bluuebunny/crossref_metadata_2025 huggingface dataset:
OX40L Inhibition Suppresses KLH‐driven Immune Responses in Healthy Volunteers: A Randomized Controlled Trial Demonstrating Proof‐of‐Pharmacology for KY1005
Authors: Saghari Mahdi , Gal Pim , Gilbert Sally , Yateman Martin , Porter‐Brown Ben , Brennan Nuala , Quaratino Sonia , Wilson Rosamund , Grievink Hendrika W. , Klaassen Erica S. , Bergmann Kirsten R. , Burggraaf Jacobus , van Doorn Martijn B. A. , Powell John , Moerland Matthijs , Rissmann Robert
Published: January 2022

The safety, tolerability, immunogenicity, and pharmacokinetic (PK) profile of an anti‐OX40L monoclonal antibody (KY1005, currently amlitelimab) were evaluated. Pharmacodynamic (PD) effects were explored using keyhole limpet hemocyanin (KLH) and tetanus toxoid (TT) immunizations. Sixty‐four healthy male subjects (26.5 ± 6.0 years) were randomized to single doses of 0.006, 0.018, or 0.05 mg/kg, or multiple doses of 0.15, 0.45, 1.35, 4, or 12 mg/kg KY1005, or placebo (6:2). Serum KY1005 concentrations were measured. Antibody responses upon KLH and TT immunizations and skin response upon intradermal KLH administration were performed. PD data were analyzed using repeated measures analysis of covariances (ANCOVAs) and post hoc exposure‐response modeling. No serious adverse events occurred and all adverse events were temporary and of mild or moderate severity. A nonlinear increase in mean serum KY1005 concentrations was observed (median time to maximum concentration (Tmax) ~ 4 hours, geometric mean terminal half‐life (t½) ~ 24 days). Cutaneous blood perfusion (estimated difference (ED) −13.4 arbitrary unit (AU), 95% confidence interval (CI) −23.0 AU to −3.8 AU) and erythema quantified as average redness (ED −0.23 AU, 95% CI −0.35 AU to −0.11 AU) decreased after KY1005 treatment at doses of 0.45 mg/kg and above. Exposure‐response analysis displayed a statistically significant treatment effect on anti‐KLH antibody titers (IgG maximum effect (Emax) −0.58 AU, 95% CI −1.10 AU to −0.06 AU) and skin response (erythema Emax −0.20 AU, 95% CI −0.29 AU to −0.11 AU). Administration of KY1005 demonstrated an acceptable safety and tolerability profile and PK analyses displayed a nonlinear profile of KY1005. Despite the observed variability, skin challenge response after KY1005 treatment indicated pharmacological activity of KY1005. Therefore, KY1005 shows potential as a novel pharmacological treatment in immune‐mediated disorders.
Triggers for and barriers to the adoption of environmental management practices by small and medium‐sized enterprises: A critical review
Authors: Dasanayaka Chamila H. , Gunarathne Nuwan , Murphy David F. , Nagirikandalage Padmi
Published: January 2022

The current literature lacks an integrated and holistic understanding of what drives and inhibits the environmental management practices (EMPs) of small and medium‐sized enterprises (SMEs), despite the large number of studies carried out in the area. In order to offer a nuanced understanding of the existing inventory of reported works on SMEs, this study provides a systematic literature review. Based on three theories (i.e., institutional isomorphism, the resource‐based view and contingency), the study uses descriptive and thematic content analytical tools to find triggers for (i.e., external and internal) and barriers to the adoption of EMPs by SMEs. The analysis shows that both coercive pressures (especially legislation and customers' demands) and internal resource capabilities serve as significant triggers for the adoption of EMPs by SMEs. This study also finds internal organisational barriers, including lack of resources, acting as the main barriers. Both descriptive and thematic content analysis suggests several avenues for future research in this area.
Effects of toluidine blue O and methylene blue on growth and viability of pancreatic cancer cells
Authors: Biberoglu Kevser , Yuksel Melike , Onder Seda , Tacal Ozden
Published: January 2022

Amyloid precursor‐like protein‐2 (APLP2) and its C‐terminal fragments (CTFs) are expressed at high levels in pancreatic cancer cells and knockdown of APLP2 expression inhibits tumor growth. CTFs are released from APLP2 by beta‐secretase (BACE). In this study, our goal was to determine whether methylene blue (MethB) and toluidine blue O (TBO) could be used to slow down the growth and viability of pancreatic cancer cells (Hs 766T). We found that TBO and MethB decreased the growth and viability of Hs 766T cells in a dose‐ and time‐dependent manner compared to vehicle‐treated control, as demonstrated by MTT and trypan blue exclusion assays. Although TBO led to decreased expression of APLP2, MethB did not show any significant effect on APLP2. However, both MethB and TBO reduced BACE activity and the levels of APLP2 CTFs in Hs 766T cells. In conclusion, MethB and TBO may be valuable candidates for the treatment of pancreatic cancer by targeting APLP2 processing.
An eco‐epidemiological modeling approach to investigate dilution effect in two different tick‐borne pathosystems
Authors: Occhibove Flavia , Kenobi Kim , Swain Martin , Risley Claire
Published: January 2022

Disease (re)emergence appears to be driven by biodiversity decline and environmental change. As a result, it is increasingly important to study host–pathogen interactions within the context of their ecology and evolution. The dilution effect is the concept that higher biodiversity decreases pathogen transmission. It has been observed especially in zoonotic vector‐borne pathosystems, yet evidence against it has been found. In particular, it is still debated how the community (dis)assembly assumptions and the degree of generalism of vectors and pathogens affect the direction of the biodiversity–pathogen transmission relationship. The aim of this study was to use empirical data and mechanistic models to investigate dilution mechanisms in two rodent–tick–pathogen systems differing in their vector degree of generalism. A community was assembled to include ecological interactions that expand from purely additive to purely substitutive. Such systems are excellent candidates to analyze the link between vector ecology, community (dis)assembly dynamics, and pathogen transmission. To base our mechanistic models on empirical data, rodent live‐trapping, including tick sampling, was conducted in Wales across two seasons for three consecutive years. We have developed a deterministic single‐vector, multi‐host compartmental model that includes ecological relationships with non‐host species, uniquely integrating theoretical and observational approaches. To describe pathogen transmission across a gradient of community diversity, the model was populated with parameters describing five different scenarios differing in ecological complexity; each based around one of the pathosystems: Ixodes ricinus (generalist tick)–Borrelia burgdorferi and I. trianguliceps (small mammals specialist tick)–Babesia microti. The results suggested that community composition and interspecific dynamics affected pathogen transmission with different dilution outcomes depending on the vector degree of generalism. The model provides evidence that dilution and amplification effects are not mutually exclusive in the same community but depend on vector ecology and the epidemiological output considered (i.e., the “risk” of interest). In our scenarios, more functionally diverse communities resulted in fewer infectious rodents, supporting the dilution effect. In the pathosystem with generalist vector we identified a hump shaped relationship between diversity and infections in hosts, while for that characterized by specialist tick, this relationship was more complex and more dependent upon specific parameter values.
Accountability in promoting representation of historically marginalized racial and ethnic populations in the eating disorders field: A call to action
Authors: Goel Neha J. , Jennings Mathis Karen , Egbert Amy H. , Petterway Felicia , Breithaupt Lauren , Eddy Kamryn T. , Franko Debra L. , Graham Andrea K.
Published: January 2022

Promoting representation of historically marginalized racial and ethnic populations in the eating disorders (EDs) field among professionals and the populations studied and served has long been discussed, with limited progress. This may be due to a reinforcing feedback loop in which individuals from dominant cultures conduct research and deliver treatment, participate in research, and receive diagnoses and treatment. This insularity maintains underrepresentation: EDs in historically marginalized populations are understudied, undetected, and undertreated. An Early Career Investigators Workshop generated recommendations for change that were not inherently novel but made apparent that accountability is missing. This paper serves as a call to action to spearhead a paradigm shift from equality to equity in the ED field. We provide a theoretical framework, suggest ways to disrupt the feedback loop, and summarize actionable steps to increase accountability in ED leadership and research toward enhancing racial/ethnic justice, equity, diversity, and inclusion (JEDI). These actionable steps are outlined in the service of challenging our field to reflect the diversity of our global community. We must develop and implement measurable metrics to assess our progress toward increasing diversity of underrepresented racial/ethnic groups and to address JEDI issues in our providers, patients, and research participants.
Body image concerns and disordered eating among older women: Identifying variables of interest for integrated models
Authors: Rodgers Rachel F , Berry Rachel A , Laveway Katherine
Published: January 2022

Objective

Research focused on developing risk and protective models of body image concerns and disordered eating among older women is scant. Models including biological, psychological, and sociocultural elements may be useful explanatory frameworks in this group. Thus, the aim of this study was to conduct formative research exploring the constructs that form part of biopsychosocial models of body image concerns and disordered eating among older women.

Method

A sample of 184 women aged 60–75 years completed an online survey assessing media pressures, thin‐ideal internalization, depression symptoms, weight and shape concerns, and disordered eating as well as positive reappraisal and acceptance of aging‐related changes to appearance.

Results

After the addition of two supplemental pathways, the model revealed good fit to the data. In the final model, age, depression, and media pressure were associated with media internalization, that was in turn associated with weight and shape concerns, and then disordered eating. Depression was also directly associated with both weight and shape concerns and disordered eating. The model varied across older women with high versus low levels of positive reappraisal and acceptance of aging‐related changes to appearance. Specifically, among those high on this trait, the pathways between depression and thin‐ideal internalization, and between weight and shape concerns and disordered eating were significantly weaker.

Discussion

These findings support the usefulness of biopsychosocial models for grounding research on body image concerns and disordered eating among older women, and suggest positive reappraisal and acceptance of aging‐related changes to appearance as a useful dimension to focus on.
Can glucose‐lowering medications improve outcomes in non‐diabetic heart failure patients? A Bayesian network meta‐analysis
Authors: Yeong Trevor , Mai Aaron Shengting , Lim Oliver Z.H. , Ng Cheng Han , Chin Yip Han , Tay Phoebe , Lin Chaoxing , Muthiah Mark , Khoo Chin Meng , Dalakoti Mayank , Loh Poay‐Huan , Chan Mark , Yeo Tiong‐Cheng , Foo Roger , Wong Raymond , Chew Nicholas W.S. , Lin Weiqin
Published: January 2022

Aims

The cardioprotective effects of glucose‐lowering medications in diabetic patients with heart failure (HF) are well known. Several large randomized controlled trials (RCTs) have recently suggested that the cardioprotective effects of glucose‐lowering medications extend to HF patients regardless of diabetic status. The aim of this study was to conduct a Bayesian network meta‐analysis to evaluate the impact of various glucose‐lowering medications on the outcomes of non‐diabetic HF patients.

Methods and results

Medline and Embase were searched for RCTs investigating the use of glucose‐lowering medications in non‐diabetic HF patients in August 2021. Studies were included in accordance with the inclusion and exclusion criteria, and data were extracted with a pre‐defined datasheet. Primary outcomes include serum N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP) levels, left ventricular ejection fraction (LVEF), and maximal oxygen consumption (PVO2). A Bayesian network meta‐analysis was performed to compare the effectiveness of different classes of glucose‐lowering medications in improving HF outcomes. Risk‐of‐bias was assessed using Cochrane Risk‐of‐Bias tool 2.0 for randomized trials (ROB2). Seven RCTs involving 2897 patients were included. Sodium‐glucose transporter 2 inhibitor (SGLT2i) was the most favourable in lowering NT‐proBNP, with the significant reduction in NT‐proBNP when compared with glucagon‐like peptide‐1 receptor agonists (GLP1‐RA) [mean differences (MD): −229.59 pg/mL, 95%‐credible intervals (95%‐CrI): −238.31 to −220.91], metformin (MD: −237.15 pg/mL, 95%‐CrI: −256.19 to −218.14), and placebo (MD: −228.00 pg/mL, 95%‐CrI: −233.99 to −221.99). SGLT2i was more effective in improving LVEF for HF with reduced ejection fraction patients relative to GLP1‐RA (MD: 8.09%, 95%‐CrI: 6.30 to 9.88) and placebo (MD: 6.10%, 95%‐CrI: 4.37 to 7.84). SGLT2i and GLP1‐RA were more favourable to placebo in improving PVO2, with significant increase of PVO2 at a MD of 1.60 mL/kg/min (95%‐CrI: 0.63 to 2.57) and 0.86 mL/kg/min (95%‐CrI: 0.66 to 1.06), respectively. All three drugs had comparable safety profiles when compared with placebo.

Conclusions

This Bayesian network meta‐analysis demonstrated that SGLT2i, when compared with GLP1‐RA and metformin, was superior in improving LVEF in HF with reduced ejection fraction patients, as well as improving PVO2 and NT‐proBNP in non‐diabetic HF patients. Further large‐scale prospective studies are needed to confirm these preliminary findings.
A population of naive‐like CD4+ T cells stably polarized to the TH1 lineage
Authors: Lo Jonathan W. , de Mucha Maria Vila , Henderson Stephen , Roberts Luke B. , Constable Laura E. , Garrido‐Mesa Natividad , Hertweck Arnulf , Stolarczyk Emilie , Houlder Emma L. , Jackson Ian , MacDonald Andrew S. , Powell Nick , Neves Joana F. , Howard Jane K. , Jenner Richard G. , Lord Graham M.
Published: January 2022

T‐bet is the lineage‐specifying transcription factor for CD4+ TH1 cells. T‐bet has also been found in other CD4+ T cell subsets, including TH17 cells and Treg, where it modulates their functional characteristics. However, we lack information on when and where T‐bet is expressed during T cell differentiation and how this impacts T cell differentiation and function. To address this, we traced the ontogeny of T‐bet‐expressing cells using a fluorescent fate‐mapping mouse line. We demonstrate that T‐bet is expressed in a subset of CD4+ T cells that have naïve cell surface markers and transcriptional profile and that this novel cell population is phenotypically and functionally distinct from previously described populations of naïve and memory CD4+ T cells. Naïve‐like T‐bet‐experienced cells are polarized to the TH1 lineage, predisposed to produce IFN‐γ upon cell activation, and resist repolarization to other lineages in vitro and in vivo. These results demonstrate that lineage‐specifying factors can polarize T cells in the absence of canonical markers of T cell activation and that this has an impact on the subsequent T‐helper response.
Gender perspectives on self‐censorship in organizations: The role of management position, procedural justice and organizational climate
Authors: Adamska Krystyna , Kosakowska‐Berezecka Natasza , Jurek Paweł , Konarski Roman
Published: January 2022

Self‐censorship in organizations is an individual's decision not to share information on observed irregularities and misconduct of others. The propensity to self‐censor, motivated by belief that voice will not be heard, may reflect gender inequalities. In Study 1 (N= 948), we test whether women manifest more self‐censorship than men and we verify whether this effect is maintained when women and men hold managerial positions. In two follow‐up studies we analyse the effects of (a) procedural justice (Study 2,N= 98) and (b) communal organizational climate (Study 3,N= 589) on women's and men's self‐censorship. The results of our studies support our assumptions: (1) self‐censorship in women is more prevalent than in men, (2) women in management positions are more likely to self‐censor than men in managerial positions, and (3) procedural justice and communal organizational climate are negatively related to employees’ self‐censorship, and this relationship is stronger for women.
A secure multi‐path transmission algorithm based on fountain codes
Authors: Liu Jianhang , Xu Jingshuai , Li Shibao , Cui Xuerong , Zhang Yucheng
Published: January 2022

Cyber security is the basis of ensuring reliable network transmission. In addition to encrypting the data, dividing the data into multiple paths for transmission is also an important way to improve the security. However, the development of semantic analysis algorithms leads to the fact that the eavesdroppers can restore the data as long as they obtain the data on the part of the paths, which reduces the security of multi‐path transmission. Additionally, in the environment of poor communication quality, retransmission mechanism leads to long transmission delay. To solve the above problems, this article proposes a secure multi‐path transmission algorithm based on fountain codes—FMPST. According to the safety level of data, the forwarding nodes are dynamically selected. Making use of the non‐feedback characteristic of fountain codes can not only reduce data delay, but also evaluate the channel packet loss rate by random forest model. FMPST can calculate the number of packets by packet loss rate, which makes it difficult for eavesdroppers to obtain enough packets to decrypt. The experiments show that compared with other multi‐path transmission algorithms, FMPST can improve the data security more than three times and reduce the communication delay by at least 50%.
Ultrasound‐assisted solubilization of calcium from micrometer‐scale ground fish bone particles
Authors: Guo Juanjuan , Zhu Siliang , Chen Hongbin , Zheng Zongping , Pang Jie
Published: January 2022

In order to promote the extraction of biological calcium from fish bone, ultrasonication was used to process micrometer‐scale fish bone particles (MFPs) and investigate the mechanism of action in relation to bone structure. With ultrasonication treatment (300 W, 60°C, 2 h), the content of calcium release increased by 25.6%. Calcium release reached 94.0% of total calcium after 24‐h treatment. The surface of the MFPs was significantly damaged by ultrasound‐induced cavitation, resulting in holes and separation of the layered structure. X‐ray diffraction (XRD) and Fourier transform infrared (FT‐IR) analysis demonstrated that the crystalline structure of hydroxyapatite was disrupted, the triple helical structure of mineralized collagen fibrils (MCFs) was loosened, and hydrogen bonding in collagen decreased, facilitating the release of hydroxyapatite crystals. Thus, ultrasonication may be a practical alternative to nanomilling for industrial processing of waste fish bones to produce soluble calcium as an ingredient in calcium supplements and supplemented foods.
Historical data of atmospheric electric field observations in Japan
Authors: Nagamachi Shingo , Arita Shin , Hirota Eiji
Published: January 2022

The Kakioka Magnetic Observatory (KMO) of the Japan Meteorological Agency (JMA) made atmospheric electric field observations at Kakioka and Memambetsu beginning in 1929 and 1949, respectively, and ending in February 2021 and December 2010, respectively. The digital numerical data are available on the KMO website, although not all observation periods are covered. In this article, we introduce the available datasets and summarize the metadata regarding the observations, such as measurement instruments, maintenance methods and data processing.
Neurodegeneration and neuroinflammation are linked, but independent of alpha‐synuclein inclusions, in a seeding/spreading mouse model of Parkinson's disease
Authors: Garcia Pierre , Jürgens‐Wemheuer Wiebke , Uriarte Huarte Oihane , Michelucci Alessandro , Masuch Annette , Brioschi Simone , Weihofen Andreas , Koncina Eric , Coowar Djalil , Heurtaux Tony , Glaab Enrico , Balling Rudi , Sousa Carole , Kaoma Tony , Nicot Nathalie , Pfander Tatjana , Schulz‐Schaeffer Walter , Allouche Ahmad , Fischer Nicolas , Biber Knut , Kleine‐Borgmann Felix , Mittelbronn Michel , Ostaszewski Marek , Schmit Kristopher J. , Buttini Manuel
Published: January 2022

A key pathological process in Parkinson's disease (PD) is the transneuronal spreading of α‐synuclein. Alpha‐synuclein (α‐syn) is a presynaptic protein that, in PD, forms pathological inclusions. Other hallmarks of PD include neurodegeneration and microgliosis in susceptible brain regions. Whether it is primarily transneuronal spreading of α‐syn particles, inclusion formation, or other mechanisms, such as inflammation, that cause neurodegeneration in PD is unclear. We used a model of spreading of α‐syn induced by striatal injection of α‐syn preformed fibrils into the mouse striatum to address this question. We performed quantitative analysis for α‐syn inclusions, neurodegeneration, and microgliosis in different brain regions, and generated gene expression profiles of the ventral midbrain, at two different timepoints after disease induction. We observed significant neurodegeneration and microgliosis in brain regions not only with, but also without α‐syn inclusions. We also observed prominent microgliosis in injured brain regions that did not correlate with neurodegeneration nor with inclusion load. Using longitudinal gene expression profiling, we observed early gene expression changes, linked to neuroinflammation, that preceded neurodegeneration, indicating an active role of microglia in this process. Altered gene pathways overlapped with those typical of PD. Our observations indicate that α‐syn inclusion formation is not the major driver in the early phases of PD‐like neurodegeneration, but that microglia, activated by diffusible, oligomeric α‐syn, may play a key role in this process. Our findings uncover new features of α‐syn induced pathologies, in particular microgliosis, and point to the necessity for a broader view of the process of α‐syn spreading.
Automatic oculomotor nerve identification based on data‐driven fiber clustering
Authors: Huang Jiahao , Li Mengjun , Zeng Qingrun , Xie Lei , He Jianzhong , Chen Ge , Liang Jiantao , Li Mingchu , Feng Yuanjing
Published: January 2022

The oculomotor nerve (OCN) is the main motor nerve innervating eye muscles and can be involved in multiple flammatory, compressive, or pathologies. The diffusion magnetic resonance imaging (dMRI) tractography is now widely used to describe the trajectory of the OCN. However, the complex cranial structure leads to difficulties in fiber orientation distribution (FOD) modeling, fiber tracking, and region of interest (ROI) selection. Currently, the identification of OCN relies on expert manual operation, resulting in challenges, such as the carries high clinical, time‐consuming, and labor costs. Thus, we propose a method that can automatically identify OCN from dMRI tractography. First, we choose the multi‐shell multi‐tissue constraint spherical deconvolution (MSMT‐CSD) FOD estimation model and deterministic tractography to describe the 3D trajectory of the OCN. Then, we rely on the well‐established computational pipeline and anatomical expertise to create a data‐driven OCN tractography atlas from 40 HCP data. We identify six clusters belonging to the OCN from the atlas, including the structures of three kinds of positional relationships (pass between, pass through, and go around) with the red nuclei and two kinds of positional relationships with medial longitudinal fasciculus. Finally, we apply the proposed OCN atlas to identify the OCN automatically from 40 new HCP subjects and two patients with brainstem cavernous malformation. In terms of spatial overlap and visualization, experiment results show that the automatically and manually identified OCN fibers are consistent. Our proposed OCN atlas provides an effective tool for identifying OCN by avoiding the traditional selection strategy of ROIs.
Diagnostic accuracy of conventional oral examination for detecting oral cavity cancer and potentially malignant disorders in patients with clinically evident oral lesions: Systematic review and meta‐analysis
Authors: Essat Munira , Cooper Katy , Bessey Alice , Clowes Mark , Chilcott James B. , Hunter Keith D.
Published: January 2022

This systematic review evaluates the diagnostic accuracy of conventional oral examination (COE) versus incisional or excisional biopsy for the diagnosis of malignant and/or dysplastic lesions in patients with clinically evident lesions. Searches were conducted across five electronic databases from inception to January 2020. Meta‐analyses were undertaken, where appropriate. Among 18 included studies, 14 studies were included in the meta‐analysis, giving summary estimates for COE of 71% sensitivity and 85% specificity for the diagnosis of dysplastic and/or malignant lesions. The pooled diagnostic accuracy of identifying malignant‐only lesions was reported in seven studies, giving a pooled estimate of 88% sensitivity and 81% specificity. Diagnostic accuracy of different types of dental/medical professionals in identifying dysplastic or malignant lesions gave varying estimates of sensitivity and specificity across three studies. Further research is needed to improve the diagnostic accuracy of COE for early detection of dysplastic and malignant oral lesions.
Nanofibrous polycaprolactone/chitosan membranes for preventing postsurgical tendon adhesion
Authors: Fakhraei Omid , Alimohammadi Mahdieh , Moradi Ali , Akbarinezhad Nogh Ali , Soudmand Salarabadi Samaneh , Ghasabzadeh Mohammad Sedigh , Panahi Reihaneh , Aghli Yasaman , Passandideh‐Fard Mohammad , Tahani Masoud , Ebrahimzadeh Mohammad Hossein , Mousavi Shaegh Seyed Ali
Published: January 2022

Peritendinous adhesion is considered a major postsurgical tendon complication in hand surgery. This complication could be mitigated partially through early tendon mobilization. However, development of new treatment modalities to guide tissue regeneration and to reduce postsurgical tendon adhesion has recently gained attentions. In this article, synthesis and characterization of electrospun nanofibrous membranes (NFMs) of polycaprolactone (PCL) and chitosan to form a physical barrier against cellular migration leading to tendon adhesion is presented. The mechanical properties of the NFMs are modulated to maintain high integrity during postsurgical tendon mobilization. The tensile strength of the NFMs is examined in wet and dry conditions after 1000 cyclic pull loadings. In addition, the mechanical strength of the NFMs is evaluated after a degradation period of 30 days. To obtain NFM with desired properties, concentrations of polymer solutions, operation parameters of electrospinning and the thickness of NFMs were optimized. Based on the biodegradation and mechanical evaluations, the optimum NFM was obtained for specified amounts of PCL (5 wt %) + chitosan (2 wt %) at an electrospinning drum speed of 400 rpm. The engineered NFM could withstand forces of 33 and 19 N before and after 1000 pull cycles that are sufficient during tendon healing process. The bonding of chitosan fibers over PCL nanofibers allowed for production of NFMs with appropriate mechanical integrity and degradation rate. In vitro cell culture tests demonstrated that PCL/chitosan could only have minor impact on decreasing fibroblast attachment over the membranes probably due to protonation of amine groups.
Pollen morphology and its implication in the taxonomy of some selected taxa of the bi and tri‐ovulate Euphorbiaceae of the Hainan Island by using multiple microscopic techniques
Authors: Bahadur Saraj , Taj Sehrish , Long Wenxing , Ahmad Mushtaq
Published: January 2022

The family Euphorbiaceae is one of the most taxonomically complex and diverse family among the angiosperm. Therefore, this study aims to document the pollen morphology of the Euphorbiaceae taxa collected from different geographical regions of the Hainan Island South China, to strengthen the taxonomy and support the subfamilial classification. The Euphorbiaceae includes 23 species and 10 genera of the bi‐ovulate subfamily Phyllanthoideae and tri‐ovulate Crotonoideae, Euphorbioideae, and Acalyphoideae were examined under light and scanning electron microscopy. The principal component analysis was performed by using six variables to show variation and relationships between the species. A significant variation was found in the pollen morphology (exine and colpus sculpturing). The croton‐type pattern of the pollen was found the diagnostic trait of the Crotonoideae. The Euhphorboideae taxa were mostly homogenous however, variation was found in the muri pattern. The Acalyphoideae, have fossulate scabrate and verrucate exine sculpturing that can delimit from the rest of sub‐families. The Phyllanthoideae, showed reticulate exine, tri to tetra‐colporate having various colpus morphology. The maximum pollen size was found in Croton hirtus (59.49 × 60.86 μm) and minimum in Acalypha indica (10.86 × 73 μm). Similarly, the maximum colpus width was observed in Euphorbia pulcherrima (8.3 μm). Hence pollen traits have relevance in the taxonomy and phylogenetic of the family to define species boundaries at various taxonomic levels. This study can support and strengthen the taxonomy of subfamilies and fill the palynological gap of these taxa in Hainan Island and will contribute to future systematic studies of the Euphorbiaceae.
Long‐term remission of extramedullary cutaneous relapse of acute myeloid leukaemia (leukaemia cutis) treated with decitabine‐venetoclax
Authors: Maravalle Denise , Filosa Alessandra , Bigazzi Catia , Collina Guido , Galieni Piero
Published: January 2022

In February 2020, a 74‐year‐old female was diagnosed with myelomonocytic acute myeloid leukaemia with FLT3 mutation and blasts positive for CD33, BCL‐2 and CD68/PGM1. Not responding to a standard Cytarabine–containing regimen plus Midostaurin, the patient achieved a complete remission (CR) of the disease in the bone marrow following a reinduction therapy with high‐dose Cytarabine but simultaneously relapsed developing leukaemia cutis with disseminated lesions in 80% of the body surface area. After receiving 10 cycles of Decitabine plus Venetoclax the patient achieved and maintains a continuous CR.
Evaluation of a PEGylated Fibroblast Growth Factor 21 Variant Using Novel Preclinical Magnetic Resonance Imaging and Magnetic Resonance Elastography in a Mouse Model of Nonalcoholic Steatohepatitis
Authors: Tang Haiying , Li Jiahui , Zinker Bradley , Boehm Stephanie , Mauer Amy , Rex‐Rabe Sandra , Glaser Kevin J. , Fronheiser Matthew , Bradstreet Thomas , Nakao Yasuhiko , Petrone Thomas , Pena Adrienne , Villano MacKenzie , Chow Patrick , Malhi Harmeet , Charles Edgar D. , Hayes Wendy , Ehman Richard L. , Du Shuyan , Yin Meng
Published: January 2022

Background

Treatments for nonalcoholic steatohepatitis (NASH) are urgently needed. Hepatic fat fraction and shear stiffness quantified by magnetic resonance imaging (MRI‐HFF) and magnetic resonance elastography (MRE‐SS), respectively, are biomarkers for hepatic steatosis and fibrosis.

Purpose

This study assessed the longitudinal effects of fibroblast growth factor 21 variant (polyethylene glycol [PEG]‐FGF21v) on MRI‐HFF and MRE‐SS in a NASH mouse model.

Study Type

Preclinical.

Animal Model

This study included a choline‐deficient, amino acid‐defined, high‐fat diet (CDAHFD) model and 6‐week‐old, male C57BL/6J mice (N = 78).

Field Strength/Sequence

This study was performed using: 3T: gradient‐echo two‐point Dixon and spin‐echo (SE) echo‐planar imaging elastography (200 Hz) and 7T: SE two‐point Dixon and SE elastography (200 Hz).

Assessment

MRI and MRE were performed before control diet (CD) or CDAHFD (BD), before PEG‐FGF21v dosing (baseline), and after PEG‐FGF21v treatment (WK4/8). Regions of interest for MRI‐HFF and MRE‐SS were delineated by J.L. and H.T. (>5 years of experience each). Fibrosis and steatosis were measured histologically after picrosirius red and H&E staining. Alkaline phosphatase, alanine transaminase, bile acids, and triglycerides (TGs) were measured.

Statistical Tests

Two‐tailed Dunnett's tests were used for statistical analysis; untreated CDAHFD or baseline was used for comparisons. Imaging and histology/biochemistry data were determined using Spearman correlations. Bayesian posterior distributions for MRE‐SS at WK8, posterior means, and 95% credible intervals were presented.

Results

CDAHFD significantly increased baseline MRI‐HFF (3T: 21.97% ± 0.29%; 7T: 40.12% ± 0.35%) and MRE‐SS (3T: 1.25 ± 0.02; 7T: 1.78 ± 0.06 kPa) vs. CD (3T: 3.45% ± 0.7%; 7T: 12.06% ± 1.4% and 3T: 1.01 ± 0.02; 7T: 0.89 ± 0.06 kPa). At 7T, PEG‐FGF21v significantly decreased MRI‐HFF (WK4: 28.97% ± 1.22%; WK8: 20.93% ± 1.15%) and MRE‐SS (WK4: 1.57 ± 0.04; WK8: 1.36 ± 0.05 kPa) vs. untreated (WK4: 36.36% ± 0.62%; WK8: 30.58% ± 0.81% and WK4: 2.03 ± 0.06; WK8: 2.01 ± 0.04 kPa); 3T trends were similar. WK8 SS posterior mean percent attenuation ratios (RDI) were −68% (−90%, −44%; 3T) and −64% (−78%, −52%; 7T). MRI‐HFF was significantly correlated with H&E (3T, r = 0.93; 7T, r = 0.94) and TGs (both, r = 0.92).

Data Conclusions

MRI‐HFF and MRE‐SS showed PEG‐FGF21v effects on hepatic steatosis and fibrosis across 3 and 7T, consistent with histological and biochemical data.

Level of Evidence

1

Technical Efficacy Stage

2
A highly complex stingless bee propolis: Composition and influence of the period of collection
Authors: Negri Giuseppina , Salatino Antonio , Pereira Leonardo L Regnier , Salatino Maria Luiza Faria , do Nascimento Roberto Manoel , Mendonça Ronaldo Zucatelli
Published: January 2022

Background

Stingless bees or meliponines (family Apidae, subfamily Meliponinae, tribe Meliponini) are eusocial bees from tropical and subtropical regions. Propolis ofScaptotrigonaaff.postica(Latreille, 1807) is used in the state of Maranhão (Northeast Brazil) in ointments to treat tumors and wounds. Samples of propolis ofS. aff.postica(Apidae, Meliponini) were collected monthly from an apiary located in Barra do Corda (state of Maranhão, Northeast Brazil). Extracts of the 12 samples were obtained with 80% ethanol. Constituents of the samples were characterized by high performance liquid chromatography coupled to photodiode array detector and electrospray ionization tandem mass spectrometry analysis, amounting to 100 substances.

Results

Representatives of several classes of secondary metabolites were characterized, including benzoic and cinnamic acids, flavonoids (chalcones, flavone‐C‐glycosides, flavonol aglycones, and glycosides), alkyl and alkenyl resorcinols, xanthones, diterpenes, cycloartane‐type triterpenoids, pentacyclic triterpenoids, pyrrolizidine alkaloids, and hydroxycinnamic acid amides (HCAAs). Considerable qualitative differences in chemical composition among samples were observed, depending on the year period of collection. Principal Coordinate Analysis recognized three distinct year periods (Jan–Mar, April–Sep, Oct–Dec) according to the corresponding chemical profiles.

Conclusion

Compared with previous studies, the present work indicates that considerable differences in chemical composition occur also from year to year. Contrary to most propolis types reported so far, which derive exclusively or mostly from a single botanical source, the propolis from Barra do Corda seemingly depends on several resin sources. It is suggested that chalcones and flavonols stem fromMimosa tenuiflora(Mimosoideae); resorcinols, xanthones, and cycloartane‐type triterpenoids, from fruits ofMangifera indica(Anacardiaceae); pyrrolizidine alkaloids, possibly from someCrotalariaspecies (Faboideae); HCAAs probably originate from pollen contaminating the propolis samples. The propolis ofS. aff.posticaposes challenges and possibilities of study for apicultural researchers, chemists, and pharmacologists.
Protective effect of surface‐layer proteins from four Lactobacillus strains on tumor necrosis factor‐α‐induced intestinal barrier dysfunction
Authors: Zhang Jiaojiao , Li Qinpei , Wu Liying , Xu Shichen , Lu Rongrong
Published: January 2022

BACKGROUND

The intestinal epithelium is considered the first defense protection against exogenous harmful substances, playing an indispensable role in regulating intestinal health. The protection offered by surface‐layer proteins (Slps) from different Lactobacillus strains on an impaired intestinal barrier was investigated in this study.

RESULTS

Four Slps pre‐incubated for 6 h significantly prevented the reduced transepithelial electrical resistance value and increased paracellular permeability in tumor necrosis factor (TNF)‐α‐induced Caco‐2 monolayers. TNF‐α induced lower protein expression of occludin and zonula occludens‐1, and abnormal distributions of occludin and zonula occludens‐1 were ameliorated by four Slps as well. Additionally, four Slps weakened TNF‐α‐evoked interleukin‐8 secretion and nuclear factor‐κB activation.

CONCLUSION

Four Slps from different strains prevent the intestinal barrier from TNF‐α‐induced dysfunction through blocking the nuclear factor‐κB signaling pathway. © 2022 Society of Chemical Industry.
Degradation of Cellulose Acetate in Simulated Aqueous Environments: One‐Year Study
Authors: Yadav Nisha , Hakkarainen Minna
Published: January 2022

Cellulose acetate (CA) is subjected to different aqueous environments (e.g., lake water, seawater, artificial seawater) under controlled laboratory conditions to investigate the degradation potential in natural water systems. The main changes in the CA films are detected during the first months of the 12‐month study. Approximately 5% and 10% weight losses are observed during the first month of aging at RT and at 60 °C, respectively. The temperature effect is rather negligible and the weight loss also does not significantly increase on prolonged aging. A quantitative high‐performance liquid chromatography analysis shows that this weight loss is mainly caused by deacetylation and depending on the aging conditions, 10–30% of the acetate groups are lost during the first 1–3 months of aging. Fourier transform infrared and nuclear magnetic resonance analyses further support this. It is well established that a high degree of substitution (DS) is the bottleneck for biodegradation of CA and a significantly higher biodegradation rate has been demonstrated for CA materials with degree of substitution, DS<2, compared to those with DS>2. The degree of deacetylation observed here is enough to decrease the DS to below 2, which can therefore have a significant effect on the subsequent biodegradation.
Impact of Intestinal Bacteria on Levodopa Pharmacokinetics in LCIG Therapy
Authors: Yamanishi Yuki , Choudhury Mohammed Emamussalehin , Yoshida Akira , Hosokawa Yuko , Miyaue Noriyuki , Tada Satoshi , Ando Rina , Murakami Shinobu , Miyamoto Hitoshi , Nagai Masahiro
Published: January 2022

Background

Levodopa‐carbidopa intestinal gel (LCIG) therapy is used in advanced Parkinson's disease (PD) and consists of continuous administration of levodopa directly into the jejunum through a percutaneous endoscopic gastro‐jejunal (PEG‐J) tube. Recently, the metabolism of levodopa by Enterococcus faecalis (E. faecalis) has been reported. Intestinal bacteria can also affect this therapy.

Objectives

To investigate intestinal bacteria and examine its impact on levodopa blood concentration in patients with PD receiving LCIG therapy.

Methods

We enrolled 6 patients receiving LCIG therapy in our department. After PEG‐J tube replacement, intestinal bacteria were collected from the tip of the tube and were identified using culture and polymerase chain reaction (PCR) tests. Moreover, the presence of tyrosine decarboxylase, which metabolizes levodopa, was also confirmed by PCR test. The ability of these bacteria to metabolize levodopa was confirmed in vitro. Levodopa blood concentrations were also examined before PEG‐J tube replacement.

Results

Bacteria were detected in all 6 patients. E. faecalis was present in 4 patients. Moreover, tyrosine decarboxylase was detected in 2 patients. The identified bacteria displayed in vitro metabolization to dopamine in the 4 E. faecalis positive samples. The addition of carbidopa did not inhibit the metabolism of levodopa. However, there was no difference in the mean blood concentration of levodopa, regardless of the presence of E. faecalis.

Conclusions

We found bacteria, including E. faecalis in the PEG‐J tube. We observed levodopa metabolism in vitro, but there was no association with levodopa blood concentration. The effect of intestinal bacteria may be limited in patients receiving LCIG therapy.
Exon skipping caused by a complex structural variation in SH2D1A resulted in X‐linked lymphoproliferative syndrome type 1
Authors: Wu Liwen , Yang Feng , Wang Jia , Yang Fan , Liang Mengmeng , Yang Haiyan
Published: January 2022

Background

X‐linked lymphoproliferative syndrome type 1 (XLP1) is a rare primary immunodeficiency disorder characterized by severe immune dysregulation often after viral infection. It is caused by hemizygous mutations in the X‐linked SH2D1A gene. People with XLP1 have complex and variable phenotype manifestations as EBV‐driven severe or fulminant mononucleosis, hemophagocytic lymphohistiocytosis (EBV‐HLH), dysgammaglobulinemia, and B‐cell lymphoma.

Methods

Immunological analyses, clinical laboratory testing, and whole exome sequencing (WES) were performed to help the disease diagnosis for the patient with severe immune dysregulation. Routine and extended WES analysis pipelines were applied to explore candidates. A complex genomic structural variation in SH2D1A was detected and verified by Inverse‐PCR, Gap‐PCR, and RT‐PCR.

Results

Here we reported that a five‐year‐old male patient manifested with EBV‐HLH, recurrent infection by severe immune dysregulation, and successfully managed with HSCT. He finally established precise disease diagnosis as XLP1 caused by a complex genomic structural variation in SH2D1A (NC_000023.11:g. [124,350,560_124365777del; 124,365,777_124365917inv; 124,365,911_124365916del]). The mother and grandmother of the proband were confirmed to be carriers. The complex variant resulted in the exon 2 skipping and was predicted to generate a prematurely truncated protein.

Conclusion

The complex structural variant combined with paracentric inversion and large size deletions was first reported in XLP1 cases. It is considered to be pathogenic based on the truncation of the mRNA sequence and cosegregation with the disease in three‐generation pedigree analysis. This finding has expanded the known XLP‐related mutation spectrum in Chinese patients and indicated remarkable effects on the early diagnosis and therapeutic implication using proper molecular testing techniques.
An analysis of shock wave propagation in a dusty gas
Authors: Singh Deepika , Arora Rajan
Published: January 2022

The present work uses a power series method to investigate the propagation of shock waves with generalized geometries generated by an intense explosion in a dusty gas. A mathematical model using a system of partial differential equations (PDEs) is presented for the considered problem. The density of the undisturbed medium is assumed to be constant. Approximate analytic solutions to the considered problem are obtained using the power series method by extending the power series of the flow variables. This work discusses the first‐order and second‐order approximate solutions and provides closed‐form solutions for the first‐order approximation. The behavior of the flow variables is depicted via figures behind the shock front for the first‐order approximation. Furthermore, the effects of geometry factorα, adiabatic exponentγ, and various dusty gas parameters such asKp(the mass fraction of the dust particles),G0(the ratio of the density of the dust particles to the initial density of the gas), andσ(the relative specific heat) are analyzed on the flow variables and total energy of disturbanceJ0for the first‐order approximation. It is observed that an increase in any of the parametersKporσcauses the fluid velocity to increase and density and pressure to decrease. Increase in the parameterG0causes the density and pressure to increase, whereas the fluid velocity does not get affected. An increase in the value ofαresults in a decrease in the density and pressure, while the fluid velocity remains the same. An increase in the value ofγresults in a decrease in the fluid velocity; however, it has opposite effect on the pressure. The density decreases near the shock front and increases as we move towards the axis/center of symmetry with an increase inγ. Also, it is observed thatJ0increases on increasing the value ofG0orσ, while it decreases on increasing the value ofKp, γorα.
Technical note: The impact of storage humidity on the response of reference‐class ionization chambers
Authors: Morishita Yuichiro , Shimizu Morihito , Takase Nobuhiro , Yamashita Wataru , Sakata Suoh
Published: January 2022

Purpose

A number of Farmer‐type ionization chambers were tested against storage humidity to confirm whether they satisfied the criteria for the long‐term stability of reference‐class ionization chambers.

Methods

The ionization chambers were stored for several months in an environment with relative humidity adjustable from 20% to 80%. The ionization chambers were removed from the storage environment at variable intervals ranging from 1 to 70 days and irradiated in a Co‐60 radiation beam. The responses for each ionization chamber were evaluated from the measured currents corrected for the atmospheric air density, and were compared with those predicted by the Co‐60 half‐life.

Results

Certain ionization chambers gave a constant relative response regardless of the storage humidity, while the relative responses of two types of ionization chambers changed as a function of the storage humidity. The difference between the relative responses for the low (20–30%) and high (70–80%) storage relative humidity was 0.7%. The response was larger for the high relative humidity storage. Immediately after the storage humidity changed, the relative response started to change by the day, and it took approximately 2 weeks to 2 months for the relative response to converge. For one type of the ionization chamber, the plastic outer wall and the outer electrode were replaced with those made of solid graphite, and it was confirmed that the remodeled ionization chamber did not exhibit the response change.

Conclusions

The present results and previous reports by other authors indicate that the magnitude of the change depends on the magnitude of the water absorption of the plastic used for the outer wall and/or the electrode of the ionization chamber. Thus, it is important in the selection of the reference‐class ionization chamber to note the material and structure of the outer wall and electrode of the ionization chamber. If the ionization chamber has a hygroscopic wall and electrode and it is used as a reference ionization chamber, it is necessary to pay additional attention to the humidity difference for the storage, daily irradiation, and yearly calibration especially in regions with large seasonal humidity fluctuations.