested that the p.Pro392Leu mutation might rigidify the UBA domain and thus decrease its possible intramolecular interaction with a novel domain, the serum response factor–transcription factor (SRF-TF)-like domain, whereas the p.Val45Ile variant may decrease SRF-TF-like activity.

Conclusion

The p.Val45Ile variant may attenuate the severity of the clinical phenotype of PDB in patient carriers of both variants. In vitro, the rare variant of the DOCK6 may have a modifier effect on the p.Pro392Leu mutation, possibly via its effect on the SRF-TF-like.
Pan-cancer analysis identifies LMNB1 as a target to redress Th1/Th2 imbalance and enhance PARP inhibitor response in human cancers
Authors: Qin Haixiang , Lu Yingqiang , Du Lin , Shi Jingyan , Yin Haoli , Jiang Bo , Chen Wei , Diao Wenli , Ding Meng , Cao Wenmin , Qiu Xuefeng , Zhao Xiaozhi , Guo Hongqian
Published: March 2022

Background

Emerging evidence suggests that LMNB1 is involved in the development of multiple cancer types. However, there is no study reporting the potential role of LMNB1 in a systematic pan-cancer manner.

Methods

The gene expression level and potential oncogenic roles of LMNB1 in The Cancer Genome Atlas (TCGA) database were analyzed with Tumor Immune Estimation Resource version 2 (TIMER2.0), Gene Expression Profiling Interactive Analysis version 2 (GEPIA2), UALCAN and Sangerbox tools. Pathway enrichment analysis was carried out to explore the possible mechanism of LMNB1 on tumorigenesis and tumor progression. The therapeutic effects of LMNB1 knockdown combined with PARP inhibition on human cancers were further investigated in vitro.

Results

LMNB1 upregulation is generally observed in the tumor tissues of most TCGA cancer types, and is verified in kidney renal clear cell carcinoma using clinical specimens of our institute. High level of LMNB1 expression usually predicts poor overall survival and disease free survival for patients with tumors. Mechanically, LMNB1 level is positively correlated with CD4+ Th2 cell infiltration and DNA homologous recombination repair gene expression. In vitro experiments reveal that targeting LMNB1 has a synergistic effect on prostate cancer with PARP inhibitor treatment.

Conclusions

LMNB1 is a biomarker of CD4+ Th2 cell infiltration and DNA homologous recombination repair in human cancers. Blockage of LMNB1 combined with PARP inhibitor treatment could be a promising therapeutic strategy for patients with cancers.
Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar
Authors: Huang Fang , Li Shigang , Tian Peng , Pu Lahpai Ja Seng , Cui Yanwen , Liu Hui , Yang Lianzhi , Bi Dahidam Yaw
Published: March 2022

Background

Anti-malarial drug resistance is still a major threat to malaria elimination in the Great Mekong Sub-region. Plasmodium vivax parasites resistant to anti-malarial drugs are now found in Myanmar. Molecular surveillance on drug resistance genes in P. vivax parasites from northeastern Myanmar was aimed at estimating the underlying drug resistance in this region.

Methods

Blood samples from patients with vivax malaria were collected from Laiza city in northeastern Myanmar in 2020. Drug resistance genes including Pvcrt-o, Pvmdr1, Pvdhfr and Pvdhps were amplified and sequenced. Genetic polymorphisms and haplotypes were analysed to evaluate the prevalence of mutant alleles associated with drug resistance.

Results

A total of 149 blood samples from P. vivax patients were collected. The prevalence of Pvmdr1 mutations at codons 958 and 1076 was 100.0% and 52.0%, respectively, whereas no single nucleotide polymorphism was present at codon 976. The proportions of single and double mutant types were 48.0% and 52.0%, respectively. A K10 “AAG” insertion in the Pvcrt-o gene was not detected. Mutations in Pvdhfr at codons 57, 58, 61, 99 and 117 were detected in 29.9%, 54.3%, 27.6%, 44.9% and 55.1% of the samples, respectively. Wild type was predominant (46.3%), followed by quadruple and double mutant haplotypes. Of three types of tandem repeat variations of Pvdhfr, Type B, with three copies of GGDN repeats, was the most common. Pvdhps mutations were only detected at codons 383 and 553 and the wild type Pvdhps was dominant (78.0%). Eleven haplotypes were identified when combining the mutations of Pvdhfr and Pvdhps, among which the predominant one was the wild type (33.9%), followed by double mutant alleles S58R/S117N /WT (24.6%).

Conclusions

This study demonstrated resistant P. vivax phenotypes exists in northeastern Myanmar. Continued surveillance of drug resistance markers is needed to update treatment guidelines in this region.
Surveillance of Plasmodium vivax transmission using serological models in the border areas of China–Myanmar
Authors: Yao Meixue , Xiao Lishun , Sun Xiaodong , Lin Zurui , Hao Xiao , Bai Qiong-qiong , Yin De-Hui
Published: March 2022

Background

To understand the Plasmodium vivax malaria transmission intensity and to assess the effectiveness of prevention and control measures taken along the China–Myanmar border, a catalytic model was used to calculate the seroconversion rate, an important indicator of malaria transmission intensity with high sensitivity, which is particularly useful in areas of low transmission.

Methods

Five counties in Yunnan Province bordering Myanmar were selected as survey sites, and subjects were obtained in each county by stratified random sampling in 2013–2014. Fingerstick blood was collected from each subject and tested for antibodies to P. vivax Merozoite Surface Protein 1-19 (PvMSP1-19) using indirect ELISA. A catalytic conversion model was used to assess the transmission intensity of P. vivax malaria based on the maximum likelihood of generating a community seroconversion rate.

Results

A total of 3064 valid blood samples were collected. Antibody levels were positively correlated with age. The seroconversion rate (SCR) values for each village were Luoping (0.0054), Jingqiao (0.0061), Longpen (0.0087), Eluo (0.0079), Banwang (0.0042) and Banbie (0.0046), respectively.

Conclusion

Overall, the intensity of P. vivax malaria transmission in the border areas of Yunnan Province is low and not entirely consistent across counties. Consecutive serological surveys are needed to provide a sensitive evaluation of transmission dynamics and can help to confirm areas where infection is no longer present.
Quality of life and informal care burden associated with duchenne muscular dystrophy in Portugal: the COIDUCH study
Authors: Andreozzi Valeska , Labisa Pedro , Mota Melina , Monteiro Susana , Alves Rita , Almeida João , Vandewalle Björn , Felix Jorge , Buesch Katharina , Canhão Hugo , Beitia Ortiz de Zarate Igor
Published: March 2022

Background

To describe the reduced health-related quality of life (HRQoL) of duchenne muscular dystrophy (DMD) patients and their caregiver burden and to present its relationship with disease progression.

Methods

This cross-sectional study assessed patient HRQoL with the 3-level version of the EuroQol-5D (EQ-5D-3L) and caregiver burden with the Work Productivity and Activity Impairment: General Health questionnaire. DMD patients and their caregivers were identified through Portuguese Neuromuscular Association (APN).

Results

A total of 46 DMD main caregivers, of eight ambulant and 38 non-ambulant patients, completed the questionnaires. Over half (58.7%) of all non-ambulant patients were on ventilation support, either full-time (15.2%) or non full-time (43.5%). Non-ambulant patients had a lower mean utility scores than ambulant patients (− 0.05 versus 0.51, p value < 0.001). Caregivers of non-ambulant patients reported a significant mean daily activity impairment as compared to caregivers of ambulant patients (68% versus 23%, p value < 0.001). Among non-ambulant patients, both utility scores and caregiver impairment appeared to deteriorate according to a higher need for ventilation support, however, these results were not statistically significant.

Conclusions

These results emphasise the significant negative impact that DMD progression has on the patient HRQoL, as well as caregivers’ ability to conduct their daily activities. Therapeutic options that stop or slow the disease progression could have a beneficial impact for both patients and caregivers.
Early results of the implementation of laparoscopic major liver resection program
Authors: Morawski Marcin , Grąt Michał , Krasnodębski Maciej , Kobryń Konrad , Hołówko Wacław , Rykowski Paweł , Dec Marta , Nowosad Małgorzata , Figiel Wojciech , Patkowski Waldemar , Zieniewicz Krzysztof
Published: March 2022

Background

Laparoscopic liver resections offer potential benefits but may require advanced laparoscopic skills and are volume dependent.

Methods

This retrospective study included 12 patients who underwent major laparoscopic resection and 24 patients after open major liver resection for liver malignancy in the time period between September 2020 and May 2021. The primary outcomes were complications according to Clavien-Dindo classification and duration of hospital stay.

Results

Median duration of hospital stay in laparoscopic resection group (6 days) was significantly shorter than in open resection group (8 days) (p = 0.046). Complications classified as grade II or higher were significantly less frequent in the laparoscopic resection group (2 patients) versus open resection group (13 patients) (p = 0.031).

Conclusions

Although laparoscopic major liver resections should be limited to expert hepatobiliary centers and are characterized by long learning curve, this approach may offer favorable short-term outcomes even during launching a new program.
Methodological challenges surrounding QALY estimation for paediatric economic evaluation
Authors: Petrou Stavros
Published: March 2022

Cost-utility analysis remains the preferred form of economic evaluation for health technology assessment, pricing and reimbursement authorities in several countries. The results of cost-utility analyses are commonly expressed in terms of incremental cost per quality-adjusted life year (QALY) gained where the QALY combines length of life and health-related quality of life in a single metric. This commentary provides an overview of key methodological challenges surrounding QALY estimation for paediatric economic evaluation. These challenges include issues surrounding the relevant attributes to incorporate into measurement instruments, appropriate respondents for the measurement and valuation tasks, perspectives adopted when completing valuation tasks, potential sources of bias in the description and valuation processes, and the paucity of psychometric evidence for existing measures. In addition, the commentary considers methodological challenges raised by research aimed at assessing whether a QALY gain by a child should be valued equally to a QALY gain by an adult.
The impact of having a dedicated obstetrics and gynecology resident to provide contraceptive counseling on immediate postpartum family planning uptake: a “pre–post” study
Authors: Sium Abraham Fessehaye , Wolderufael Mekdes , Lucero-Prisno Don Eliseo , Grentzer Jaclyn M.
Published: March 2022

Background

Providing effective, high quality, antenatal and postpartum contraceptive counseling can reduce unintended pregnancies, decrease maternal and fetal morbidity and mortality, and prevent unsafe abortions. The postpartum period is a critical time to address unmet family planning need and to reduce the risks of short interpregnancy interval. This study aimed at determining the impact of assigning a dedicated obstetrics and gynecology resident for postpartum family planning counselling on the uptake of immediate postpartum family planning.

Methods

A “pre-post” observational study was conducted at Saint Paul’s Hospital Millennium Medical College (SPHMMC), in Addis Ababa-Ethiopia, from May 1, 2021 to June 30, 2021. Immediate postpartum family planning uptake between the months of June (when there was a dedicated resident assigned for postpartum family planning counselling and provison on weekdays) and May (when there was no such dedicated resident for similar purpose) were compared. Data was analyzed using SPSS version 20 software packages. Simple descriptive was used to describe baseline characteristics. Chi-square test of association was done to determine the correlation between dependent and independent variables. Multivariate regression analysis was applied to determine factors associated with uptake of family planning methods in the immediate postpartum period. Odds ratio, 95% CI, and p-value < 0.05 were used to describe results significance.

Results

Out of 776 mothers who delivered at SPHMMC in the month of June 2021, 158 (20.4%) of them used immediate postpartum family planning. This finding during the month of June is higher than a 15.4% immediate postpartum family planning uptake observed during the preceding month of May. Having a dedicated resident for postpartum family planning counselling was associated with an increase in immediate postpartum family planning use (AOR = 1.31, 95% CI [1.01, 1.69]).

Conclusion

In this study, presence of a dedicated obstetrics and gynecology resident for postpartum family planning counselling was associated with an increase in the uptake of immediate postpartum family planning. This implies the importance of assigning a dedicated care provider for the purpose of postpartum family planning counselling within the immediate postpartum, which gives postpartum women another opportunity of adequate counselling before they are discharge from Hospitals or obstetric service centers.
Establishment of prognostic models for adenocarcinoma of oesophagogastric junction patients with neoadjuvant chemoradiotherapy: a real-world study
Authors: Du Rongxu , Ming Jiao , Geng Jianhao , Zhu Xianggao , Zhang Yangzi , Li Shuai , Liu Zhiyan , Wang Hongzhi , Wang Zhilong , Tang Lei , Zhang Xiaotian , Wu Aiwen , Bu Zhaode , Yan Yan , Li Zhongwu , Li Yongheng , Li Ziyu , Wang Weihu
Published: March 2022

Background

Multimodal therapies based on surgical resection have been recommended for the treatment of adenocarcinoma of the oesophagogastric junction (AEG). We aimed to evaluate prognostic factors in AEG patients receiving neoadjuvant chemoradiotherapy and to build predictive models.

Methods

T3 − T4N + M0 AEG patients with resectable Siewert type II/III tumours were enrolled in this study. All patients underwent neoadjuvant chemoradiation, followed by radical surgery or systemic therapy according to clinical response. Survival analysis was performed using the Kaplan–Meier method; multivariate analysis using the Cox proportional hazards method was also conducted. The Harrell concordance index (C-index) was used to test the prognostic value of models involving prognostic factors, and consistency between actual and predicted survival rates was evaluated by calibration curves.

Results

From February 2009 to February 2018, 79 patients were treated with neoadjuvant chemoradiotherapy; 60 patients of them underwent radical surgery. The R0 resection rate was 98.3%, and 46.7% of patients achieved a major pathologic response (MPR), namely, a residual tumour issue less than 10%. The 5-year overall survival (OS) rate was 63%, and the 5-year progression-free survival (PFS) rate was 48%. The incidence of grade 3 complications was 21.5%, and no grade 4 complications were reported. According to the results of univariate and multivariate analyses, we included the neutrophil–lymphocyte ratio (NLR), prognostic nutrition index (PNI), eosinophilic granulocyte (EOS) and postoperative pathologic stage in nomogram analysis to establish prediction models for OS and PFS; the C-index of each model was 0.814 and 0.722, respectively. Both the C-index and calibration curves generated to validate consistency between the actual and predicted survival indicated that the models were well calibrated and of good predictive value.

Conclusions

AEG patients achieved favourable downstaging and pathologic response after neoadjuvant chemoradiation, with acceptable adverse effects. Inflammation-based and nutrition-related factors and postoperative pathologic stage had a significant influence on OS and PFS, and the predictive value was verified through prognostic models.
Optimal timing for intermittent administration of parathyroid hormone (1–34) for distraction osteogenesis in rabbits
Authors: Inada Narisaku , Ohata Tetsuya , Maruno Hideto , Morii Takeshi , Hosogane Naobumi , Ichimura Shoichi
Published: March 2022

Background

To date, the usefulness of parathyroid hormone [PTH (1–34)] in distraction osteogenesis has been reported in several studies. We aimed to determine the optimal timing of PTH (1–34) administration in a rabbit distraction osteogenesis model.

Methods

The lower hind leg of a Japanese white rabbit was externally fixed, and tibial osteotomy was performed. One week after the osteotomy, bone lengthening was carried out at 0.375 mm/12 h for 2 weeks. After 5 weeks, the lower leg bone was collected. Bone mineral density (BMD), peripheral quantitative computed tomography (pQCT), micro-computed tomography (micro-CT), and mechanical tests were performed on the distracted callus. The rabbits were divided into three groups according to the timing of PTH (1–34) administration: 4 weeks during the distraction and consolidation phases (group D + C), 2 weeks of the distraction phase (group D), and the first 2 weeks of the consolidation phase (group C). A control group (group N) was administered saline for 4 weeks during the distraction and consolidation phases. Furthermore, to obtain histological findings, lower leg bones were collected from each rabbit at 2, 3, and 4 weeks after osteotomy, and tissue sections of the distracted callus were examined histologically.

Results

The BMD was highest in group C and was significantly higher than group D. In pQCT, the total cross-sectional area was significantly higher in groups D + C, D, and C than group N, and the cortical bone area was highest in group C and was significantly higher than group D. In micro-CT, group C had the highest bone mass and number of trabeculae. Regarding the mechanical test, group C had the highest callus failure strength, and this value was significantly higher compared to group N. There was no significant difference between groups D and N. The histological findings revealed that the distracted callus mainly consisted of endochondral ossification in the distraction phase. In the consolidation phase, the chondrocytes were almost absent, and intramembranous ossification was the main type of ossification.

Conclusion

We found that the optimal timing of PTH (1–34) administration is during the consolidation phase, which is mainly characterized by intramembranous ossification.
Identification of three novel homozygous variants in COL9A3 causing autosomal recessive Stickler syndrome
Authors: Rad Aboulfazl , Najafi Maryam , Suri Fatemeh , Abedini Soheila , Loum Stephen , Karimiani Ehsan Ghayoor , Daftarian Narsis , Murphy David , Doosti Mohammad , Moghaddasi Afrooz , Ahmadieh Hamid , Sabbaghi Hamideh , Rajati Mohsen , Hashemi Narges , Vona Barbara , Schmidts Miriam
Published: March 2022

Background

Stickler syndrome (STL) is a rare, clinically and molecularly heterogeneous connective tissue disorder. Pathogenic variants occurring in a variety of genes cause STL, mainly inherited in an autosomal dominant fashion. Autosomal recessive STL is ultra-rare with only four families with biallelicCOL9A3variants reported to date.

Results

Here, we report three unrelated families clinically diagnosed with STL carrying different novel biallelic loss of function variants inCOL9A3. Further, we have collectedCOL9A3genotype–phenotype associations from the literature.

Conclusion

Our report substantially expands the molecular genetics and clinical basis of autosomal recessive STL and provides an overview about allelic COL9A3 disorders.
Impact of the SARS-CoV-2 pandemic and associated restrictions on Pediatric Emergency Department utilization in Sardinia: a retrospective bicentric observational study
Authors: Antonucci Roberto , Clemente Maria Grazia , Antonucci Luca , Canetto Alessandro , Mastromattei Stefania , Chiapello Noemi , Vacca Nadia , Saderi Laura , Sotgiu Giovanni , Locci Cristian
Published: March 2022

Background

The COVID-19 pandemic and associated public health measures have had a profound impact on health systems worldwide. The aim of this study was to assess quantitative and qualitative changes in Pediatric Emergency Department (PED) visits in Sardinia, Italy, during the early period of the COVID-19 pandemic.

Methods

We retrospectively investigated the number and characteristics of visits to two major Sardinian PEDs, in the periods January-June 2020 and January-June 2019.

Results

From January to June 2020, 8399 PED visits with 1160 hospital admissions (13.8% of PED visits) were registered, compared with 15,692 PED visits (Δ = -46.5%) and 1819 hospital admissions (11.6% of PED visits) occurring from January to June 2019.

Comparing January-June 2020 with January-June 2019, we found differences in the percentage of visits for age groups, and significant changes in the proportion of triage codes, with a decrease in green codes (72.1% vs 74.2%, respectively) and an increase in white codes (19.0% vs 16.5%, respectively). Moreover, in the period January-June 2020, the frequency of skin disorders and acute respiratory disease significantly decreased, while the frequency of trauma, acute surgical disease, intoxication, and neuropsychiatric disease significantly increased.

Conclusions

After the beginning of the Italian lockdown, we observed a marked drop in the number of PED visits, an increase in hospital admission rate, and radical changes in the reason for visit.
Enhanced protein isoform characterization through long-read proteogenomics
Authors: Miller Rachel M. , Jordan Ben T. , Mehlferber Madison M. , Jeffery Erin D. , Chatzipantsiou Christina , Kaur Simi , Millikin Robert J. , Dai Yunxiang , Tiberi Simone , Castaldi Peter J. , Shortreed Michael R. , Luckey Chance John , Conesa Ana , Smith Lloyd M. , Deslattes Mays Anne , Sheynkman Gloria M.
Published: March 2022

Background

The detection of physiologically relevant protein isoforms encoded by the human genome is critical to biomedicine. Mass spectrometry (MS)-based proteomics is the preeminent method for protein detection, but isoform-resolved proteomic analysis relies on accurate reference databases that match the sample; neither a subset nor a superset database is ideal. Long-read RNA sequencing (e.g., PacBio or Oxford Nanopore) provides full-length transcripts which can be used to predict full-length protein isoforms.

Results

We describe here a long-read proteogenomics approach for integrating sample-matched long-read RNA-seq and MS-based proteomics data to enhance isoform characterization. We introduce a classification scheme for protein isoforms, discover novel protein isoforms, and present the first protein inference algorithm for the direct incorporation of long-read transcriptome data to enable detection of protein isoforms previously intractable to MS-based detection. We have released an open-source Nextflow pipeline that integrates long-read sequencing in a proteomic workflow for isoform-resolved analysis.

Conclusions

Our work suggests that the incorporation of long-read sequencing and proteomic data can facilitate improved characterization of human protein isoform diversity. Our first-generation pipeline provides a strong foundation for future development of long-read proteogenomics and its adoption for both basic and translational research.
Data management in diabetes clinical trials: a qualitative study
Authors: Nourani Aynaz , Ayatollahi Haleh , Solaymani Dodaran Masoud
Published: March 2022

Background

Clinical trials play an important role in expanding the knowledge of diabetes prevention, diagnosis, and treatment, and data management is one of the main issues in clinical trials. Lack of appropriate planning for data management in clinical trials may negatively influence achieving the desired results. The aim of this study was to explore data management processes in diabetes clinical trials in three research institutes in Iran.

Method

This was a qualitative study conducted in 2019. In this study, data were collected through in-depth semi-structured interviews with 16 researchers in three endocrinology and metabolism research institutes. To analyze data, the method of thematic analysis was used.

Results

The five themes that emerged from data analysis included (1) clinical trial data collection, (2) technologies used in data management, (3) data security and confidentiality management, (4) data quality management, and (5) data management standards. In general, the findings indicated that no clear and standard process was used for data management in diabetes clinical trials, and each research center executed its own methods and processes.

Conclusion

According to the results, the common methods of data management in diabetes clinical trials included a set of paper-based processes. It seems that using information technology can help facilitate data management processes in a variety of clinical trials, including diabetes clinical trials.
Metabolic syndrome and breast cancer survivors: a follow-up analysis after completion of chemotherapy
Authors: Dieli-Conwright Christina M. , Wong Louise , Waliany Sarah , Mortimer Joanne E.
Published: March 2022

Background

We previously reported that (neo)adjuvant chemotherapy adversely altered metabolic syndrome (MetS) components, body composition, and related biomarkers after a 12 to 18-week chemotherapy treatment course in women. Here, we sought to determine whether these measures worsened within 4–5 years post-chemotherapy among the same sample of early stage breast cancer survivors.

Methods

Twenty-eight breast cancer survivors were reassessed within 4–5 years post-chemotherapy. Participants were tested for MetS, lipid profile (total cholesterol; TC, low-density lipoprotein cholesterol; LDL-C), glucose metabolism (insulin, homeostatic model- insulin resistance; HOMA-IR, glycosylated hemoglobin; HbA1c), inflammation (C-reactive protein; CRP) and body composition (body weight; BW, percent body fat; BF, fat mass; FM) during follow-up physical exams. A comparison of measurements between post-chemotherapy and follow-up periods was performed using repeated measures analysis of covariance.

Results

Most study patients were Caucasian (44%) or Hispanic (30%) with a mean age of 48.2 years. Average time from completion of chemotherapy was 4.75 years. At follow-up, MetS components significantly increased (p < 0.01) compared with the post chemotherapy assessment. Additionally, BF, FM, lipids (TC, LDL), glucose metabolism (HOMA-IR, insulin, HbA1c), and inflammation (CRP) significantly increased (p < 0.01). Notably BW significantly increased; mean weight gain after chemotherapy was 6.1 kg and increased an additional 8.2% at follow-up (p < 0.01).

Conclusion

MetS components, body composition, and biomarkers continued to worsen within 4–5 years post-chemotherapy in breast cancer survivors. Energy balance interventions should target breast cancer patients to reduce the exacerbation of MetS.
Comparison of two cell-free therapeutics derived from adipose tissue: small extracellular vesicles versus conditioned medium
Authors: He Chuan , Dai Minjia , Zhou Xiaojie , Long Jie , Tian Weidong , Yu Mei
Published: March 2022

Background

Cell-free therapy has been inspired as a promising approach to overcome the limitations of traditional stem cell therapy. However, the therapeutic effect between extracellular vesicles and conditioned medium with the same source had not been compared. Our previous studies have shown that both the conditioned medium of adipose tissue (adipose tissue extract, ATE) and its further purification product small extracellular vesicles (sEV-AT) contributed to adipose tissue regeneration. In this study, we aimed to compare the ATE and sEV-AT in composition, inductivity on cells and de novo adipose regenerative potential.

Methods

The characteristics of sEV-AT and ATE were compared through protein and particle yield, particle size distribution and composition. The inductivity of sEV-AT and ATE on cells were compared through co-culture of sEV-AT or ATE with ASC, HUVEC and RAW264.7 in vitro. The capacity of promoting de novo adipogenesis was compared by implanting the silicone tube containing sEV-AT or ATE subcutaneously in vivo.

Results

More particles and concentrated particle size distribution were detected in sEV-AT. In turn, more soluble factors and multiple peaks in particle size distribution were detected in ATE. In 1662 common proteins of sEV-AT and ATE, there were 984 (59.2%) proteins enriched twice more in sEV-AT than in ATE. With the prerequisite of equivalent protein concentration, sEV-AT outperformed ATE in promoting proliferation, migration and regeneration potential of cells those contributing adipose tissue regeneration in vitro.Furthermore, sEV-AT expedited the de novo adipose tissue regeneration and angiogenesis at the early stage than ATE in vivo, but sEV-AT and ATE group formed similar neoadipose tissue and new vessels at week 12.

Conclusions

Our results provided a direct comparison between EV and conditioned medium as cell-free therapeutic strategy. Both sEV and ATE had specific biological signature to facilitate tissue repair. Considering the convenience of extraction and acceptable effect, ATE represented a feasible product of cell-free therapy, providing another option for different situations in clinical application. Furthermore, the complex contents of both sEV-AT and ATE should be studied comprehensively to avoid possible negative effects and to ensure sufficient safety for clinical applications.
Small extracellular vesicles from dental follicle stem cells provide biochemical cues for periodontal tissue regeneration
Authors: Ma Liya , Rao Nanquan , Jiang Hui , Dai Yuzhe , Yang Songtao , Yang Hefeng , Hu Jiangtian
Published: March 2022

Background

Treatments based on stem cell-derived small extracellular vesicles (sEVs) have been explored as an alternative to stem cell transplantation-based therapies in periodontal regeneration. Dental follicle stem cells (DFSCs) have shown great potential for regenerative medicine applications. However, it is unclear whether sEVs derived from DFSCs (DFSCs-sEVs) could be used in periodontal regeneration. This study investigates whether DFSCs-sEVs could regenerate damaged periodontal tissue and the potential underlying mechanism.

Methods

DFSCs-sEVs were isolated and identified, and periodontal ligament stem cells (PDLSCs) were cocultured with the isolated sEVs. The effect of DFSCs-sEVs on the biological behaviour of PDLSCs was examined using EdU assay, CCK-8 assay, cell cycle analysis, wound healing, alizarin red staining, qRT-PCR, and western blot analysis. RNA sequencing and functional enrichment analysis were used to detect the signal pathway involved in the effect of DFSCs-sEVs on PDLSCs. PDLSCs were pretreated with ERK1/2 or p38 MAPK inhibitors to investigate the possible involvement of the ERK1/2 and p38 MAPK pathways. Additionally, DFSCs-sEVs were combined with collagen sponges and transplanted into the periodontal defects in SD rats, and then, pathological changes in periodontal tissue were examined using haematoxylin and eosin (HE) staining and micro-CT.

Results

PDLSCs could internalize DFSCs-sEVs, thereby enhancing the proliferation assessed using EdU assay, CCK-8 assay and cell cycle analysis. DFSCs-sEVs significantly enhanced the migration of PDLSCs. DFSCs-sEVs promoted osteogenic differentiation of PDLSCs, showing deep Alizarin red staining, upregulated osteogenic genes (RUNX2, BSP, COL1), and upregulated protein expression (RUNX2, BSP, COL1, ALP). We found that p38 MAPK signalling was activated via phosphorylation. Inhibition of this signalling pathway with a specific inhibitor (SB202190) partially weakened the enhanced proliferation. After DFSCs-sEVs transplantation, new periodontal ligament-like structures and bone formation were observed in the damaged periodontal area in rats. Labelled DFSCs-sEVs were observed in the newly formed periodontal ligament and soft tissue of the defect area.

Conclusions

Our study demonstrated that DFSCs-sEVs promoted periodontal tissue regeneration by promoting the proliferation, migration, and osteogenic differentiation of PDLSCs. The effect of DFSCs-sEVs in promoting PDLSCs proliferation may be partially attributed to the activation of p38 MAPK signalling pathway. DFSCs-sEVs provide us with a novel strategy for periodontal regeneration in the future.
Serotyping, antibiogram, and detection of bacterial pathogens associated with bovine respiratory disease in selected areas of Ethiopia
Authors: Akalu Mirtneh , Vemulapati BhadraMurthy , Abayneh Takele , Degefa Teferi , Deresse Getaw , Gelaye Esayas
Published: March 2022

Background

Bovine Respiratory Disease (BRD) is a multifactorial and economically important illness of cattle. The current study was designed to characterize the major bacterial pathogens associated with BRD and determine the antibiotic susceptibility patterns of isolates. Samples were collected from 400 pneumonic cases of cattle.

Results

Laboratory assay revealed isolation of 376 (94.0%) bacterial pathogens. The most prevalent bacterial pathogens recovered were Mannheimia haemolytica (M. haemolytica) followed by Pasteurella multocida (P. multocida), Histophilus somni (H. somni), and Bibersteinia trehalosi (B. trehalosi) from 191 (50.80%), 81 (21.54%), 56 (14.89%), and 48 (12.77%) samples, respectively. M. haemolytica strains were confirmed using multiplex PCR assay through the amplification of PHSSA (~ 325 bp) and Rpt2 (~ 1022 bp) genes. Capsular typing of P. multocida revealed amplification of serogroup A (hyaD-hyaC) gene (~ 1044 bp) and serogroup D (dcbF) gene (~ 657 bp). B. trehalosi isolates displayed amplification of the sodA gene (~ 144 bp). Besides, serotyping of M. haemolytica showed the distribution of serotype A:1 (82.20%), A:2 (10.47%), and A:6 (7.33%). Whereas, biotyping of P. multocida revealed a higher prevalence of biotype A:3 (83.95%), then A:1 (8.64%), A:2 (4.94%), and A:12 (2.47%). The majority of the retrieved isolates showed remarkable susceptibility to enrofloxacin, ciprofloxacin, sulfamethoxazole-trimethoprim, florfenicol, and ceftiofur (100%). Besides, varying degree of antimicrobial resistance was observed against streptomycin, gentamicin, penicillin-G, and ampicillin.

Conclusions

The current findings confirmed that M. haemolytica (A:1) strain is the most common bacterial pathogen identified from BRD cases in the study areas of Ethiopia. Hence, continuous outbreak monitoring and evaluation of antibiotics susceptibility patterns of bacterial pathogens associated with BRD are indispensable to reduce the impact of BRD in the study areas. Further investigation of bacterial pathogens and genotypic analysis of pathogens from a wider area of the country is essential to design a cost-efficient control strategy.
Asymptotic equivalence relations for rapidly varying solutions of sublinear differential equations of Emden–Fowler type
Authors: Manojlović Jelena , Milošević Jelena
Published: March 2022

We discuss sublinear differential equations of the Emden–Fowler type $x''=q(t) x^{\gamma }$

x
″

=
q
(
t
)

x
γ

under the assumption that the coefficient q is a rapidly varying function. We show that all of their strongly decreasing and strongly increasing solutions are rapidly varying functions and are in the asymptotic equivalence relation with a precisely defined function determined by the coefficient q.
Knowledge and perception on antimicrobial resistance and antibiotics prescribing attitude among physicians and nurses in Lambaréné region, Gabon: a call for setting-up an antimicrobial stewardship program
Authors: Adegbite Bayode Romeo , Edoa Jean Ronald , Schaumburg Frieder , Alabi Abraham S. , Adegnika Ayola Akim , Grobusch Martin P.
Published: March 2022

Background

Africa is challenged by the emergence of antimicrobial resistance (AMR). In order to improve patient management and to optimise approaches to curb the spread of antimicrobial resistance, we examined knowledge and perceptions of AMR and antibiotics prescription practices of HCW (healthcare workers) in Lambaréné, Gabon.

Methods

We conducted a self-administered, questionnaire-based survey in HCW at the regional referral hospital, a medical research centre, and peripheral health care facilities. The proportions of correct responses to questions were determined and compared between physicians and nurses using Fisher’s Exact test.

Results

A total of 47 HCW took part in the survey. Of those, 64% (30/47) recognised antibiotic resistance as a major public health issue in Gabon, but only 14/47 (30%) recognised it as a problem in their health facility. Of note, 37/47 (79%) recognised excessive use of antibiotics without microbiological confirmation in case of infection, and buying antibiotics without a prescription, as possible cause of antimicrobial resistance. Some HCW (28%; 13/47) reported having prescribed antibiotics because the patients asked for them; and a total of 15/47 (32%) responded that antibiotics could help patients recover faster when added to malaria treatment. Compared to nurses, most of the physicians recognised that excessive use of antibiotics without microbiological confirmation of infection could contribute to AMR spread (18/19 (95%) vs 19/28 (68%); p = 0.028).

Conclusion

Most HCW recognised AMR as public health issue. However, a quarter of the participants did not know about the causes fostering the emergence of antimicrobial resistance. There is a need to perform regular HCW training in antimicrobial prescription, and to set up an antimicrobial stewardship program.
Determinants of market participation among smallholder farmers in Southwest Ethiopia: double-hurdle model approach
Authors: Haile Kusse , Gebre Engida , Workye Agegnehu
Published: March 2022

Background

Agricultural production by smallholder farm households is a means of livelihood for many rural households in developing economies, including Africa. Commercializing smallholder farmers in the agricultural sector is an indispensable path to boost economic growth and development of most developing countries, like Ethiopia. But, maize marketing has not been given due attention, which has potential production volume and marketability. Therefore, this study is designed to identify determinants of market participation decision and volume of supply among smallholder maize producer farmers in Southwest Ethiopia.

Methods

Data for this study were collected through cross‑sectional survey from maize producer farm households. The primary data were generated by household survey using a pre-tested structured questionnaire. A both purposive and random sampling technique was used to draw an appropriate sample of 546 maize producer households for this cross-sectional survey study. The data were analyzed using descriptive statistics and double-hurdle econometric model.

Results

The result of the survey indicates that out of total 546 maize producers, 381 households are maize market participants and 165 households are non-participants. First hurdle model results show that nine variables—education level, farming experience, quantity of maize produced, cooperative membership, distance to nearest market, amount of credit received, off/non-farming income, number of oxen and perception about lagged price—significantly affect the market participation decision among maize producer farmers. The second hurdle result confirmed that seven variables—sex, family size, land allocated for maize, number of oxen, distance to nearest market, livestock holding and perception about lagged price—significantly affect the level of market participation by maize producer farmers.

Conclusion

The findings of this study revealed that understanding the factors and its extent is very important for policy-making to address the problem of market participation decision and level of participation among smallholder farm households. Therefore, the study suggests that important resource and socio-economic factors must take into consideration to enhance the productivity and strength supportive institutions or infrastructural facilities in the study area to improve market participation decision and level of participation of smallholders.
The efficacy of eye movement desensitization and reprocessing in reducing anxiety among female university students with primary dysmenorrhea
Authors: Valedi Sahar , MoradiBaglooei Mohammad , Ranjbaran Mehdi , Chegini Venus , Griffiths Mark D. , Alimoradi Zainab
Published: March 2022

Background

Unpleasant experiences of dysmenorrhea can lead to increased anxiety. The anxiety associated with dysmenorrhea is a pain-related anxiety which might reduce the efficacy of medication as well as enhance the perception of pain. The present study evaluated the efficacy of eye movement desensitization and reprocessing (EMDR) in reducing anxiety among female university students with primary dysmenorrhea.

Methods

In this randomized controlled trial, 88 female university students were recruited from April 2019 to February 2020. Eligible participants were selected by convenience sampling and were allocated into study groups (44 individuals in the intervention group and comparison group) using balanced block randomization. The final sample comprised 78 participants who completed the study (39 individuals in each group). Data were collected using the Spielberger State-Trait Anxiety Inventory, Subjective Units of Distress Scale, and Validity of Cognition Scale before the intervention and at the time of the first menstrual period after completion of the intervention. The intervention group received EMDR in two individual interventional sessions which lasted approximately one hour. Data analysis was performed using analysis of variance with control of covariance method at a significance level of 0.05.

Results

The results of the study showed that EMDR did not have a statistically significant effect on State-Trait Anxiety of patients with dysmenorrhea (p > 0.05). Based on the Cohen’s d effect size of 0.06 for state-anxiety, -0.01 for trait-anxiety, and partial eta square less than 0.059 for both uncorrected and corrected models, the intervention was within a trivial effect.

Conclusion

EMDR intervention did not have a statistically and clinically significant effect on State-Trait Anxiety of patients with dysmenorrhea. Therefore, the efficacy of EMDR in treating dysmenorrhea-related anxiety remains inconclusive.

Trial registration IRCT20180823040851N2 on 2019-02-09.
Identification of pigments used in a Qajar manuscript from Iran by using atomic and molecular spectroscopy and technical photography methods
Authors: Koochakzaei Alireza , Alizadeh Gharetapeh Samane , Jelodarian Bidgoli Behrooz
Published: March 2022

The present study aimed to identify pigments used in writing and decorating a Qur'an manuscript related to the early years of the Qajar era, a royal dynasty ruling over Iran from 1789 to 1925. The pigments were analysed using µ-XRF, SEM–EDS, Raman, and FTIR spectroscopy. Also, various technical photography methods were used to study the pigments including visible-reflected (VIS), infrared photography (IR), ultraviolet-reflected (UVR), and ultraviolet-induced visible luminescence (UVL) along with infrared false color (IRFC) and ultraviolet false color (UVFC) methods. Carbon black, red lead, and indigo were identified as black ink, orange, and blue pigments, respectively. A mixture of red lead and vermilion was also detected in the red/orange ink. White lead and calcite were also used as additives in blue color. A cochineal-based pigment was also used as red ink in some parts of the manuscript. However, the evaluation of golden color showed two types pigments of gold and brass alloys in different parts of the manuscript. Copper carboxylate was identified as the product of the destruction of this pigment. According to the results of the study, technical photography methods along with spectroscopic methods are a good tool to examine manuscripts and identify included pigments and reduce the amount of possible error and the need for destructive sampling.