bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitonuclear mismatch alters nuclear gene expression in naturally introgressed Rhinolophus bats
Authors: Ding Yuting , Chen Wenli , Li Qianqian , Rossiter Stephen J. , Mao Xiuguang
Published: September 2021

Background

Mitochondrial function involves the interplay between mitochondrial and nuclear genomes. Such mitonuclear interactions can be disrupted by the introgression of mitochondrial DNA between taxa or divergent populations. Previous studies of several model systems (e.g. Drosophila) indicate that the disruption of mitonuclear interactions, termed mitonuclear mismatch, can alter nuclear gene expression, yet few studies have focused on natural populations.

Results

Here we study a naturally introgressed population in the secondary contact zone of two subspecies of the intermediate horseshoe bat (Rhinolophus affinis), in which individuals possess either mitonuclear matched or mismatched genotypes. We generated transcriptome data for six tissue types from five mitonuclear matched and five mismatched individuals. Our results revealed strong tissue-specific effects of mitonuclear mismatch on nuclear gene expression with the largest effect seen in pectoral muscle. Moreover, consistent with the hypothesis that genes associated with the response to oxidative stress may be upregulated in mitonuclear mismatched individuals, we identified several such gene candidates, including DNASE1L3, GPx3 and HSPB6 in muscle, and ISG15 and IFI6 in heart.

Conclusion

Our study reveals how mitonuclear mismatch arising from introgression in natural populations is likely to have fitness consequences. Underlying the processes that maintain mitonuclear discordance is a step forward to understand the role of mitonuclear interactions in population divergence and speciation.
Physical therapy treatments incorporating equine movement: a pilot study exploring interactions between children with cerebral palsy and the horse
Authors: Lightsey Priscilla , Lee Yonghee , Krenek Nancy , Hur Pilwon
Published: September 2021

Background

Physical therapy treatments incorporating equine movement are recognized as an effective tool to treat functional mobility and balance in children with cerebral palsy (CP). To date, only a few studies examined kinematic outputs of the horses and children when mounted. In this pilot study, to better understand the effectiveness of this type of treatment, we examined the interaction between the horses and children with CP during physical therapy sessions where equine movement was utilized.

Methods

Four children with CP participated in eight physical therapy sessions incorporating hippotherapy as a treatment intervention. Functional mobility was assessed using the Timed Up Go or the 10 m Walk Test. Inertial measurement unit sensors, attached to children and horses, recorded movements and tracked acceleration, angular velocity, and body orientation. Correlation between vertical accelerations of children and horses were analyzed. In addition, peak frequencies of vertical accelerations of children and horses were compared.

Results

Functional tests modestly improved over time. The children’s movements, (quantified in frequency and temporal domains) increasingly synchronized to the vertical movement of the horse’s walk, demonstrated by reduced frequency errors and increased correlation.

Conclusions

The findings suggest that as the sessions progressed, the participants appeared to become more familiar with the horse’s movement. Since the horse’s gait at a walk mimics the human gait this type of treatment may provide individuals with CP, who have abnormal gait patterns, an opportunity for their neuromuscular system to experience a typical gait pattern. The horse’s movement at the walk are consistent, cyclical, rhythmical, reciprocal and multi-dimensional, all of which can facilitate motor learning. The increased synchronization between horse and the mounted participant suggests that physical therapy utilizing equine movement is a viable treatment tool to enhance functional mobility. This study may provide a useful baseline for future work.

Trial registrationTexas A&M University Institutional Review Board. IRB2018-0064. Registered 8 March 2018. Link: https://rcb.tamu.edu/humans/irb and https://github.com/pilwonhur/HPOT
A chair at the table: a scoping review of the participation of refugees in community-based participatory research in healthcare
Authors: Filler Tali , Benipal Pardeep Kaur , Torabi Nazi , Minhas Ripudaman Singh
Published: September 2021

Background

Refugees often face psychosocial complexity and multi-dimensional healthcare needs. Community-Based Participatory Research (CBPR) methods have been previously employed in designing health programs for refugee communities and in building strong research partnerships in refugee communities. However, the extent to which these communities are involved remains unknown.

Objective

To review the evidence on the involvement of refugees in CBPR processes to inform healthcare research.

Methods

A scoping review was performed, using Arksey & O’Malley’s methodological framework. A literature search in Medline, PubMed, PsycINFO, CINAHL, Embase, Global Health, Scopus, and Policy File Index for articles published until August 2020 was conducted. Articles were included if they focused on CBPR, had refugee involvement, and discussed healthcare/health policy.

Results

4125 articles were identified in the database searches. After removal of duplicates, 2077 articles underwent title and abstract review by two authors, yielding an inter-reviewer kappa-statistic of 0.85. 14 studies were included in the final analysis. The purpose of CBPR use for 6 (42.9%) of the articles was developing and implementing mental health/social support interventions, 5 (35.7%) focused on sexual and reproductive health interventions, 1 (7.1%) focused on domestic violence interventions, 1 (7.1%) focused on cardiovascular disease prevention and 1 (7.1%) focused on parenting interventions. In terms of refugee involvement in the various stages in the research process, 9 (64.3%) articles reported refugees having a role in the inception of the research, no articles reported including refugees in obtaining funding, all articles included refugees in the design of the research study, 10 (71.4%) articles reported having refugees involved in community engagement/recruitment, 8 (57.1%) articles reported involvement throughout the data collection process, 4 (28.6%) articles reported involvement in data analysis, 6 (42.9%) articles reported having refugees involved in knowledge translation/dissemination and 1 article (7.1%) reported having refugees contribute to scale up initiatives.

Conclusions

CBPR has been identified as a methodology with the potential to make substantial contributions to improving health and well-being in traditionally disenfranchised populations. As the needs of refugee communities are so diverse, efforts should be made to include refugees as partners in all stages of the research process.
Radiotherapy dose–volume parameters predict facial lymphedema after concurrent chemoradiation for nasopharyngeal carcinoma
Authors: Kim Donghyun , Nam Jiho , Kim Wontaek , Park Dahl , Joo Jihyeon , Jeon Hosang , Ki Yongkan
Published: September 2021

Background

To investigate risk factors for developing radiation-associated facial lymphedema (FL) in nasopharyngeal carcinoma (NPC) patients after concurrent chemoradiation (CCRT).

Methods

Clinical data from 87 patients who underwent definitive CCRT for NPC in 2010–2018 was retrospectively evaluated. FL severity was graded using MD Anderson Cancer Center head and neck lymphedema rating scale. Logistic regression analysis was used to examine the factors associated with the presence of moderate/severe FL (grade ≥ 2).

Results

At a median follow-up of 34 months (range, 18–96), 26/87 (29.9%) patients experienced grade ≥ 2 FL. A majority (84.6%) was experienced grade ≥ 2 FL 3–6 months after CCRT. Mean dose to the level IV, level I-VII neck node and N stage were significantly correlated with grade ≥ 2 FL at univariate analysis. At multivariate analysis, mean dose of level IV neck node (hazard ratio [HR], 1.238; 95% confidence interval [CI] = 1.084–1.414; p = 0.002) and level I-VII neck node (HR, 1.384; 95% CI = 1.121–1.708; p = 0.003) were independent predictors. Receiver Operating Characteristics (ROC) curve analysis showed that cut-off value of mean level IV neck node dose was 58.7 Gy (area under the curve [AUC] = 0.726; 95% CI = 0.614–0.839, p = 0.001) and mean level I-VII neck node dose was 58.6 Gy (AUC = 0.720; 95% CI = 0.614–0.826, p = 0.001) for grade ≥ 2 FL.

Conclusions

Keeping mean dose to the level IV and level I-VII below 58.7 Gy and 58.6 Gy may reduce the likelihood of moderate/severe FL after CCRT for NPC.
Aspiration versus peritoneal lavage in appendicitis: a meta-analysis
Authors: Burini Gloria , Cianci Maria Chiara , Coccetta Marco , Spizzirri Alessandro , Di Saverio Salomone , Coletta Riccardo , Sapienza Paolo , Mingoli Andrea , Cirocchi Roberto , Morabito Antonino
Published: September 2021

Background

Acute appendicitis is one of the most frequent abdominal surgical emergencies. Intra-abdominal abscess is a frequent post-operative complication. The aim of this meta-analysis was to compare peritoneal irrigation and suction versus suction only when performing appendectomy for complicated appendicitis.

Methods

According to PRISMA guidelines, a systematic review was conducted and registered into the Prospero register (CRD42020186848). The risk of bias was defined to be from low to moderate.

Results

Seventeen studies (9 RCTs and 8 CCTs) were selected, including 5315 patients. There was no statistical significance in post-operative intra-abdominal abscess in open (RR 1.27, 95% CI 0.75–2.15; I2 = 74%) and laparoscopic group (RR 1.51, 95% CI 0.73–3.13; I2 = 83%). No statistical significance in reoperation rate in open (RR 1.27, 95% CI 0.04–2.49; I2 = 18%) and laparoscopic group (RR 1.42, 95% CI 0.64–2.49; I2 = 18%). In both open and laparoscopic groups, operative time was lower in the suction group (RR 7.13, 95% CI 3.14–11.12); no statistical significance was found for hospital stay (MD − 0.39, 95% CI − 1.07 to 0.30; I2 = 91%) and the rate of wound infection (MD 1.16, 95% CI 0.56–2.38; I2 = 71%).

Conclusions

This systematic review has failed to demonstrate the statistical superiority of employing intra-operative peritoneal irrigation and suction over suction-only to reduce the rate of post-operative complications after appendectomy, but all the articles report clinical superiority in terms of post-operative abscess, wound infection and operative times in suction-only group.
Peripheral nervous system manifestations of Shiga toxin-producing E. coli-induced haemolytic uremic syndrome in children
Authors: Santangelo Luisa , Netti Giuseppe Stefano , Torres Diletta Domenica , Piscopo Giovanni , Carbone Vincenza , Losito Luciana , Milella Leonardo , Lasorella Maria Luigia , Conti Pasquale , Gagliardi Delio , Chironna Maria , Spadaccino Federica , Bresin Elena , Trabacca Antonio , Ranieri Elena , Giordano Mario
Published: September 2021

Background

The Neurological involvement is the most common extra-renal complication of Shiga toxin-producing E. coli-hemolytic uremic syndrome (HUS) or typical HUS. On brain magnetic resonance examination, main neurological signs encompass acute lesions of the basal ganglia and the white matter, which could usually regress after Eculizumab infusion. In contrast, peripheral nervous system (PNS) manifestations in typical HUS are very rare and, when occurring, they require a careful management of neurological sequelae and an intensive multidisciplinary neuro-rehabilitation program.

Case presentation

Here, we present two pediatric cases of severe and complicated typical HUS with PNS manifestations who required therapeutic treatment and an intensive multidisciplinary neuro-rehabilitation program.

In both cases, PNS manifestations were followed by the recovery from typical HUS-related severe central neurological damage and manifested mainly with marked bilateral motor deficit and hyporeflexia/areflexia in the lower limbs. The peripheral polyneuropathy was treated with immunosuppressive therapy (methylprednisolone boluses, i.v. immunoglobulins, plasma exchange), followed by a prolonged intensive neuro-rehabilitation program. After 8 months of rehabilitation, both patients gained complete functional recovery.

Conclusions

PNS manifestations during typical HUS are a rare event and potentially leading to severe disability. A timely clinical assessment is mandatory to set up a prompt therapeutic and rehabilitation program and to obtain a complete clinical and functional recovery.
Additional effect of pain neuroscience education to craniocervical manual therapy and exercises for pain intensity and disability in temporomandibular disorders: a study protocol for a randomized controlled trial
Authors: dos Santos Aguiar Aroldo , Bataglion Cesar , Felício Lilian Ramiro , Azevedo Beatriz , Chaves Thaís Cristina
Published: September 2021

The objective of this study will be to investigate the additional effect of pain neuroscience education program compared to a craniocervical manual therapy and exercises program for pain intensity and disability in patients with temporomandibular disorders (TMD). This study will be a randomized controlled trial comprising a sample of 148 participants. Subjects between 18 and 55 years, both genders, will undergo a screening process to confirm painful TMD by the Research Diagnostic Criteria (RDC/TMD), and then the volunteers will be randomized into two groups (G1: pain neuroscience education + craniocervical manual therapy and exercises vs. G2: craniocervical manual therapy and exercises). The volunteers will be recruited at the dentistry clinic. The intervention will be administered twice a week for 6 weeks by a single therapist lasting 1 h per session. The primary outcome will be pain intensity and disability and the secondary outcomes will be pain self-efficacy, kinesiophobia, and global perceived effect of improvement. The participants will be assessed immediately after the last session and at one- and three-month follow-ups. All statistical analyses will be conducted following intention-to-treat principles, and the treatment effects will be calculated using linear mixed models. The results of this study may contribute to understand the additional effect of pain neuroscience education intervention on TMD patients submitted to manual therapy and exercise.

Trial registration

ClinicalTrials.gov NCT03926767. Registered on April 29, 2019.
A meta-collection of nitrogen stable isotope data measured in Arctic marine organisms from the Canadian Beaufort Sea, 1983–2013
Authors: Ehrman Ashley , Hoover Carie , Giraldo Carolina , MacPhee Shannon A. , Brewster Jasmine , Michel Christine , Reist James D. , Power Michael , Swanson Heidi , Niemi Andrea , Walkusz Wojciech , Loseto Lisa
Published: September 2021

Objectives

Existing information on Arctic marine food web structure is fragmented. Integrating data across research programs is an important strategy for building a baseline understanding of food web structure and function in many Arctic regions. Naturally-occurring stable isotope ratios of nitrogen (δ15N) and carbon (δ13C) measured directly in the tissues of organisms are a commonly-employed method for estimating food web structure. The objective of the current dataset was to synthesize disparate δ15N, and secondarily δ13C, data in the Canadian Beaufort continental shelf region relevant to trophic and ecological studies at the local and pan-Arctic scales.

Data description

The dataset presented here contains nitrogen and carbon stable isotope ratios (δ15N, δ13C) measured in marine organisms from the Canadian Beaufort continental shelf region between 1983 and 2013, gathered from 27 published and unpublished sources with associated sampling metadata. A total of 1077 entries were collected, summarizing 8859 individual organisms/samples representing 333 taxa across the Arctic food web, from top marine mammal predators to primary producers.
Cellular reprogramming and epigenetic rejuvenation
Authors: Simpson Daniel J. , Olova Nelly N. , Chandra Tamir
Published: September 2021

Ageing is an inevitable condition that afflicts all humans. Recent achievements, such as the generation of induced pluripotent stem cells, have delivered preliminary evidence that slowing down and reversing the ageing process might be possible. However, these techniques usually involve complete dedifferentiation, i.e. somatic cell identity is lost as cells are converted to a pluripotent state. Separating the rejuvenative properties of reprogramming from dedifferentiation is a promising prospect, termed epigenetic rejuvenation. Reprogramming-induced rejuvenation strategies currently involve using Yamanaka factors (typically transiently expressed to prevent full dedifferentiation) and are promising candidates to safely reduce biological age. Here, we review the development and potential of reprogramming-induced rejuvenation as an anti-ageing strategy.
Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease
Authors: Borkowski Kamil , Pedersen Theresa L. , Seyfried Nicholas T. , Lah James J. , Levey Allan I. , Hales Chadwick M. , Dammer Eric B. , Blach Colette , Louie Gregory , Kaddurah-Daouk Rima , Newman John W. ,   Alzheimer’s Disease Metabolomics Consortium
Published: September 2021

Background

Alzheimer’s disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. Here, we describe the analysis of plasma and cerebrospinal fluid lipid mediators in a case–control comparison of ~150 individuals with Alzheimer’s disease and ~135 healthy controls, to investigate this knowledge gap.

Methods

Lipid mediators were measured using targeted quantitative mass spectrometry. Data were analyzed using the analysis of covariates, adjusting for sex, age, and ethnicity. Partial least square discriminant analysis identified plasma and cerebrospinal fluid lipid mediator discriminates of Alzheimer’s disease. Alzheimer’s disease predictive models were constructed using machine learning combined with stepwise logistic regression.

Results

In both plasma and cerebrospinal fluid, individuals with Alzheimer’s disease had elevated cytochrome P450/soluble epoxide hydrolase pathway components and decreased fatty acid ethanolamides compared to healthy controls. Circulating metabolites of soluble epoxide hydrolase and ethanolamides provide Alzheimer’s disease predictors with areas under receiver operator characteristic curves ranging from 0.82 to 0.92 for cerebrospinal fluid and plasma metabolites, respectively.

Conclusions

Previous studies report Alzheimer’s disease-associated soluble epoxide hydrolase upregulation in the brain and that endocannabinoid metabolism provides an adaptive response to neuroinflammation. This study supports the involvement of P450-dependent and endocannabinoid metabolism in Alzheimer’s disease. The results further suggest that combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease.
A new classification of congenital abnormalities of UPVS: sonographic appearances, screening strategy and clinical significance
Authors: Qin Yue , Wen Huaxuan , Liang Meiling , Luo Dandan , Zeng Qing , Liao Yimei , Zhang Mengyu , Ding Yan , Wen Xin , Tan Ying , Yuan Ying , Li Shengli
Published: September 2021

The umbilical–portal venous system (UPVS) plays an important role in embryonic development, as well as a significant blood circulation system to ensure the normal blood supply of fetal heart and brain and other vital organs. Congenital anomalies of UPVS contain many subtypes with a broad spectrum of manifestations and prognoses. Furthermore, because of fetal small lumen of UPVS, the sonographic evaluation remains difficult in utero. Appreciation of normal embryology and anatomy of UPVS is essential to an understanding of sonographic characteristics of anomalies of UPVS and fetal sequential changes. Through reviewing previous references and our experience with congenital abnormalities of UPVS, a new comprehensive classification is proposed. The new classification identifies three types of congenital abnormalities of UPVS based on morphological abnormalities and shunts. The embryology and etiology, sonographic, clinical and prognostic characteristics of each subtype of the new classification are described in detail. Knowledge of congenital abnormalities of UPVS can give sonographers a clue and aid prenatal sonographic diagnosis. The purpose of this article is to help the sonographers to understand the new classification of congenital abnormalities of UPVS, master the sonographic characteristics of each subtype and prenatal ultrasonographic screening strategy, and guide subsequent appropriate counseling and management.
Ischemic preconditioning protects the heart against ischemia-reperfusion injury in chronic kidney disease in both males and females
Authors: Sárközy Márta , Márványkövi Fanni Magdolna , Szűcs Gergő , Kovács Zsuzsanna Z. A. , Szabó Márton R. , Gáspár Renáta , Siska Andrea , Kővári Bence , Cserni Gábor , Földesi Imre , Csont Tamás
Published: September 2021

Background

Uremic cardiomyopathy is a common cardiovascular complication of chronic kidney disease (CKD) characterized by left ventricular hypertrophy (LVH) and fibrosis enhancing the susceptibility of the heart to acute myocardial infarction. In the early stages of CKD, approximately 60% of patients are women. We aimed to investigate the influence of sex on the severity of uremic cardiomyopathy and the infarct size-limiting effect of ischemic preconditioning (IPRE) in experimental CKD.

Methods

CKD was induced by 5/6 nephrectomy in 9-week-old male and female Wistar rats. Two months later, serum and urine laboratory parameters were measured to verify the development of CKD. Transthoracic echocardiography was performed to assess cardiac function and morphology. Cardiomyocyte hypertrophy and fibrosis were measured by histology. Left ventricular expression of A- and B-type natriuretic peptides (ANP and BNP) were measured by qRT-PCR and circulating BNP level was measured by ELISA. In a subgroup of animals, hearts were perfused according to Langendorff and were subjected to 35 min global ischemia and 120 min reperfusion with or without IPRE (3 × 5 min I/R cycles applied before index ischemia). Then infarct size or phosphorylated and total forms of proteins related to the cardioprotective RISK (AKT, ERK1,2) and SAFE (STAT3) pathways were measured by Western blot.

Results

The severity of CKD was similar in males and females. However, CKD males developed more severe LVH compared to females as assessed by echocardiography. Histology revealed cardiac fibrosis only in males in CKD. LV ANP expression was significantly increased due to CKD in both sexes, however, LV BNP and circulating BNP levels failed to significantly increase in CKD. In both sexes, IPRE significantly decreased the infarct size in both the sham-operated and CKD groups. IPRE significantly increased the phospho-STAT3/STAT3 ratio in sham-operated but not in CKD animals in both sexes. There were no significant differences in phospho-AKT/AKT and phospho-ERK1,2/ERK1,2 ratios between the groups.

Conclusion

The infarct size-limiting effect of IPRE was preserved in both sexes in CKD despite the more severe uremic cardiomyopathy in male CKD rats. Further research is needed to identify crucial molecular mechanisms in the cardioprotective effect of IPRE in CKD.
A novel read methodology to evaluate the optimal dose of 68Ga-satoreotide trizoxetan as a PET imaging agent in patients with gastroenteropancreatic neuroendocrine tumours: a phase II clinical trial
Authors: Miller Colin G. , Grønbæk Henning , Virgolini Irene , Kjaer Andreas , Terve Pierre , Bahri Shadfar , Iversen Peter , Svirydenka Hanna , Rohban Thomas , McEwan Sandy
Published: September 2021

Background

68Ga-satoreotide trizoxetan is a novel somatostatin receptor antagonist exhibiting higher tumour-to-background ratios and sensitivity compared to 68Ga-DOTATOC. This randomised, 2 × 3 factorial, phase II study aimed to confirm the optimal peptide mass and radioactivity ranges for 68Ga-satoreotide trizoxetan, using binary visual reading. To that end, 24 patients with metastatic gastroenteropancreatic neuroendocrine tumours received 5–20 µg of 68Ga-satoreotide trizoxetan on day 1 of the study and 30–45 µg on day 16–22, with one of three gallium-68  radioactivity ranges (40–80, 100–140, or 160–200 MBq) per visit. Two 68Ga-satoreotide trizoxetan PET/CT scans were acquired from each patient post-injection, and were scored by experienced independent blinded readers using a binary system (0 for non-optimal image quality and 1 for optimal image quality). For each patient pair of 68Ga-satoreotide trizoxetan scans, one or both images could score 1.

Results

Total image quality score for 68Ga-satoreotide trizoxetan PET scans was lower in the 40–80 MBq radioactivity range (56.3%) compared to 100–140 MBq (90.6%) and 160–200 MBq (81.3%). Both qualitative and semi-quantitative analysis showed that peptide mass (5–20 or 30–45 µg) did not influence 68Ga-satoreotide trizoxetan imaging. There was only one reading where readers diverged on scoring; one reader preferred one image because of higher lesion conspicuity, and the other reader preferred the alternative image because of the ability to identify more lesions.

Conclusions

Binary visual reading, which was associated with a low inter-reader variability, has further supported that the optimal administered radioactivity of 68Ga-satoreotide trizoxetan was 100–200 MBq with a peptide mass up to 50 µg.

Trial registration ClinicalTrials.gov, NCT03220217. Registered 18 July 2017, https://clinicaltrials.gov/ct2/show/NCT03220217
EANM recommendations based on systematic analysis of small animal radionuclide imaging in inflammatory musculoskeletal diseases
Authors: Aarntzen Erik H. J. G. , Noriega-Álvarez Edel , Artiko Vera , Dias André H. , Gheysens Olivier , Glaudemans Andor W. J. M. , Lauri Chiara , Treglia Giorgio , van den Wyngaert Tim , van Leeuwen Fijs W. B. , Terry Samantha Y. A.
Published: September 2021

Inflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings.
The metabolic parameters based on volume in PET/CT are associated with clinicopathological N stage of colorectal cancer and can predict prognosis
Authors: Kido Hidenori , Kato Shunsuke , Funahashi Kimihiko , Shibuya Kazutoshi , Sasaki Yousuke , Urita Yoshihisa , Hori Masaaki , Mizumura Sunao
Published: September 2021

Background

A combination of positron emission tomography and computed tomography (PET/CT) is an important modality for the diagnosis of carcinoma. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been reported as metabolic parameters in PET/CT since the late 1990s, and they are expected to be useful in diagnosing diverse cancers and as prognostic biomarkers. We evaluated the potential of these parameters in the prognosis of colorectal cancer (CRC) by comparing them with conventional parameters, including the maximum standardized uptake value (SUVmax). We enrolled 84 patients who underwent surgery for CRC without distal metastasis between April 2015 and April 2019. SUVmax, MTV, and TLG were measured by 18F-fluorodeoxyglucose (FDG)-PET/CT. To find an optimal threshold value related to prognosis, the volume of interest in the primary carcinoma was measured at fixed relative and absolute thresholds based on SUVmax (30%, 40%, and 50%; 2.5, 3.0, and 3.5, respectively), tumor-to-liver standardized uptake ratios, TLR (1.0, 1.5, and 2.0), and SUV normalized to lean body mass, SUL (2.0, 2.5, and 3.0). After classifying the patients into two groups according to pathological N stage, the optimal threshold values of all metabolic parameters were compared between groups using a non-parametric comparison test.

Result

The most suitable thresholds for MTV were a SUVmax of 3.5 and a TLR 2.0. TLG with a SUVmax value of 40% showed the most significant difference. The MTV standard uptake ratio of 2.0 was significantly associated with pathological N stage.

Conclusion

Our results suggest that an MTV TLR 2.0 on PET/CT reflects pathological N stage in local patients with CRC.
Recursion formulas for certain quadruple hypergeometric functions
Authors: Younis Jihad , Verma Ashish , Aydi Hassen , Nisar Kottakkaran Sooppy , Alsamir Habes
Published: September 2021

A remarkably large number of hypergeometric (and generalized) functions and a variety of their extensions have been presented and investigated in the literature by many authors. In this paper, we introduce five new hypergeometric functions in four variables and then establish several recursion formulas for these new functions. Some interesting particular cases and consequences of the main results are also considered.
Pharmacokinetic herb-drug interactions between Aidi injection and doxorubicin in rats with diethylnitrosamine-induced hepatocellular carcinoma
Authors: Lu Yuan , Pan Jie , Zhu Xiaoqing , Zhang Shuai , Liu Chunhua , Sun Jia , Li Yueting , Chen Siying , Huang Jing , Cao Chuang , Wang Yonglin , Li Yongjun , Liu Ting
Published: September 2021

Background

Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC.

Methods

Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Results

Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI.

Conclusions

Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.
The Wnt signaling pathway in tumorigenesis, pharmacological targets, and drug development for cancer therapy
Authors: Wang Zhuo , Zhao Tingting , Zhang Shihui , Wang Junkai , Chen Yunyun , Zhao Hongzhou , Yang Yaxin , Shi Songlin , Chen Qiang , Liu Kuancan
Published: September 2021

Wnt signaling was initially recognized to be vital for tissue development and homeostasis maintenance. Further studies revealed that this pathway is also important for tumorigenesis and progression. Abnormal expression of signaling components through gene mutation or epigenetic regulation is closely associated with tumor progression and poor prognosis in several tissues. Additionally, Wnt signaling also influences the tumor microenvironment and immune response. Some strategies and drugs have been proposed to target this pathway, such as blocking receptors/ligands, targeting intracellular molecules, beta-catenin/TCF4 complex and its downstream target genes, or tumor microenvironment and immune response. Here we discuss the roles of these components in Wnt signaling pathway in tumorigenesis and cancer progression, the underlying mechanisms that is responsible for the activation of Wnt signaling, and a series of drugs targeting the Wnt pathway provide multiple therapeutic values. Although some of these drugs exhibit exciting anti-cancer effect, clinical trials and systematic evaluation should be strictly performed along with multiple-omics technology.
The influence of light and relative humidity on the formation of epsomite in cadmium yellow and French ultramarine modern oil paints
Authors: Harrison Jessie , Lee Judith , Ormsby Bronwyn , Payne David J.
Published: September 2021

The effect of relative humidity (RH) and light on the development of epsomite (MgSO4·7H2O) in Winsor & Newton cadmium yellow (CY) and French ultramarine (FU) artists’ oil colour paints was investigated. Tube paint samples were aged for 12 weeks at either 50% or 75% RH, under ambient light (200 ± 1 lx), elevated light (11,807 ± 328 lx), and near-dark conditions. Aged paint samples were characterised using light microscopy (LM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Results indicated that ageing at 75% RH in elevated light conditions, promoted the formation of hydrated magnesium sulphate (MgSO4·6–7H2O) crystals on the surface of both paints. The formation of sodium sulphate (Na2SO4) as a degradation product of French ultramarine oil paints after ageing at 75% RH in elevated light conditions is described. The formation of magnesium sulphate crystals in the absence of elevated SO2 is a new finding. For both cadmium yellow and French ultramarine oil paints, the pigments present are a likely source of sulphur, enabling the formation of sulphate salts, i.e., cadmium sulphide (CdS) yellow, and the sulphur radical anions (S3
−) present in ultramarine pigment. Sulphur-containing impurities arising from pigment manufacture are an additional possibility. It was previously theorised that epsomite formation in water-sensitive twentieth century oil paintings resulted from exposure to the elevated atmospheric sulphur dioxide (SO2) levels of the 1950s–1970s. This study demonstrates that hydromagnesite-containing cadmium yellow and French ultramarine oil paints of any period may be vulnerable to water-soluble sulphate salts formation and that this process is promoted by exposure to light and high (75%) RH environments. The formation of sulphate salts as a degradation product is known to contribute toward the development of water sensitivity of modern oil paintings which can pose significant challenges to conservation. Therefore this study highlights the importance of minimising exposure to light and raised relative humidity for paintings containing such CY and FU oil paint passages, to help slow down these types of degradation phenomena which have implications for preservation.
Cumulative deviation of a subpopulation from the full population
Authors: Tygert Mark
Published: September 2021

Assessing equity in treatment of a subpopulation often involves assigning numerical “scores” to all individuals in the full population such that similar individuals get similar scores; matching via propensity scores or appropriate covariates is common, for example. Given such scores, individuals with similar scores may or may not attain similar outcomes independent of the individuals’ memberships in the subpopulation. The traditional graphical methods for visualizing inequities are known as “reliability diagrams” or “calibrations plots,” which bin the scores into a partition of all possible values, and for each bin plot both the average outcomes for only individuals in the subpopulation as well as the average outcomes for all individuals; comparing the graph for the subpopulation with that for the full population gives some sense of how the averages for the subpopulation deviate from the averages for the full population. Unfortunately, real data sets contain only finitely many observations, limiting the usable resolution of the bins, and so the conventional methods can obscure important variations due to the binning. Fortunately, plotting cumulative deviation of the subpopulation from the full population as proposed in this paper sidesteps the problematic coarse binning. The cumulative plots encode subpopulation deviation directly as the slopes of secant lines for the graphs. Slope is easy to perceive even when the constant offsets of the secant lines are irrelevant. The cumulative approach avoids binning that smooths over deviations of the subpopulation from the full population. Such cumulative aggregation furnishes both high-resolution graphical methods and simple scalar summary statistics (analogous to those of Kuiper and of Kolmogorov and Smirnov used in statistical significance testing for comparing probability distributions).
Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital
Authors: Adachi Koichiro , Sugitani Yuki , Unita Ryo , Yoshida Kosuke , Beppu Satoru , Terashima Mariko , Fujii Masaya , Shimizu Makiko , Yamazaki Hiroshi
Published: September 2021

Background

Loxoprofen is a propionic acid derivative and is the most widely prescribed non-steroidal anti-inflammatory drug in Japan. Loxoprofen is generally considered to be relatively nontoxic.

Case presentation

A 33-year-old man (body weight, 55 kg) who intentionally took an overdose of 100 tablets of loxoprofen (6000 mg) as a suicide attempt was emergently admitted to Kyoto Medical Center. On arrival, the patient was suffering disorders of consciousness. His plasma concentrations of loxoprofen and its reduced trans-alcohol metabolite were 52 and 24 μg/mL, 3.7 and 2.3 μg/mL, 0.81 and 0.54 μg/mL, and 0.015 and 0.011 μg/mL, respectively, at 4, 26, 50, and 121 h after the oral overdose. The observed apparent terminal elimination half-life of loxoprofen during days 1 and 2 of hospitalization was in the range 6–12 h, which is several times longer than the reported normal value. This finding implied nonlinearity of loxoprofen pharmacokinetics over the current 100-fold dose range, which could affect the accuracy of values simulated by a simplified physiologically based pharmacokinetic (PBPK) model founded on data from a normal dose of 60 mg. The reasons for the delayed eliminations from plasma of loxoprofen and its trans-alcohol metabolite in this case are uncertain, but slight renal impairment (low eGFR values) developed on the second and third hospital days and could be a causal factor.

Conclusions

Because the patient’s level of consciousness had gradually improved, he was discharged on the fourth day of hospitalization. The virtual plasma exposures of loxoprofen and its reduced trans-alcohol metabolite estimated using the current simplified PBPK model were lower than the measured values in the overdose case. The present results based on drug monitoring data and pharmacokinetic predictions could serve as a useful guide in cases of loxoprofen overdose.
Colloid carcinoma derived from intraductal papillary mucinous neoplasm of the pancreatic head with calcification: A case report and literature review
Authors: Miyamoto Ryoichi , Amikura Katsumi , Matsudaira Shinichi , Ishida Hiroyuki , Ogura Toshiro , Takahashi Amane , Kihara Atsushi , Kanda Hiroaki , Kawashima Yoshiyuki
Published: September 2021

Background

Colloid carcinoma derived from intraductal papillary mucinous neoplasm (IPMN) of the pancreatic head with prominent calcification is exceedingly rare. Only a few studies about this entity have been reported in the literature. Therefore, its biological behavior, appropriate treatment modalities, and overall patient prognosis remain largely unclear. In this report, we present a case of a resected colloid carcinoma derived from IPMN with prominent calcification. In addition, we review the relevant literature and discuss the clinical management of colloid carcinoma derived from IPMN with prominent calcification, including the histopathological features.

Case presentation

A 75-year-old man presented with a pancreatic tumor measuring 58 mm on the head of the pancreas that was incidentally detected by abdominal ultrasonography. Abdominal computed tomography and endosonography revealed a multilobular cystic lesion with a 17 mm mural nodule in the pancreatic head. Furthermore, prominent calcification was observed on part of the cyst wall. Magnetic resonance cholangiopancreatography showed a multilobular cyst in the branch duct lacking communication between the cystic lesion and the main pancreatic duct. Thus, the lesion was diagnosed as intraductal papillary mucinous carcinoma (IPMC) with a preoperative classification of T1N0M0 stage IA according to the 8th Union for International Cancer Control (UICC) guidelines, and the patient underwent conventional pancreatoduodenectomy. The resected specimen was microscopically found to contain colloid carcinoma, probably derived from IPMN. In addition, marked calcification was confirmed in the partition wall of the cystic mass. The postoperative course was uneventful, and no evidence of recurrence or metastasis was observed after 10 months of follow-up.

Conclusions

We consider that colloid carcinoma derived from IPMN should be differentially diagnosed as a pancreatic multilobular cystic lesion with prominent calcification that shows no sign of systemic chronic pancreatitis.
Polymorphism in the symmetries of gastric pouch arrangements in the sea anemone D. lineata
Authors: Sarper Safiye E. , Hirai Tamami , Matsuyama Take , Kuratani Shigeru , Fujimoto Koichi
Published: September 2021

Symmetry in the arrangement of body parts is a distinctive phylogenetic feature of animals. Cnidarians show both bilateral and radial symmetries in their internal organs, such as gastric pouches and muscles. However, how different symmetries appear during the developmental process remains unknown. Here, we report intraspecific variations in the symmetric arrangement of gastric pouches, muscles, and siphonoglyphs, the Anthozoan-specific organ that drives water into the organism, in D. lineata (Diadumenidae, Actiniaria). We found that the positional arrangement of the internal organs was apparently constrained to either biradial or bilateral symmetries depending on the number of siphonoglyphs. Based on the morphological observations, a mathematical model of internal organ positioning was employed to predict the developmental backgrounds responsible for the biradial and bilateral symmetries. In the model, we assumed that the specification of gastric pouches is orchestrated by lateral inhibition and activation, which results in different symmetries depending on the number of siphonoglyphs. Thus, we propose that a common developmental program can generate either bilateral or biradial symmetries depending on the number of siphonoglyphs formed in the early developmental stages.
Delivery and evaluation of an e-Learning framework through computer-aided analysis of learners’ reflection text in a teacher development course
Authors: Kong Siu-Cheung
Published: September 2021

This study aimed at proposing an e-Learning framework in school education. The proposed framework consisted of technology and pedagogy dimensions. The method of computer-aided analysis of learners’ reflection text was used to evaluate the pedagogical delivery of the proposed framework. A study involving 33 in-service teachers in a teacher development course was conducted to investigate the effectiveness of the pedagogical delivery. The computer-aided analysis of learners’ reflection text on “what is e-Learning” before and after the teaching of the course showed that learners deepened their understanding about the technology use and the importance of pedagogy in e-Learning, to consider more the component on theories/models/principles/strategies in pedagogical design and practices, emphasize more the reflection and discussion in learning and teaching activities, and also realize more the possibility of pedagogical decision-making using data collected from online learning. The questionnaire survey and focus group interview with learners also indicated that the pedagogical delivery of the e-Learning framework with the support from the computer-aided analysis of learners’ reflection text coupled with hierarchical visualization of analysis results was positively perceived. The research findings contribute pioneering insights into the use of a computer-aided approach for an accurate and efficient evaluation in teacher development courses on e-Learning.
Maternal death due to ruptured uterus consequent to abruptio placentae: 2 case reports
Authors: Jaiswani Arun Kumar , Tripathi Utkarsh , Bansal Snigdha Jain , Singh Vartika , Jaiswani Kanchan
Published: September 2021

Background

Abruptio placentae is a complication of pregnancy that can lead to uterine rupture, increasing maternal and fetal mortality, especially when there is a lack of medical outreach in remote areas.

Case presentation

We present two maternal deaths due to uterine rupture in a term pregnancy consequent to abruptio placentae. In one case, the uterus ruptured at the previous lower segment Caesarean section (LSCS) scar site and in another over the lateral wall of Couvelaire uterus. In both cases, the fetus was partially lying outside the uterus in the peritoneal cavity, and there was a massive retro-placental clot.

Conclusions

Early identification of high-risk factors, followed by institutional delivery, may reduce maternal and fetal mortality due to abruption followed by uterine rupture.