bluuebunny/crossref_metadata_2025 huggingface dataset:
Foot orthoses for first metatarsophalangeal joint osteoarthritis: study protocol for the FORT randomised controlled trial
Authors: Paterson Kade L. , Hinman Rana S. , Metcalf Ben R. , Jones Sarah E. , Menz Hylton B. , Munteanu Shannon E. , Kasza Jessica , Bennell Kim L.
Published: December 2020

Background

First metatarsophalangeal (MTP) joint osteoarthritis (OA) is a painful and debilitating condition affecting nearly one in 10 people aged over 50 years. Non-drug, non-surgical treatments are recommended by OA clinical guidelines, yet there have only ever been two randomised controlled trials (RCTs) evaluating such strategies in people with first MTP joint OA. Foot orthoses are a common non-drug, non-surgical strategy used by allied health professionals for people with first MTP joint OA, however, it is unknown whether these devices are effective in improving the symptoms associated with the condition. This clinical trial aimed to determine whether contoured foot orthoses lead to greater reductions in first MTP joint pain on walking compared to sham flat insoles in people with first MTP joint OA.

Methods

The FORT trial (Foot ORthoses for big Toe joint osteoarthritis) is a two-arm participant- and assessor-blinded, multi-site RCT conducted in Melbourne, Sydney, Brisbane and the Gold Coast, Australia. We are recruiting 88 community-dwelling people with symptomatic radiographic first MTP joint OA. Following baseline assessment, participants are randomized to receive either: i) contoured foot orthoses; or ii) sham flat insoles following baseline assessment. Participants have two visits with a study podiatrist where they are provided with their allocated insoles, to be worn daily for 12 weeks at all times when wearing shoes. The primary outcome is self-reported first MTP joint pain on walking (numerical rating scale), assessed at baseline and 12 weeks. Secondary outcomes include additional measures of first MTP joint and foot pain, physical function, quality of life, participant-perceived global ratings of change (pain and function), and level of physical activity.

Discussion

This study will provide novel evidence about whether contoured foot orthoses improve pain and other symptoms compared to sham insoles in people with first MTP joint OA. Outcomes will help to inform clinical guidelines and practice about the use of foot orthoses for managing symptoms in this under-researched group of people with OA.

Trial registration

Prospectively registered with the Australian New Zealand Clinical Trials Registry (reference: ACTRN12619000926134) on 3/07/2019.
The morphology of patella changed significantly after soft tissue correction for children with recurrent patella dislocation
Authors: Niu Jinghui , Qi Qi , Hao Kuo , Lin Wei , Piao Kang , Wang Fei
Published: December 2020

Background

Although morphological improvement of femoral trochlea has been investigated in children with patellar dislocation after surgery, whether the patellar shape changed under the same condition is still unknown. The purpose of the study was to investigate the changes of patellar morphology in transverse plane following surgical correction of recurrent patellar dislocation in children.

Methods

A total of 22 patients with a mean age of 9.9 years (7 to 12) were included. All had unilateral recurrent patellar dislocation. The knees with recurrent patellar dislocation were treated with medial patellar retinaculum plasty and defined as the affected side. The contralateral knees with no symptom of patellar instability were considered as the unaffected side. All patients were treated between October 2014 and August 2018. Axial CT (Computed Tomography) scans were undertaken in all patients to assess the patella morphological characteristics on a particular axial image preoperatively and at the final follow-up.

Results

There were not significant differences about patellar transverse diameter, thickness and Wiberg angle between affected side and unaffected side before surgery and at the last follow-up respectively (The mean follow-up period: 28.0 ± 3.3 months). However, before surgery, the Wiberg-index in the affected side (0.74 ± 0.06) was significantly different from that in the unaffected side (0.64 ± 0.04). At the last follow-up, the Wiberg-index in the affected side (0.67 ± 0.05) and the unaffected side (0.65 ± 0.04) were not significantly different. Also, in the affected side, the Wiberg-index at the last follow-up was significantly lower than that before surgery (P < 0.05). The Wiberg-index in the unaffected side was not significantly different before surgery and at the last follow-up.

Conclusion

The patellar morphology can change significantly after surgical procedures in children with patellar recurrent dislocation whose epiphysis is not closed.
Clinical outcomes of transforaminal endoscopic lateral recess decompression by using the visualized drilled foraminoplasty and visualized reamed foraminoplasty: a comparison study
Authors: Wu Boyu , Xiong Chengjie , Huang Biwang , Zhao Dongdong , Yao Zhipeng , Yao Yawei , Xu Feng , Kang Hui
Published: December 2020

Background

Lateral recess stenosis (LRS) is a common degenerative disease in the elderly. Since the rise of comorbidity is associated with increasing age, transforaminal endoscopic lateral recess decompression (TE-LRD) is advocated. The objective of this study was to compare the clinical outcomes of TE-LRD in patients with LRS via visualized drilled foraminoplasty (VDF) or visualized reamed foraminoplasty (VRF) technique.

Methods

A total of 45 and 42 consecutive patients with limp or unilateral radiculopathy symptoms underwent TE-LRD using the VDF and VRF technique, respectively. The radiation exposure and operation time, time to return to work, and complications were compared between two groups. Their clinical outcomes were evaluated with the visual analogue scale (VAS) leg pain score, VAS back pain score, Oswestry Disability Index (ODI) and modified MacNab’s criteria.

Results

The average values of radiation exposure and operative time in the VDF group were significantly higher than those in the VRF group (P <  0.05). The postoperative VAS and ODI scores in both groups were significantly improved compared with those before the operation (P <  0.05). In addition, the VAS score of the leg pain and ODI score in the VRF group were significantly lower than those in the VDF group at the 1-week follow-up (P <  0.05). The good-to-excellent rates of the VDF group and VRF group were 88.89 and 90.48%, respectively, whereas the complication occurrence rates were 6.67 and 4.76% in the VDF group and VRF group, respectively.

Conclusions

TE-LRD performed by using VRF technique can be applied to treat LRS safely and effectively with short radiation exposure and operation time. This technique was comparable to the VDF technique with improved VAS leg pain and ODI scores in the short period after the operation. However, potential complications and risks still need to be considered.
Classification and morphology of middle mesial canals of mandibular first molars in a southern Chinese subpopulation: a cone-beam computed tomographic study
Authors: Yang Yeqing , Wu Buling , Zeng Junkai , Chen Ming
Published: December 2020

Background

Cone-beam computed tomography (CBCT) was employed to study the morphology and curvature of middle mesial canals (MMCs) of mandibular first molars (MFMs).

Methods

CBCT scanning was performed on MFMs of 1100 patients. Patients' images that met the inclusion criteria were divided into group A (< 40 years old) and group B (≥ 40 years old) for further study. The images were used to study the incidence of MMCs at different ages, measure the curvature of MMCs in the mesiodistal and buccolingual directions using the Schneider method, and observe the anatomical morphology of the mesial root canal system. All statistical analyses were performed by using SPSS 21.0 software. Quantitative data were presented as mean ± standard deviation. Student’s t-test was used to calculate the statistical significance. P < 0.05 was considered statistically significant.

Results

In 875 patients, 1750 MFM images met the inclusion criteria. Among these cases, 158 MFMs contained an MMC, yielding an incidence rate of 9.03%. The incidence rate of MMCs was 11.22% in group A and 6.61% in group B, and this difference was statistically significant (P < 0.05). The curvature in the mesiodistal direction was 29.39 ± 8.53° in group A and 26.06 ± 8.50° in group B, and this difference was also significant (P < 0.05). The curved regions in groups A and B were often located in the middle 1/3 of canal. No significant difference in the distance between MMC orifices and mesiobuccal canal orifices or mesiolingual canal orifices was noted (P > 0.05). The most common mesial root canal morphological type was type II (3-2) (53.80%).

Conclusion

The incidence of MMCs in MFMs declined as age increased. The canal systems of MMCs were varied and complex, mainly exhibiting an obvious mesiodistal curve. CBCT is an outstanding method to help guide root canal therapy.

*Yeqing Yang and Buling Wu have contribute equally to this article.
Monitoring of noninvasive ventilation: comparative analysis of different strategies
Authors: Georges Marjolaine , Rabec Claudio , Monin Elise , Aho Serge , Beltramo Guillaume , Janssens Jean-Paul , Bonniaud Philippe
Published: December 2020

Background

Noninvasive ventilation (NIV) represents an effective treatment for chronic respiratory failure. However, empirically determined NIV settings may not achieve optimal ventilatory support. Therefore, the efficacy of NIV should be systematically monitored. The minimal recommended monitoring strategy includes clinical assessment, arterial blood gases (ABG) and nocturnal transcutaneous pulsed oxygen saturation (SpO2). Polysomnography is a theoretical gold standard but is not routinely available in many centers. Simple tools such as transcutaneous capnography (TcPCO2) or ventilator built-in software provide reliable informations but their role in NIV monitoring has yet to be defined. The aim of our work was to compare the accuracy of different combinations of tests to assess NIV efficacy.

Methods

This retrospective comparative study evaluated the efficacy of NIV in consecutive patients through four strategies (A, B, C and D) using four different tools in various combinations. These tools included morning ABG, nocturnal SpO2, TcPCO2and data provided by built-in software via a dedicated module. Strategy A (ABG + nocturnal SpO2), B (nocturnal SpO2 + TcPCO2) and C (TcPCO2 + builtin software) were compared to strategy D, which combined all four tools (NIV was appropriate if all four tools were normal).

Results

NIV was appropriate in only 29 of the 100 included patients. Strategy A considered 53 patients as appropriately ventilated. Strategy B considered 48 patients as appropriately ventilated. Strategy C misclassified only 6 patients with daytime hypercapnia.

Conclusion

Monitoring ABG and nocturnal SpO2is not enough to assess NIV efficacy. Combining data from ventilator built-in software and TcPCO2seems to represent the best strategy to detect poor NIV efficacy.

TrialregistrationInstitutional Review Board of the Société de Pneumologie de Langue Française (CEPRO 2016 Georges)
Linking household surveys and facility assessments: a comparison of geospatial methods using nationally representative data from Malawi
Authors: Peters Michael A. , Mohan Diwakar , Naphini Patrick , Carter Emily , Marx Melissa A.
Published: December 2020

Background

Linking facility and household surveys through geographic methods is a popular technique to draw conclusions about the relationship between health services and population health outcomes at local levels. These methods are useful tools for measuring effective coverage and tracking progress towards Universal Health Coverage, but are understudied. This paper compares the appropriateness of several geospatial methods used for linking individuals (within displaced survey cluster locations) to their source of family planning (at undisplaced health facilities) at a national level.

Methods

In Malawi, geographic methods linked a population health survey, rural clusters from the Woman’s Questionnaire of the 2015 Malawi Demographic and Health Survey (MDHS 2015), to Malawi’s national health facility census to understand the service environment where women receive family planning services. Individuals from MDHS 2015 clusters were linked to health facilities through four geographic methods: (i) closest facility, (ii) buffer (5 km), (iii) administrative boundary, and (iv) a newly described theoretical catchment area method. Results were compared across metrics to assess the number of unlinked clusters (data lost), the number of linkages per cluster (precision of linkage), and the number of women linked to their last source of modern contraceptive (appropriateness of linkage).

Results

The closest facility and administrative boundary methods linked every cluster to at least one facility, while the 5-km buffer method left 288 clusters (35.3%) unlinked. The theoretical catchment area method linked all but one cluster to at least one facility (99.9% linked). Closest facility, 5-km buffer, administrative boundary, and catchment methods linked clusters to 1.0, 1.4, 21.1, and 3.3 facilities on average, respectively. Overall, the closest facility, 5-km buffer, administrative boundary, and catchment methods appropriately linked 64.8%, 51.9%, 97.5%, and 88.9% of women to their last source of modern contraceptive, respectively.

Conclusions

Of the methods studied, the theoretical catchment area linking method loses a marginal amount of population data, links clusters to a relatively low number of facilities, and maintains a high level of appropriate linkages. This linking method is demonstrated at scale and can be used to link individuals to qualities of their service environments and better understand the pathways through which interventions impact health.
RBE-weighted dose conversions for patients with recurrent nasopharyngeal carcinoma receiving carbon-ion radiotherapy from the local effect model to the microdosimetric kinetic model
Authors: Zhang Liwen , Wang Weiwei , Hu Jiyi , Lu Jiade , Kong Lin
Published: December 2020

Background

We sought to establish a conversion curve to convert the RBE-weighted doses calculated by local effect model I (LEM) (LEM RBE-weighted doses) in patients with locally recurrent nasopharyngeal carcinoma (rNPC) to the RBE-weighted doses calculated by microdosimetric kinetic model (MKM) (MKM RBE-weighted doses). We also converted the LEM dose constraints (RBE-weighted dose constraints in LEM plans) for the brain stem, spinal cord, and optic nerve based on this curve.

Methods

Data from 20 patients with rNPC receiving carbon-ion radiotherapy (CIRT) in our hospital were collected. LEM in Raystation (V8A, Raystation, Sweden) was used to generate treatment plans. The clinical target volume CTV1 (GTV + 5 mm) was given 3 Gy (RBE) per fraction. Ninety-nine percent of target volumes should be covered by 95% of the prescriptions; the maximum doses of the brainstem and spinal cord were < 45 Gy (RBE) and < 30 Gy (RBE), respectively. The doses covering 20% volumes of optical nerves/chiasms D20 were < 30 Gy (RBE). Then physical doses of the LEM plans were recalculated by using MKM in Raystation to generate MKM plans. A series of conversion factors (i.e., the ratio of LEM RBE-weighted dose to MKM RBE-weighted dose) was then obtained by using an isovolumetric dose method. The LEM plan prescriptions (LEM prescription) and dose constraints of the organs at risk (OARs) (OAR constraints) were converted to the corresponding MKM prescriptions and dose constraints using this conversion curve.

Results

For the CTV1 fractional RBE-weighted dose prescription of 3.00 Gy (RBE) and CTV2 of 2.70 Gy (RBE) in LEM plans, the conversion factors (LEM RBE-weighted dose/MKM RBE-weighted dose) were 1.37 (CI 95% 1.35–1.39) and 1.46 (1.41–1.51), respectively. The average conversion factors from 1.37 (CI 95% 1.33–1.41) to 3.09 (2.94–3.24) corresponded to the LEM fractionated doses from 2.86 Gy (RBE) to 0.24 Gy (RBE), including the doses constraining upon OARs. LEM RBE-weighted doses of 30 Gy (RBE) and 45 Gy (RBE) in 21 fractions were converted to MKM RBE-weighted doses of 16.64 Gy (RBE) and 30.72 Gy (RBE) in 16 fractions.

Conclusions

This conversion curve could be used to convert LEM RBE-weighted doses to MKM RBE-weighted doses for patients with rNPC receiving CIRT, providing dose references for re-irradiation therapy.
Is local radiotherapy a viable option for patients with an opening of the ventricles during surgical resection of brain metastases?
Authors: Scharl Sophia , Kessel Kerstin A. , Diehl Christian , Gempt Jens , Meyer Bernhard , Zimmer Claus , Straube Christoph , Combs Stephanie E.
Published: December 2020

Background

Local hypofractionated stereotactic radiotherapy (HFSRT) of the resection cavity is emerging as the standard of care in the treatment of patients with a limited number of brain metastases as it warrants less neurological impairment compared to whole brain radiotherapy. In periventricular metastases surgical resection can lead to an opening of the ventricles and subsequently carries a potential risk of cerebrospinal tumour cell dissemination. The aim of this study was to assess whether local radiotherapy of the resection cavity is viable in these cases.

Methods

From our institutional database we analyzed the data of 125 consecutive patients with resected brain metastases treated in our institution with HFSRT between 2009 and 2017. The incidence of LMD, overall survival (OS), local recurrence (LC) and distant recurrence were evaluated depending on ventricular opening (VO) during surgery.

Results

From all 125 patients, the ventricles were opened during surgery in 14 cases (11.2%). None of the patients with VO and 7 patients without VO during surgery developed LMD (p = 0.371). OS (p = 0.817), LC (p = 0.524) and distant recurrence (p = 0.488) did not differ in relation to VO during surgical resection. However, the incidence of distant intraventricular recurrence was slightly increased in patients with VO (14.3% vs. 2.7%, p < 0.01).

Conclusion

VO during neurosurgical resection did not affect the outcome after HFSRT of the resection cavity in patients with brain metastases. Particularly, the incidence of LMD was not increased in patients receiving local HFSRT after VO. HFSRT can therefore be offered independently of VO as a local treatment of tumor bed after resection of brain metastases.
Naringin increases osteoprotegerin expression in fibroblasts from periprosthetic membrane by the Wnt/β-catenin signaling pathway
Authors: Yang Chao , Liu Wei , Zhang Xianlong , Zeng Bingfang , Qian Yebin
Published: December 2020

Background

The osteoclast bone resorption is critical in aseptic loosening after joint replacement. The balance between activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) is considered to play a central role in osteoclast maturation. Fibroblasts from the periprosthetic membrane express RANKL and promote osteoclast formation. Studies have demonstrated that naringin inhibited osteoclastogenesis and wear particle-induced osteolysis. In this study, the naringin-induced OPG/RANKL effects and its underlying mechanism were studied in fibroblasts from periprosthetic membrane.

Methods

Fibroblasts were isolated from the periprosthetic membrane during hip arthroplasty for revision due to aseptic loosening. Fibroblasts were cultured and treated with or without naringin and DKK-1 (the classical inhibitor of Wnt/β-catenin signaling pathway). OPG and RANKL mRNA and protein levels, gene expression of β-catenin, and cyclin D1, which participate in the Wnt signaling pathway, were examined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay.

Results

The mRNA and protein levels of OPG were enhanced by naringin in a dose-dependent manner compared to that of the non-treated control. In contrast, naringin did not affect the expression of RANKL. Importantly, DKK-1 attenuated OPG expression in fibroblasts under naringin treatment. Moreover, naringin stimulated the gene expression of β-catenin and cyclin D1 in fibroblasts, and the effect could be inhibited by DKK-1.

Conclusion

The results indicated that naringin enhanced OPG expression through Wnt/β-catenin signaling pathway in fibroblasts from periprosthetic membrane, which may be useful to inhibit periprosthetic osteolysis during aseptic loosening after total joint arthroplasty.
Cell-autonomous role of Presenilin in age-dependent survival of cortical interneurons
Authors: Kang Jongkyun , Shen Jie
Published: December 2020

Background

Mutations in thePSEN1andPSEN2genes are the major cause of familial Alzheimer’s disease. Previous studies demonstrated that Presenilin (PS), the catalytic subunit of γ-secretase, is required for survival of excitatory neurons in the cerebral cortex during aging. However, the role of PS in inhibitory interneurons had not been explored.

Methods

To determine PS function in GABAergic neurons, we generated inhibitory neuron-specificPSconditional double knockout (IN-PScDKO) mice, in which PS is selectively inactivated by Cre recombinase expressed under the control of the endogenousGAD2promoter. We then performed behavioral, biochemical, and histological analyses to evaluate the consequences of selective PS inactivation in inhibitory neurons.

Results

IN-PScDKO mice exhibit earlier mortality and lower body weight despite normal food intake and basal activity. Western analysis of protein lysates from various brain sub-regions of IN-PScDKO mice showed significant reduction of PS1 levels and dramatic accumulation of γ-secretase substrates. Interestingly, IN-PScDKO mice develop age-dependent loss of GABAergic neurons, as shown by normal number of GAD67-immunoreactive interneurons in the cerebral cortex at 2–3 months of age but reduced number of cortical interneurons at 9 months. Moreover, age-dependent reduction of Parvalbumin- and Somatostatin-immunoreactive interneurons is more pronounced in the neocortex and hippocampus of IN-PScDKO mice. Consistent with these findings, the number of apoptotic cells is elevated in the cerebral cortex of IN-PScDKO mice, and the enhanced apoptosis is due to dramatic increases of apoptotic interneurons, whereas the number of apoptotic excitatory neurons is unaffected. Furthermore, progressive loss of interneurons in the cerebral cortex of IN-PScDKO mice is accompanied with astrogliosis and microgliosis.

Conclusion

Our results together support a cell-autonomous role of PS in the survival of cortical interneurons during aging. Together with earlier studies, these findings demonstrate a universal, essential requirement of PS in the survival of both excitatory and inhibitory neurons during aging.
LRP4 LDLα repeats of astrocyte enhance dendrite arborization of the neuron
Authors: Yan Min , Guo Amin , Chen Peng , Jing Hongyang , Ren Dongyan , Zhong Yanzi , Wu Yongqiang , Fei Erkang , Lai Xinsheng , Zou Suqi , Wang Shunqi
Published: December 2020

The low-density lipoprotein receptor-related protein 4 (LRP4) is essential for inducing the neuromuscular junction (NMJ) formation in muscle fibers, and LRP4 plays a critical role in dendritic development and synaptogenesis in the central nervous system (CNS). As a single transmembrane protein, LRP4 contains an enormously sizeable extracellular domain (ECD), containing multiple LDLα repeats in the N-terminal of ECD. LRP4 only with extracellular domain acts as a similar mechanism of full-length LRP4 in muscles to stimulate acetylcholine receptor clustering. In this study, we elucidated that LDLα repeats of LRP4 maintained the body weight and survival rate. Dendritic branches of the pyramidal neurons in Lrp4-null mice with LRP4 LDLα repeats residue were more than in Lrp4-null mice without residual LRP4 domain. Supplement with conditioned medium from LRP4 LDLα overexpression cells, the primary culture pyramidal neurons achieved strong dendritic arborization ability. Besides, astrocytes with LRP4 LDLα repeats residue could promote pyramidal neuronal dendrite arborization in the primary co-cultured system. These observations signify that LRP4 LDLα repeats play a prominent underlying role in dendrite arborization.
Trajectory of chemical cocktail-induced neutrophil reprogramming
Authors: Zhou Yi , Wei Chuijin , Xiong Shumin , Dong Liaoliao , Chen Zhu , Chen Sai-Juan , Cheng Lin
Published: December 2020

Hematopoietic reprogramming holds great promise for generating functional target cells and provides new angle for understanding hematopoiesis. We reported before for the first time that diverse differentiated hematopoietic cell lineages could be reprogrammed back into hematopoietic stem/progenitor cell-like cells by chemical cocktail. However, the exact cell types of induced cells and reprogramming trajectory remain elusive. Here, based on genetic tracing method CellTagging and single-cell RNA sequencing, it is found that neutrophils could be reprogrammed into multipotent progenitors, which acquire multi-differentiation potential both in vitro and in vivo, including into lymphoid cells. Construction of trajectory map of the reprogramming procession shows that mature neutrophils follow their canonical developmental route reversely into immature ones, premature ones, granulocyte/monocyte progenitors, common myeloid progenitors, and then the terminal cells, which is stage by stage or skips intermediate stages. Collectively, this study provides a precise dissection of hematopoietic reprogramming procession and sheds light on chemical cocktail-induction of hematopoietic stem cells.
GD2 or HER2 targeting T cell engaging bispecific antibodies to treat osteosarcoma
Authors: Park Jeong A. , Cheung Nai-Kong V.
Published: December 2020

Background

The cure rate for metastatic osteosarcoma has not substantially improved over the past decades. Clinical trials of anti-HER2 trastuzumab or anti-GD2 dinutuximab for metastatic or refractory osteosarcoma were not successful, and neither was immune checkpoint inhibitors (ICIs).

Methods

We tested various target antigen expressions on osteosarcoma cell lines using flow cytometry and analyzed in vitro T cell engaging BsAb (T-BsAb)-dependent T cell-mediated cytotoxicity using 4-h 51Cr release assay. We tested in vivo anti-tumor activities of T-BsAb targeting GD2 or HER2 in established osteosarcoma cell line or patient-derived xenograft (PDX) mouse models carried out in BALB-Rag2−/−IL-2R-γc-KO (BRG) mice. We also generated ex vivo BsAb-armed T cells (EATs) and studied their tumor-suppressive effect against osteosarcoma xenografts. In order to improve the anti-tumor response, ICIs, anti-human PD-1 (pembrolizumab) or anti-human PD-L1 (atezolizumab) antibodies were tested their synergy with GD2- or HER2-BsAb against osteosarcoma.

Results

GD2 and HER2 were chosen from a panel of surface markers on osteosarcoma cell lines and PDXs. Anti-GD2 BsAb or anti-HER2 BsAb exerted potent anti-tumor effect against osteosarcoma tumors in vitro and in vivo. T cells armed with anti-GD2-BsAb (GD2-EATs) or anti-HER2-BsAb (HER2-EATs) showed significant anti-tumor activities as well. Anti-PD-L1 combination treatment enhanced BsAb-armed T cell function in vivo and improved tumor control and survival of the mice, when given sequentially and continuously.

Conclusion

Anti-GD2 and anti-HER2 BsAbs were effective in controlling osteosarcoma. These data support the clinical investigation of GD2 and HER2 targeted T-BsAb treatment in combination with immune checkpoint inhibitors, particularly anti-PD-L1, in patients with osteosarcoma to improve their treatment outcome.
Improved analysis of arabinoxylan-bound hydroxycinnamate conjugates in grass cell walls
Authors: Eugene Alexis , Lapierre Catherine , Ralph John
Published: December 2020

Background

Arabinoxylan in grass cell walls is acylated to varying extents by ferulate and p-coumarate at the 5-hydroxy position of arabinosyl residues branching off the xylan backbone. Some of these hydroxycinnamate units may then become involved in cell wall radical coupling reactions, resulting in ether and other linkages amongst themselves or to monolignols or oligolignols, thereby crosslinking arabinoxylan chains with each other and/or with lignin polymers. This crosslinking is assumed to increase the strength of the cell wall, and impedes the utilization of grass biomass in natural and industrial processes. A method for quantifying the degree of acylation in various grass tissues is, therefore, essential. We sought to reduce the incidence of hydroxycinnamate ester hydrolysis in our recently introduced method by utilizing more anhydrous conditions.

Results

The improved methanolysis method minimizes the undesirable ester-cleavage of arabinose from ferulate and p-coumarate esters, and from diferulate dehydrodimers, and produces more methanolysis vs. hydrolysis of xylan-arabinosides, improving the yields of the desired feruloylated and p-coumaroylated methyl arabinosides and their diferulate analogs. Free ferulate and p-coumarate produced by ester-cleavage were reduced by 78% and 68%, respectively, and 21% and 39% more feruloyl and p-coumaroyl methyl arabinosides were detected in the more anhydrous method. The new protocol resulted in an estimated 56% less combined diferulate isomers in which only one acylated arabinosyl unit remained, and 170% more combined diferulate isomers conjugated to two arabinosyl units.

Conclusions

Overall, the new protocol for mild acidolysis of grass cell walls is both recovering more ferulate- and p-coumarate-arabinose conjugates from the arabinoxylan and cleaving less of them down to free ferulic acid, p-coumaric acid, and dehydrodiferulates with just one arabinosyl ester. This cleaner method, especially when coupled with the orthogonal method for measuring monolignol hydroxycinnamate conjugates that have been incorporated into lignin, provides an enhanced tool to measure the extent of crosslinking in grass arabinoxylan chains, assisting in identification of useful grasses for biomass applications.
Cell-based and cell-free biocatalysis for the production of d-glucaric acid
Authors: Chen Lu-Zhou , Huang Si-Ling , Hou Jin , Guo Xue-Ping , Wang Feng-Shan , Sheng Ju-Zheng
Published: December 2020

d-Glucaric acid (GA) is a value-added chemical produced from biomass, and has potential applications as a versatile platform chemical, food additive, metal sequestering agent, and therapeutic agent. Marketed GA is currently produced chemically, but increasing demand is driving the search for eco-friendlier and more efficient production approaches. Cell-based production of GA represents an alternative strategy for GA production. A series of synthetic pathways for GA have been ported intoEscherichia coli,Saccharomyces cerevisiaeandPichia pastoris, respectively, and these engineered cells show the ability to synthesize GA de novo. Optimization of the GA metabolic pathways in host cells has leapt forward, and the titer and yield have increased rapidly. Meanwhile, cell-free multi-enzyme catalysis, in which the desired pathway is constructed in vitro from enzymes and cofactors involved in GA biosynthesis, has also realized efficient GA bioconversion. This review presents an overview of studies of the development of cell-based GA production, followed by a brief discussion of potential applications of biosensors that respond to GA in these biosynthesis routes.
Changes in cancer incidence and mortality in Australia over the period 1996–2015
Authors: Luo Qingwei , Steinberg Julia , O’Connell Dianne L. , Grogan Paul B. , Canfell Karen , Feletto Eleonora
Published: December 2020

Objective

A previous Australian study compared the observed numbers of cancer cases and deaths in 2007 with the expected numbers based on 1987 rates. This study examines the impact of cancer rate changes over the 20-year period 1996–2015, for people aged under 75 years.

Results

The overall age-standardised cancer incidence rate increased from 350.7 in 1995 to 364.4 per 100,000 in 2015. Over the period 1996–2015, there were 29,226 (2.0%) more cases (males: 5940, 0.7%; females: 23,286, 3.7%) than expected numbers based on 1995 rates. Smaller numbers of cases were observed compared to those expected for cancers of the lung for males and colorectum, and cancers with unknown primary. Larger numbers of cases were observed compared to those expected for cancers of the prostate, thyroid and female breast. The overall age-standardised cancer mortality rate decreased from 125.6 in 1995 to 84.3 per 100,000 in 2015. During 1996 to 2015 there were 106,903 (− 20.6%) fewer cancer deaths (males: − 69,007, − 22.6%; females: − 37,896, − 17.9%) than expected based on the 1995 mortality rates. Smaller numbers of deaths were observed compared to those expected for cancers of the lung, colorectum and female breast, and more cancer deaths were observed for liver cancer.
Identifying elephant flows using dynamic thresholds in programmable IXP networks
Authors: Silva Marcus Vinicius Brito da , Marques Jonatas Adilson , Gaspary Luciano Paschoal , Granville Lisandro Zambenedetti
Published: December 2020

Internet eXchange Points (IXPs) are Internet infrastructures composed of high-performance networks that allow multiple autonomous systems to exchange traffic. Given the challenges of managing the flows that cross an IXP, identifying elephant flows may help improve the quality of services provided to its participants. In this context, we leverage the new flexibility and resources of programmable data planes to identify elephant flows in IXP networks adaptively via the dynamic adjustment of thresholds. Our mechanism uses the information reported by the data plane to monitor network utilization in the control plane, calculating new thresholds based on previous flow sizes and durations percentiles and configuring them back into switches to support the local classification of flows. Thus, the thresholds are updated to make the identification process better aligned with the network behavior. The experimental results show that it is possible to identify and react to elephant flows quickly, less than 0.4ms, and efficiently, with only 98.4KB of data inserted into the network by the mechanism. In addition, the threshold updating mechanism achieved accuracy of up to 90% in our evaluation scenarios.
European Society of Emergency Radiology: guideline on radiological polytrauma imaging and service (short version)
Authors: Wirth Stefan , Hebebrand Julian , Basilico Raffaella , Berger Ferco H. , Blanco Ana , Calli Cem , Dumba Maureen , Linsenmaier Ulrich , Mück Fabian , Nieboer Konraad H. , Scaglione Mariano , Weber Marc-André , Dick Elizabeth
Published: December 2020

Background

Although some national recommendations for the role of radiology in a polytrauma service exist, there are no European guidelines to date. Additionally, for many interdisciplinary guidelines, radiology tends to be under-represented. These factors motivated the European Society of Emergency Radiology (ESER) to develop radiologically-centred polytrauma guidelines.

Results

Evidence-based decisions were made on 68 individual aspects of polytrauma imaging at two ESER consensus conferences. For severely injured patients, whole-body CT (WBCT) has been shown to significantly reduce mortality when compared to targeted, selective CT. However, this advantage must be balanced against the radiation risk of performing more WBCTs, especially in less severely injured patients. For this reason, we recommend a second lower dose WBCT protocol as an alternative in certain clinical scenarios. The ESER Guideline on Radiological Polytrauma Imaging and Service is published in two versions: a full version (download from the ESER homepage, https://www.eser-society.org) and a short version also covering all recommendations (this article).

Conclusions

Once a patient has been accurately classified as polytrauma, each institution should be able to choose from at least two WBCT protocols. One protocol should be optimised regarding time and precision, and is already used by most institutions (variant A). The second protocol should be dose reduced and used for clinically stable and oriented patients who nonetheless require a CT because the history suggests possible serious injury (variant B). Reading, interpretation and communication of the report should be structured clinically following the ABCDE format, i.e. diagnose first what kills first.
A smart scaffold composed of three-dimensional printing and electrospinning techniques and its application in rat abdominal wall defects
Authors: Yang Zhi , Song Zhicheng , Nie Xin , Guo Kaijin , Gu Yan
Published: December 2020

Background

Biological composite scaffolds are increasingly being used in abdominal wall reconstruction but still have certain shortcomings. The present study describes here a novel three-dimensional (3D) scaffold fabricated by combining 3D printing (3DP) and electrospinning (ESP).

Methods

Biological composite scaffolds are composed of integrated 3DP interconnected macrofiber and random ESP microfiber networks. The 3DP scaffold retains intact 3D architecture and mechanical properties, while the ESP network serves as a cell entrapment system at the extracellular matrix (ECM) scale. Biological composite scaffolds are implanted in a defective rat abdominal wall to detect if it could induce early vascularization and reconstruction of the tissue defect.

Results

SEM analysis reveals a pore diameter of 424.47 ± 58.49 μm and a porosity of 70.46 ± 2.48% for biological composite scaffolds. In the in vitro test of cell proliferation, biological composite scaffolds do not affect rat dermal fibroblast proliferation in a time- and dose-dependent manner. The animal experiments show tissue remodeling and early angiogenesis as compared to 3DP scaffolds.

Conclusions

Our experiment prepares a biological scaffold with both a macro- and microscale structure by ESP and 3DP technology. Thus, the integration of 3DP and ESP techniques provides a new set of smart scaffolds for abdominal wall defect and hernia repair.
Regulatory T cell induction by mesenchymal stem cells depends on the expression of TNFR2 by T cells
Authors: Naserian Sina , Shamdani Sara , Arouche Nassim , Uzan Georges
Published: December 2020

Mesenchymal stem/stromal cells can modulate the effector immune cells especially T lymphocytes. Due to this important feature, they can regulate the development of a variety of disorders including inflammatory and autoimmune disorders, cancers, and transplantation outcomes. One of the most important MSC immunoregulatory functions is their capacity to convert conventional T cells into regulatory T cells. Several mechanisms, mostly related to MSCs but not T cells, have been shown essential for this aspect. The inflammatory microenvironment majorly caused by pro-inflammatory cytokines has been demonstrated to govern the direction of the immune response. In this respect, we have recently revealed that the TNFα-TNFR2 signaling controls several aspects of MSC immunomodulatory properties including their ability to suppress T cells and their conversion towards Foxp3-expressing Tregs. Here in this work, we have looked from another angle by investigating the impact of TNFR2 expression by T cells on their ability to be converted to suppressive Tregs by MSCs. We showed that unlike WT-T cells, their TNFR2 KO counterparts are remarkably less able to convert into Foxp3+ and Foxp3− Tregs. Furthermore, TNFR2 blockade diminished the anti-inflammatory cytokine secretion by iTregs and consequently resulted in less T cell immunosuppression. This work is the first evidence of the crucial association of TNFR2 expression by T cells with their iTreg conversion capacity by MSCs. It strengthens once more the potential of anti-TNFR2 administration for a strong and effective interference with the immunosuppression exerted by TNFR2-expressing cells.
Global existence, energy decay and blow-up of solutions for wave equations with time delay and logarithmic source
Authors: Park Sun-Hye
Published: December 2020

In this paper, we study the wave equation with frictional damping, time delay in the velocity, and logarithmic source of the form $$ u_{tt}(x,t) - \Delta u (x,t) + \alpha u_{t} (x,t) + \beta u_{t} (x, t- \tau ) = u(x,t) \ln \bigl\vert u(x,t) \bigr\vert ^{\gamma } . $$

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There is much literature on wave equations with a polynomial nonlinear source, but not much on the equations with logarithmic source. We show the local and global existence of solutions using Faedo–Galerkin’s method and the logarithmic Sobolev inequality. And then we investigate the decay rates and infinite time blow-up for the solutions through the potential well and perturbed energy methods.
Some inequalities for Csiszár divergence via theory of time scales
Authors: Ansari Iqrar , Khan Khuram Ali , Nosheen Ammara , Pečarić Ðilda , Pečarić Josip
Published: December 2020

In this paper, we present some inequalities for Csiszárf-divergence between two probability measures on time scale. These results extend some known results in the literature and offer new results inh-discrete calculus and quantum calculus. We also present several inequalities for divergence measures.
Clinical physiology aspects of chloremia in fluid therapy: a systematic review
Authors: Astapenko David , Navratil Pavel , Pouska Jiri , Cerny Vladimir
Published: December 2020

Background

This systematic review discusses a clinical physiology aspect of chloride in fluid therapy. Crystalloid solutions are one of the most widely used remedies. While generally used in medicine for almost 190 years, studies focused largely on their safety have only been published since the new millennium. The most widely used solution, normal saline, is most often referred to in this context. Its excessive administration results in hyperchloremic metabolic acidosis with other consequences, including higher mortality rates.

Methods

Original papers and review articles eligible for developing the present paper were identified by searching online in the electronic MEDLINE database. The keywords searched for included hyperchloremia, hypochloremia, and compound words containing the word “chloride,” infusion therapy, metabolic acidosis, renal failure, and review.

Results

A total of 21,758 papers published before 31 May 2020 were identified; of this number, 630 duplicates were removed from the list. Upon excluding articles based on their title or abstract, 1850 papers were screened, of which 63 full-text articles were assessed.

Conclusions

According to the latest medical concepts, dyschloremia (both hyperchloremia and hypochloremia) represents a factor indisputably having a negative effect on selected variables of clinical outcome. As infusion therapy can significantly impact chloride homeostasis of the body, the choice of infusion solutions should always take into account the potentially adverse impact of chloride content on chloremia and organ function.
Deep mantle melting, global water circulation and its implications for the stability of the ocean mass
Authors: Karato Shun-ichiro , Karki Bijaya , Park Jeffrey
Published: December 2020

Oceans on Earth are present as a result of dynamic equilibrium between degassing and regassing through the interaction with Earth’s interior. We review mineral physics, geophysical, and geochemical studies related to the global water circulation and conclude that the water content has a peak in the mantle transition zone (MTZ) with a value of 0.1–1 wt% (with large regional variations). When water-rich MTZ materials are transported out of the MTZ, partial melting occurs. Vertical direction of melt migration is determined by the density contrast between the melts and coexisting minerals. Because a density change associated with a phase transformation occurs sharply for a solid but more gradually for a melt, melts formed above the phase transformation depth are generally heavier than solids, whereas melts formed below the transformation depth are lighter than solids. Consequently, hydrous melts formed either above or below the MTZ return to the MTZ, maintaining its high water content. However, the MTZ water content cannot increase without limit. The melt-solid density contrast above the 410 km depends on the temperature. In cooler regions, melting will occur only in the presence of very water-rich materials. Melts produced in these regions have high water content and hence can be buoyant above the 410 km, removing water from the MTZ. Consequently, cooler regions of melting act as a water valve to maintain the water content of the MTZ near its threshold level (~ 0.1–1.0 wt%). Mass-balance considerations explain the observed near-constant sea-level despite large fluctuations over Earth history. Observations suggesting deep-mantle melting are reviewed including the presence of low-velocity anomalies just above and below the MTZ and geochemical evidence for hydrous melts formed in the MTZ. However, the interpretation of long-term sea-level change and the role of deep mantle melting in the global water circulation are non-unique and alternative models are reviewed. Possible future directions of studies on the global water circulation are proposed including geodynamic modeling, mineral physics and observational studies, and studies integrating results from different disciplines.
Ensemble flash flood predictions using a high-resolution nationwide distributed rainfall-runoff model: case study of the heavy rain event of July 2018 and Typhoon Hagibis in 2019
Authors: Sayama Takahiro , Yamada Masafumi , Sugawara Yoshito , Yamazaki Dai
Published: December 2020

The heavy rain event of July 2018 and Typhoon Hagibis in October 2019 caused severe flash flood disasters in numerous parts of western and eastern Japan. Flash floods need to be predicted over a wide range with long forecasting lead time for effective evacuation. The predictability of flash floods caused by the two extreme events is investigated by using a high-resolution (~ 150 m) nationwide distributed rainfall-runoff model forced by ensemble precipitation forecasts with 39 h lead time. Results of the deterministic simulation at nowcasting mode with radar and gauge composite rainfall could reasonably simulate the storm runoff hydrographs at many dam reservoirs over western Japan for the case of heavy rainfall in 2018 (F18) with the default parameter setting. For the case of Typhoon Hagibis in 2019 (T19), a similar performance was obtained by incorporating unsaturated flow effect in the model applied to Kanto Region. The performance of the ensemble forecast was evaluated based on the bias ratios and the relative operating characteristic curves, which suggested the higher predictability in peak runoff for T19. For the F18, the uncertainty arises due to the difficulty in accurately forecasting the storm positions by the frontal zone; as a result, the actual distribution of the peak runoff could not be well forecasted. Overall, this study showed that the predictability of flash floods was different between the two extreme events. The ensemble spreads contain quantitative information of predictive uncertainty, which can be utilized for the decision making of emergency responses against flash floods.