bluuebunny/crossref_metadata_2025 huggingface dataset:
All-fiber SPR microfluidic chip for GDF11 detection
Authors: Wei Yong , Ren Zhuo , Ran Ze , Wang Rui , Liu Chun-Biao , Shi Chen , Liu Chun-Lan , Wang Chen , Zhang Yong-Hui
Published: November 2022

In order to perform microfluidic detection of cytokines with low concentration, such as growth differentiation factor 11 (GDF11), the most common method is to construct microfluidic channels and integrate them with SPR sensing units. In this paper, we proposed a novel all-fiber SPR microfluidic chip for GDF11 detection. The method was to construct the SPR sensing area on a designed D-shaped multimode fiber, which was nested inside a quartz tube to form a semi-cylindrical microfluidic channel. The surface of the SPR sensing area experienced sensitization and specifically modification to achieve the specific detection of GDF11. When the sensitivity of detection was 1.38 nm/lg(g/mL) and the limit of detection was 0.52 pg/mL, the sample consumption was only 0.4 µL for a single detection. The novel all-fiber SPR microfluidic detection chip has the advantages of flexible design, compact structure and low sample consumption, which is expected to be used in wearable biosensing devices for real-time online monitoring of trace cytokines in vivo.
Estimating the economic burden of typhoid in children and adults in Blantyre, Malawi: A costing cohort study
Authors: Limani Fumbani , Smith Christopher , Wachepa Richard , Chafuwa Hlulose , Meiring James , Noah Patrick , Patel Pratiksha , Patel Priyanka D. , Debellut Frédéric , Pecenka Clint , Gordon Melita A. , Bar-Zeev Naor
Published: November 2022

Background

Typhoid causes preventable death and disease. The World Health Organization recommends Typhoid Conjugate Vaccine for endemic countries, but introduction decisions depend on cost-effectiveness. We estimated household and healthcare economic burdens of typhoid in Blantyre, Malawi.

Methods

In a prospective cohort of culture-confirmed typhoid cases at two primary- and a referral-level health facility, we collected direct medical, non-medical costs (2020 U.S. dollars) to healthcare provider, plus indirect costs to households.

Results

From July 2019-March 2020, of 109 cases, 63 (58%) were <15 years old, 44 (40%) were inpatients. Mean hospitalization length was 7.7 days (SD 4.1). For inpatients, mean total household and provider costs were $93.85 (95%CI: 68.87–118.84) and $296.52 (95%CI: 225.79–367.25), respectively. For outpatients, these costs were $19.05 (95%CI: 4.38–33.71) and $39.65 (95%CI: 33.93–45.39), respectively. Household costs were due mainly to direct non-medical and indirect costs, medical care was free. Catastrophic illness cost, defined as cost >40% of non-food monthly household expenditure, occurred in 48 (44%) households.

Conclusions

Typhoid can be economically catastrophic for families, despite accessible free medical care. Typhoid is costly for government healthcare provision. These data make an economic case for TCV introduction in Malawi and the region and will be used to derive vaccine cost-effectiveness.
VARIAÇÃO MORFOLÓGICA DOS ECOSSISTEMAS DE PLANÍCIE DE MARÉ NA FOZ DO RIO CACHOEIRA, PARANÁ
Authors: Branco José Carlos
Published: November 2022

O Rio Cachoeira deságua no estuário da baía de Antonina que faz parte do Complexo Estuarino de Paranaguá. A média anual da vazão do Rio Cachoeira antes da transposição era de 21,13 m3/s. Pesquisas recentes evidenciaram uma vazão anual média de 31,45 m3/s, caracterizando um acréscimo de aproximadamente 33% na vazão original. Devido Ã  relação entre a vazão e a capacidade de carga de transporte de um rio, o aumento da vazão do Rio Cachoeira pode ter ocasionado as mudanças batimétricas e sedimentológicas verificadas na cabeceira do estuário. A análise temporal aplicada na foz do Rio Cachoeira através de fotointerpretação detectou as modificações morfológicas mais relevantes na área de estudo e quantificou um balanço da variação de área dos principais ecossistemas de planície de maré. Com base nas modificações dos ecossistemas dispostos na região da foz do Rio Cachoeira e nas áreas de estudos comparativas, foi constatada uma tendência erosiva que pode aproximar ainda mais a relação entre a transposição e as mudanças morfológicas, sedimentológicas e batimétricas na cabeceira de estuário da baía de Antonina.
HMAB
Authors: Perera R. Malinga , Oetomo Bastian , Rubinstein Benjamin I. P. , Borovica-Gajic Renata
Published: November 2022

Effective physical database design tuning requires selection of several physical design structures (PDS), such as indices and materialised views, whose combination influences overall system performance in a non-linear manner. While the simplicity of combining the results of iterative searches for individual PDSs may be appealing, such a greedy approach may yield vastly suboptimal results compared to an integrated search. We propose a new self-driving approach (HMAB) based on hierarchical multi-armed bandit learners, which can work in an integrated space of multiple PDS while avoiding the full cost of combinatorial search. HMAB eschews the optimiser cost misestimates by direct performance observations through a strategic exploration, while carefully leveraging its knowledge to prune the less useful exploration paths. As an added advantage, HMAB comes with a provable guarantee on its expected performance. To the best of our knowledge, this is the first learned system to tune both indices and materialised views in an integrated manner. We find that our solution enjoys superior empirical performance relative to state-of-the-art commercial physical database design tools that search over the integrated space of materialised views and indices. Specifically, HMAB achieves up to 96% performance gain over a state-of-the-art commercial physical database design tool when running industrial benchmarks.
SHiFT
Authors: Renggli Cedric , Yao Xiaozhe , Kolar Luka , Rimanic Luka , Klimovic Ana , Zhang Ce
Published: November 2022

Transfer learning can be seen as a data- and compute-efficient alternative to training models from scratch. The emergence of rich model repositories, such as TensorFlow Hub, enables practitioners and researchers to unleash the potential of these models across a wide range of downstream tasks. As these repositories keep growing exponentially, efficiently selecting a good model for the task at hand becomes paramount. However, a single generic search strategy (e.g., taking the model with the highest linear classifier accuracy) does not lead to optimal model selection for diverse downstream tasks. In fact, using hybrid or mixed strategies can often be beneficial. Therefore, we propose SHiFT, the first downstream task-aware, flexible, and efficient model search engine for transfer learning. Users interface with SHiFT using the SHiFT-QL query language, which gives users the flexibility to customize their search criteria. We optimize SHiFT-QL queries using a cost-based decision maker and evaluate them on a wide rang of tasks. Motivated by the iterative nature of machine learning development, we further support efficient incremental executions of our queries, which requires a special implementation when jointly used with our optimizations.
Staining of Gfap, Iba1,and NeuN on PFA-fixed mouse brain sections v1
Authors: Manrique-Castano Daniel
Published: November 2022

Staining protocol for Gfap, Iba1, and NeuN on PFA-fixed mouse brain sections.
NEBNext Single Cell/ Low Input RNA Library Prep Kit for Illumina Protocol for Low Input RNA E6420 v1
Authors: England Biolabs New
Published: November 2022

The NEBNext® Single Cell/Low Input RNA Library Prep Kit for Illumina® uses a template switching method to generate full length cDNAs directly from single cells or 2 pg – 200 ng RNA, followed by conversion to sequence-ready libraries using the Ultra™ II FS workflow. This unique workflow enables generation of the highest yields from a broad range of inputs, and superior transcript detection, while providing reliably consistent performance.
P9b Generación informe anual Garantía de Calidad v1
Authors: not provided cgarcia
Published: November 2022

Procedimiento de Generación informe anual revisión garantía de calidad
​Production Performance and Economics of Forage Cropping Systems under Irrigated Condition of Western Maharashtra
Authors: Takawale P.S. , Kauthale V.K. , Kale R.V.
Published: November 2022

Background: Green forages have important role in livestock sector as they are the main source of nutrition. Even then there is always deficit in green fodder supply as against the demand. Out of the total cultivated land at national level, area under fodder crops is about 4%. Under these circumstances the only way is to increase the productivity of fodder crops by adopting best forage cropping system. Growing of cereal-legume fodder crops, as intercrop, mixed crop and sequence crop increase the fodder production and also help to meet the balanced diet for livestock. Methods: A field study was conducted at Central Research Station of BAIF Development Research Foundation, Urulikanchan in three successive years from 2013-14 to 2015-16. The experiment was laid in a randomized block design with four replications and six different forage cropping systems. The experiment was conducted in light gravel soil. Result: Among the six different cropping systems studied, significantly higher green fodder yield of 792 q/ha/year, net monetary returns of Rs. 92891/ha/year and benefit-cost ratio of 1.92 was recorded in intercropping sequence of maize + cowpea (kharif), oat + berseem (rabi) and bajra + cowpea (summer). This cropping system has confirmed more fodder production from the cereal and legume inter crops with further additional benefits of provision of high quality fodder and net monetary returns.
Pengaruh harga, promosi dan lokasi terhadap keputusan pembelian rumah KPR subsidi di PT Sinar Jaya Putra Kampar Batam
Authors: Sembiring Elwin Frandika , Sunargo Sunargo
Published: November 2022

PT Sinar Jaya Putra Kampar is one of the developer companies in Batam City. This study aimed to determine the effect of price, promotion, and location on purchasing decisions at PT Sinar Jaya Putra Kampar. The sampling technique in this study used a saturated sampling technique for as many as 114 consumers in the Oleana Park Tanjung Piayu housing project. Data were obtained by distributing questionnaires directly to respondents. The data analysis method in this study is multiple regression which includes: a validity test, reliability test, normality test, multicollinearity test, heteroscedasticity test, multiple linear regression analysis test, coefficient of determination test, T-test, and F test. The results showed that price had a positive effect. And partially significant on purchasing decisions with t count 6.781 > t table 1.658 and sig 0.000 < 0.05, the promotion has a positive and somewhat substantial influence on decisions with t count 2.998 > t table 1.658 and sig 0.003 < 0.05, location has a positive effect and partially significant on purchasing decisions with t count 7.677 > t table 1.658 and sig 0.000 < 0.05 and price, promotion and site have a positive and significant effect simultaneously on buying decisions can be seen from F-count with a value of 120.368 > F-Table 2, 68 and with a sig value of 0.000 < 0.05.
The Relationship Between Social Capital, the Happiness of Others, and the Happiness of Korean Adults: A National Sample Study
Authors: Lee Jo-Eun , Bae Sung-Man
Published: November 2022

Objective This study aimed to reveal the relationship between social capital, the happiness of others, and the happiness of Korean adults.Methods Data from 4,890 participants (2,092 males [42.78%] and 2,798 females [57.22%]) aged 19 to 79 years were used. Data used in the analysis were provided by the Survey on Koreans’ Happiness and Quality of Life (2019) conducted by the Korea Institute for Health and Social Affairs.Results First, age, education, marital status, and subjective economic level were found to be significantly related to individual happiness. Second, social capital, which including trust and social participation, was positively related to individual happiness. Third, the key result of this study was that the happiness of close people was positively associated with individual happiness. Fourth, belonging showed a significant moderating effect on the relationship between the happiness of others and individual happiness.Conclusion This study contributes by examining the relationship between the happiness of others and individual happiness after controlling for social capital and demographic variables and examining the moderating effect of social capital on the relationship between the happiness of self and others. These results are expected to help understand the factors that determine the happiness of Korean adults.
Unraveling the Role of K2P Channels in Atrial Fibrillation
Authors: Mondéjar-Parreño Gema
Published: November 2022

Atrial fibrillation (AF) is a condition in which the electrical signals in the upper heart chambers (atria) are rapid and disorganized, producing an irregular and chaotical heartbeat. The sinus rhythm should be between 60 to 100 bpm at rest, while the heart rhythm in AF patients may be over 140 bpm. Either structural and electro-mechanical remodeling of the atrial tissue underlies the perpetuation and evolution of AF from the paroxysmal to persistent form. Unravelling the different pathological pathways involved in AF that lead to arrhythmogenesis and atrial remodeling is needed to discovery new and effective therapeutic approaches. A variety of drugs are available to convert and maintain the AF patient in a normal sinus rhythm; however, these strategies have limited chances of success or fail with the progression of AF to more persistent/permanent forms. Consequently, it is necessary to find new therapeutic targets for the relief of persistent or chronic AF forms, as well as the development of new and more effective pharmacological tools. The atrial specific two-pore domain K+ channels (K2P) constitute the background K+ current on atrial cardiomyocytes and modulate cell excitability emerging as novel targets in this disease and avoiding ventricle side effects. Moreover, several antiarrhythmic drugs used in AF treatment exert their mechanism of action in part by modulation of K2P channels. Thus far, TWIK-1, TREK-1, TASK-1, TASK-2 and TASK-3 channel have been identified as responsible for background currents IK2P current in atrial cells; however, it is not excluded that other K2PX subunits or subfamilies have physiological roles in atria. To date, a great diversity openers, activators and blockers of K2P channel have been identified, particularly those targeting TASK and TREK channels. Several studies have demonstrated that the expression of TWIK-1, TREK-1, TASK-1, TASK-2 and TASK-3 are dysregulated in AF and their pharmacology rescue could suppose a novel therapy in AF. The main objective is to examine the regulation of K2P channels and the current K2P channels pharmacological modulators for AF treatment.
Effectiveness of Pregabalin in Treatment of Burning Mouth Syndrome
Authors: Choi Seok-Youl , Choi Hyunseok , Cho Jae-Gu
Published: November 2022

Background and Objectives Burning mouth syndrome (BMS) is a chronic pain disorder involving a burning sensation of the oral cavity without any identifiable oral lesion. According to the recent studies, the pathogenesis of BMS is presumed to be caused by a neuropathic condition. Gabapentin and pregabalin have been used for various neuropathic pains, but pregabalin has several pharmacokinetic advantages over gabapentin. To our best knowledge, there are no recent studies reported on the administration of pregabalin in treating BMS in Korea. Therefore, in this study, we investigated the therapeutic effect of pregabalin in treating BMS.Subjects and Method We chose as candidates 33 patients diagnosed as BMS and took pregabalin for more than four weeks. Pregabalin was administered at 75 mg once a day for 2 to 4 weeks at first, and then the dose was modified depending on whether or not symptoms improved. Effectiveness of treatment was evaluated in the way that the patients subjectively answered whether or not symptoms were improved.Results A total of 21 (63.6%) out of 33 patients were responsive to the treatment. Among those, at the last follow-up, 8 patients (38.1%) showed slight improvement, and 13 patients (61.9%) showed mostly improvement or disappearance of symptoms. The average time interval from starting pregabalin to the first symptom improvement was 50.1 days, and most patients showed symptom improvement within 8 weeks.Conclusion This study concludes that pregabalin can be added as a meaningful option in the treatment of BMS. The additional double-blind clinical study should be followed to further prove the effectiveness of pregabalin.
In vitro and in vivo assessment of caprine origin Staphylococcus aureus ST398 strain UTCVM1 as an osteomyelitis pathogen
Authors: Billings Caroline , Rifkin Rebecca , Abouelkhair Mohamed , Jones Rebekah Duckett , Bow Austin , Kolape Jaydeep , Rajeev Sreekumari , Kania Stephen , Anderson David E.
Published: November 2022

Staphylococcus aureus (SA) is a significant and well-recognized causative organism of bacterial osteomyelitis. Osteomyelitis is an inflammatory bone disease characterized by progressive bone destruction and loss. This disease causes significant morbidity and mortality to the patient and poses therapeutic challenges for clinicians. To improve the efficacy of therapeutic strategies to combat bacterial osteomyelitis, there is a need to define the molecular epidemiology of bacterial organisms more clearly and further the understanding of the pathogenesis of SA osteomyelitis. We conducted in vitro characterization of the pathogenic capabilities of an isolate of SA ST398 derived from a clinical case of osteomyelitis in a goat. We also report a rodent mandibular defect model to determine the ability of ST398 to cause reproducible osteomyelitis. Our results indicate that ST398 can invade and distort pre-osteoblastic cells in culture, induce significant inflammation and alter expression of osteoregulatory cytokines. We also demonstrate the ability of ST398 to induce osteomyelitis in a rat mandibular model. When compiled, these data support ST398 as a competent osteomyelitis pathogen.
Coronary microvascular dysfunction as assessed by angiography-derived index of microvascular resistance co-localizes with and may explain the presence of ischemia in stress-cardiac magnetic resonance imaging in the absence of coronary artery disease
Authors: Milzi Andrea , Dettori Rosalia , Lubberich Richard Karl , Burgmaier Kathrin , Marx Nikolaus , Reith Sebastian , Burgmaier Mathias
Published: November 2022

Introduction

Ischemia with no obstructive coronary disease (INOCA) is a frequent phenomenon in the cath lab. A possible cause is coronary microvascular dysfunction (CMD), which may be assessed by invasive testing with possible complications; therefore, less invasive approaches have emerged, such as the angiography-derived index of microvascular resistance (aIMR). The aim of our study was to investigate the association of single-vessel aIMR as a measure of CMD with areas of INOCA in stress testing.

Methods

We measured aIMR in 286 vessels from 102 patients undergoing both stress cMRI and coronary angiography. Groups were (a) INOCA group (93 vessels, 32 patients); (b) coronary artery disease (CAD) control group (116 vessels, 42 patients) with ischemia due to relevant stenosis; and (c) control group (77 vessels, 28 patients) without ischemia or relevant stenosis.

Results

INOCA patients presented higher mean aIMR (28.3 ± 5.7) compared to both CAD patients (17.4 ± 5.7, p < 0.001) and controls (22.1 ± 5.9, p < 0.001). Furthermore, in INOCA patients aIMR was significantly increased (33.0 ± 8.1 vs. 25.8 ± 6.3, p = 0.021) in vessels with vs. without ischemia. Single vessel aIMR presented a very good diagnostic efficiency in detecting INOCA [AUC 0.865 (0.804–0.925), optimal cut-off 27.1, p < 0.001].

Conclusion

CMD, as assessed by 3-vessel aIMR, co-localizes with and may explain the presence of ischemia in stress-cMRI in INOCA.
Case report: A rare case of imiquimod-induced atypical pemphigus vulgaris
Authors: Moro Francesco , Ciccone Davide , Fania Luca , Mariotti Feliciana , Salemme Adele , Rahimi Siavash , Pallotta Sabatino , Di Zenzo Giovanni
Published: November 2022

Background

Pemphigus vulgaris is an autoimmune intraepithelial bullous disease involving the skin and the mucous membranes. Imiquimod, a topical therapy for skin basal cell carcinoma, is an amine that induces the production of tumor necrosis factor alfa, interleukin-1 and other cytokines. Pemphigus induced by drugs has been frequently reported, mostly after systemic therapy.

Case presentation

We present the case of a 50-year-old man who developed skin, intraoral, and genital mucosae lesions 3 days after a treatment with Imiquimod for multiple superficial basal cell carcinoma of the trunk. Direct and indirect immunofluorescence results were compatible with the diagnosis of pemphigus vulgaris. Enzyme-linked immunosorbent assay was negative for desmoglein 1 and 3, but interestingly, by immunoblotting on keratinocyte extracts a band of 170 kDa was obtained by IgG. The patient, after interrupting Imiquimod application, started a treatment with prednisolone and in 4 weeks showed a complete remission.

Conclusion

Topical Imiquimod therapy might induce atypical pemphigus vulgaris in some patients.
An overview of brain-like computing: Architecture, applications, and future trends
Authors: Ou Wei , Xiao Shitao , Zhu Chengyu , Han Wenbao , Zhang Qionglu
Published: November 2022

With the development of technology, Moore's law will come to an end, and scientists are trying to find a new way out in brain-like computing. But we still know very little about how the brain works. At the present stage of research, brain-like models are all structured to mimic the brain in order to achieve some of the brain's functions, and then continue to improve the theories and models. This article summarizes the important progress and status of brain-like computing, summarizes the generally accepted and feasible brain-like computing models, introduces, analyzes, and compares the more mature brain-like computing chips, outlines the attempts and challenges of brain-like computing applications at this stage, and looks forward to the future development of brain-like computing. It is hoped that the summarized results will help relevant researchers and practitioners to quickly grasp the research progress in the field of brain-like computing and acquire the application methods and related knowledge in this field.
Sex as a biological variable in determining the metabolic changes influencing acute ischemic stroke outcomes—Where is the data: A systematic review
Authors: Dylla Layne , Higgins Hannah M. , Piper Christi , Poisson Sharon N. , Herson Paco S. , Monte Andrew A.
Published: November 2022

Women continue to face a greater lifetime morbidity and mortality from stroke and have been shown to respond differently to stroke treatments compared to men. Since 2016, updated National Institutes of Health (NIH) policies require research studies to consider sex as a biological variable. However, the way in which this policy affects study design, analysis, and reporting is variable, with few studies performing and reporting a subgroup analysis based on biological sex. In acute ischemic stroke, the underlying biological explanation for sex-based differences in patient outcomes and response to treatments remains understudied. We performed a systematic review of preclinical and clinical research studies that explored sex differences in the metabolic response to acute ischemic stroke as it relates to neurological outcomes. Through a literature search in Ovid Medline, Embase, and Web of Science, 1,004 potential references were identified for screening. After abstract and full-text review, we identified only two studies which assessed metabolic response to acute ischemic stroke (within 72 h of last known well) and neurological outcome [Barthel Index, modified Rankin Scale (mRS) or an equivalent in preclinical models] and reported results based on biological sex. One article was a preclinical rat model and the other a clinical cohort study. In both studies, metabolites involved in amino acid metabolism, energy metabolism, fat metabolism, or oxidative stress were identified. We review these results and link to additional articles that use metabolomics to identify metabolites differentially expressed by sex or regulated based on stroke outcomes, but not both. The results of this systematic review should not only help identify targets in need of further investigation to improve the understanding of sex differences in the pathophysiology of acute ischemic stroke, but also highlight the critical need to expand the incorporation of sex as a biological variable in acute stroke research beyond simply including both sexes and reporting the proportion of males/females in each population studied.
Activation of farnesoid X receptor suppresses ER stress and inflammation via the YY1/NCK1/PERK pathway in large yellow croaker (Larimichthys crocea)
Authors: Du Jianlong , Zhang Junzhi , Xiang Xiaojun , Xu Dan , Cui Kun , Mai Kangsen , Ai Qinghui
Published: November 2022

Unfolded protein responses from endoplasmic reticulum (ER) stress have been implicated in inflammatory signaling. The vicious cycle of ER stress and inflammation makes regulation even more difficult. This study examined effects of farnesoid X receptor (FXR) in ER-stress regulation in large yellow croakers. The soybean-oil-diet-induced expression of ER stress markers was decreased in fish with FXR activated. In croaker macrophages, FXR activation or overexpression significantly reduced inflammation and ER stress caused by tunicamycin (TM), which was exacerbated by FXR knockdown. Further investigation showed that the TM-induced phosphorylation of PERK and EIF2α was inhibited by the overexpression of croaker FXR, and it was increased by FXR knockdown. Croaker NCK1 was then confirmed to be a regulator of PERK, and its expression in macrophages is increased by FXR overexpression and decreased by FXR knockdown. The promoter activity of croaker NCK1 was inhibited by yin-yang 1 (YY1). Furthermore, the results show that croaker FXR overexpression could suppress the P65-induced promoter activity of YY1 in HEK293t cells and decrease the TM-induced expression of yy1 in macrophages. These results indicate that FXR could suppress P65-induced yy1 expression and then increase NCK1 expression, thereby inhibiting the PERK pathway. This study may benefit the understanding of ER stress regulation in fish, demonstrating that FXR can be used in large yellow croakers as an effective target for regulating ER stress and inflammation.
The role of liver transplantation in the care of primary hepatic vascular tumours in children
Authors: Grimaldi Chiara , de Ville de Goyet Jean , Bici Kejd , Cianci Maria Chiara , Callea Francesco , Morabito Antonino
Published: November 2022

Liver transplantation (LT) is the standard of care for many liver conditions, such as end-stage liver diseases, inherited metabolic disorders, and primary liver malignancies. In the latter group, indications of LT for hepatoblastoma and hepatocellular carcinoma evolved and are currently available for many non-resectable cases. However, selection criteria apply, as the absence of active metastases. Evidence of good long-term outcomes has validated the LT approach for managing these malignancies in the context of specialist and multidisciplinary approach. Nevertheless, LT’s role in treating primary vascular tumours of the liver in children, both benign and malignant, remains somewhat controversial. The rarity of the different diseases and the heterogeneity of pathological definitions contribute to the controversy and make evaluating the benefit/risk ratio and outcomes quite difficult. In this narrative review, we give an overview of primary vascular tumours of the liver in children, the possible indications and the outcomes of LT.
Photodynamic therapy for malignant brain tumors in children and young adolescents
Authors: Chiba Kentaro , Aihara Yasuo , Oda Yuichi , Fukui Atsushi , Tsuzuki Shunsuke , Saito Taiichi , Nitta Masayuki , Muragaki Yoshihiro , Kawamata Takakazu
Published: November 2022

Photodynamic therapy (PDT) targets tumor cell remnants after resection. Here, we evaluated the feasibility of PDT for malignant brain tumors in children and young adolescents. This was a single-center, non-randomized, phase I/II clinical study. The primary endpoints were the safety of treatment with talaporfin sodium (TS) (phase I) and overall survival (OS) after PDT (phase II). The secondary endpoint was progression-free survival (PFS) after PDT. The TS dose was determined by dose escalation from 10 to 20 to 40 mg/m2 for every three cases starting from the initial enrolled case. Eight patients with a mean age of 170.2 months (129–214 months) at the time of PDT received nine procedures with a mean follow-up duration of 16.8 months (1–42 months) after PDT. Histopathological diagnoses included supratentorial anaplastic ependymoma (n = 2), anaplastic astrocytoma (n = 1), diffuse midline glioma with H3K27M mutation (n = 1), glioblastoma (n = 3), and pediatric high-grade glioma (n = 1). The outcome was survival in five patients and death in three patients. Recurrence occurred in six of the eight patients; the remaining two were recurrence-free after PDT. Therefore, OS and PFS were calculated as 21 and 6 months, respectively. Seizures and fevers, which were likely surgery-related symptoms, were commonly observed. Photosensitive skin rashes or liver dysfunction, which are common adverse effects in adults, were not observed. Our results showed that TS can be used safely in children at doses comparable to those used in adults, as there was no major complication associated with TS administration. However, we cannot make a definitive conclusion about the efficacy of PDT because of the small number of participants. Accumulating cases was difficult because of the rarity of pediatric brain tumors and the difficulty in making a preoperative differential diagnosis, considering the wide range of histopathological findings. Moreover, the psychological stress associated with light-shielding management in pediatric patients was more severe than initially expected. In conclusion, TS at doses comparable to those used in adults may be safe for use in children and young adolescents between the ages of 6 and 20 years. However, further studies are needed to clarify its efficacy.
Association of cannabis and/or opioid with quality of life and healthcare utilization in patients with chronic pain
Authors: Salmasi Vafi , Nelson Lorene M. , Hong Juliette , Mackey Sean C.
Published: November 2022

Background

Opioids have been commonly used to treat chronic pain, but they are associated with significant morbidity and mortality. Cannabis has been advocated as an alternative; however, a growing number of patients are now using a combination of opioid and cannabis and the impact of this combination is not well-studied.

Aim

We characterized use of opioid and/or cannabis in patients with chronic pain; and compared utilization of healthcare resources.

Methods

We conducted a cross-sectional study to determine if measures of physical, psychological and social functioning differed among patients according to whether they used opioids and/or cannabis. We used our learning healthcare system – CHOIR – to capture NIH Patient Reported Outcomes Measure Information System surveys, and legacy pain and treatment specific questions.

Results

Patients who report use of opioid and/or cannabis experience higher levels of physical, psychological and social distress. After adjusting for inversed weight of propensity scores, they have higher odds of visiting an emergency room, staying overnight at the hospital, and visiting a physician.

Conclusion

Our results show that use of opioid and/or cannabis is associated with worse baseline characteristics and outcomes. Our study however cannot determine if worse outcomes are due to the opioids and/or cannabis or simply that these patients are worse off before using opioids and/or cannabis. Thus, it is important to characterize the trajectory of these patients in a prospective longitudinal study.
Serum and brain metabolomic study reveals the protective effects of Bai-Mi-Decoction on rats with ischemic stroke
Authors: Yang Lingling , Su Xiaojuan , Lu Fangfang , Zong Rong , Ding Shuqin , Liu Jing , Wilson Gidion , Li Liuyan , Yang Youyue , Wang Weibiao , Wang Xiaoying , Chen Jianyu , Ma Xueqin
Published: November 2022

Bai-Mi-Decoction (BMD), which is composed of Eugenia caryophyllata, Myristica fragrans, Moschus berezovskii, and Crocus sativu, is a characteristic TCM multi-herb formula for brain disease. However, the mechanism of protective effects of BMD on ischemic stroke (IS) still has not been clarified. Our study is designed to elucidate the protective effects and underlying mechanisms of BMD on IS by employing pharmacodynamic and serum and brain metabolomic methods. In this experiment, 90 adult male Sprague–Dawley rats were randomly divided into the sham operation group (SHAM, vehicle), middle cerebral artery occlusion–reperfusion injury model group (MCAO/R, vehicle), positive control group (NMDP, 36 mg/kg/day nimodipine), and low (BMDL, 0.805 g/kg/day), moderate (BMDM, 1.61 g/kg/day), and high (BMDH, 3.22 g/kg/day) dosage of BMD prophylactic administration groups. The drugs were dissolved in 0.5% CMC-Na and orally administered to rats with equal volumes (100 g/ml body weight) once a day for 14 consecutive days. Neurological deficit score, cerebral infarct volume, change in body weight, and serum NO, SOD, MDA, GSH, and GSSG levels were determined. Pathological abnormalities using hematoxylin and eosin staining and the expression of VEGF, caspase-3, and NF-κB were analyzed. Furthermore, serum and brain metabolic profiles were explored to reveal the underlying mechanism using UHPLC-QTOF-MS/MS technology. BMD exhibited significant neuroprotective effects on MCAO/R rats. As compared to the MCAO/R model group, it could reduce the neurological deficit score and cerebral infarct volume, increase body weight, enhance GSH, SOD, and GSSG activities, and decrease NO and MDA contents of MCAO/R rats. Meanwhile, BMD could ameliorate pathological abnormalities of MCAO/R rats through reducing neuronal loss, vacuolated spaces, shrunken neurons, and destructed neuron structure, as well as regulating the expression of VEGF, caspase-3, and NF-κB. UHPLC-QTOF-MS/MS-based serum and brain metabolomics analysis found a total of 53 differential metabolites between MCAO/R and SHAM groups, of which 30 were significantly regulated by BMD intervention, and further metabolic pathway analysis implied that the protective effects were mainly associated with amino acid and glycerophospholipid metabolisms. Our pharmacodynamic and metabolomic results revealed the neuroprotective effects of BMD on MCAO/R rats, and the underlying mechanisms were probably related to amino acid and glycerophospholipid metabolisms.
Application of temperature-responsive HIS-tag fluorophores to differential scanning fluorimetry screening of small molecule libraries
Authors: Ronzetti Michael H. , Baljinnyam Bolormaa , Itkin Zina , Jain Sankalp , Rai Ganesha , Zakharov Alexey V. , Pal Utpal , Simeonov Anton
Published: November 2022

Differential scanning fluorimetry is a rapid and economical biophysical technique used to monitor perturbations to protein structure during a thermal gradient, most often by detecting protein unfolding events through an environment-sensitive fluorophore. By employing an NTA-complexed fluorophore that is sensitive to nearby structural changes in histidine-tagged protein, a robust and sensitive differential scanning fluorimetry (DSF) assay is established with the specificity of an affinity tag-based system. We developed, optimized, and miniaturized this HIS-tag DSF assay (HIS-DSF) into a 1536-well high-throughput biophysical platform using the Borrelial high temperature requirement A protease (BbHtrA) as a proof of concept for the workflow. A production run of the BbHtrA HIS-DSF assay showed a tight negative control group distribution of Tm values with an average coefficient of variation of 0.51% and median coefficient of variation of compound Tm of 0.26%. The HIS-DSF platform will provide an additional assay platform for future drug discovery campaigns with applications in buffer screening and optimization, target engagement screening, and other biophysical assay efforts.
Recent developments of phosphodiesterase inhibitors: Clinical trials, emerging indications and novel molecules
Authors: Bondarev Andrey D. , Attwood Misty M. , Jonsson Jörgen , Chubarev Vladimir N. , Tarasov Vadim V. , Liu Wen , Schiöth Helgi B.
Published: November 2022

The phosphodiesterase (PDE) enzymes, key regulator of the cyclic nucleotide signal transduction system, are long-established as attractive therapeutic targets. During investigation of trends within clinical trials, we have identified a particularly high number of clinical trials involving PDE inhibitors, prompting us to further evaluate the current status of this class of therapeutic agents. In total, we have identified 87 agents with PDE-inhibiting capacity, of which 85 interact with PDE enzymes as primary target. We provide an overview of the clinical drug development with focus on the current clinical uses, novel molecules and indications, highlighting relevant clinical studies. We found that the bulk of current clinical uses for this class of therapeutic agents are chronic obstructive pulmonary disease (COPD), vascular and cardiovascular disorders and inflammatory skin conditions. In COPD, particularly, PDE inhibitors are characterised by the compliance-limiting adverse reactions. We discuss efforts directed to appropriately adjusting the dose regimens and conducting structure-activity relationship studies to determine the effect of structural features on safety profile. The ongoing development predominantly concentrates on central nervous system diseases, such as schizophrenia, Alzheimer’s disease, Parkinson’s disease and fragile X syndrome; notable advancements are being also made in mycobacterial infections, HIV and Duchenne muscular dystrophy. Our analysis predicts the diversification of PDE inhibitors’ will continue to grow thanks to the molecules in preclinical development and the ongoing research involving drugs in clinical development.
Validity and reliability of capillary vs. Venous blood for the assessment of haemoglobin mass and intravascular volumes
Authors: Royal Joshua T. , Fisher Jason T. , Mlinar Tinkara , Mekjavic Igor B. , McDonnell Adam C.
Published: November 2022

Objectives: Haemoglobin mass (Hbmass) assessment with the carbon monoxide rebreathing method is a more accurate estimate than other measures of oxygen-carrying capacity. Blood may be collected by several means and differences in the measured variables may exist as a result. The present study assessed the validity and reliability of calculated Hbmass and intravascular volumes obtained from capillary blood (CAP) when compared to venous blood (VEN) draws.

Methods: Twenty-two adults performed a carbon monoxide rebreathing procedure with paired VEN and CAP draws at baseline, pre-rebreathing and post-rebreathing (POST). Thirteen of these participants performed this protocol on two occasions to assess the data reliability from both blood sampling sites. In a second experiment, 14 adults performed a 20-min seated and a 20-min supine rest to assess for the effect of posture on haematological parameters.

Results: Haemoglobin mass (CAP = 948.8 ± 156.8 g; VEN = 943.4 ± 157.3 g, p = 0.108) and intravascular volume (CAP = 6.5 ± 1 L; VEN = 6.5 ± 0.9 L, p = 0.752) were statistically indifferent, had low bias (Hbmass bias = 14.45 ± 40.42 g, LoA -64.78 g—93.67 g) and were highly correlated between sampling techniques. Reliability analysis demonstrated no difference in the mean change in variables calculated from both sampling sites and good to excellent intraclass correlation coefficients (>0.700), however, typical measurement error was larger in variables measured using CAP (VEN Hbmass TE% = 2.1%, CAP Hbmass TE% = 5.5%). The results indicate that a supine rest prior to the rebreathing protocol would have a significant effect on haemoglobin concentration and haematocrit values compared to a seated rest, with no effect on carboxyhaemoglobin %.

Conclusion: The present study demonstrates that CAP and VEN were comparable for the calculation of Hbmass and intravascular volumes in terms of accuracy. However, reduced reliability and increased error in the CAP variables indicates that there are methodological considerations to address when deciding which blood drawing technique to utilise. To reduce this CAP error, increased replicate analyses are required.
The interaction of ABA and ROS in plant growth and stress resistances
Authors: Li Shenghui , Liu Sha , Zhang Qiong , Cui Meixiang , Zhao Min , Li Nanyang , Wang Suna , Wu Ruigang , Zhang Lin , Cao Yunpeng , Wang Lihu
Published: November 2022

The plant hormone ABA (abscisic acid) plays an extremely important role in plant growth and adaptive stress, including but are not limited to seed germination, stomatal closure, pathogen infection, drought and cold stresses. Reactive oxygen species (ROS) are response molecules widely produced by plant cells under biotic and abiotic stress conditions. The production of apoplast ROS is induced and regulated by ABA, and participates in the ABA signaling pathway and its regulated plant immune system. In this review, we summarize ABA and ROS in apoplast ROS production, plant response to biotic and abiotic stresses, plant growth regulation, ABA signal transduction, and the regulatory relationship between ABA and other plant hormones. In addition, we also discuss the effects of protein post-translational modifications on ABA and ROS related factors.
An effective deep learning approach for the classification of Bacteriosis in peach leave
Authors: Akbar Muneer , Ullah Mohib , Shah Babar , Khan Rafi Ullah , Hussain Tariq , Ali Farman , Alenezi Fayadh , Syed Ikram , Kwak Kyung Sup
Published: November 2022

Bacteriosis is one of the most prevalent and deadly infections that affect peach crops globally. Timely detection of Bacteriosis disease is essential for lowering pesticide use and preventing crop loss. It takes time and effort to distinguish and detect Bacteriosis or a short hole in a peach leaf. In this paper, we proposed a novel LightWeight (WLNet) Convolutional Neural Network (CNN) model based on Visual Geometry Group (VGG-19) for detecting and classifying images into Bacteriosis and healthy images. Profound knowledge of the proposed model is utilized to detect Bacteriosis in peach leaf images. First, a dataset is developed which consists of 10000 images: 4500 are Bacteriosis and 5500 are healthy images. Second, images are preprocessed using different steps to prepare them for the identification of Bacteriosis and healthy leaves. These preprocessing steps include image resizing, noise removal, image enhancement, background removal, and augmentation techniques, which enhance the performance of leaves classification and help to achieve a decent result. Finally, the proposed LWNet model is trained for leaf classification. The proposed model is compared with four different CNN models: LeNet, Alexnet, VGG-16, and the simple VGG-19 model. The proposed model obtains an accuracy of 99%, which is higher than LeNet, Alexnet, VGG-16, and the simple VGG-19 model. The achieved results indicate that the proposed model is more effective for the detection of Bacteriosis in peach leaf images, in comparison with the existing models.
Reading comprehension and strategy use: Comparing bilingual children to their monolingual peers and to bilingual adults
Authors: Friesen Deanna C. , Schmidt Katherine , Atwal Taninder , Celebre Angela
Published: November 2022

The current study investigated the predictive ability of language knowledge and reported strategy use on reading comprehension performance in English-speaking monolingual and bilingual students. One hundred fifty-five children in grade 4 through 6 (93 bilinguals and 62 monolinguals) were assessed on receptive vocabulary, word reading fluency, reading comprehension, and reading strategy use in English. An additional 38 adult bilinguals (i.e., English Language Learners) were assessed on the same measures. Although, the bilingual adult group and bilingual children had significantly lower English vocabulary knowledge relative to the monolingual children, the bilingual adults exhibited reading comprehension performance that was on par with the monolingual children; both groups outperformed the bilingual children. This discrepancy was accounted for by reported strategy use, wherein bilingual adults reported more inferencing, more connecting between sections of text and more reference to the text structure than the children. Reported strategy use also accounted for unique variance in reading comprehension performance above and beyond the contributions of English vocabulary knowledge and word reading fluency. Findings highlight the strategies that successful readers report and emphasize the value of promoting effective strategy selection in addition to language instruction in the development of reading comprehension skill.
A qualitative analysis of collaborative efforts to build a school-based intervention for multiple common adolescent mental health difficulties in India
Authors: Gellatly Resham , Knudsen Kendra , Boustani Maya M. , Michelson Daniel , Malik Kanika , Mathur Sonal , Nair Pooja , Patel Vikram , Chorpita Bruce F.
Published: November 2022

Introduction

In low- and middle-income countries (LMICs), the gap between need for mental health (MH) treatment and access to services is stark, particularly among children and adolescents. In service of addressing this treatment gap, the current study provides an in-depth illustration of later-stage collaborative design of a school-based, transdiagnostic MH intervention in New Delhi and Goa, India, using a combination of contextual insights from local stakeholders and knowledge derived from the global evidence base.

Methods

Using an inductive-deductive approach to qualitative thematic analysis, we examined coded data from qualitative sources related to experiences of developing and implementing an intervention prototype. These sources included notes from meetings attended by treatment development team members and providers, written feedback on protocol materials (e.g., provider manual, student handouts), field notes reflecting researcher observations, and minutes from weekly clinical supervision meetings.

Results

Results revealed that codes involving cultural/contextual considerations, protocol material and content, and intervention complexity arose consistently throughout treatment development and across document types, illustrating their central role in finalizing protocol design.

Discussion

These findings have implications for the future of mental health treatment development and implementation globally.