bluuebunny/crossref_metadata_2025 huggingface dataset:
The carbonate concentration mechanism of Pyropia yezoensis (Rhodophyta): evidence from transcriptomics and biochemical data
Authors: Zhang Baoyu , Xie Xiujun , Liu Xuehua , He Linwen , Sun Yuanyuan , Wang Guangce
Published: September 2020

Background

Pyropia yezoensis(Rhodophyta) is widely cultivated in East Asia and plays important economic, ecological and research roles. Although inorganic carbon utilization ofP. yezoensishas been investigated from a physiological aspect, the carbon concentration mechanism (CCM) ofP. yezoensisremains unclear. To explore the CCM ofP. yezoensis, especially during its different life stages, we tracked changes in the transcriptome, photosynthetic efficiency and in key enzyme activities under different inorganic carbon concentrations.

Results

Photosynthetic efficiency demonstrated that sporophytes were more sensitive to low carbon (LC) than gametophytes, with increased photosynthesis rate during both life stages under high carbon (HC) compared to normal carbon (NC) conditions. The amount of starch and number of plastoglobuli in cells corresponded with the growth reaction to different inorganic carbon (Ci) concentrations. We constructed 18 cDNA libraries from 18 samples (three biological replicates per Ci treatment at two life cycles stages) and sequenced these using the Illumina platform. De novo assembly generated 182,564 unigenes, including approximately 275 unigenes related to CCM. Most genes encoding internal carbonic anhydrase (CA) and bicarbonate transporters involved in the biophysical CCM pathway were induced under LC in comparison with NC, with transcript abundance of somePyCAs in gametophytes typically higher than that in sporophytes. We identified all key genes participating in the C4 pathway and showed that their RNA abundances changed with varying Ci conditions. High decarboxylating activity of PEPCKase and low PEPCase activity were observed inP. yezoensis. Activities of other key enzymes involved in the C4-like pathway were higher under HC than under the other two conditions. Pyruvate carboxylase (PYC) showed higher carboxylation activity than PEPC under these Ci conditions. Isocitrate lyase (ICL) showed high activity, but the activity of malate synthase (MS) was very low.

Conclusion

We elucidated the CCM ofP. yezoensisfrom transcriptome and enzyme activity levels. All results indicated at least two types of CCM inP. yezoensis, one involving CA and an anion exchanger (transporter), and a second, C4-like pathway belonging to the PEPCK subtype. PYC may play the main carboxylation role in this C4-like pathway, which functions in both the sporophyte and gametophyte life cycles.
Exploring the concept and structure of obstetric triage: a qualitative content analysis
Authors: Moudi Asieh , Iravani Mina , Najafian Mahin , Zareiyan Armin , Forouzan Arash , Mirghafourvand Mojgan
Published: September 2020

Background

Obstetric triage is a new idea, so the design and implementation of it requires identification of its concept and structure. The aim of this qualitative study was to explore the concept and structure of the obstetric triage in Iran.

Methods

The purposive sampling was done and it continued until reaching the theoretical saturation. Thirty-seven semi-structured interviews were conducted individually and face-to-face. Interviews were audio recorded, transcribed, and analyzed using conventional content analysis.

Results

Two themes, 8 main categories, and 16 subcategories emerged from the content analysis of the interviews and observations. The themes were the concept and structure of obstetric triage. The concept of obstetric triage consisted of three categories of nature, process, and philosophy of obstetric triage. The structure of obstetric triage included five categories of assessment criteria, emergency grading, determining the appropriate location for patient guidance, initiation of diagnostic and therapeutic measures, and timeframe for initial assessment and reassessment.

Conclusion

Findings highlighted that obstetric triage is a process with a dual and dynamic nature. This process involves clinical decision making to prioritize the pregnant mother and her fetus based on the severity and acuity of the disease in order to allocate medical resources and care for providing appropriate treatment at the right time and place to the right patient. The results of this study could be used for the design and implementation of the obstetric triage system.
Evaluating the care provision of a community-based serious-illness care program via chart measures
Authors: Kistler Christine E. , Van Dongen Matthew J. , Ernecoff Natalie C. , Daaleman Timothy P. , Hanson Laura C.
Published: September 2020

Background

Although quality-of-care domains for home-based primary and palliative programs have been proposed, they have had limited testing in practice. Our aim was to evaluate the care provision in a community-based serious-illness care program, a combined home-based primary and palliative care model.

Methods

Retrospective chart review of patients in an academic community-based serious-illness care program in central North Carolina from August 2014 to March 2016 (n = 159). Chart review included demographics, health status, and operationalized measures of seven quality-of-care domains: medical assessment, care coordination, safety, quality of life, provider competency, goal attainment, and access.

Results

Patients were mostly women (56%) with an average age of 70 years. Patients were multi-morbid (53% ≥3 comorbidities), functionally impaired (45% had impairment in ≥2 activities of daily living) and 32% had dementia. During the study period, 31% of patients died. Chart review found high rates assessment of functional status (97%), falls (98%), and medication safety (96%). Rates of pain assessment (70%), advance directive discussions (65%), influenza vaccination (59%), and depression assessment (54% of those with a diagnosis of depression) were lower. Cognitive barriers, spiritual needs, and behavioral issues were assessed infrequently (35, 22, 21%, respectively).

Conclusion

This study is one of the first to operationalize and examine quality-of-care measures for a community-based serious-illness care program, an emerging model for vulnerable adults. Our operationalization should not constitute validation of these measures and revealed areas for improvement; however, the community-based serious-illness care program performed well in several key quality-of-care domains. Future work is needed to validate these measures.
Postpartum depression in mothers and fathers: a structural equation model
Authors: Duan Zhizhou , Wang Yuanyuan , Jiang Ping , Wilson Amanda , Guo Yan , Lv Yongliang , Yang Xiaonan , Yu Renjie , Wang Shuilan , Wu Zhengyan , Xia Mengqing , Wang Guosheng , Tao Ye , Xiaohong L , Ma Ling , Shen Hong , Sun Jue , Deng Wei , Yang Yong , Chen Runsen
Published: September 2020

Background

Post-partum depression (PPD) is a growing mental health concern worldwide. There is little evidence in the Chinese context of the relationship between paternal PPD and maternal PPD. Given the growing global concerns this relationship requires further exploration.

Methods

A survey was conducted with 950 total couples from March 2017 to December 2018. The study was conducted using a standardized questionnaire that included basic demographic information, information on the relationship between the mother-in-law and daughter-in-law, marital satisfaction (both maternal and paternal), and PPD symptoms. Structural Equation Modelling (SEM) analysis was used to explore the underlying mechanism for PPD symptoms in mothers and fathers.

Results

In 4.4% of the couples both the wife and the husband showed depressive symptoms. Maternal marital satisfaction showed a significant mediating effect on paternal PPD (B = -0.114, p < 0.01), and there was a direct effect of maternal PPD on paternal PPD (B = 0.31, p < 0.001).

Conclusions

This is the first study to investigate the possible correlation between maternal PPD, mother-in-law and daughter-in-law relationship satisfaction, maternal marital satisfaction, paternal marital satisfaction, and paternal PPD. It is important for future PPD interventions to target both maternal and paternal mental health, as well as the mechanisms identified that can lead to PPD.
Prediction of vaginal birth after cesarean delivery in Southeast China: a retrospective cohort study
Authors: Zhang Hua-Le , Zheng Liang-Hui , Cheng Li-Chun , Liu Zhao-Dong , Yu Lu , Han Qin , Miao Geng-Yun , Yan Jian-Ying
Published: September 2020

Background

We aimed to develop and validate a nomogram for effective prediction of vaginal birth after cesarean (VBAC) and guide future clinical application.

Methods

We retrospectively analyzed data from hospitalized pregnant women who underwent trial of labor after cesarean (TOLAC), at the Fujian Provincial Maternity and Children’s Hospital, between October 2015 and October 2017. Briefly, we included singleton pregnant women, at a gestational age above 37 weeks who underwent a primary cesarean section, in the study. We then extracted their sociodemographic data and clinical characteristics, and randomly divided the samples into training and validation sets. We employed the least absolute shrinkage and selection operator (LASSO) regression to select variables and construct VBAC success rate in the training set. Thereafter, we validated the nomogram using the concordance index (C-index), decision curve analysis (DCA), and calibration curves. Finally, we adopted the Grobman’s model to perform comparisons with published VBAC prediction models.

Results

Among the 708 pregnant women included according to inclusion criteria, 586 (82.77%) patients were successfully for VBAC. Multivariate logistic regression models revealed that maternal height (OR, 1.11; 95% CI, 1.04 to 1.19), maternal BMI at delivery (OR, 0.89; 95% CI, 0.79 to 1.00), fundal height (OR, 0.71; 95% CI, 0.58 to 0.88), cervix Bishop score (OR, 3.27; 95% CI, 2.49 to 4.45), maternal age at delivery (OR, 0.90; 95% CI, 0.82 to 0.98), gestational age (OR, 0.33; 95% CI, 0.17 to 0.62) and history of vaginal delivery (OR, 2.92; 95% CI, 1.42 to 6.48) were independently associated with successful VBAC. The constructed predictive model showed better discrimination than that from the Grobman’s model in the validation series (c-index 0.906 VS 0.694, respectively). On the other hand, decision curve analysis revealed that the new model had better clinical net benefits than the Grobman’s model.

Conclusions

VBAC will aid in reducing the rate of cesarean sections in China. In clinical practice, the TOLAC prediction model will help improve VBAC’s success rate, owing to its contribution to reducing secondary cesarean section.
The Sandwich principle: assessing the didactic effect in lectures on “cleft lips and palates”
Authors: Bock Anna , Idzko-Siekermann Bianca , Lemos Martin , Kniha Kristian , Möhlhenrich Stephan Christian , Peters Florian , Hölzle Frank , Modabber Ali
Published: September 2020

Background

A teaching concept, that takes individual learning and personal belongings into account, is called the “sandwich principle.” This didactic method is an educational concept that alternates consecutively between individual and collective learning phases during a course. This study aimed to prove whether the application of the sandwich principle in lectures increases the learning outcome compared with classical lectures.

Methods

All participants (n = 64) were randomly allocated into two groups. One group attended a classical face-to-face lecture and the other attended a lecture that was modified according to the sandwich principle, including activating elements. To compare knowledge gain after the lectures, all the participants had to answer a test comprising40 single-choice questions. In addition, the lectures were evaluated.

Results

Students attending the sandwich lecture had significantly better scores in the test than those who attending the classical lecture (p <  0.001). The mean test score of the sandwich group was 63.9% [standard deviation (SD) = 10] points and of the control group 50.2% (SD = 13.7 points). Overall, both the class conditions showed good evaluation results; however, students of the sandwich lecture were more satisfied with the lecture format compared with the other group.

Conclusion

Our study results confirm the thesis that the application of the sandwich principle in lectures increases the learning outcome compared with classical lectures. Even with a big audience, the sandwich design presents a concept that helps maintain high attention levels and addresses individual learning styles.
Response hierarchy models and their application in health and medicine: understanding the hierarchy of effects
Authors: Elrod James K. , Fortenberry John L.
Published: September 2020

Background

Successful patient engagement pursuits naturally require healthcare providers to possess a detailed understanding of their target audiences, with one of the most important processes to comprehend being the manner in which they learn about particular establishments and decide to extend their patronage. While health services patronage pathways vary between and among consumers, general patronage patterns exist which can provide enlightenment regarding this important process. Achieving knowledge on this front can help healthcare providers maximize opportunities to engage audiences and acquire all-important market share.

Discussion

The discipline of marketing, in part, focuses on customer engagement practices and, in describing the patronage process, it often uses what are referred to as response hierarchy models. Also known as hierarchy of effects models, these representations can help healthcare providers to understand the course through which individuals become customers of given establishments, aiding them particularly in devising appeals that can accelerate the patronage process. This particular article describes response hierarchy models, presents examples, and discusses the benefits that they offer healthcare institutions in their efforts to engage patients.

Conclusions

As institutional viability and vitality are predicated on abilities to successfully attract and retain patients, healthcare establishments must direct keen attention toward developing associated skills. This necessitates that health and medical providers possess a detailed understanding of their target audiences, notably including the stages through which they pass on their way to becoming patrons. Response hierarchy models present the patronage process, depicting given stages, permitting insights which can assist healthcare providers in their quests to hasten desired exchange and capture market share.
Effects of long-distance transportation on blood constituents and composition of the nasal microbiota in healthy donkeys
Authors: Zhao Fuwei , Jiang Guimiao , Ji Chuanliang , Zhang Zhiping , Gao Weiping , Feng Peixiang , Li Haijing , Li Min , Liu Haibing , Liu Guiqin , Magalhaes Humberto B. , Li Jianji
Published: September 2020

Background

This study aims to determine the effects of transportation on the nasal microbiota of healthy donkeys using 16S rRNA sequencing.

Results

Deep nasal swabs and blood were sampled from 14 donkeys before and after 21 hours’ long-distance transportation. The values of the plasma hormone (cortisol (Cor), adrenocorticotrophic hormone (ACTH)), biochemical indicators (total protein (TP), albumin (ALB), creatinine (CREA), lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase (CK), blood urea (UREA), plasma glucose (GLU)) and blood routine indices (white blood cell (WBC), lymphocyte (LYM), neutrophil (NEU), red blood cell (RBC), hemoglobin (HGB)) were measured. 16S rRNA sequencing was used to assess the nasal microbiota, including alpha diversity, beta diversity, and phylogenetic structures. Results showed that levels of Cor, ACTH, and heat-shock protein 90 (HSP90) were significantly increased (p < 0.05) after long-distance transportation. Several biochemical indicators (AST, CK) and blood routine indices (Neu, RBC, and HGB) increased markedly (p < 0.05), but the LYM decreased significantly (p < 0.05). Nine families and eight genera had a mean relative abundance over 1%. The predominant phyla in nasal microbiota after and before transportation wereProteobacteria,Firmicutes,Actinobacteria, andBacteroidetes. Transportation stress induced significant changes in terms of nasal microbiota structure compared with those before transportation based on principal coordinate analysis (PCoA) coupled with analysis of similarities (ANOSIM) (p < 0.05). Among these changes, a notably gain inProteobacteriaand loss inFirmicutesat the phylum level was observed.

Conclusions

These results suggest transportation can cause stress to donkeys and change the richness and diversity of nasal microbiota. Further studies are required to understand the potential effect of these microbiota changes on the development of donkey respiratory diseases.
Geographic and host distribution of haemosporidian parasite lineages from birds of the family Turdidae
Authors: Harl Josef , Himmel Tanja , Valkiūnas Gediminas , Ilgūnas Mikas , Bakonyi Támas , Weissenböck Herbert
Published: September 2020

Background

Haemosporidians (Apicomplexa, Protista) are obligate heteroxenous parasites of vertebrates and blood-sucking dipteran insects. Avian haemosporidians comprise more than 250 species traditionally classified into four genera,Plasmodium,Haemoproteus,Leucocytozoon, andFallisia. However, analyses of the mitochondrialCytBgene revealed a vast variety of lineages not yet linked to morphospecies. This study aimed to analyse and discuss the data of haemosporidian lineages isolated from birds of the family Turdidae, to visualise host and geographic distribution using DNA haplotype networks and to suggest directions for taxonomy research on parasite species.

Methods

HaemosporidianCytBsequence data from 350 thrushes were analysed for the present study and complemented withCytBdata of avian haemosporidians gathered from Genbank and MalAvi database. Maximum Likelihood trees were calculated to identify clades featuring lineages isolated from Turdidae species. For each clade, DNA haplotype networks were calculated and provided with information on host and geographic distribution.

Results

In species of the Turdidae, this study identified 82Plasmodium, 37Haemoproteus, and 119Leucocytozoonlineages, 68, 28, and 112 of which are mainly found in this host group. Most of these lineages cluster in the clades, which are shown as DNA haplotype networks. The lineages of theLeucocytozoonclades were almost exclusively isolated from thrushes and usually were restricted to one host genus, whereas thePlasmodiumandHaemoproteusnetworks featured multiple lineages also recovered from other passeriform and non-passeriform birds.

Conclusion

This study represents the first attempt to summarise information on the haemosporidian parasite lineages of a whole bird family. The analyses allowed the identification of numerous groups of related lineages, which have not been linked to morphologically defined species yet, and they revealed several cases in whichCytBlineages were probably assigned to the wrong morphospecies. These taxonomic issues are addressed by comparing distributional patterns of theCytBlineages with data from the original species descriptions and further literature. The authors also discuss the availability of sequence data and emphasise that MalAvi database should be considered an extremely valuable addition to GenBank, but not a replacement.
Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members
Authors: Räsänen Joel , Huovinen Joel , Korhonen Ville E. , Junkkari Antti , Kastinen Sami , Komulainen Simo , Oinas Minna , Avellan Cecilia , Frantzen Janek , Rinne Jaakko , Ronkainen Antti , Kauppinen Mikko , Lönnrot Kimmo , Perola Markus , Koivisto Anne M. , Remes Anne M. , Soininen Hilkka , Hiltunen Mikko , Helisalmi Seppo , Kurki Mitja I. , Jääskeläinen Juha E. , Leinonen Ville
Published: September 2020

Background

The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families.

Methods

Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their ≥ 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher’s exact test (two-tailed), the Mann–Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses.

Results

Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1–12.9, p = 0.030).

Conclusions

Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.
Application of dose-volume histogram prediction in biologically related models for nasopharyngeal carcinomas treatment planning
Authors: Cao Wufei , Zhuang Yongdong , Chen Lixin , Liu Xiaowei
Published: September 2020

Purpose

In this study, we employed a gated recurrent unit (GRU)-based recurrent neural network (RNN) using dosimetric information induced by individual beam to predict the dose-volume histogram (DVH) and investigated the feasibility and usefulness of this method in biologically related models for nasopharyngeal carcinomas (NPC) treatment planning.

Methods and materials

One hundred patients with NPC undergoing volumetric modulated arc therapy (VMAT) between 2018 and 2019 were randomly selected for this study. All the VMAT plans were created using the Monaco treatment planning system (Elekta, Sweden) and clinically approved: > 98% of PGTVnx received the prescribed doses of 70 Gy, > 98% of PGTVnd received the prescribed doses of 66 Gy and > 98% of PCTV received 60 Gy. Of these, the data from 80 patients were used to train the GRU-RNN, and the data from the other 20 patients were used for testing. For each NPC patient, the DVHs of different organs at risk were predicted by a trained GRU-based RNN using the information given by individual conformal beams. Based on the predicted DVHs, the equivalent uniform doses (EUD) were calculated and applied as dose constraints during treatment planning optimization. The regenerated VMAT experimental plans (EPs) were evaluated by comparing them with the clinical plans (CPs).

Results

For the 20 test patients, the regenerated EPs guided by the GRU-RNN predictive model achieved good consistency relative to the CPs. The EPs showed better consistency in PTV dose distribution and better dose sparing for many organs at risk, and significant differences were found in the maximum/mean doses to the brainstem, brainstem PRV, spinal cord, lenses, temporal lobes, parotid glands and larynx with P-values < 0.05. On average, compared with the CPs, the maximum/mean doses to these OARs were altered by − 3.44 Gy, − 1.94 Gy, − 1.88 Gy, 0.44 Gy, 1.98 Gy, − 1.82 Gy and 2.27 Gy, respectively. In addition, significant differences were also found in brainstem and spinal cord for the dose received by 1 cc volume with 4.11 and 1.67 Gy dose reduction in EPs on average.

Conclusion

The GRU-RNN-based DVH prediction method was capable of accurate DVH prediction. The regenerated plans guided by the predicted EUDs were not inferior to the manual plans, had better consistency in PTVs and better dose sparing in critical OARs, indicating the usefulness and effectiveness of biologically related model in knowledge-based planning.
Long-term results after thoracoscopic anterior spondylodesis with or without posterior stabilization of unstable incomplete burst fractures of the thoracolumbar junction: a prospective cohort study
Authors: Hoffmann Christof , Spiegl Ulrich Josef , Paetzold Robert , Devitt Brian , Hauck Stefan , Weiss Thomas , Bühren Volker , Gonschorek Oliver
Published: September 2020

Background

Minimally invasive, thoracoscopic anterior spondylodesis (MIAS) is an established treatment for burst fractures of the thoracolumbar spine. Good restoration of the local sagittal alignment and good functional results have been reported. The aim of this study was to evaluate long-term results of MIAS in patients with incomplete burst fractures and to analyze the influence on global sagittal alignment, clinical outcomes, and adjacent segment degeneration.

Methods

From 2002 to 2003, 18 patients were treated with MIAS for incomplete thoracolumbar burst fractures. Mono-segmental spondylodesis was performed with an iliac crest bone graft and bisegmental spondylodesis with a titanium cage. In this single-center prospective cohort study, 15 patients were available for follow-up (FU) after an average of 12.9 years (12.1–14.4). Seven patients were treated with a combined anterior and posterior instrumentation and eight patients with anterior spondylodesis only. The primary clinical outcome parameter was the Oswestry Disability Index (ODI); secondary parameters were the Short Form 36 (SF36) and the visual analog scale (VAS spine). Full spine radiographs were assessed for bisegmental Cobb angle, alignment parameters, and signs of adjacent segment degeneration (ASD).

Results

ODI evaluation showed a mean impairment of 11.7% with minimal limitations in 13 patients. Neither a significant deterioration over time nor significant differences between both therapy strategies were found in the clinical scores at the latest follow-up. The mean bisegmental increase of regional malalignment of reduction was 8.8° (± 7.3°) with no significant correlation to any clinical outcome scores. The majority of patients had no signs of adjacent segment degeneration. Two patients showed minor radiologic changes. All patients had a balanced sagittal spine profile.

Conclusions

In conclusion, MIAS leads to good clinical results with—in majority—minimal spine-related impairment at the latest follow-up. No significant deterioration at 12-year FU was detectable compared to the 6-year results for the SF36 and VAS spine scores. There was no association between sagittal alignment, clinical outcome scores, and ASD.

Trial registration

The study was retrospectively registered in the German Clinical Trials Register (Nr.00015656).
Comparing the efficacy of syngeneic iliac and femoral allografts with iliac crest autograft in a rat model of lumbar spinal fusion
Authors: Holmes Christina , Elder Benjamin D. , Ishida Wataru , Perdomo-Pantoja Alexander , Locke John , Cottrill Ethan , Lo Sheng-Fu L. , Witham Timothy F.
Published: September 2020

Background

Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer–irrigator–aspirator (RIA) autograft in clinical bone grafting, few studies have examined the efficacy of femoral grafts compared to iliac crest grafts in spinal fusion. The objective of this study was to directly compare the use of autologous iliac crest with syngeneic femoral and iliac allograft bone in the rat model of lumbar spinal fusion.

Methods

Single-level bilateral posterolateral intertransverse process lumbar spinal fusion surgery was performed on Lewis rats divided into three experimental groups: iliac crest autograft, syngeneic iliac crest allograft, and syngeneic femoral allograft bone. Eight weeks postoperatively, fusion was evaluated via microCT analysis, manual palpation, and histology. In vitro analysis of the colony-forming and osteogenic capacity of bone marrow cells derived from rat femurs and hips was also performed to determine whether there was a correlation with the fusion efficacy of these graft sources.

Results

Although no differences were observed between groups in CT fusion mass volumes, iliac allografts displayed an increased number of radiographically fused fusion masses and a higher rate of bilateral fusion via manual palpation. Histologically, hip-derived grafts showed better integration with host bone than femur derived ones, likely associated with the higher concentration of osteogenic progenitor cells observed in hip-derived bone marrow.

Conclusions

This study demonstrates the feasibility of using syngeneic allograft bone in place of autograft bone within inbred rat fusion models and highlights the need for further study of femoral-derived grafts in fusion.
Correction to: Deciphering cellular transcriptional alterations in Alzheimer’s disease brains
Authors: Wang Xue , Allen Mariet , Li Shaoyu , Quicksall Zachary S. , Patel Tulsi A. , Carnwath Troy P. , Reddy Joseph S. , Carrasquillo Minerva M. , Lincoln Sarah J. , Nguyen Thuy T. , Malphrus Kimberly G. , Dickson Dennis W. , Crook Julia E. , Asmann Yan W. , Ertekin-Taner Nilüfer
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
CDK4/6 inhibitors: a novel strategy for tumor radiosensitization
Authors: Yang Yilan , Luo Jurui , Chen Xingxing , Yang Zhaozhi , Mei Xin , Ma Jinli , Zhang Zhen , Guo Xiaomao , Yu Xiaoli
Published: September 2020

Recently, the focus of enhancing tumor radiosensitivity has shifted from chemotherapeutics to targeted therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a novel class of selective cell cycle therapeutics that target the cyclin D-CDK4/6 complex and induce G1 phase arrest. These agents have demonstrated favorable effects when used as monotherapy or combined with endocrine therapy and targeted inhibitors, stimulating further explorations of other combination strategies. Multiple preclinical studies have indicated that CDK4/6 inhibitors exhibit a synergistic effect with radiotherapy both in vitro and in vivo. The principal mechanisms of radiosensitization effects include inhibition of DNA damage repair, enhancement of apoptosis, and blockade of cell cycle progression, which provide the rationale for clinical use. CDK4/6 inhibitors also induce cellular senescence and promote anti-tumor immunity, which might represent potential mechanisms for radiosensitization. Several small sample clinical studies have preliminarily indicated that the combination of CDK4/6 inhibitors and radiotherapy exhibited well-tolerated toxicity and promising efficacy. However, most clinical trials in combined therapy remain in the recruitment stage. Further work is required to seek optimal radiotherapy-drug combinations. In this review, we describe the effects and underlying mechanisms of CDK4/6 inhibitors as a radiosensitizer and discuss previous clinical studies to evaluate the prospects and challenges of this combination.
Failure of target attainment of beta-lactam antibiotics in critically ill patients and associated risk factors: a two-center prospective study (EXPAT)
Authors: Abdulla Alan , Dijkstra Annemieke , Hunfeld Nicole G. M. , Endeman Henrik , Bahmany Soma , Ewoldt Tim M. J. , Muller Anouk E. , van Gelder Teun , Gommers Diederik , Koch Birgit C. P.
Published: September 2020

Background

Early and appropriate antibiotic dosing is associated with improved clinical outcomes in critically ill patients, yet target attainment remains a challenge. Traditional antibiotic dosing is not suitable in critically ill patients, since these patients undergo physiological alterations that strongly affect antibiotic exposure. For beta-lactam antibiotics, the unbound plasma concentrations above at least one to four times the minimal inhibitory concentration (MIC) for 100% of the dosing interval (100%ƒT > 1–4×MIC) have been proposed as pharmacodynamic targets (PDTs) to maximize bacteriological and clinical responses. The objectives of this study are to describe the PDT attainment in critically ill patients and to identify risk factors for target non-attainment.

Methods

This prospective observational study was performed in two ICUs in the Netherlands. We enrolled adult patients treated with the following beta-lactam antibiotics: amoxicillin (with or without clavulanic acid), cefotaxime, ceftazidime, ceftriaxone, cefuroxime, and meropenem. Based on five samples within a dosing interval at day 2 of therapy, the time unbound concentrations above the epidemiological cut-off (ƒT > MICECOFF and ƒT > 4×MICECOFF) were determined. Secondary endpoints were estimated multivariate binomial and binary logistic regression models, for examining the association of PDT attainment with patient characteristics and clinical outcomes.

Results

A total of 147 patients were included, of whom 63.3% achieved PDT of 100%ƒT > MICECOFF and 36.7% achieved 100%ƒT > 4×MICECOFF. Regression analysis identified male gender, estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2, and high body mass index (BMI) as risk factors for target non-attainment. Use of continuous renal replacement therapy (CRRT) and high serum urea significantly increased the probability of target attainment. In addition, we found a significant association between the 100%ƒT > MICECOFF target attainment and ICU length of stay (LOS), but no significant correlation was found for the 30-day survival.

Conclusions

Traditional beta-lactam dosing results in low target attainment in the majority of critically ill patients. Male gender, high BMI, and high eGFR were significant risk factors for target non-attainment. These predictors, together with therapeutic drug monitoring, may help ICU clinicians in optimizing beta-lactam dosing in critically ill patients.

Trial registration

Netherlands Trial Registry (EXPAT trial), NTR 5632. Registered on 7 December 2015.
Long-term physical activity on prescription intervention for patients with insufficient physical activity level—a randomized controlled trial
Authors: Lundqvist Stefan , Börjesson Mats , Cider Åsa , Hagberg Lars , Ottehall Camilla Bylin , Sjöström Johan , Larsson Maria E. H.
Published: September 2020

Background

Physical activity (PA) can be used to prevent and treat diseases. In Sweden, licensed healthcare professionals use PA on prescription (PAP) to support patients to increase their PA level. The aim of this randomized controlled trial was to evaluate a 2-year intervention of two different strategies of PAP treatment for patients with insufficient PA level, after a previous 6-month period of ordinary PAP treatment in a primary health care setting.

Methods

We included 190 patients, 27–77 years, physically inactive with metabolic risk factors where the patients were not responding to a previous 6-month PAP treatment with increased PA. The patients were randomized to either enhanced support from a physiotherapist (PT group) or continued ordinary PAP treatment at the health care centre (HCC group). The PAP treatment included an individualized dialogue; an individually dosed PA recommendation, including a written prescription; and a structured follow-up. In addition to PAP, the PT group received aerobic fitness tests and more frequent scheduled follow-ups. The patient PA level, metabolic health, and health-related quality of life (HRQOL) were measured at baseline and at 1- and 2-year follow-ups.

Results

At the 2-year follow-up, 62.9% of the PT group and 50.8% of the HCC group had increased their PA level and 31.4% vs. 38.5% achieved ≥ 150 min of moderate-intensity PA/week (difference between groups n.s.). Over 2 years, both groups displayed increased high-density lipoproteins (HDL) (p = 0.004 vs. baseline), increased mental health status (MCS) (p = 0.036), and reduced body mass index (BMI) (p = 0.001), with no difference between groups.

Conclusion

During long-term PAP interventions, the PA level, metabolic health, and HRQOL increased in patients at metabolic risk without significant differences between groups. The results indicate to be independent of any changes in pharmacological treatment. We demonstrated that the PAP treatment was feasible in ordinary primary care. Both the patients and the healthcare system benefitted from the improvement in metabolic risk factors. Future studies should elucidate effective long-term PAP-treatment strategies.

Trial registration

ClinicalTrials.gov NCT03012516. Registered on 30 December 2016—retrospectively registered.
Effect of individual allergen sensitization on omalizumab treatment outcomes in patients with severe allergic asthma determined using data from the Czech Anti-IgE Registry
Authors: Vaník Petr , Novosad Jakub , Kirchnerová Olga , Krčmová Irena , Teřl Milan ,   Czech Anti-IgE Registry collaborators
Published: September 2020

Background

Omalizumab is an efficient drug for patients with uncontrolled severe allergic asthma (SAA). However, little is known about the differences in omalizumab treatment outcomes among patients with different types of atopic sensitization. Here, we assessed the effect of sensitization to individual allergens or their combinations on the outcomes of anti-IgE therapy in patients with SAA.

Methods

We performed a post hoc analysis of data of subgroups of patients enrolled in the Czech Anti-IgE Registry (CAR). The patients were evaluated at baseline and 16 weeks and 12 months after omalizumab treatment initiation. We analyzed the dependence of primary treatment outcomes [global evaluation of treatment effectiveness (GETE) after 16 weeks of treatment, a reduction in severe exacerbation rate (ER), and an improvement in the asthma control test (ACT) result during 12 months of treatment] and secondary outcomes [a reduction in systemic corticosteroid (SCS) use, an improvement in lung functions, and a fraction of exhaled nitric oxide] of patients with SAA treated with omalizumab for 12 months on sensitization to different perennial aeroallergens. We assessed sensitization to house dust mites, molds, and pets at baseline using skin prick tests and/or specific IgE measurement (semiquantitative evaluation). We compared polysensitized patients (sensitized to all tested allergens) with monosensitized (single positivity) or partially polysensitized patients (combined positivity but not to all allergens).

Results

We enrolled 279 patients (58.3% women, mean age 52.9 years). Omalizumab treatment presented an 82.8% response rate (according to GETE). It significantly reduced severe asthma exacerbations and SCS use, and improved the ACT result in 161 responders. We identified a subgroup of responders with distinct sensitization patterns (polysensitization to all tested perennial allergens) with higher odds of being responders (OR = 2.217, p = 0.02) and lower tendency to improve ACT result (OR 0.398, p = 0.023) and reduce ER (OR 0.431, p = 0.034) than non-polysensitized patients.

Conclusions

The clinical benefit of sensitization for patients with SAA receiving omalizumab may be particularly dependent on sensitization pattern. Polysensitized patients showed a higher tendency to be responders (GETE), but a lower tendency to improve the ACT result and reduce ER than non-polysensitized patients.
Van Wyk-Grumbach syndrome and oligosyndactyly in a 6-year-old girl: a case report
Authors: Egodawaththe Niranjalee Samanthika , Seneviratne Sumudu Nimali , Gunasekara Suvini , Amarasekara Sathika Manori , Weerasekara Kumudu
Published: September 2020

Background

Van Wyk-Grumbach syndrome refers to the development of isosexual precocious pseudopuberty and multicystic enlarged ovaries in the presence of hypothyroidism and delayed bone age. It is a rare presentation of untreated hypothyroidism. The prepubertal response in Van Wyk-Grumbach syndrome is always isosexual and mediated by very high thyroid-stimulating hormone levels acting through the follicle-stimulating hormone receptors inducing a follicle-stimulating hormonal effect. Early recognition and thyroid hormone replacement can completely regress precocious puberty and ovarian enlargement, while improving the final height achievement.

Oligosyndactly is a congenital bony abnormality and can manifest either as an isolated malformation or as a component of a syndromic diagnosis. However, development of hypothyroidism in children with this peculiar bony deformity has rarely been described in the medical literature, with the exception of Cenani-Lenz Syndactyly syndrome.

Case presentation

We report the case of a 6-year-old Sri Lankan girl who presented with a 2-day history of vaginal bleeding and exertional dyspnea. She had marked short stature (well below −3 standard deviations) with an upper segment to lower segment ratio of 1.47. This girl had isolated breast development of Tanner stage 2. She was diagnosed to have acquired hypothyroidism secondary to autoimmune thyroiditis and also had macrocytic anemia, pericardial effusion, gonadotropin-releasing hormone-independent precocious puberty with radiological evidence of pubertal changes in the uterus, and multicystic ovaries. Interestingly, she also had post-axial oligosyndactyly in both feet and right-sided clubfoot. The diagnosis of Van Wyk-Grumbach syndrome was made based on the clinical and laboratory features. Her symptoms were successfully managed with L-thyroxine therapy.

Conclusions

Acquired hypothyroidism is a relatively common endocrine disorder among children and early recognition is important to prevent serious complications like Van Wyk-Grumbach syndrome. Sexual precocity with delayed bone age and stunting should direct our minds toward this unique diagnosis. It is always necessary to identify the other associated anomalies in addition to the primary diagnosis since these features may direct to a syndromic diagnosis.
Some unity results on entire functions and their difference operators related to 4 CM theorem
Authors: Chen BaoQin , Li Sheng
Published: September 2020

This paper is to consider the unity results on entire functions sharing two values with their difference operators and to prove some results related to 4 CM theorem. The main result reads as follows: Let $f(z)$
f
(
z
)
be a nonconstant entire function of finite order, and let $a_{1}$

a
1

, $a_{2}$

a
2

be two distinct finite complex constants. If $f(z)$
f
(
z
)
and $\Delta _{\eta }^{n}f(z)$

Δ
η
n

f
(
z
)
share $a_{1}$

a
1

and $a_{2}$

a
2

“CM”, then $f(z)\equiv \Delta _{\eta }^{n} f(z)$
f
(
z
)
≡

Δ
η
n

f
(
z
)
, and hence $f(z)$
f
(
z
)
and $\Delta _{\eta }^{n}f(z)$

Δ
η
n

f
(
z
)
share $a_{1}$

a
1

and $a_{2}$

a
2

CM.
Existence of solutions for subquadratic convex operator equations at resonance and applications to Hamiltonian systems
Authors: Song Mingliang , Chen Ping
Published: September 2020

This paper investigates the existence of solutions to subquadratic operator equations with convex nonlinearities and resonance by means of the index theory for self-adjoint linear operators developed by Dong and dual least action principle developed by Clarke and Ekeland. Applying the results to subquadratic convex Hamiltonian systems satisfying several boundary value conditions including Bolza boundary value conditions, generalized periodic boundary value conditions and Sturm–Liouville boundary value conditions yield some new theorems concerning the existence of solutions or nontrivial solutions. In particular, some famous results about solutions to subquadratic convex Hamiltonian systems by Mawhin and Willem and Ekeland are special cases of the theorems.
Computation of certain integral formulas involving generalized Wright function
Authors: Khan Nabiullah , Usman Talha , Aman Mohd , Al-Omari Shrideh , Araci Serkan
Published: September 2020

The aim of the paper is to derive certain formulas involving integral transforms and a family of generalized Wright functions, expressed in terms of the generalized Wright hypergeometric function and in terms of the generalized hypergeometric function as well. Based on the main results, some integral formulas involving different special functions connected with the generalized Wright function are explicitly established as special cases for different values of the parameters. Moreover, a Gaussian quadrature formula has been used to compute the integrals and compare with the main results by using graphical representations.
Further explanations for the eq. (3) in “Estimating the daily trend in the size of the COVID-19 infected population in Wuhan”
Authors: Lin Qiu-Shi , Hu Tao-Jun , Zhou Xiao-Hua
Published: September 2020

To avoid possible confusions to the readers, we provide further explanations for the eq. (3) in the research article “Estimating the daily trend in the size of the COVID-19 infected population in Wuhan” published in the Infectious Diseases of Poverty.
Epigenetic based synthetic lethal strategies in human cancers
Authors: Gao Aiai , Guo Mingzhou
Published: September 2020

Over the past decades, it is recognized that loss of DNA damage repair (DDR) pathways is an early and frequent event in tumorigenesis, occurring in 40-50% of many cancer types. The basis of synthetic lethality in cancer therapy is DDR deficient cancers dependent on backup DNA repair pathways. In cancer, the concept of synthetic lethality has been extended to pairs of genes, in which inactivation of one by deletion or mutation and pharmacological inhibition of the other leads to death of cancer cells whereas normal cells are spared the effect of the drug. The paradigm study is to induce cell death by inhibiting PARP in BRCA1/2 defective cells. Since the successful application of PARP inhibitor, a growing number of developed DDR inhibitors are ongoing in preclinical and clinical testing, including ATM, ATR, CHK1/2 and WEE1 inhibitors. Combination of PARP inhibitors and other DDR inhibitors, or combination of multiple components of the same pathway may have great potential synthetic lethality efficiency. As epigenetics joins Knudson’s two hit theory, silencing of DDR genes by aberrant epigenetic changes provide new opportunities for synthetic lethal therapy in cancer. Understanding the causative epigenetic changes of loss-of-function has led to the development of novel therapeutic agents in cancer. DDR and related genes were found frequently methylated in human cancers, including BRCA1/2, MGMT, WRN, MLH1, CHFR, P16 and APC. Both genetic and epigenetic alterations may serve as synthetic lethal therapeutic markers.