bluuebunny/crossref_metadata_2025 huggingface dataset:
Gefitinib induced Pemphigus Vulgaris with PRIDE complex
Authors: Kumar Chaudhary Raushan , Bhandari Ramesh , Doshi Bhavana , Karoli Satish S , Spoorthi Marripalli Sowmya , Ganachari MS
Published: February 2022

Introduction: Pemphigus Vulgaris is a rare, noncommunicable, non-hereditary fatal autoimmune dermatological manifestation in which a painful blister initiates from the oral cavity. PRIDE complex stands for Papulopustules or paronychia, regulatory abnormality of hair and nails, itching, and dryness due to inhibition of EGFR. Both of these mucocutaneous manifestations are rare and are often caused by drugs. Case report: Our case reports 53-year-old patient presented with multiple crusted plaques, multiple hyperpigmented macules to patches, Solitary fluid-filled lesions on several parts of the body, and numerous erosions positive over buccal mucosa on initial follow up which was diagnosed as Pemphigus Vulgaris with PRIDE complex induced by Gefitinib. Management and outcome: The patient was treated with almost all possible treatment options, i.e., both steroids plus adjuvant therapy for pemphigus and antihistaminic, antibiotics, moisturizer, and lotions for PRIDE complex. The patient was initially admitted for infusion of the first dose of rituximab and later for management of flare-up condition and infusion of the second dose of rituximab infusion. Discussion: The complexity of the management of Pemphigus Vulgaris and PRIDE complex demands adequate monitoring of the patient's anti-cancerous therapy by clinical pharmacists, which can impact the clinical outcomes by providing pharmaceutical care and minimize the economic burden.
Heritability and Clinical Characteristics of Neuropsychological Profiles in Youth With and Without Elevated ADHD Symptoms
Authors: Arnett Anne B. , McGrath Lauren M. , Flaherty Brian P. , Pennington Bruce F. , Willcutt Erik G.
Published: February 2022

Objective:

In the last decade, there has been an increase in research that aims to parse heterogeneity in attention deficit hyperactivity disorder (ADHD). The current study tests heritability of latent class neuropsychological subtypes.

Method:

Latent class analysis was used to derive subtypes in a sample of school-age twins ( N = 2,564) enriched for elevated ADHD symptoms.

Results:

Five neuropsychological profiles replicated across twin 1 and twin 2 datasets. Latent class membership was heritable overall, but heritability varied by profile and was lower than heritability of ADHD status. Variability in neuropsychological performance across domains was the strongest predictor of elevated ADHD symptoms. Neuropsychological profiles showed distinct associations with age, psychiatric symptoms and reading ability.

Conclusion:

Neuropsychological profiles are associated with unique neurocognitive presentations, but are not strong candidate endophenotypes for ADHD diagnosis.
Nocebo Response in Attention Deficit Hyperactivity Disorder: Meta-Analysis and Meta-Regression of 105 Randomized Clinical Trials
Authors: Ramírez-Saco David , Barcheni Maghie , Cunill Ruth , Sáez Marc , Farré Magí , Castells Xavier
Published: February 2022

Objective:

To determine nocebo response in ADHD, identify covariates modifying nocebo response, and study the relationship between nocebo response and drug safety.

Method:

Systematic review of randomized, double-blind, placebo-controlled clinical trials (RCT) investigating the efficacy and safety of pharmacological interventions for ADHD patients. The influence of covariates was studied using meta-regression.

Results:

A total of 105 studies with 8,743 patients in placebo arms were included. Slightly over half (55.5%) of the patients experienced adverse events (AE) while receiving placebo. Nocebo response was associated positively with age, treatment length and method for collecting AEs. Studies with the largest nocebo response showcased the greatest drug response and the best outcome for drug safety.

Conclusion:

Nocebo response in ADHD RCTs is remarkable, showing a positive relationship with drug response, and a negative relationship with drug safety.
The ‘onto-logics’ of perspectival multi-naturalism: A realist critique
Authors: Bråten Eldar
Published: February 2022

In this article, I argue for a realist anthropology based on the recognition of mind-independent reality; pitching this premise against concerted anti-dualist tendencies in contemporary anthropological thinking. I spell out core analytical entailments of these, in my view, profoundly conflicting premises. In particular, I focus on perspectival multi-naturalism, arguing that despite adherents’ claims to reinvigorate studies of ‘ontology’, this approach instead exaggerates epistemological dimensions. When assessed from a realist stance, its ground position engenders a series of epistemic fallacies by which the ontological is, effectively, subordinated under epistemology. Advocates’ reluctance to appreciate a distinction between mind and mind-independent reality entails a profound contraction of perspective in terms of empirical and methodological scope, and, analytically, a disregard for ontological complexity and depth, thus curtailing the importance of anthropology in wider academic discourse.
Over-all performance analysis of a dual-entry turbocharger compressor with variable geometry orifice
Authors: Zhao Ben , Shang Wentao , Ke Hongying
Published: February 2022

A dual-entry turbocharger compressor has a dual-entry impeller with the same blades on both sides of an impeller disc. Flows merge into a common diffuser from two sides of the disc, contributing to over-all mass flow rate of the compressor, and the mass flow rate at either side is distributed with self-adaptation. With the self-adaptive distribution, the difference in the mass flow rates between two impeller sides is slight at the near choke point and gradually raises with the reduction of the compressor over-all mass flow rate. The increased mass flow rate difference can prematurely trigger compressor instability, even surge. When a turbocharged engine operates at high-altitude locations, this becomes a serious issue so that the engine fails to work. To overcome the problem, we propose a new method of using a variable geometry orifice plate at the rear entry of the dual-entry impeller. The orifice can improve the mas flow rate distribution at both impeller sides. The dual-entry compressor performance variations prove the effectiveness of the orifice in terms of the compressor stability boundary extension and suggest a control strategy of variable geometry orifice. The mechanism of the orifice extending the compressor stall margin is the pressure gradient change in front of the rear inducer. An experiment was conducted on a centrifugal compressor, and the test results support the numerical findings.
Children’s language play as collaborative improvisations–rethinking paths to literacy
Authors: Holm Lars , Ahrenkiel Annegrethe
Published: February 2022

Inspired by research in language play and linguistic ethnography, this article examines children’s language play in early childhood education and care (ECEC) as a locally situated generic practice created through children’s semiotic repertoires. The article is based on video-recorded linguistic ethnographic fieldwork in a Danish day care centre. By analysing two play sequences with 3–4 year old children, we examine how the children align to each other in an improvised way while co-creating social worlds. The multimodal micro-ethnographic analysis reveals how an assemblage of chunks of language, musicality, movements, affect and materiality is constitutive of children’s language play, and how language play appears as an integral part of children’s local language practices. The children’s use of a broad range of semiotic repertoires in language play represents a unique practice that might enhance our theoretical and empirical understanding of child language. We argue that empirical insight into children’s language play has the potential for developing paths to language and literacy that challenge the often highly prioritised ‘precursors to literacy’ strategy as the central aim for language learning in ECEC.
Narrative, the Chilean social explosion, and affective geography: on the catharsis of the ‘artistic candlelight vigil’ of Valparaíso
Authors: Woods Maxwell
Published: February 2022

In response to State violence during the so-called ‘Chilean social explosion’ [ estallido social], the Valparaíso Coordinator of Cultural Action [ Coordinadora acción cultural Valparaíso] (CAC) in collaboration with other cultural groups of Valparaíso as well as other artists who spontaneously improvised during the performance organized on 31 October 2019 an ‘artistic candlelight vigil for human rights’ that passed through the center of the Chilean coastal town of Valparaíso, one ostensible effect of which was to rewrite the affective geography of Valparaíso in response to the violence that had erupted in the city during the 2 weeks prior. This article examines the relationship between this candlelight vigil, the revolutionary autonomist foundations of the Chilean social explosion, and the affective geography of Valparaíso, in addition to developing a broader theorization of the relationship between narrative, revolution, the politics of autonomy, and affective geography through this analysis. In the end, this article makes a double intervention: (1) The ‘artistic candlelight vigil’ in Valparaíso on 31 October 2019 memorializing the victims of State violence was an effective catharsis of the discordant affects held by Chilean protestors during the social explosion. (2) This example of catharsis demonstrates a new resolution to the relationship between narrative, revolution, and affective geography by proposing that art can work through the discordant affects of a polity in order to arrive at an autonomous urban communality from below.
Public Impacts from Elite Audit Experiments: Aggregate and Response Delay Harms
Authors: Desposato Scott
Published: February 2022

What are the potential harms from elite audit experiments? Such studies seem genuinely harmless and all in a day’s work for elites. In addition, such studies may provide valuable information about elites’ performance and service to their publics. However, there are a number of potential harms of such studies which are generally not captured by the standard human subjects framework. In this essay, I consider the various harms that can result from excessive experimentation on elites. I identify several previously ignored public harms, including aggregate and response delay harms. I offer several potential strategies to assuage and avoid these harms.
COVID-19 Preventive Practices and their Relation to Knowledge, Attitude, and Risk Perception: Results of a Telephone Survey in Ethiopia
Authors: Kebede Sindu W. , Geda Nigatu R. , Legesse Belaineh , Fekadu Belay
Published: February 2022

The first case of coronavirus was reported in Ethiopia on March 13, 2020, and the number of cases has been rising continually. This study examined the level and correlates of risk perception, knowledge, and attitude in relation to COVID-19 in Ethiopia. It also assessed the level of adoption of various preventive practices and their association with risk perception, knowledge, and attitude. The rapid assessment was made using data collected in a telephone survey. Correlates of knowledge, attitude, and risk/impact perception were assessed using Poisson regression. Econometric estimation was used to identify the correlations of knowledge, attitude, and risk/impact perception scores with the adoption of preventive practices. A total of 1,037 respondents participated in the survey. Although the level of knowledge about the pandemic was generally good among the population, a significant proportion of the population (the elderly and less educated) still do not have correct knowledge about the disease symptoms and means of transmission. Some respondents revealed unfavorable attitudes about the virus, and around two-thirds of respondents did not perceive the fast-expanding pandemic to be a major risk. A significant correlation was found between the adoption of preventive practices and knowledge, attitude, and impact perception in relation to COVID-19. Health education interventions would be more effective if they were to target certain demographic groups, such as the elderly and less educated, whose overall average knowledge about COVID-19 is lower. The use of a multiple media outlet for disseminating information on COVID-19 may improve choices and enhance knowledge.
Short-Term Complications Following Total Ankle Arthroplasty and Associated Risk Factors: A NSQIP Database Analysis
Authors: Kwon Nicholas F. , Danilkowicz Richard M. , Kim Jaewhan , Grimm Nathan L. , Adams Samuel B.
Published: February 2022

Introduction

Total ankle arthroplasty (TAA) has become increasingly utilized over the past 20 years to treat osteoarthritis of the ankle. The efficacy and safety of this procedure has been previously reported, but relatively few studies have documented the risk of postoperative complications associated with TAA over the past 10 years. Thus, the aim of this study is to provide a current report on the safety of TAA, particularly in association with a number of preoperative risk factors.

Methods

A retrospective review of all patients in the American College of Surgeons National Surgical Quality Improvement Program database who underwent TAA between 2012 and 2018 was performed. A total of 1333 patients were included in this analysis. Penalized logistic regression to consider small numbers of the postoperative complications was used to identify factors associated with incidence of the complications.

Results

The rate of readmission and superficial wound infection were found to be 1.4% and 0.6%, respectively. Risk factors associated with a prolonged hospital stay were black race, Hispanic race, and smoking. Diabetes was associated with a significantly increased risk of readmission. Age, sex, body mass index, and steroid use were not associated with increased risk of postoperative complications.

Conclusion

In this study, the rate of surgical site infection and readmission in TAA was found to be relatively low, compared to published data on total knee arthroplasty and total hip arthroplasty. Both race and smoking increase the risk of prolonged hospital stay, while diabetes increases the risk of readmission.

Levels of Evidence:

Level III, retrospective comparative trial.
Time interval between alfentanil and rocuronium administration necessary to prevent rocuronium-induced withdrawal movement
Authors: Wang Xiao-Dan , Chen Ling-yang , Zhou Chun-Lian , Cong Hai-tao , Chen Nan-jin , Wang Ming-Cang
Published: February 2022

Background

We aimed to determine the time interval between alfentanil and rocuronium administration, at a 50% probability of preventing pain-induced withdrawal movement from rocuronium injection (TimeAR50).

Methods

A total of 64 patients scheduled for general anesthesia were enrolled in this study (33 men and 31 women). Anesthesia was induced with target-controlled infusion of propofol, at an effect-site target concentration of 3 μg/mL. Then, alfentanil 15 μg/kg was injected for 30 s. After 60 s, rocuronium 0.6 mg/kg was administered to the first patient. The Dixon’s up-and-down method was used to determine the time interval for each subsequent patient (interval of 5 s). Mean arterial pressure (MAP) and heart rate (HR) were recorded at three time points: T0, pre-induction; T1, before rocuronium injection; and T2, 1 min after rocuronium injection.

Results

The TimeAR50 ± standard deviation (SD) was 5.6 ± 3.7 s and 21.9 ± 5.6 s in the male and female patients, respectively. Based on the probit regression, the TimeAR50 was 4.7 s (95% confidence interval [CI], 1.2–7.6 s) and 20.3 s (95% CI, 7.7–26.1 s) in the male and female patients, respectively. The TimeAR95 was 10.6 s (95% CI, 7.7–25.3 s) and 35.0 s (95% CI, 28.1–95.5 s) in the male and female patients, respectively, with significantly higher values in females than in males (P < 0.001). Compared with the T0, MAP and HR decreased significantly at T1 and T2 in both groups.

Conclusion

The TimeAR50 required for preventing rocuronium-induced withdrawal movement were 4.7 s and 20.3 s in male and female patients, respectively.

Trial registration

This study was registered with the Chinese Clinical Trials Registry on April 7, 2021 (URL:http://www.chictr.org.cn. Registry number:ChiCTR2100045137) .
Impact of neoadjuvant intensity-modulated radiation therapy on borderline resectable pancreatic cancer with arterial abutment; a prospective, open-label, phase II study in a single institution
Authors: Masui Toshihiko , Nagai Kazuyuki , Anazawa Takayuki , Sato Asahi , Uchida Yuichiro , Nakano Kenzo , Yogo Akitada , Kaneda Akihiro , Nakamura Naoto , Yoshimura Michio , Mizowaki Takashi , Uza Norimitsu , Fukuda Akihisa , Matsumoto Shigemi , Kanai Masashi , Isoda Hiroyoshi , Mizumoto Masaki , Seo Satoru , Hata Koichiro , Taura Kojiro , Kawaguchi Yoshiya , Takaori Kyoichi , Uemoto Shinji , Hatano Etsuro
Published: February 2022

Background

Borderline resectable pancreatic cancer (BRPC) is a category of pancreatic cancer that is anatomically widely spread, and curative resection is uncommon with upfront surgery. Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that delivers precise radiation to a tumor while minimizing the dose to surrounding normal tissues. Here, we conducted a phase 2 study to estimate the curability and efficacy of neoadjuvant chemoradiotherapy using IMRT (NACIMRT) for patients with BRPC with arterial abutment (BRPC-A).

Methods

A total of 49 BRPC-A patients were enrolled in this study and were treated at our hospital according to the study protocol between June 2013 and March 2021. The primary endpoint was microscopically margin-negative resection (R0) rates and we subsequently analyzed safety, histological effect of the treatment as well as survivals among patients with NACIMRT.

Results

Twenty-nine patients (59.2%) received pancreatectomy after NACIMRT. The R0 rate in resection patients was 93.1% and that in the whole cohort was 55.1%. No mortality was encountered. Local therapeutic effects as assessed by Evans classification showed good therapeutic effect (Grade 1, 3.4%; Grade 2a, 31.0%; Grade 2b, 48.3%; Grade 3, 3.4%; Grade 4, 3.4%). Median disease-free survival was 15.5 months. Median overall survival in the whole cohort was 35.1 months. The only independent prognostic pre-NACIMRT factor identified was serum carbohydrate antigen 19–9 (CA19-9) > 400 U/ml before NACIMRT.

Conclusions

NACIMRT showed preferable outcome without significant operative morbidity for BRPC-A patients. NACIMRT contributes to good local tumor control, but a high initial serum CA19-9 implies poor prognosis even after neoadjuvant treatment.

Trial Registration

UMIN-CTR Clinical Trial: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011776

Registration number: UMIN000010113.

Date of first registration: 01/03/2013,
Growth of exclusively breastfed small for gestational age term infants in the first six months of life: a prospective cohort study
Authors: Nurani Neti , Wibowo Tunjung , Susilowati Rina , Hastuti Janatin , Julia Madarina , Van Weissenbruch Mirjam M.
Published: February 2022

Background

Compared to their appropriate-for-gestational-age (AGA) peers, small-for-gestational-age (SGA) infants are prone to growth deficits. As the first 6 months of exclusive breastfeeding is generally recommended, it is essential to understand how this intervention might impact SGA infants’ growth. This study aims to assess growth of exclusively breastfed SGA term infants in the first 6 months of life.

Methods

A prospective cohort study was conducted on term infants born in Dr. Sardjito General Hospital and two private hospitals in Yogyakarta, Indonesia. SGA was defined as birth weight less than the 10th percentile according to Fenton criteria. Weight, length, and head circumference (HC) were measured at birth and monthly until 6 months old.

Results

A total of 39 AGA and 17 SGA term infants who were exclusively breastfed in their first 6 months were included and followed. In SGA compared to AGA, birth weight, length, and HC (mean ± SD) were significantly lower (p < 0.001). During the first 6 months, the SGAs grew in weight and length in parallel with the AGAs. At sixth months of age, the weight and length (mean ± SD) of the SGAs were significantly lower compared to the AGAs (p < 0.001). However, HC (mean ± SD) of SGAs grew significantly faster than the AGAs (p < 0.005). At sixth months of age, there were no significant differences in HC between the two groups (p = 0.824).

Conclusions

In the first 6 months, exclusively breastfed SGA term infants, in contrast to weight and length, only show catch up growth in HC, leading to HC comparable to their AGA peers at the age of 6 months.
Cell-free culture supernatants of Lactobacillus spp. and Pediococcus spp. inhibit growth of pathogenic Escherichia coli isolated from pigs in Thailand
Authors: Kaewchomphunuch Thotsapol , Charoenpichitnunt Thunyathorn , Thongbaiyai Varissara , Ngamwongsatit Natharin , Kaeoket Kampon
Published: February 2022

Background

Pathogenic Escherichia coli (E. coli) is an important causative agent for infectious diseases in pigs and causes significant economic loss. The global concern of antimicrobial resistance of bacteria raises awareness of the alternative ways of using antimicrobial peptides (AMPs). The study was aimed to identify and test the efficacy of AMPs from Lactobacillus spp. against the growth of pathogenic E. coli isolated from pigs in Thailand. Briefly, cell-free culture supernatants (CFCS) from 3 strains of lactic acid bacteria (LAB) consisting of Lactobacillus acidophilus (strain KMP), Lactobacillus plantarum (strain KMP), and Pediococcus pentosaceus (strain KMP) were tested against pathogenic E. coli via agar well diffusion assay in quadruplicates. The presence of a zone of inhibition (ZOI) around wells was evaluated at different incubation time. Acid and bile tolerance test was performed for bacterial viability in acid and bile salt conditions. In addition, LAB cross-streaking assay was evaluated for antagonist activity.

Results

The study showed that CFCS from L. acidophilus KMP, L. plantarum KMP, and P. pentosaceus KMP could inhibit the growth of pathogenic E. coli isolated from pigs in a time-dependent manner. To exemplify, the ZOI of L. plantarum KMP against E. coli (ETEC) at 8, 10, 12, 14, and 16 h incubation, were 26.6 ± 1.1, 24.9 ± 1.9, 22.5 ± 2.4, 20.3 ± 2.9, and 17.9 ± 3.3 mm, respectively. The ZOI was significantly different between 8, 10, 12, 14 h incubation, and the ZOI of the CFCS from L. plantarum KMP was larger than others (P-value < 0.05). Furthermore, L. acidophilus KMP, L. plantarum KMP, and P. pentosaceus KMP showed viability in pH 3.0, 0.3, and 0.5% (w/v) bile salt concentration. They exhibited no antagonist activity among each other.

Conclusions

According to the results, the CFCS from LAB including L. acidophilus KMP, L. plantarum KMP and P. pentosaceus KMP can inhibit the growth of pathogenic E. coli, isolated from pigs in Thailand. The antimicrobial activity observed was incubation time dependent.
Pyrroline-5-Carboxylate Reductase 1: a novel target for sensitizing multiple myeloma cells to bortezomib by inhibition of PRAS40-mediated protein synthesis
Authors: Oudaert Inge , Satilmis Hatice , Vlummens Philip , De Brouwer Wouter , Maes Anke , Hose Dirk , De Bruyne Elke , Ghesquière Bart , Vanderkerken Karin , De Veirman Kim , Menu Eline
Published: February 2022

Background

Multiple myeloma (MM) remains an incurable cancer despite advances in therapy. Therefore, the search for new targets is still essential to uncover potential treatment strategies. Metabolic changes, induced by the hypoxic bone marrow, contribute to both MM cell survival and drug resistance. Pyrroline-5-carboxylate reductase 1 and 2 (PYCR1 and PYCR2) are two mitochondrial enzymes that facilitate the last step in the glutamine-to-proline conversion. Overexpression of PYCR1 is involved in progression of several cancers, however, its’ role in hematological cancers is unknown. In this study, we investigated whether PYCR affects MM viability, proliferation and response to bortezomib.

Methods

Correlation of PYCR1/2 with overall survival was investigated in the MMRF CoMMpass trial (653 patients). OPM-2 and RPMI-8226 MM cell lines were used to perform in vitro experiments. RPMI-8226 cells were supplemented with 13C-glutamine for 48 h in both normoxia and hypoxia (< 1% O2, by chamber) to perform a tracer study. PYCR1 was inhibited by siRNA or the small molecule inhibitor pargyline. Apoptosis was measured using Annexin V and 7-AAD staining, viability by CellTiterGlo assay and proliferation by BrdU incorporation. Differential protein expression was evaluated using Western Blot. The SUnSET method was used to measure protein synthesis. All in vitro experiments were performed in hypoxic conditions.

Results

We found that PYCR1 and PYCR2 mRNA expression correlated with an inferior overall survival. MM cells from relapsed/refractory patients express significantly higher levels of PYCR1 mRNA. In line with the strong expression of PYCR1, we performed a tracer study in RPMI-8226 cells, which revealed an increased conversion of 13C-glutamine to proline in hypoxia. PYCR1 inhibition reduced MM viability and proliferation and increased apoptosis. Mechanistically, we found that PYCR1 silencing reduced protein levels of p-PRAS40, p-mTOR, p-p70, p-S6, p-4EBP1 and p-eIF4E levels, suggesting a decrease in protein synthesis, which we also confirmed in vitro. Pargyline and siPYCR1 increased bortezomib-mediated apoptosis. Finally, combination therapy of pargyline with bortezomib reduced viability in CD138+ MM cells and reduced tumor burden in the murine 5TGM1 model compared to single agents.

Conclusions

This study identifies PYCR1 as a novel target in bortezomib-based combination therapies for MM.
High expression of TRIM24 predicts worse prognosis and promotes proliferation and metastasis of epithelial ovarian cancer
Authors: Zhang Liwei , Chen Hong , Ding Baijuan , Jiang Wei
Published: February 2022

Background

Tripartite Motif-Containing 24 (TRIM24) is a member of the tripartite motif family. TRIM24 is claimed aberrantly activated in a number of cancers, such as breast cancer, prostate cancer and lung cancer. However, the expression of TRIM24 in epithelial ovarian cancer (EOC) and its relationship with prognosis remain unclear. In this study, we investigated the expression pattern and underlying clinical significance of TRIM24 in EOC.

Results

Data from Oncomine and immunohistochemistry of tissue samples demonstrated that TRIM24 expression was obviously elevated in ovarian carcinoma compared with normal ovary tissues. Elevated TRIM24 expression was closely correlated with serum CA-125 (P = 0.0294), metastasis (P = 0.0022), FIGO (International Federation of Gynecology and Obstetrics) stage (P = 0.0068) and Ki-67 level (P = 0.0395). Kaplan–Meier survival analysis found that TRIM24 expression increased inversely with the clinical prognosis of patients with EOC. Moreover, colony formation and CCK-8 assays showed that TRIM24 promoted EOC cell growth, and tumorigenic experiments in nude mice showed that TRIM24 knockdown inhibited tumor growth in vivo. The Spearman’s correlations revealed that the expression of TRIM24 was significantly correlated with levels of Ki-67 (P = 0.01), at a correlation coefficient of 0.517. Wound-healing and transwell migration assays demonstrated TRIM24 facilitated cell migration. Mechanism studies showed that TRIM24 could promote the phosphorylation level of Akt and the process of EMT.

Conclusion

Our results confirmed that TRIM24 could predict poor prognosis of EOC patients and promote tumor progression by regulating Akt pathway and EMT. TRIM24 may be used as a new prognostic marker for EOC and may provide a new strategy for targeted therapy of epithelial ovarian cancer.
Glucosylceramide synthase inhibition reduces ganglioside GM3 accumulation, alleviates amyloid neuropathology, and stabilizes remote contextual memory in a mouse model of Alzheimer’s disease
Authors: Dodge James C. , Tamsett Thomas J. , Treleaven Christopher M. , Taksir Tatyana V. , Piepenhagen Peter , Sardi S. Pablo , Cheng Seng H. , Shihabuddin Lamya S.
Published: February 2022

Background

Gangliosides are highly enriched in the brain and are critical for its normal development and function. However, in some rare neurometabolic diseases, a deficiency in lysosomal ganglioside hydrolysis is pathogenic and leads to early-onset neurodegeneration, neuroinflammation, demyelination, and dementia. Increasing evidence also suggests that more subtle ganglioside accumulation contributes to the pathogenesis of more common neurological disorders including Alzheimer’s disease (AD). Notably, ganglioside GM3 levels are elevated in the brains of AD patients and in several mouse models of AD, and plasma GM3 levels positively correlate with disease severity in AD patients.

Methods

Tg2576 AD model mice were fed chow formulated with a small molecule inhibitor of glucosylceramide synthase (GCSi) to determine whether reducing glycosphingolipid synthesis affected aberrant GM3 accumulation, amyloid burden, and disease manifestations in cognitive impairment. GM3 was measured with LC-MS, amyloid burden with ELISA and amyloid red staining, and memory was assessed using the contextual fear chamber test.

Results

GCSi mitigated soluble Aβ42 accumulation in the brains of AD model mice when treatment was started prophylactically. Remarkably, GCSi treatment also reduced soluble Aβ42 levels and amyloid plaque burden in aged (i.e., 70 weeks old) AD mice with preexisting neuropathology. Our analysis of contextual memory in Tg2576 mice showed that impairments in remote (cortical-dependent) memory consolidation preceded deficits in short-term (hippocampal-dependent) contextual memory, which was consistent with soluble Aβ42 accumulation occurring more rapidly in the cortex of AD mice compared to the hippocampus. Notably, GCSi treatment significantly stabilized remote memory consolidation in AD mice—especially in mice with enhanced cognitive training. This finding was consistent with GCSi treatment lowering aberrant GM3 accumulation in the cortex of AD mice.

Conclusions

Collectively, our results indicate that glycosphingolipids regulated by GCS are important modulators of Aβ neuropathology and that glycosphingolipid homeostasis plays a critical role in the consolidation of remote memories.
MCGNet+: an improved motor imagery classification based on cosine similarity
Authors: Li Yan , Zhong Ning , Taniar David , Zhang Haolan
Published: February 2022

It has been a challenge for solving the motor imagery classification problem in the brain informatics area. Accuracy and efficiency are the major obstacles for motor imagery analysis in the past decades since the computational capability and algorithmic availability cannot satisfy complex brain signal analysis. In recent years, the rapid development of machine learning (ML) methods has empowered people to tackle the motor imagery classification problem with more efficient methods. Among various ML methods, the Graph neural networks (GNNs) method has shown its efficiency and accuracy in dealing with inter-related complex networks. The use of GNN provides new possibilities for feature extraction from brain structure connection. In this paper, we proposed a new model called MCGNet+, which improves the performance of our previous model MutualGraphNet. In this latest model, the mutual information of the input columns forms the initial adjacency matrix for the cosine similarity calculation between columns to generate a new adjacency matrix in each iteration. The dynamic adjacency matrix combined with the spatial temporal graph convolution network (ST-GCN) has better performance than the unchanged matrix model. The experimental results indicate that MCGNet+ is robust enough to learn the interpretable features and outperforms the current state-of-the-art methods.
Analysis of the variable factors affecting changes in the blood concentration of cyclosporine before and after transfusion of red blood cell concentrate
Authors: Uchida Masashi , Hanada Natsumi , Yamazaki Shingo , Takatsuka Hirokazu , Imai Chiaki , Utsumi Akari , Shiko Yuki , Kawasaki Yohei , Suzuki Takaaki , Ishii Itsuko
Published: February 2022

Background

The blood concentration of cyclosporine (CyA) is frequently elevated following the transfusion of red blood cell concentrate (RCC) to patients after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this retrospective study was to identify the variable factors affecting changes in the blood concentration of CyA before and after transfusion of RCC.

Methods

We enrolled 105 patients (age, 5–66 years) who received both CyA and transfusion after HSCT. The ratio of the measurement after transfusion to the measurement before transfusion was calculated for the hematocrit and blood concentration/dose ratio of CyA (termed the HCT ratio and the CyA ratio, respectively).

Results

The blood concentration/dose ratio of CyA was increased after transfusion compared with before transfusion (P < 0.001). The HCT ratio was significantly correlated with the CyA ratio (P = 0.23,P < 0.001). The HCT ratio, concomitant medication that could elevate CyA concentration after RCC transfusion, and difference in the alkaline phosphatase level between before and after transfusion (ΔALP) were explanatory variables associated with the variation in the CyA ratio. There was no correlation between the CyA concentration after transfusion and the change in the estimated glomerular filtration rate.

Conclusions

A change in the blood concentration/dose ratio of CyA was found to be associated with a change in the HCT, concomitant medication that could elevate CyA concentration after RCC transfusion, and ALP levels. If the HCT level rises significantly after RCC transfusion, clinicians and pharmacists should pay attention to changes in the blood CyA concentration.
A complicated case of myocardial infarction with nonobstructive coronary arteries with an underlying pheochromocytoma: a case report
Authors: Jung Sodam , Kang In Sook
Published: February 2022

Background

The signs and symptoms of pheochromocytoma can imitate those of many other diseases, which may result in confusion. Therefore, diagnosing and treating secondary hypertension due to pheochromocytoma in deteriorating patients becomes challenging.

Case presentation

A 63-year-old female patient presented to the emergency room with severe and progressive nausea. The initial diagnosis was an acute myocardial infarction based on ST-segment depression on electrocardiogram and elevated cardiac markers. Elective coronary angiography revealed nonobstructive coronary arteries. However, she suffered from a complicated clinical course for several weeks during her life-or-death crisis. She was subsequently diagnosed with a cerebral hemorrhage and a pheochromocytoma. It is unclear whether her initial presentation was due to the neurogenic stunned myocardium caused by a cerebral hemorrhage or type 2 myocardial infarction caused by a pheochromocytoma, or both. However, this case showed the significance of accurately diagnosing and treating underlying causes in patients presenting with myocardial infarction with nonobstructive coronary arteries. Early diagnosis and treatment of the pheochromocytoma may have prevented the complications experienced by the patient.

Conclusions

A catecholamine surge and blood pressure fluctuation caused severe complications. When a patient presents with an unusual clinical presentation, secondary hypertension due to pheochromocytoma should be suspected.
Demographics, clinical features, and prognosis of rare lymphoepithelioma-like carcinoma across different anatomic sites
Authors: Zhai Xiaoqian , Liu Jiewei , Lu Donghao , Zhou Qinghua
Published: February 2022

Background

Lymphoepithelioma-like carcinoma (LELC) is an unusual histological malignancy type. Due to the rarity of this disease, we used the Surveillance, Epidemiology, and End Results (SEER) database to investigate comprehensively and systematically the prognosis factor of LELC.

Methods

We identified 2079 patients diagnosed with LELC during 1973–2015 from the SEER database. LELC was classified according to the tumor site. We analyzed the clinical characteristics and estimated the hazard ratio (HR) of overall mortality of LELC at each site.

Results

The nasopharynx was the most frequent site where LELC (58%) occurred. A large percentage of nasopharyngeal and pulmonary LELC patients were of Asian descent (44.5 and 32.56%, respectively). Furthermore, the majority of LELC patients were rather young when diagnosed. However, urinary bladder LELC and digestive system LELC (mean age: 69.03 and 68.05 years, respectively) were mainly to be found in older patients. Then according to Kaplan–Meier survival analysis, we found that patients with pulmonary LELC had worse survival. After adjusting for clinical tumor characteristics, pulmonary LELC patients were at increased risk of overall mortality compared with nasopharyngeal LELC either at the localized stage (HR 3.12, 95% confidence interval [CI], 1.55–6.26. P < 0.01) or at the regional stage (HR 1.72, 95% CI 1.03–2.88 P = 0.04).

Conclusions

In conclusion, we found that urinary bladder and digestive system LELCs mainly were diagnosed in old people and different from other LELCs. Pulmonary LELC patients might have a bad prognosis. The origination site may represent a predictive factor for determining survival in patients with LELC.
Policy Brief 7: Reducing the social acceptability of wildlife trafficking through behaviour change interventions
Authors: Kassa Saba , Costa Jacopo , Lugolobi Robert , Baez Camargo Claudia
Published: February 2022

Behaviour change interventions aimed at reducing the social acceptability of wildlife trafficking are an important part of efforts to prevent wildlife crime. This policy brief summarises lessons learned about how to develop and frame effective messages in the context of these interventions, based on field work conducted in Uganda. 

A key first step is to narrowly identify the right target audience. While a general public awareness campaign may have its merits, it may be more effective to focus on those identified as most vulnerable to participating in wildlife trafficking, namely young men, those that live around wildlife trafficking hotspots and those involved in trade.

Second, it appears most promising to formulate messages that challenge narrow utilitarian perceptions of wildlife by highlighting the hidden costs of trafficking and its negative impact on the economy and the environment. Messages that focus on legal risks should showcase successes in detection and sanctions, especially in a context in which impunity is perceived to be high. Other messages that seek to challenge the overvalued benefits of engaging in wildlife trafficking in relation to wealth and social status should be carefully nuanced to avoid rejection.

Third, how we frame such messages is equally important. The research suggests that appealing to social identity and highlighting personal consequences are the most promising frames to adopt.

Overall, practitioners are advised to develop and test messages and approaches that are personal and precise.

This report was funded by PMI IMPACT, a grant award initiative of Philip Morris International (PMI). In the performance of their research, the authors maintained full independence from PMI. The views and opinions expressed in this document are those of the authors and do not necessarily reflect the views of PMI. Neither PMI, nor any of its affiliates, nor any person acting on their behalf may be held responsible for any use which may be made of the information contained herein.
Alliteration as a Rhythmic Device in Latin Literature: General Clarifications and Proposal for a New Vertical Variant, Alliteration Before or After the Caesura
Authors: Salvador-Gimeno Marina
Published: February 2022

In this article, two types of alliteration in Latin are analyzed: the one that occurs horizontally in the verse (Saepe Solet Scintilla Suos Se Spargere…, Lucr. 4.606) and the one that develops vertically in successive verses (Aurea … || Asper… || Arboris…, Lucr. 5.32–34 or … Annis || … hAbendo, || … ARatri || … ARuis, Lucr. 1.311–314). We propose a vertical variant that has not been studied to date and that we have called alliteration before or after caesura, insofar as it takes place between terms placed immediately before or after the caesura of two or more contiguous verses (…Manus |… ||… Memores |… ||… Musis |…, Claud. 26.5–7; or … | Palantia… || … | PRaeclara … || … | PRimum …, Lucr. 2.1029–1031); This article shows that both horizontal and vertical alliteration constitutes an element of delimitation and cohesion of contiguous hemistichs or verses.
THE HISTORY OF ORTHODOXY IN THE ARTICLES OF THE «YEARBOOK» OF THE STATE MUSEUM OF THE HISTORY OF RELIGION AND ATHEISM OF THE ACADEMY OF SCIENCES OF THE USSR
Authors: Pyzikov Denis D.
Published: February 2022

Nowadays the theme of the scientist’s place in the situation of ideological restrictions and censorship is still relevant. So, from this point of view, it is very important to speak about humanities in the USSR and separate propaganda and scientific research. Despite the politicization of the discourse, not all religious studies of the Soviet period were the product of agitation and propaganda of atheism. Materials on the history of Orthodoxy in the «Yearbook» of the Museum of the History of Religion and Atheism are considered as an example of a scientific approach.

The aim of this research is to determine the main topics and directions of research on the history of Orthodoxy in articles of periodical «Yearbook» of the Museum of the History of Religion and Atheism. Being an important part of the scientific potential of the St. Petersburg school of religious studies, the «Yearbook» covered topical issues on the history of religion in articles by the classics of Russian religious studies.

The author uses the method of analytical study of sources and the method of comparative historical analysis to study the problem.

As a result, we can conclude that, 1) depending on the object of research, the articles can be divided into thematic groups, 2) and the «Yearbook» itself was the personification of the creative and scientific work of the Museum of the History of Religion and Atheism of the USSR Academy of Sciences.

This suggests that we can look at Soviet religious studies through the wall of propaganda and discover science itself.
O narracji historii Kaszubów na wystawie stałej w Książnicy profesora Gerarda Labudy w Wejherowie
Authors: Hinc Michał
Published: February 2022

Artykuł przedstawia metodę narracyjną i narzędzia komunikacji o dziejach Kaszubów w nowej instytucji kultury na Pomorzu i Kaszubach — Bibliotece prof. Gerarda Labudy należącej do Muzeum Literatury i Muzyki Kaszubsko-Pomorskiej w Wejherowie. To właśnie ten badacz z Kaszub ustalił przed laty, że rozpoczynając naukowe badanie historii Kaszub należy pisać o dziejach Kaszubów jako historii gminy i etnosu pomorskiego. W ten sposób narracyjny zastosował się również zespół przygotowujący wystawę stałą w Bibliotece.
Tymczasowo zamknięte
Authors: Cieplińska-Jaglarz Anna
Published: February 2022

Niniejszy artykuł dotyka kwestii edukacji w muzeach podczas okresu pandemii, zarówno w czasie zupełnego zamknięcia muzeów dla zwiedzających, jak i podczas chwilowego otwarcia. Dynamiczny rozwój sytuacji, który zaskoczył wszystkich wpłynął na działalność muzeów, które jednak podjęły próbę dostosowania się do panujących warunków i nieustannie realizowały statutowe założenia, w tym edukację muzealną. Działania edukacyjne podejmowane były w dużej mierze drogą on-line, z wykorzystaniem wszelkich rozwiązań technicznych i cyfrowych. Muzealnicy jednak niejednokrotnie stawali przed dylematem, jak przekazać „zdalnie” daną wiedzę, np. dotyczącą eksponatów oraz jak dotrzeć do różnego rodzaju odbiorców, zarówno dzieci, dorosłych, jak i seniorów.
„O powrót muzealnych kapci” czyli wskazanie wybranych możliwości reagowania przez muzea na trendy zmian w środowisku naturalnym i otoczeniu kulturowym
Authors: Barańska Katarzyna
Published: February 2022

Opublikowany w sierpniu 2021 Raport IPCC dotyczący przyszłości zmian klimatycznych nie pozostawiają wątpliwości, że wszyscy muszą podjąć starania o odwrócenie śmiertelnych trendów. Instytucje muzealne również są współodpowiedzialne za przyszłość planety , od tego zależy także i ich racja bytu. W tekście poruszony został zaledwie wycinek działań muzealnych, które są lub mogą być podejmowane w celu uczestnictwa w ratowaniu Ziemi. Dotyczą one ostatniego i wydawałoby się najmniej ważnego z ogniw działań muzealnych – sklepików i pamiątek tam oferowanych. Wskazane zostały  sposoby myślenia i organizowania sprzedaży pamiątek oraz argumenty na rzecz przeciwdziałania nadmiernemu konsumpcjonizmowi, potraktowane to zostało jako realizacja misji i istoty muzealnictwa.
Automated and Clinically Optimal Treatment Planning for Cancer Radiotherapy
Authors: Zarepisheh Masoud , Hong Linda , Zhou Ying , Huang Qijie , Yang Jie , Jhanwar Gourav , Pham Hai D. , Dursun Pınar , Zhang Pengpeng , Hunt Margie A. , Mageras Gig S. , Yang Jonathan T. , Yamada Yoshiya (Josh) , Deasy Joseph O.
Published: February 2022

Each year, approximately 18 million new cancer cases are diagnosed worldwide, and about half must be treated with radiotherapy. A successful treatment requires treatment planning with the customization of penetrating radiation beams to sterilize cancerous cells without harming nearby normal organs and tissues. This process currently involves extensive manual tuning of parameters by an expert planner, making it a time-consuming and labor-intensive process, with quality and immediacy of critical care dependent on the planner’s expertise. To improve the speed, quality, and availability of this highly specialized care, Memorial Sloan Kettering Cancer Center developed and applied advanced optimization tools to this problem (e.g., using hierarchical constrained optimization, convex approximations, and Lagrangian methods). This resulted in both a greatly improved radiotherapy treatment planning process and the generation of reliable and consistent high-quality plans that reflect clinical priorities. These improved techniques have been the foundation of high-quality treatments and have positively impacted over 5,000 patients to date, including numerous patients in severe pain and in urgent need of treatment who might have otherwise required longer hospital stays or undergone unnecessary surgery to control the progression of their disease. We expect that the wide distribution of the system we developed will ultimately impact patient care more broadly, including in resource-constrained countries.
Designing Advance Market Commitments for New Vaccines
Authors: Kremer Michael , Levin Jonathan , Snyder Christopher M.
Published: February 2022

Advance market commitments (AMCs) provide a mechanism to stimulate investment by suppliers of products to low-income countries. In an AMC, donors commit to a fund from which a specified subsidy is paid per unit purchased by low-income countries until the fund is exhausted, strengthening suppliers’ incentives to invest in research, development, and capacity. Last decade saw the launch of a $1.5 billion pilot AMC to distribute pneumococcal vaccine to the developing world; in the current pandemic, variations on AMCs are being used to fund COVID-19 vaccines. This paper undertakes the first formal analysis of AMCs. We construct a model in which an altruistic donor negotiates on behalf of a low-income country with a vaccine supplier after the supplier has sunk investments. We use this model to explain the logic of an AMC—as a solution to a hold-up problem—and to analyze alternative design features under various economic conditions (cost uncertainty, supplier competition). A key finding is that optimal AMC design differs markedly depending on where the product is in its development cycle.

This paper was accepted by Joshua Gans, business strategy.