bluuebunny/crossref_metadata_2025 huggingface dataset:
Canalization and developmental stability of the yellow-necked mouse (Apodemus flavicollis) mandible and cranium related to age and nematode parasitism
Authors: Jojić Vida , Čabrilo Borislav , Bjelić-Čabrilo Olivera , Jovanović Vladimir M. , Budinski Ivana , Vujošević Mladen , Blagojević Jelena
Published: October 2021

Background

Mammalian mandible and cranium are well-established model systems for studying canalization and developmental stability (DS) as two elements of developmental homeostasis. Nematode infections are usually acquired in early life and increase in intensity with age, while canalization and DS of rodent skulls could vary through late postnatal ontogeny. We aimed to estimate magnitudes and describe patterns of mandibular and cranial canalization and DS related to age and parasite intensity (diversity) in adult yellow-necked mice (Apodemus flavicollis).

Results

We found the absence of age-related changes in the levels of canalization for mandibular and cranial size and DS for mandibular size. However, individual measures of mandibular and cranial shape variance increased, while individual measures of mandibular shape fluctuating asymmetry (FA) decreased with age. We detected mandibular and cranial shape changes during postnatal ontogeny, but revealed no age-related dynamics of their covariance structure among and within individuals. Categories regarding parasitism differed in the level of canalization for cranial size and the level of DS for cranial shape. We observed differences in age-related dynamics of the level of canalization between non-parasitized and parasitized animals, as well as between yellow-necked mice parasitized by different number of nematode species. Likewise, individual measures of mandibular and cranial shape FA decreased with age for the mandible in the less parasitized category and increased for the cranium in the most parasitized category.

Conclusions

Our age-related results partly agree with previous findings. However, no rodent study so far has explored age-related changes in the magnitude of FA for mandibular size or mandibular and cranial FA covariance structure. This is the first study dealing with the nematode parasitism-related canalization and DS in rodents. We showed that nematode parasitism does not affect mandibular and cranial shape variation and covariance structure among and within individuals. However, parasite intensity (diversity) is related to ontogenetic dynamics of the levels of canalization and DS. Overall, additional studies on animals from natural populations are required before drawing some general conclusions.
Small but mighty: old and new parvoviruses of veterinary significance
Authors: Jager Mason C. , Tomlinson Joy E. , Lopez-Astacio Robert A. , Parrish Colin R. , Van de Walle Gerlinde R.
Published: October 2021

In line with the Latin expression “sed parva forti” meaning “small but mighty,” the family Parvoviridae contains many of the smallest known viruses, some of which result in fatal or debilitating infections. In recent years, advances in metagenomic viral discovery techniques have dramatically increased the identification of novel parvoviruses in both diseased and healthy individuals. While some of these discoveries have solved etiologic mysteries of well-described diseases in animals, many of the newly discovered parvoviruses appear to cause mild or no disease, or disease associations remain to be established. With the increased use of animal parvoviruses as vectors for gene therapy and oncolytic treatments in humans, it becomes all the more important to understand the diversity, pathogenic potential, and evolution of this diverse family of viruses. In this review, we discuss parvoviruses infecting vertebrate animals, with a special focus on pathogens of veterinary significance and viruses discovered within the last four years.
Diagnostic performance of Midkine ratios in fine-needle aspirates for evaluation of Cytologically indeterminate thyroid nodules
Authors: Zhou Le , Jiang Jinxi , Fu Yantao , Zhang Daqi , Li Tong , Fu Qingfeng , Yan Chao , Zhong Yifan , Dionigi Gianlorenzo , Liang Nan , Sun Hui
Published: October 2021

Background

Fine-needle aspiration cytology (FNAC) is a basic diagnostic tool for thyroid nodules. However, 15–30% of nodules are cytologically indeterminate. Midkine (MK), a pleiotropic growth factor, is often upregulated in patients with cancers. This study aimed to evaluate the role of MK and its ratios in fine-needle aspirates (FNA) for predicting thyroid malignancy.

Methods

This retrospective study included patients with thyroid nodules who underwent preoperative FNA and/or thyroidectomy between April 2017 and September 2017. MK levels in FNA washout were measured by enzyme-linked immunosorbent assay, and thyroglobulin (TG) and free thyroxine (FT4) levels in FNA washout were measured by chemiluminescent immunometric assays.

Results

A total of 217 patients with 242 nodules were included in this study. The concentrations of TG, FT4, MK/TG, MK/FT4, and FT4/MK were significantly different between papillary thyroid carcinomas and benign thyroid nodules. Both MK/TG and MK/FT4 ratios were positively correlated with maximum tumor diameter, extrathyroidal extension, and T and N stages. The area under the curve for MK/TG was 0.719 with a cutoff value of 55.57 ng/mg, while the area under the curve for MK/FT4 was 0.677 with a cutoff value of 0.11 μg/pmol. FNAC in combination with MK/FT4 had a higher sensitivity (95% vs. 91%) and accuracy (96% vs. 92%) than FNAC alone for cytologically indeterminate specimens, those of unknown significance, or those suspected of malignancy.

Conclusions

MK/FT4 and MK/TG may have diagnostic utility for evaluation of papillary thyroid carcinomas, particularly for cytologically indeterminate thyroid nodules.
CircRNA NRIP1 promotes papillary thyroid carcinoma progression by sponging mir-195-5p and modulating the P38 MAPK and JAK/STAT pathways
Authors: Li Chuang , Zhu Lijuan , Fu Lijun , Han Mingli , Li Ya , Meng Zhaozhong , Qiu Xinguang
Published: October 2021

Background

Circular RNAs (circRNAs) have become a hot topic in the area of tumor biology due to its closed structure and the post-transcriptional regulatory effect. This study aims to clarify the roles of circRNA nuclear receptor-interacting protein 1 (NRIP1; circNRIP1) and the possible mechanisms in papillary thyroid carcinoma (PTC).

Methods

The real-time PCR was used to detect the expression level of CircRNA NRIP1 in PTC specimens and cell lines. The effects of CircRNA NRIP1 and miR-195-5p on the PTC cell functions were detected by MTT, transwell, and flow cytometry assays. Dual-luciferase reporter assays and pull down assays were used to verify the association between circRNA NRIP1 and miR-195-5p. The murine xenograft models were constructed to detect the roles of CircRNA NRIP1 and miR-195-5p. Western blot was applied to detect the effects of CircRNA NRIP1 and miR-195-5p on the P38 MAPK and JAK/STAT singling pathways.

Results

CircRNA NRIP1 was over-expressed in PTC tissues and cells and the high levels of CircRNA NRIP1 were correlated with advanced PTC stage. Depletion of CircRNA NRIP1 inhibited PTC cell proliferation, invasion, while accelerated apoptosis. miR-195-5p upregulation repressed proliferation and invasion capabilities, and accelerated apoptosis of PTC cell lines and restraining the growth of tumor xenografts, while the functions were reversed following CircRNA NRIP1 overexpression in PTC cells and tumor xenografts. Besides, the protein levels of p-p38, p-JAK2 and p-STAT1 were remarkably down-regulated in miR-195-5p overexpressed PTC cells and tumor xenografts, whereas CircRNA NRIP1 up-regulation overturned the impacts.

Conclusions

In conclusion, CircRNA NRIP1 promoted PTC progression by accelerating PTC cells proliferation, invasion and tumor growth, while impeding apoptosis by way of sponging miR-195-5p and regulating the P38 MAPK and JAK/STAT pathways.
Clear cell endometrial carcinoma precursors: presentation of two cases and diagnostic issues
Authors: Santoro Angela , Travaglino Antonio , Inzani Frediano , Arciuolo Damiano , Angelico Giuseppe , D’Alessandris Nicoletta , Scaglione Giulia , Valente Michele , Martini Maurizio , Raffone Antonio , Zannoni Gian Franco
Published: October 2021

Background

The precursors of clear cell endometrial carcinoma (CC-EC) are still undefined. Here, we deal with the diagnostic issues related to CC-EC precursors by presenting a morphological, immunophenotypical and molecular study of two representative cases and discussing the relevant literature.

Case presentation

Our and previous cases suggest that clear cell endometrial intraepithelial carcinoma (CC-EIC) is a real entity, which may be distinguished from metaplastic/reactive changes and from its serous counterpart. CC-EIC appears associated with atrophic polyps and may be diagnosed based on morphological and immunophenotypical features of CC-EC in the absence of invasive disease. We described a p53-mutant putative precursor characterized by high-grade nuclei in the absence of other distinctive features. Two putative low-grade precursors resembled atypical tubal metaplasia and endometrial intraepithelial neoplasia, although immunohistochemistry could not support their relationship with CC-EC.

Conclusions

In conclusion, pathologists should be aware of the existence of CC-EIC, since its correct diagnosis may be crucial for a correct patient management. Although several putative earlier precursors have been described, they does not show univocal features that allow their recognition in the common practice. Further studies are necessary in this field.
Comparison of 2-octyl cyanoacrylate skin adhesive and interrupted polypropylene sutures for wound closure in total ankle arthroplasty
Authors: Lee Gun-Woo , Kwak Woo Kyoung , Lee Keun-Bae
Published: October 2021

Background

Adhesive skin materials have increasingly been used in orthopedic surgery. We aimed to compare the efficacy and safety of skin adhesive (2-octyl cyanoacrylate and polymer mesh, Dermabond Prineo) and interrupted polypropylene sutures for wound closure in patients undergoing total ankle arthroplasty (TAA).

Methods

We prospectively enrolled 107 consecutive patients (108 ankles) undergoing TAA and divided them into two groups: skin adhesive group (36 ankles) and suture group (72 ankles). The primary outcome assessment included wound complications and patient satisfaction for wound cosmesis. The secondary outcome assessment included duration of surgery, length of hospital stay, and the Ankle Osteoarthritis Scale (AOS) pain and disability score.

Results

There was one case of allergic contact dermatitis, three cases of wound dehiscence, and one case of superficial surgical site infection in the skin adhesive group. Among them, one case each with allergic contact dermatitis and wound dehiscence finally progressed to deep surgical site infection. Three cases of wound dehiscence were also reported in the suture group; however, there was no case of surgical site infection. Patient satisfaction for wound cosmesis was significantly higher in the skin adhesive group than in the suture group (p = 0.001). There was no statistically significant difference between the groups in terms of secondary outcomes (p > 0.05).

Conclusions

Although the use of Dermabond Prineo showed better patient satisfaction for wound cosmesis, it showed significantly high wound complication rates and no other clinical benefits compared to interrupted polypropylene suture in TAA. Our results suggest that awareness of the possibility of wound complications is necessary when Dermabond Prineo is used in TAA.
High-resolution 3T magnetic resonance imaging and histological analysis of capsuloligamentous complex of the first metatarsophalangeal joint
Authors: Wang Jin-e , Bai Rong-jie , Zhan Hui-li , Li Wen-ting , Qian Zhan-hua , Wang Nai-li , Yin Yuming
Published: October 2021

Background

There are discrepancies in the understanding of the structure of the capsuloligamentous complex of the first metatarsophalangeal joint (MTPJ); this study aims to investigate the differences with previous anatomical reports of high-resolution 3T magnetic resonance imaging (MRI) and histological analysis in illustrating the structure of the capsuloligamentous complex of the first MTPJ.

Methods

Nine fresh frozen cadaveric feet specimens (from two women and three men; aged 32 to 58 years) were used in this study. All specimens underwent MR examination with T1-weighted imaging and T2-weighted spectral attenuated inversion recovery in three planes. Subsequently, all cadaveric feet specimens were sliced into 2-mm-thick sections. The MRI features of the capsuloligamentous complex of the first MTPJ were analyzed in these specimens. Hematoxylin–eosin and Masson’s trichrome staining methods were used to explore the histologic features of the capsuloligamentous complex of the first MTPJ.

Results

Different from most previous studies, our results showed that the plantar plate could be divided into four portions including the central portion of the plantar plate, the intersesamoid, the sesamoid phalangeal and the metatarsosesamoid ligaments. The normal central portion of the plantar plate could be clearly visualized in the sagittal and coronal plane MR images. The intersesamoid ligament is a continuation of the central portion of the plantar plate on the sagittal plane on the gross specimen, the MR imaging, and the histological examination. On the coronal plane of the gross specimen and MR imaging, the sesamoid phalangeal ligaments and the central portion of the plantar plate can be seen as separate ligaments, but they appeared interwoven with the same continuous collagenous fibers on the histological analysis.

Conclusion

High-resolution 3T MRI allows accurate demonstration of the different anatomical details of the capsuloligamentous complex of the first MTPJ from previous anatomical reports. The histological analysis provides further understanding of the structures of the capsuloligamentous complex of the first MTPJ from previous studies.
Multi-predictor mapping of soil organic carbon in the alpine tundra: a case study for the central Ecuadorian páramo
Authors: Ayala Izurieta Johanna Elizabeth , Márquez Carmen Omaira , García Víctor Julio , Jara Santillán Carlos Arturo , Sisti Jorge Marcelo , Pasqualotto Nieves , Van Wittenberghe Shari , Delegido Jesús
Published: October 2021

Background

Soil organic carbon (SOC) affects essential biological, biochemical, and physical soil functions such as nutrient cycling, water retention, water distribution, and soil structure stability. The Andean páramo known as such a high carbon and water storage capacity ecosystem is a complex, heterogeneous and remote ecosystem complicating field studies to collect SOC data. Here, we propose a multi-predictor remote quantification of SOC using Random Forest Regression to map SOC stock in the herbaceous páramo of the Chimborazo province, Ecuador.

Results

Spectral indices derived from the Landsat-8 (L8) sensors, OLI and TIRS, topographic, geological, soil taxonomy and climate variables were used in combination with 500 in situ SOC sampling data for training and calibrating a suitable predictive SOC model. The final predictive model selected uses nine predictors with a RMSE of 1.72% and a R2of 0.82 for SOC expressed in weight %, a RMSE of 25.8 Mg/ha and a R2of 0.77 for the model in units of Mg/ha. Satellite-derived indices such as VARIG, SLP, NDVI, NDWI, SAVI, EVI2, WDRVI, NDSI, NDMI, NBR and NBR2 were not found to be strong SOC predictors. Relevant predictors instead were in order of importance: geological unit, soil taxonomy, precipitation, elevation, orientation, slope length and steepness (LS Factor), Bare Soil Index (BI), average annual temperature and TOA Brightness Temperature.

Conclusions

Variables such as the BI index derived from satellite images and the LS factor from the DEM increase the SOC mapping accuracy. The mapping results show that over 57% of the study area contains high concentrations of SOC, between 150 and 205 Mg/ha, positioning the herbaceous páramo as an ecosystem of global importance. The results obtained with this study can be used to extent the SOC mapping in the whole herbaceous ecosystem of Ecuador offering an efficient and accurate methodology without the need for intensive in situ sampling.
Hearing problems in patients with hereditary gelsolin amyloidosis
Authors: Mustonen Tuuli , Sivonen Ville , Atula Sari , Kiuru-Enari Sari , Sinkkonen Saku T.
Published: October 2021

Background

Gelsolin amyloidosis (AGel amyloidosis) is a hereditary form of systemic amyloidosis featuring ophthalmological, neurological and cutaneous symptoms. Previous studies based mainly on patients’ self-reporting have indicated that hearing impairment might also be related to the disease, considering the progressive cranial neuropathy characteristic for AGel amyloidosis. In order to deepen the knowledge of possible AGel amyloidosis-related hearing problems, a clinical study consisting of the Speech, Spatial and Qualities of Hearing Scale (SSQ) questionnaire, clinical examination, automated pure-tone audiometry and a speech-in-noise test was designed.

Results

Of the total 46 patients included in the study, eighteen (39%) had self-reported hearing loss. The mean scores in the SSQ were 8.2, 8.3 and 8.6 for the Speech, Spatial and Qualities subscales, respectively. In audiometry, the mean pure tone average (PTA) was 17.1 (SD 12.2) and 17.1 (SD 12.3) dB HL for the right and left ears, respectively, with no difference to gender- and age-matched, otologically normal reference values. The average speech reception threshold in noise (SRT) was − 8.2 (SD 1.5) and − 8.0 (SD 1.7) dB SNR for the right and left ears, respectively, which did not differ from a control group with a comparable range in PTA thresholds.

Conclusion

Although a significant proportion of AGel amyloidosis patients experience subjective difficulties in hearing there seems to be no peripheral or central hearing impairment at least in patients up to the age of 60 years.
Predictors of neutralizing antibody response to BNT162b2 vaccination in allogeneic hematopoietic stem cell transplant recipients
Authors: Canti Lorenzo , Humblet-Baron Stéphanie , Desombere Isabelle , Neumann Julika , Pannus Pieter , Heyndrickx Leo , Henry Aurélie , Servais Sophie , Willems Evelyne , Ehx Grégory , Goriely Stanislas , Seidel Laurence , Michiels Johan , Willems Betty , Liston Adrian , Ariën Kevin K. , Beguin Yves , Goossens Maria E. , Marchant Arnaud , Baron Frédéric
Published: October 2021

Background

Factors affecting response to SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients remain to be elucidated.

Methods

Forty allo-HCT recipients were included in a study of immunization with BNT162b2 mRNA vaccine at days 0 and 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD) were assessed at days 0, 21, 28, and 49 while neutralizing Ab against SARS-CoV-2 wild type (NT50) were assessed at days 0 and 49. Results observed in allo-HCT patients were compared to those obtained in 40 healthy adults naive of SARS-CoV-2 infection. Flow cytometry analysis of peripheral blood cells was performed before vaccination to identify potential predictors of Ab responses.

Results

Three patients had detectable anti-RBD Ab before vaccination. Among the 37 SARS-CoV-2 naive patients, 20 (54%) and 32 (86%) patients had detectable anti-RBD Ab 21 days and 49 days postvaccination. Comparing anti-RBD Ab levels in allo-HCT recipients and healthy adults, we observed significantly lower anti-RBD Ab levels in allo-HCT recipients at days 21, 28 and 49. Further, 49% of allo-HCT patients versus 88% of healthy adults had detectable NT50 Ab at day 49 while allo-HCT recipients had significantly lower NT50 Ab titers than healthy adults (P = 0.0004). Ongoing moderate/severe chronic GVHD (P < 0.01) as well as rituximab administration in the year prior to vaccination (P < 0.05) correlated with low anti-RBD and NT50 Ab titers at 49 days after the first vaccination in multivariate analyses. Compared to healthy adults, allo-HCT patients without chronic GVHD or rituximab therapy had comparable anti-RBD Ab levels and NT50 Ab titers at day 49. Flow cytometry analyses before vaccination indicated that Ab responses in allo-HCT patients were strongly correlated with the number of memory B cells and of naive CD4+ T cells (r > 0.5, P < 0.01) and more weakly with the number of follicular helper T cells (r = 0.4, P = 0.01).

Conclusions

Chronic GVHD and rituximab administration in allo-HCT recipients are associated with reduced Ab responses to BNT162b2 vaccination. Immunological markers could help identify allo-HCT patients at risk of poor Ab response to mRNA vaccination.

Trial registration

The study was registered at clinicaltrialsregister.eu on 11 March 2021 (EudractCT # 2021-000673-83).
The effect of opioids on gastrointestinal function in the ICU
Authors: Yan Yun , Chen Yu , Zhang Xijing
Published: October 2021

Gastrointestinal (GI) dysfunction is common in the critical care setting and is highly associated with clinical outcomes. Opioids increase the risk for GI dysfunction and are frequently prescribed to reduce pain in critically ill patients. However, the role of opioids in GI function remains uncertain in the ICU. This review aims to describe the effect of opioids on GI motility, their potential risk of increasing infection and the treatment of GI dysmotility with opioid antagonists in the ICU setting.
Clinical trial recruiters’ experiences working with trial eligibility criteria: results of an exploratory, cross-sectional, online survey in the UK
Authors: Cragg William J. , McMahon Kathryn , Oughton Jamie B. , Sigsworth Rachel , Taylor Christopher , Napp Vicky
Published: October 2021

Background

Eligibility criteria are a fundamental element of clinical trial design, defining who can and who should not participate in a trial. Problems with the design or application of criteria are known to occur and pose risks to participants’ safety and trial integrity, sometimes also negatively impacting on trial recruitment and generalisability. We conducted a short, exploratory survey to gather evidence on UK recruiters’ experiences interpreting and applying eligibility criteria and their views on how criteria are communicated and developed.

Methods

Our survey included topics informed by a wider programme of work at the Clinical Trials Research Unit, University of Leeds, on assuring eligibility criteria quality. Respondents were asked to answer based on all their trial experience, not only on experiences with our trials. The survey was disseminated to recruiters collaborating on trials run at our trials unit, and via other mailing lists and social media. The quantitative responses were descriptively analysed, with inductive analysis of free-text responses to identify themes.

Results

A total of 823 eligible respondents participated. In total, 79% of respondents reported finding problems with eligibility criteria in some trials, and 9% in most trials. The main themes in the types of problems experienced were criteria clarity (67% of comments), feasibility (34%), and suitability (14%). In total, 27% of those reporting some level of problem said these problems had led to patients being incorrectly included in trials; 40% said they had led to incorrect exclusions. Most respondents (56%) reported accessing eligibility criteria mainly in the trial protocol. Most respondents (74%) supported the idea of recruiter review of eligibility criteria earlier in the protocol development process.

Conclusions

Our survey corroborates other evidence about the existence of suboptimal trial eligibility criteria. Problems with clarity were the most often reported, but the number of comments on feasibility and suitability suggest some recruiters feel eligibility criteria and associated assessments can hinder recruitment to trials. Our proposal for more recruiter involvement in protocol development has strong support and some potential benefits, but questions remain about how best to implement this. We invite other trialists to consider our other suggestions for how to assure quality in trial eligibility criteria.
Endogenous CRISPR-assisted microhomology-mediated end joining enables rapid genome editing in Zymomonas mobilis
Authors: Sui Xin , Wang Xiaojie , Liu Tao , Ye Qing , Wu Bo , Hu Guoquan , Yang Shihui , He Mingxiong , Peng Nan
Published: October 2021

Background

Zymomonas mobilis is a natural ethanologen with many desirable characteristics, making it an ideal platform for future biorefineries. Recently, an endogenous CRISPR-based genome editing tool has been developed for this species. However, a simple and high-efficient genome editing method is still required.

Results

We developed a novel gene deletion tool based on the endogenous subtype I–F CRISPR-Cas system and the microhomology-mediated end joining (MMEJ) pathway. This tool only requires a self-interference plasmid carrying the mini-CRISPR (Repeat–Spacer–Repeat) expression cassette, where the spacer matches the target DNA. Transformation of the self-interference plasmid leads to target DNA damage and subsequently triggers the endogenous MMEJ pathway to repair the damaged DNA, leaving deletions normally smaller than 500 bp. Importantly, the MMEJ repair efficiency was increased by introducing mutations at the second repeat of the mini-CRISPR cassette expressing the guide RNA. Several genes have been successfully deleted via this method, and the phenotype of a σ28 deletion mutant generated in this study was characterized. Moreover, large fragment deletions were obtained by transformation of the self-interference plasmids expressing two guide RNAs in tandem.

Conclusions

Here, we report the establishment of an efficient gene deletion tool based on the endogenous subtype I–F CRISPR-Cas system and the MMEJ pathway in Zymomonas mobilis. We achieved single gene deletion and large-fragment knockout using this tool. In addition, we further promoted the editing efficiency by modifying the guide RNA expression cassette and selecting lower GC% target sites. Our study has provided an effective method for genetic manipulation in Z. mobilis.
The acceptability of targeted mass treatment with primaquine for local elimination of vivax malaria in a northern Myanmar township: a mixed-methods study
Authors: Aung Pyae Linn , Soe Myat Thu , Soe Than Naing , Oo Thit Lwin , Aung Poh Poh , Khin Aung , Thi Aung , Phuanukoonnon Suparat , Okanurak Kamolnetr , Cui Liwang , Kyaw Myat Phone , Parker Daniel M.
Published: October 2021

Background

Radical cure of the Plasmodium vivax latent liver stage is required to effectively manage vivax malaria. Targeted mass treatment with primaquine may be an effective mechanism for reducing reservoirs of the disease. Since community engagement and high coverage are essential for mass treatment programs, this study aimed to determine the acceptability of mass primaquine treatment in a targeted community in a northern Myanmar township.

Methods

A cross-sectional mixed-methods study was deployed among household leaders in July 2019. Face-to-face interviews using structured questionnaires and standardized qualitative guidelines were conducted to gather information. Descriptive and inferential statistics, including logistic regression models, were applied.

Results

Among 609 study respondents, > 90% agreed to participate in an upcoming targeted mass primaquine treatment (TPT) program. Factors contributing to higher odds of acceptability of the program were older age [adjusted odds ratios (aOR): 2.38, 95% confidence intervals (CI) 1.08–8.96], secondary education level (aOR: 3.99, 95% CI 1.12–20.01), having good knowledge of malaria (aOR: 2.12, 95% CI 1.04–4.76), experiencing malaria within the family (aOR: 1.92, 95% CI 1.14–5.13), and believing eliminating malaria from the village is possible (aOR: 2.83, 95% CI 1.07–4.07). Furthermore, 50 community respondents, 6 midwives, and 4 public health staff (grade II) participated in the qualitative component of the study. Many thought that TPT seemed feasible and stressed that high coverage of underserved groups and health education are needed before commencing the activity.

Conclusions

Most respondents agreed to participate in the proposed mass treatment campaign. Older people with secondary education level and those who had experienced malaria within their families were most likely to report willingness to participate. These same individuals may be important in the community engagement process to increase community acceptance of the program.

Graphical abstract
Ten-year follow-up of sitagliptin treatment in patients with type 2 diabetes mellitus
Authors: Hattori Sachiko
Published: October 2021

Background

Early and effective intervention with a dipeptidyl peptidase 4 inhibitor (DPP4i) before the development of advanced atherosclerosis in type 2 diabetes mellitus (T2DM) patients without a history of cardiovascular disease (CVD) is reported to increase the chance of significant reductions in not only microvascular disease, but also CVD.

Method

This study aimed to investigate whether sitagliptin is effective and tolerated for glycemic control and whether renoprotective effects and β-cell function are preserved for as long as ten years in Japanese patients with T2DM without a history of CVD.

Results

The situation is equivalent to improving glycemic control as assessed by hemoglobin A1c both in a sitagliptin group [sitagliptin 50 mg as either monotherapy or combination therapy with other oral glucose-lowering drugs (n = 17)] or a control group [placebo as either monotherapy or combination therapy with other glucose-lowering drugs (n = 9)], while anti-inflammatory effects as assessed by high-sensitivity C-reactive peptide in the sitagliptin group were superior to those in the control group. In the sitagliptin group, mean urinary albumin excretion (measured as urinary albumin-to-creatinine ratio) was markedly decreased, but no changes in estimated glomerular filtration rate were seen throughout the study. Beta-cell function as evaluated by homeostatic model assessment of β-cell function values was reduced at baseline in both groups, improved significantly in the sitagliptin group, and continued unchanged in the control group during the study.

Conclusion

These observations suggest that early intervention with sitagliptin in patients with T2DM may have long-lasting renoprotective and islet-protective effects.

Trial registration: UMIN Clinical Registry (UMIN000038459). Registered 01 November (retrospectively registered): https://upload.umin.ac.jp/UMIN000038459
A toolkit for haptic force feedback in a telerobotic ultrasound system
Authors: Fotouhi Reza , Najafi Semnani Atieh , Zhang QianWei , Adams Scott J. , Obaid Haron
Published: October 2021

Objective

To develop a collision engine (haptic force feedback simulator) compatible with a 5-degrees-of-freedom (DOF) haptic wand. This has broad applications such as telerobotic ultrasound systems. Integrating force feedback into systems is critical to optimize remote scanning. A collision engine compatible with a 5-DOF haptic wand was developed based on the Gilbert–Johnson–Keerthi algorithm. The collision engine calculated force during collision between the wand and a virtual object based on code developed using MATLAB. A proportional force was subsequently returned to a user via the haptic wand, thereby simulating the collision force for the user. Three experiments were conducted to assess the accuracy of the collision engine on curved and flat surfaces.

Results

The average errors in calculation of distances between the wand and virtual object were 2.1 cm, 3.4 cm, and 4.2 cm for the model of the human hand, cylinder, and cuboid, respectively. The collision engine accurately simulated forces on a flat surface, though was less accurate on curved surfaces. Future work will incorporate haptic force feedback into a telerobotic ultrasound system. The haptic force simulator presented here may also be used in the development of ultrasound simulators for training and education.
Cell-free DNA 5-hydroxymethylcytosine profiles of long non-coding RNA genes enable early detection and progression monitoring of human cancers
Authors: Zhou Meng , Hou Ping , Yan Congcong , Chen Lu , Li Ke , Wang Yiran , Zhao Jingting , Su Jianzhong , Sun Jie
Published: October 2021

Background

5-Hydroxymethylcytosine (5hmC) is a significant DNA epigenetic modification. However, the 5hmC modification alterations in genomic regions encoding long non-coding RNA (lncRNA) and their clinical significance remain poorly characterized.

Results

A three-phase discovery–modeling–validation study was conducted to explore the potential of the plasma-derived 5hmC modification level in genomic regions encoding lncRNAs as a superior alternative biomarker for cancer diagnosis and surveillance. Genome-wide 5hmC profiles in the plasma circulating cell-free DNA of 1632 cancer and 1379 non-cancerous control samples from different cancer types and multiple centers were repurposed and characterized. A large number of altered 5hmC modifications were distributed at genomic regions encoding lncRNAs in cancerous compared with healthy subjects. Furthermore, most 5hmC-modified lncRNA genes were cancer-specific, with only a relatively small number of 5hmC-modified lncRNA genes shared by various cancer types. A 5hmC-LncRNA diagnostic score (5hLD-score) comprising 39 tissue-shared 5hmC-modified lncRNA gene markers was developed using elastic net regularization. The 5hLD-score was able to accurately distinguish tumors from healthy controls with an area under the curve (AUC) of 0.963 [95% confidence interval (CI) 0.940–0.985] and 0.912 (95% CI 0.837–0.987) in the training and internal validation cohorts, respectively. Results from three independent validations confirmed the robustness and stability of the 5hLD-score with an AUC of 0.851 (95% CI 0.786–0.916) in Zhang’s non-small cell lung cancer cohort, AUC of 0.887 (95% CI 0.852–0.922) in Tian’s esophageal cancer cohort, and AUC of 0.768 (95% CI 0.746–0.790) in Cai’s hepatocellular carcinoma cohort. In addition, a significant association was identified between the 5hLD-score and the progression from hepatitis to liver cancer. Finally, lncRNA genes modified by tissue-specific 5hmC alteration were again found to be capable of identifying the origin and location of tumors.

Conclusion

The present study will contribute to the ongoing effort to understand the transcriptional programs of lncRNA genes, as well as facilitate the development of novel invasive genomic tools for early cancer detection and surveillance.
Cumulative evidence for association of rhinitis and depression
Authors: Wang Jing , Xiao Dongqiong , Chen Huayou , Hu Juan
Published: October 2021

Background

Several primary studies evaluated the association between rhinitis and the incidence of depression and yielded inconsistent results. We conducted a meta-analysis of studies evaluating the association between rhinitis and depression.

Methods

We searched the EMBASE, PubMed and Cochrane Library databases for studies published in English before April 1, 2019. The studies were included if they reported any type of rhinitis in relation to depression. Two authors independently extracted the data. The odds ratios (ORs) were pooled using a random-effects model. Stratified analyses were conducted to evaluate the association.

Results

Among the 3472 initially identified studies, we included 14 studies involving a total of 19.36 ± 1.1 million participants according to predefined inclusion criteria. The associations between rhinitis (R), allergic rhinitis (AR), and nonallergic rhinitis (NAR) and depression were significant with ORs of 1.86 (95% CI 1.32 to 2.62, p < 0.05), 1.54 (95% CI 1.24 to 1.90, p < 0.05), and 2.15 (95% CI 1.49 to 3.09, p < 0.05), respectively. The results were consistent and statistically significant in all subgroup analyses.

Conclusions

Rhinitis was associated with an increased risk of depression. Further prospective studies involving large sample sizes are required to confirm the results by considering more confounders and clarify the mechanisms.
Activation of the EGFR-PI3K-CaM pathway by PRL-1-overexpressing placenta-derived mesenchymal stem cells ameliorates liver cirrhosis via ER stress-dependent calcium
Authors: Kim Se Ho , Kim Jae Yeon , Park Soo Young , Jeong Won Tae , Kim Jin Man , Bae Si Hyun , Kim Gi Jin
Published: October 2021

Background

Cholesterol accumulation and calcium depletion induce hepatic injury via the endoplasmic reticulum (ER) stress response. ER stress regulates the calcium imbalance between the ER and mitochondria. We previously reported that phosphatase of regenerating liver-1 (PRL-1)-overexpressing placenta-derived mesenchymal stem cells (PD-MSCsPRL−1) promoted liver regeneration via mitochondrial dynamics in a cirrhotic rat model. However, the role of PRL-1 in ER stress-dependent calcium is not clear. Therefore, we demonstrated that PD-MSCsPRL−1 improved hepatic functions by regulating ER stress and calcium channels in a rat model of bile duct ligation (BDL).

Methods

Liver cirrhosis was induced in Sprague–Dawley (SD) rats using surgically induced BDL for 10 days. PD-MSCs and PD-MSCsPRL−1 (2 × 106 cells) were intravenously administered to animals, and their therapeutic effects were analyzed. WB-F344 cells exposed to thapsigargin (TG) were cocultured with PD-MSCs or PD-MSCsPRL−1.

Results

ER stress markers, e.g., eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were increased in the nontransplantation group (NTx) compared to the control group. PD-MSCsPRL−1 significantly decreased ER stress markers compared to NTx and induced dynamic changes in calcium channel markers, e.g., sarco/endoplasmic reticulum Ca2+ -ATPase 2b (SERCA2b), inositol 1,4,5-trisphosphate receptor (IP3R), mitochondrial calcium uniporter (MCU), and voltage-dependent anion channel 1 (VDAC1) (*p < 0.05). Cocultivation of TG-treated WB-F344 cells with PD-MSCsPRL−1 decreased cytosolic calmodulin (CaM) expression and cytosolic and mitochondrial Ca2+ concentrations. However, the ER Ca2+ concentration was increased compared to PD-MSCs (*p  < 0.05). PRL-1 activated phosphatidylinositol-3-kinase (PI3K) signaling via epidermal growth factor receptor (EGFR), which resulted in calcium increase via CaM expression.

Conclusions

These findings suggest that PD-MSCsPRL−1 improved hepatic functions via calcium changes and attenuated ER stress in a BDL-injured rat model. Therefore, these results provide useful data for the development of next-generation MSC-based stem cell therapy for regenerative medicine in chronic liver disease.
A high abundance of Firmicutes in the intestine of chinese mitten crabs (Eriocheir sinensis) cultured in an alkaline region
Authors: Guan Weibing , Li Kui , Zhao Shuang , Li Kejun
Published: October 2021

The Chinese mitten crab (Eriocheir sinensis) is a popular aquaculture product in East Asia, especially in China. In the last decade, rice–crab co-culture has rapidly expanded in China. Under this model, crabs are raised in rice fields instead of in traditional aquaculture ponds. In this study, we cultured two varieties of Chinese mitten crabs (Changjiang and Liaohe) in an alkaline region in northwest China and used Illumina MiSeq sequencing to compare the intestinal bacterial alpha diversity and community structure between traditional and co-culture aquaculture models, between two crab varieties, and between female and male crabs. Significant variations in intestinal bacterial communities were found between crab varieties and between female and male crabs but not between aquaculture models. These results show that rice–crab co-culture operations did not obviously impact the crab intestinal bacterial community compared with traditional pond aquaculture. Firmicutes was the most abundant bacterial phylum in the crab intestines (78%, relative abundance). Three dominant operational taxonomic units (OTUs) represented 73.2% of Firmicutes sequences and 56.8% of all sequences. A dominant OTU assigned as Firmicutes that was negatively correlated with crab body length, width, and weight was found in the source water for the experimental area. The results of this study suggest that the aquaculture of Chinese mitten crabs in alkaline regions requires more study to improve cultivation techniques.
A class of backward stochastic Bellman–Bihari’s inequality and its applications
Authors: Hao Wu , Wang Jinxia
Published: October 2021

In this paper, we propose and prove several different forms of backward stochastic Bellman–Bihari’s inequality. Then, as two applications, two different types of the comparison theorems for backward stochastic differential equation with stochastic non-Lipschitz condition are presented.
Global strong solution to the 2D inhomogeneous incompressible magnetohydrodynamic fluids with density-dependent viscosity and vacuum
Authors: Su Menglong
Published: October 2021

In this paper, we investigate an initial boundary value problem for two-dimensional inhomogeneous incompressible MHD system with density-dependent viscosity. First, we establish a blow-up criterion for strong solutions with vacuum. Precisely, the strong solution exists globally if $\|\nabla \mu (\rho )\|_{L^{\infty }(0, T; L^{p})}$

∥
∇
μ
(
ρ
)
∥

L
∞

(
0
,
T
;

L
p

)

is bounded. Second, we prove the strong solution exists globally (in time) only if $\|\nabla \mu (\rho _{0})\|_{L^{p}}$

∥
∇
μ
(

ρ
0

)
∥

L
p

is suitably small, even the presence of vacuum is permitted.
On a fractional cantilever beam model in the q-difference inclusion settings via special multi-valued operators
Authors: Etemad Sina , Hussain Azhar , Imran Atika , Alzabut Jehad , Rezapour Shahram , Selvam A. George Maria
Published: October 2021

The fundamental goal of the study under consideration is to establish some of the existence criteria needed for a particular fractional inclusion model of cantilever beam in the setting of quantum calculus using new arguments of existence theory. In this way, we investigate a fractional integral equation that corresponds to the aforementioned boundary value problem. In a more concrete sense, we design new multi-valued operators based on this integral equation, which belong to the certain subclasses of functions, called α-admissible and α-ψ-contractive multi-functions, in combination with the AEP-property. Also, we use some inequalities such as Ω-inequality and set-valued version inequalities. Moreover, we add a simulative example for a numerical analysis of our results obtained in this study.
Risk factors for colonization with multiple species of extended-spectrum beta-lactamase producing Enterobacterales: a case-case–control study
Authors: Vock Isabelle , Aguilar-Bultet Lisandra , Egli Adrian , Tamma Pranita D. , Tschudin-Sutter Sarah
Published: October 2021

Background

Approximately 11% of patients colonized with extended-spectrum beta-lactamase producing Enterobacterales (ESBL-PE) are colonized with more than one ESBL-producing species. We investigated risk factors associated with colonization with multiple ESBL-PE species.

Methods

We performed a case-case–control study at the University Hospital Basel, Switzerland, including hospitalized patients colonized with ESBL-PE between 01/2008 and 12/2018. Patients colonized with multiple species of ESBL-PE during the same hospitalization were assigned to group 1. Group 2 consisted of patients with ESBL-PE and a newly acquired ESBL-PE-species identified during subsequent hospitalization. Controls (i.e., group 3) were patients with only one species of ESBL-PE identified over multiple hospitalizations. Controls were frequency-matched 3:1 to group 2 cases according to time-at-risk (i.e., days between ESBL-PE detection during first and subsequent hospitalizations) to standardize the duration of colonization. ESBL was identified with phenotypic assay and the presence of ESBL genes was confirmed by whole genome sequencing.

Results

Among 1559 inpatients, 154 cases met eligibility criteria (67 in group 1, 22 in group 2, 65 in group 3). International travel within the previous 12 months (OR 12.57, 95% CI 3.48–45.45, p < 0.001) and antibiotic exposure within the previous 3 months (OR 2.96, 95% CI 1.37–6.41, p = 0.006) were independently associated with co-colonization with multiple ESBL-PE species. Admission from another acute-care facility was the only predictor of replacement of one ESBL-PE species with another during subsequent hospitalizations (OR 6.02, 95% CI 1.15–31.49, p = 0.003).

Conclusion

These findings point to strain-related factors being the main drivers of co-colonization with different ESBL-PE and may support stratification of infection prevention and control measures according to ESBL-PE species/strains.
An updated calculator for determining levodopa-equivalent dose
Authors: Nyholm D. , Jost W. H.
Published: October 2021

Calculation of levodopa-equivalent dose in Parkinson’s disease has become common in research, but is also a useful tool in clinical practice, especially when initiating device-aided treatments (deep brain stimulation, apomorphine and levodopa infusions). The aim with the present calculator is to provide an updated conversion table, including dose calculation of the recently developed levodopa/entacapone/carbidopa intestinal gel infusion. Future versions of the calculator should be made conducive to learning by means of artificial intelligence.
SGLT2 inhibitors in heart failure with reduced ejection fraction
Authors: Das Uday Sankar , Paul Aritra , Banerjee Suvro
Published: October 2021

Sodium – glucose co-transporter 2 (SGLT2) inhibitors reduce blood glucose by inhibiting reabsorption of glucose from the proximal renal tubules. Initial studies showed that apart from reducing blood glucose they also reduce the combined endpoint of myocardial infarction, stroke, and cardiovascular death, hospitalization from heart failure, and occurrence of renal failure in patients with known cardiovascular disease or at high risk of developing cardiovascular disease. Recent studies have shown that these drugs also could be used in patients to treat heart failure or to slow the progression of renal failure, irrespective of whether the patients have diabetes or not. In this review, we discuss the clinical trial evidence for the use of SGLT2 inhibitors for the treatment of patients with heart failure with reduced ejection fraction and for the prevention of heart failure in patients with diabetes who are at high risk of cardiovascular events. We also discuss the plausible mechanisms of action for the cardiovascular beneficial effects of SGLT2 inhibitors. EMPA-REG OUTCOME TRIAL, DECLARE-TIMI 58, CANVAS, VERTIS-CV studies have shown that SGLT2 inhibitors namely empagliflozin, dapagliflozin, canagliflozin and ertugliflozin reduce the chances of hospitalisation in patients who have cardiovascular disease or at high risk of cardiovascular disease. The DAPA-HF study and the EMPEROR-REDUCED TRIAL have further shown that Dapagliflozin and Empagliflozin could be used to treat patients with heart failure, with or without diabetes. SGLT2 inhibitors provide us with a new armamentarium for treatment of patients with a triad of diabetes, heart or renal disease. Their mechanism of action in prevention or treatment of patients with heart failure however still remains speculative.