bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of point of care testing for prevention and management of breast cancer therapy associated comorbidities in 6 African countries: short communication
Authors: Milambo Jean Paul Muambngu , Ndirangu James , Nyasulu Peter S , Akudugu John M
Published: October 2022

Objective:

Obesity and mediators of inflammation have been identified as the most important risk and predictive factors in postmenopausal breast cancer (BC) survivors using aromatase inhibitors (AIs). This study was conducted to assess the impact of point of care technology (PCOT) as part of pathology supported genetic testing (PSGT) to prevent BC therapy-associated comorbidities in African settings.

Results

The study revealed that high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI) are predictors of cardiovascular (CVD) related adverse events in obese postmenopausal patients subjected to AIs. There were statistically significant variations in total body fat (TBF), weight, hs-CRP, body mass index (BMI), homocysteine, ferritin, and calcium between baseline and after 24 months of follow-up. The above inflammatory markers can be incorporated in pathology supported genetic testing (PSGT) using HyBeacon® probe technology at POC for prediction and management of AI-associated adverse events among postmenopausal breast cancer survivors and associated comorbidities. The barriers for implementation of POCT application among six African countries for diagnosis of breast cancer were documented as insufficient of BC diagnosis and management capacity at different levels of health system.
Reliability and validity of the Japanese version of the weight bias internalization scale
Authors: Endo Shota , Kasuga Hideaki , Yusuke Masuishi , Hidaka Tomoo , Kakamu Takeyasu , Fukushima Tetsuhito
Published: October 2022

Objective

The weight bias internalization scale (WBIS) is widely used in several languages. However, there is no Japanese version of the WBIS. The purpose of this study is to develop a Japanese version of the WBIS and to verify its reliability and validity. We translated the original version of the WBIS and had approval from the scale developer. Adults who perceived themselves to be obese completed online baseline survey (N = 285) and two-week follow-up survey (N = 100). We used the Japanese WBIS and scales for obesity-related quality of life, self-esteem, self-efficacy, and depression. We calculated Cronbach’s alpha and intra-class correlation coefficient (ICC) to assess reliability of the WBIS and conducted confirmatory factor analysis (CFA) and correlation analysis to assess its validity.

Results

Cronbach’s alpha was 0.91 at baseline and 0.92 at follow-up, and the ICC was 0.87. CFA showed that a one-factor model demonstrated an acceptable fit (χ2 (44) = 158.6, CFI = 0.93, RMSEA = 0.096, SRMR = 0.051), similar to the original version. As we had hypothesized, overall, the Japanese version of the WBIS was significantly correlated with obesity-related quality of life, self-esteem, self-efficacy, and depression. These results confirmed its adequate reliability and validity.
Delayed pharyngocutaneous fistula caused by molecular targeted therapy: a case report
Authors: Matsuo Mioko , Hashimoto Kazuki , Jiromaru Rina , Nakagawa Takashi
Published: October 2022

Background

Molecular-targeted agents used as a treatment for cancer can cause some rare and serious adverse events such as, delayed wound healing. Depending on the anticancer drug used, temporary withdrawal may be recommended before and after surgery to avoid complications. Once a surgical incision has healed and closed completely, wounds rarely open because of the initiation of molecular targeted therapy several months to years after surgery. Here, we aimed to describe a rare complication of pharyngocutaneous fistula in two patients that was thought to be caused by molecular targeted therapy.

Case presentation

Case 1 involved a 64-year-old asian man who developed a delayed pharyngocutaneous fistula 3 months after total laryngectomy for laryngeal cancer. Ramucirumab, a vascular endothelial growth factor receptor inhibitor used for recurrent gastric cancer, was speculated to be involved. Case 2 involved a 71-year-old japanese man who developed a delayed pharyngocutaneous fistula 2 years and 1 month after total pharyngeal laryngectomy for pharyngeal cancer. It was speculated that imatinib, a platelet-derived growth factor receptor alpha inhibitor used for chronic myeloid leukemia, was involved.

Conclusions

Although the incidence of late drug-induced anastomotic leakage is very low, when it occurs, it makes oral intake impossible for an extended period and interferes with the appropriate cancer treatment. In this report, we demonstrate the details of these two patients with such a rare complication, which may help accumulate essential data on this topic.
Mesenchymal stem cell aggregation mediated by integrin α4/VCAM-1 after intrathecal transplantation in MCAO rats
Authors: Ran Ye , Dong Yankai , Li Yuejiao , Xie Jundong , Zeng Shubin , Liang Chuanlei , Dai Wei , Tang Wenjing , Wu Yaojiong , Yu Shengyuan
Published: October 2022

Background

Mesenchymal stem cells (MSCs) have shown immense therapeutic potential for various brain diseases. Intrathecal administration of MSCs may enhance their recruitment to lesions in the central nervous system, but any impact on cerebrospinal fluid (CSF) flow remains unclear.

Methods

Rats with or without middle cerebral artery occlusion (MCAO) received intrathecal injections of 2D cultured MSCs, 3D cultured MSCs or an equal volume of artificial cerebrospinal fluid (ACSF). Ventricle volume was assessed by MRI on Days 2 and 14 post-MCAO surgery. A beam walking test was used to assess fine motor coordination and balance. Aggregation of MSCs was evaluated in CSF and frozen brain tissue. Differential expression of cell adhesion molecules was evaluated by RNA-Seq, flow cytometry and immunofluorescence analyses. The influence of VCAM-1 blockade in mediating the aggregation of 2D MSCs was investigated in vitro by counting cells that passed through a strainer and in vivo by evaluating ventricular dilation.

Results

MSC expanded in 2D culture formed aggregates in the CSF and caused ventricular enlargement in both MCAO and normal rats. Aggregates were associated with impaired motor function. 2D MSCs expressed higher levels of integrin α4 and VCAM-1 than 3D MSCs. Blockade of VCAM-1 in 2D MSCs reduced their aggregation in vitro and reduced lateral ventricular enlargement after intrathecal infusion. 3D MSCs exhibited lower cell aggregation and reduced cerebral ventricular dilation after intrathecal transplantation

Conclusions

The aggregation of 2D MSCs, mediated by the interaction of integrin α4 and VCAM-1, is a potential risk for obstruction of CSF flow after intrathecal transplantation.
Tumour-associated macrophages enhance breast cancer malignancy via inducing ZEB1-mediated DNMT1 transcriptional activation
Authors: Li Zhongwei , Wang Pengfei , Cui Wenjie , Yong Hongmei , Wang Diandian , Zhao Tiesuo , Wang Wenwen , Shi Ming , Zheng Junnian , Bai Jin
Published: October 2022

Background

DNMT1 has been shown to be highly expressed in a variety of cancers, including breast cancer. However, the mechanism is not very clear. Therefore, we aim to reveal the mechanism of DNMT1 highly express in breast cancer. And we also want to explore the role of DNMT1 in tumour microenvironment promoting breast cancer progression.

Results

In this study, we demonstrate that DNMT1 is overexpressed in breast cancer and that DNMT1 promotes breast cancer tumorigenesis and metastasis. We discovered that ZEB1 activates DNMT1 expression in breast cancer cells by recruiting P300 binding to the DNMT1 promoter and increasing its acetylation. Moreover, we revealed that tumour-associated macrophages (TAMs) increase DNMT1 expression in breast cancer cells via the IL-6-pSTAT3-ZEB1-DNMT1 axis in the tumour microenvironment. DNMT1 is required for TAM-mediated breast cancer cell migration. In addition, we confirmed that there were positive correlations among CD163 (TAM marker) expression, ZEB1 expression and DNMT1 expression in breast cancer patient tissues.

Conclusions

Our study indicates that DNMT1 is necessary for TAM-mediated breast cancer metastasis. Decitabine (DAC), as a specific DNA methylation inhibitor and FDA-approved drug, is a bona fide drug for breast cancer treatment.
Fidelity varies in the symbiosis between a gutless marine worm and its microbial consortium
Authors: Sato Yui , Wippler Juliane , Wentrup Cecilia , Ansorge Rebecca , Sadowski Miriam , Gruber-Vodicka Harald , Dubilier Nicole , Kleiner Manuel
Published: October 2022

Background

Many animals live in intimate associations with a species-rich microbiome. A key factor in maintaining these beneficial associations is fidelity, defined as the stability of associations between hosts and their microbiota over multiple host generations. Fidelity has been well studied in terrestrial hosts, particularly insects, over longer macroevolutionary time. In contrast, little is known about fidelity in marine animals with species-rich microbiomes at short microevolutionary time scales, that is at the level of a single host population. Given that natural selection acts most directly on local populations, studies of microevolutionary partner fidelity are important for revealing the ecological and evolutionary processes that drive intimate beneficial associations within animal species.

Results

In this study on the obligate symbiosis between the gutless marine annelid Olavius algarvensis and its consortium of seven co-occurring bacterial symbionts, we show that partner fidelity varies across symbiont species from strict to absent over short microevolutionary time. Using a low-coverage sequencing approach that has not yet been applied to microbial community analyses, we analysed the metagenomes of 80 O. algarvensis individuals from the Mediterranean and compared host mitochondrial and symbiont phylogenies based on single-nucleotide polymorphisms across genomes. Fidelity was highest for the two chemoautotrophic, sulphur-oxidizing symbionts that dominated the microbial consortium of all O. algarvensis individuals. In contrast, fidelity was only intermediate to absent in the sulphate-reducing and spirochaetal symbionts with lower abundance. These differences in fidelity are likely driven by both selective and stochastic forces acting on the consistency with which symbionts are vertically transmitted.

Conclusions

We hypothesize that variable degrees of fidelity are advantageous for O. algarvensis by allowing the faithful transmission of their nutritionally most important symbionts and flexibility in the acquisition of other symbionts that promote ecological plasticity in the acquisition of environmental resources.
Biallelic mutations of TTC12 and TTC21B were identified in Chinese patients with multisystem ciliopathy syndromes
Authors: Chen Weicheng , Wang Feifei , Zeng Weijia , Zhang Xinyan , Shen Libing , Zhang Yuan , Zhou Xiangyu
Published: October 2022

Background

Abnormalities in cilia ultrastructure and function lead to a range of human phenotypes termed ciliopathies. Many tetratricopeptide repeat domain (TTC) family members have been reported to play critical roles in cilium organization and function.

Results

Here, we describe five unrelated family trios with multisystem ciliopathy syndromes, including situs abnormality, complex congenital heart disease, nephronophthisis or neonatal cholestasis. Through whole-exome sequencing and Sanger sequencing confirmation, we identified compound heterozygous mutations of TTC12 and TTC21B in six affected individuals of Chinese origin. These nonsynonymous mutations affected highly conserved residues and were consistently predicted to be pathogenic. Furthermore, ex vivo cDNA amplification demonstrated that homozygous c.1464 + 2 T > C of TTC12 would cause a whole exon 16 skipping. Both mRNA and protein levels of TTC12 were significantly downregulated in the cells derived from the patient carrying TTC12 mutation c.1464 + 2 T > C by real-time qPCR and immunofluorescence assays when compared with two healthy controls. Transmission electron microscopy analysis further identified ultrastructural defects of the inner dynein arms in this patient. Finally, the effect of TTC12 deficiency on cardiac LR patterning was recapitulated by employing a morpholino-mediated knockdown of ttc12 in zebrafish.

Conclusions

To the best of our knowledge, this is the first study reporting the association between TTC12 variants and ciliopathies in a Chinese population. In addition to nephronophthisis and laterality defects, our findings demonstrated that TTC21B should also be considered a candidate gene for biliary ciliopathy, such as TTC26, which further expands the phenotypic spectrum of TTC21B deficiency in humans.
Assessment of performance for a key indicator of One Health: evidence based on One Health index for zoonoses in Sub-Saharan Africa
Authors: Zhao Han-Qing , Fei Si-Wei , Yin Jing-Xian , Li Qin , Jiang Tian-Ge , Guo Zhao-Yu , Xue Jing-Bo , Han Le-Fei , Zhang Xiao-Xi , Xia Shang , Zhang Yi , Guo Xiao-Kui , Kassegne Kokouvi
Published: October 2022

Background

Zoonoses are public health threats that cause severe damage worldwide. Zoonoses constitute a key indicator of One Health (OH) and the OH approach is being applied for zoonosis control programmes of zoonotic diseases. In a very recent study, we developed an evaluation system for OH performance through the global OH index (GOHI). This study applied the GOHI to evaluate OH performance for zoonoses in sub-Saharan Africa.

Methods

The framework for the OH index on zoonoses (OHIZ) was constructed including five indicators, 15 subindicators and 28 datasets. Publicly available data were referenced to generate the OHIZ database which included both qualitative and quantitative indicators for all sub-Sahara African countries (n = 48). The GOHI algorithm was used to estimate scores for OHIZ. Indicator weights were calculated by adopting the fuzzy analytical hierarchy process.

Results

Overall, five indicators associated with weights were generated as follows: source of infection (23.70%), route of transmission (25.31%), targeted population (19.09%), capacity building (16.77%), and outcomes/case studies (15.13%). Following the indicators, a total of 37 sub-Sahara African countries aligned with OHIZ validation, while 11 territories were excluded for unfit or missing data. The OHIZ average score of sub-Saharan Africa was estimated at 53.67/100. The highest score was 71.99 from South Africa, while the lowest score was 40.51 from Benin. It is also worth mentioning that Sub-Sahara African countries had high performance in many subindicators associated with zoonoses, e.g., surveillance and response, vector and reservoir interventions, and natural protected areas, which suggests that this region had a certain capacity in control and prevention or responses to zoonotic events.

Conclusions

This study reveals that it is possible to perform OH evaluation for zoonoses in sub-Saharan Africa by OHIZ. Findings from this study provide preliminary research information in advancing knowledge of the evidenced risks to strengthen strategies for effective control of zoonoses and to support the prevention of zoonotic events.
Plasma proteome profiling identifies changes associated to AD but not to FTD
Authors: Mofrad R. Babapour , del Campo M. , Peeters C. F. W. , Meeter L. H. H. , Seelaar H. , Koel-Simmelink M. , Ramakers I. H. G. B. , Middelkoop H. A. M. , De Deyn P. P. , Claassen J. A. H. R. , van Swieten J. C. , Bridel C. , Hoozemans J. J. M. , Scheltens P. , van der Flier W. M. , Pijnenburg Y. A. L. , Teunissen Charlotte E.
Published: October 2022

Background

Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of FTD. We aimed to identify specific FTD plasma biomarker profiles discriminating FTD from AD and controls, and between FTD pathological subtypes. In addition, we compared plasma results with results in post-mortem frontal cortex of FTD cases to understand the underlying process.

Methods

Plasma proteins (n = 1303) from pathologically and/or genetically confirmed FTD patients (n = 56; FTLD-Tau n = 16; age = 58.2 ± 6.2; 44% female, FTLD-TDP n = 40; age = 59.8 ± 7.9; 45% female), AD patients (n = 57; age = 65.5 ± 8.0; 39% female), and non-demented controls (n = 148; 61.3 ± 7.9; 41% female) were measured using an aptamer-based proteomic technology (SomaScan). In addition, exploratory analysis in post-mortem frontal brain cortex of FTD (n = 10; FTLD-Tau n = 5; age = 56.2 ± 6.9, 60% female, and FTLD-TDP n = 5; age = 64.0 ± 7.7, 60% female) and non-demented controls (n = 4; age = 61.3 ± 8.1; 75% female) were also performed. Differentially regulated plasma and tissue proteins were identified by global testing adjusting for demographic variables and multiple testing. Logistic lasso regression was used to identify plasma protein panels discriminating FTD from non-demented controls and AD, or FTLD-Tau from FTLD-TDP. Performance of the discriminatory plasma protein panels was based on predictions obtained from bootstrapping with 1000 resampled analysis.

Results

Overall plasma protein expression profiles differed between FTD, AD and controls (6 proteins; p = 0.005), but none of the plasma proteins was specifically associated to FTD. The overall tissue protein expression profile differed between FTD and controls (7-proteins; p = 0.003). There was no difference in overall plasma or tissue expression profile between FTD subtypes. Regression analysis revealed a panel of 12-plasma proteins discriminating FTD from AD with high accuracy (AUC: 0.99). No plasma protein panels discriminating FTD from controls or FTD pathological subtypes were identified.

Conclusions

We identified a promising plasma protein panel as a minimally-invasive tool to aid in the differential diagnosis of FTD from AD, which was primarily associated to AD pathophysiology. The lack of plasma profiles specifically associated to FTD or its pathological subtypes might be explained by FTD heterogeneity, calling for FTD studies using large and well-characterize cohorts.
Exploring the private universe of Henri Matisse in The Red Studio
Authors: Haddad Abed , Pastorelli Gianluca , Ortiz Miranda Annette S. , Ludvigsen Loa , Centeno Silvia A. , Duvernois Isabelle , Hoover Caroline , Duffy Michael , Aviram Anny , Zycherman Lynda
Published: October 2022

The exhibition Matisse: The Red Studio allowed for an in-depth study of The Red Studio (1911) and six of the works featured in the painting by Henri Matisse (1869–1954) of his studio in Issy-les-Moulineaux near Paris. The grouping includes three paintings from the collection of the Statens Museum for Kunst (Le Luxe II, 1907, Nude with White Scarf, c. 1909, and Bathers, c. 1909), one painting from the collection of The Metropolitan Museum of Art (Young Sailor II, 1906), a painting from a private collection (Cyclamen, c. 1911), and a glazed and hand-painted earthenware plate from the collection of the Museum of Modern Art (Untitled (Female Nude), 1907). The six paintings were investigated using technical (X-radiography, ultraviolet-induced fluorescence, infrared reflectography) and chemical imaging (MA-XRF) and, in some cases, spectroscopic techniques (FORS, SEM–EDS, Raman, SERS, and μ-FTIR), to better elucidate Matisse’s materials and working techniques for this selection of paintings; the plate was also analyzed using MA-XRF. New findings revealed the full extent to which Matisse had completed The Red Studio before applying its hallmark color, referred to as Venetian red in his correspondence, over the original palette of blue, pink, and ochre that dominated the composition. Particular attention was given to identifying the wide range of pigment choices made by Matisse in the execution of the works from 1906 and 1911 that are depicted in The Red Studio. These pigments include lead white, zinc white, bone black, earth reds, madder lake, carmine lake, vermilion, cadmium yellow, yellow ochre, aureolin (cobalt) yellow, orpiment, viridian green, chromium-oxide green, cobalt blue, ultramarine blue, Prussian blue, cobalt violet (deep and light), and other cobalt violets, as well as possibly manganese violet and eosin red lake. The results of these analyses allowed for a direct comparison between the original works and their depictions and revealed that Matisse, unsurprisingly given his strong association with color, often translated the pigment choices faithfully between the actual works and their depictions in The Red Studio.
Transfer learning: a friendly introduction
Authors: Hosna Asmaul , Merry Ethel , Gyalmo Jigmey , Alom Zulfikar , Aung Zeyar , Azim Mohammad Abdul
Published: October 2022

Infinite numbers of real-world applications use Machine Learning (ML) techniques to develop potentially the best data available for the users. Transfer learning (TL), one of the categories under ML, has received much attention from the research communities in the past few years. Traditional ML algorithms perform under the assumption that a model uses limited data distribution to train and test samples. These conventional methods predict target tasks undemanding and are applied to small data distribution. However, this issue conceivably is resolved using TL. TL is acknowledged for its connectivity among the additional testing and training samples resulting in faster output with efficient results. This paper contributes to the domain and scope of TL, citing situational use based on their periods and a few of its applications. The paper provides an in-depth focus on the techniques; Inductive TL, Transductive TL, Unsupervised TL, which consists of sample selection, and domain adaptation, followed by contributions and future directions.
Evaluating the impact of price regulation (Drug Price Control Order 2013) on antibiotic sales in India: a quasi-experimental analysis, 2008–2018
Authors: Selvaraj Sakthivel , Farooqui Habib Hasan , Mehta Aashna , Mathur Manu Raj
Published: October 2022

Background

In India, due to a lack of population-level financial risk protection mechanisms, the expenditure on healthcare is primarily out-of-pocket in nature. Through Drug Price Control Orders (DPCOs), the Indian Government attempts to keep medicine prices under check. The aim of this study was to measure the potential impact of DPCO 2013 on the utilization of antibiotics under price regulation in India using large nationally representative pharmaceutical sales data.

Methods

We used interrupted time series analysis, a quasi-experimental research design to estimate the impact of DPCO 2013 on the utilization of antibiotics in the private sector in India. Indian pharmaceutical sales data set, PharmaTrac from a market research company—All Indian Origin Chemists and Distributors Limited—was used for the study. The data are collected from a panel of around 18,000 stockists across 23 different regions of the country. The primary outcome measure is the percentage change (increase or decrease) in the sales volume of the antibiotics under DPCO 2013, measured in standard units (SUs).

Results

Our estimates suggest that post-intervention (after notification of DPCO 2013) there was an immediate reduction (level change) in the sales of antibiotics under DPCO 2013 by 3.7% (P > 0.05), followed by a sustained decline (trend change) of 0.3% (P > 0.05) as compared to the pre-intervention trend at the molecule level, but both changes were statistically insignificant. However, in terms of ‘average monthly market share,’ the DPCO 2013 notification resulted in a sharp reduction of 579% (P < 0.05) (level change) followed by a sustained increase of 9.5% (P > 0.05) (trend change) in the ‘market share of antibiotics under DPCO’ as compared to pre-intervention trend.

Conclusions

The impact of DPCO 2013 in terms of the overall increase in the utilization of antibiotics under price regulation was limited but there was a switch from non-price controlled antibiotics to price regulated antibiotics (notified under DPCO 2013). We argue that policies on price control need to be complemented with continuous monitoring of market behavior to have a measurable and long-term impact.
Probabilistic tsunami hazard assessment based on the Gutenberg–Richter law in eastern Shikoku, Nankai subduction zone, Japan
Authors: Baba Toshitaka , Kamiya Masato , Tanaka Naoki , Sumida Yusuke , Yamanaka Ryoichi , Watanabe Kojiro , Fujiwara Hiroyuki
Published: October 2022

Earthquake and tsunami predictions comprise huge uncertainties, thus necessitating probabilistic assessments for the design of defense facilities and urban planning. In recent years, computer development has advanced probabilistic tsunami hazard assessments (PTHAs), where hazard curves show the exceedance probability of the maximum tsunami height. However, owing to the lack of historical and geological tsunami records, this method is generally insufficient for validating the estimated hazard curves. The eastern coast of Shikoku in the Nankai subduction zone, Japan, is suitable for validation because tsunami records from historical Nankai Trough earthquakes are available. This study evaluated PTHAs by comparing the tsunami hazard curves and exceedance frequencies of historical Nankai Trough tsunamis. We considered 3480 earthquake scenarios representing the rupture patterns of past Nankai earthquakes and calculated all tsunamis. The probability of earthquake occurrence was based on the Gutenberg–Richter law. We considered uncertainty in tsunami calculations with astronomical tide variations. The estimated tsunami hazard curves are consistent with the exceedance frequencies obtained from historical tsunamis. In addition, sensitivity tests indicate the significance of the earthquake slip heterogeneity and tsunami defense facilities in PTHAs. We also extended the PTHAs to tsunami inundation maps in high resolution and proposed an effective new method for reducing the tsunami computation load.

Graphical Abstract
Hemodynamic management of acute brain injury caused by cerebrovascular diseases: a survey of the European Society of Intensive Care Medicine
Authors: Messina Antonio , Villa Federico , Lionetti Giulia , Galarza Laura , Meyfroidt Geert , van der Jagt Mathieu , Monnet Xavier , Pelosi Paolo , Cecconi Maurizio , Robba Chiara
Published: October 2022

Background

The optimal hemodynamic targets and management of patients with acute brain injury are not completely elucidated, but recent evidence points to important impact on clinical outcomes. We performed an international survey with the aim to investigate the practice in the hemodynamic targets, monitoring, and management of patients with acute ischemic stroke (AIS), intracranial hemorrhage (ICH) and subarachnoid hemorrhage (SAH).

Methods

This survey was endorsed by the European Society of Intensive Care (ESICM). An electronic questionnaire of 76 questions divided in 4 sections (general information, AIS, ICH, SAH specific questions) was available between January 2022 to March 2022 on the ESICM website.

Results

One hundred fifty-four healthcare professionals from 36 different countries and at least 98 different institutions answered the survey. Routine echocardiography is routinely performed in 37% of responders in AIS, 34% in ICH and 38% in SAH. Cardiac output monitoring is used in less than 20% of cases by most of the responders. Cardiovascular complications are the main reason for using advanced hemodynamic monitoring, and norepinephrine is the most common drug used to increase arterial blood pressure. Most responders target fluid balance to neutral (62% in AIS, 59% in ICH,44% in SAH), and normal saline is the most common fluid used. Large variability was observed regarding the blood pressure targets.

Conclusions

Hemodynamic management and treatment in patients with acute brain injury from cerebrovascular diseases vary largely in clinical practice. Further research is required to provide clear guidelines to physicians for the hemodynamic optimization of this group of patients.
Spatiotemporal vertical velocity variation in the western tropical Pacific and its relation to decadal ocean variability
Authors: Nagano Akira , Hasegawa Takuya , Wakita Masahide
Published: October 2022

Prior to the cold phase of the Pacific decadal oscillation (PDO), sea surface water in the western tropical North Pacific is heated. To evaluate the impact of the subsurface water on the upper-ocean ($$<100$$

<
100

 m depth) temperature variation, we examined the vertical velocity variation. We applied altimetry-based gravest empirical mode (AGEM) method to Argo hydrographic profile (2001–2017) and altimetric sea surface height (1993–2017) data in the western tropical Pacific and obtained a time-varying three-dimensional (3D) potential density field in the layer from 100 to 1000 m depth. From the AGEM-derived potential density, we derived a 3D field of vertical velocity below 100 m depth by the P-vector inverse method, which is based on potential density and vorticity conservations, and examined the spatiotemporal characteristics, focusing on the seasonal to quasi-decadal (QD) variations. In the mean state, substantial upward current ($$>10^{-6}\,{\text {m\,s}}^{-1}$$

>

10

-
6

m\,s

-
1

) is observed in the region of $$10^{\circ }$$

10
∘

–$$17^{\circ }$$

17
∘

N, $$140^{\circ }$$

140
∘

E–$$180^{\circ }$$

180
∘

in the North Equatorial Current, southern part of the North Pacific subtropical gyre. Possibly besides the Ekman upwelling, the upward current contributes to the cooling of the upper ocean in the western tropical North Pacific through the upward advection of the deep cold water. The upward current was found to be intensified (attenuated) by the strengthening (weakening) of the subtropical gyre interior southward flow on the QD timescale in association with frequent occurrences of La Niña (El Niño) events. The weakening of the upward current is responsible for the QD increase in upper-ocean temperature in the western tropical North Pacific, which is equivalent to or larger than $$0.2~^{\circ }$$

0.2

∘

C, several years after the warm phase of the PDO. The QD temperature variation may affect the phase reversal of the PDO through the heat transport of the western boundary current of the subtropical gyre, i.e., the Kuroshio.
Antenatal preventative pelvic floor muscle exercise intervention led by midwives to reduce postnatal urinary incontinence (APPEAL): protocol for a feasibility and pilot cluster randomised controlled trial
Authors: Bick D. , Bishop J. , Coleman T. , Dean S. , Edwards E. , Frawley H. , Gkini E. , Hay-Smith J. , Hemming K. , Jones E. , Oborn E. , Pearson M. , Salmon V. , Webb S. , MacArthur C.
Published: October 2022

Background

Antenatal pelvic floor muscle exercises (PFME) in women without prior urinary incontinence (UI) are effective in reducing postnatal UI; however, UK midwives often do not provide advice and information to women on undertaking PFME, with evidence that among women who do receive advice, many do not perform PFME.

Methods

The primary aim of this feasibility and pilot cluster randomised controlled trial is to provide a potential assessment of the feasibility of undertaking a future definitive trial of a midwifery-led antenatal intervention to support women to perform PFME in pregnancy and reduce UI postnatally.

Community midwifery teams in participating NHS sites comprise trial clusters (n = 17). Midwives in teams randomised to the intervention will be trained on how to teach PFME to women and how to support them in undertaking PFME in pregnancy. Women whose community midwifery teams are allocated to control will receive standard antenatal care only.

All pregnant women who give birth over a pre-selected sample month who receive antenatal care from participating community midwifery teams (clusters) will be sent a questionnaire at 10–12 weeks postpartum (around 1400–1500 women). Process evaluation data will include interviews with midwives to assess if the intervention could be implemented as planned. Interviews with women in both trial arms will explore their experiences of support from midwives to perform PFME during pregnancy. Data will be stored securely at the Universities of Birmingham and Exeter.

Results will be disseminated through publications aimed at maternity service users, clinicians, and academics and inform a potential definitive trial of effectiveness. The West Midlands–Edgbaston Research Ethics Committee approved the study protocol.

Discussion

Trial outcomes will determine if criteria to progress to a definitive cluster trial are met. These include women’s questionnaire return rates, prevalence of UI, and other health outcomes as reported by women at 10–12 weeks postpartum. Progress to a definitive trial however is likely to be prevented in the UK context by new perinatal pelvic health service, although this may be possible elsewhere.

Trial registration

https://doi.org/10.1186/ISRCTN10833250. Registered 09/03/2020
Clinical feasibility and preliminary outcomes of a novel mixed reality system to manage phantom pain: a pilot study
Authors: Annaswamy Thiru M , Bahirat Kanchan , Raval Gargi , Chung Yu Yen , Pham Tri , Prabhakaran Balakrishnan
Published: October 2022

Background

To assess the clinical feasibility of a virtual mirror therapy system in a pilot sample of patients with phantom pain.

Methods

Our Mixed reality system for Managing Phantom Pain (Mr. MAPP) mirrors the preserved limb to visualize the amputated limb virtually and perform exercises. Seven patients with limb loss and phantom pain agreed to participate and received the system for 1-month home use. Outcome measures were collected at baseline and 1 month.

Results

Four (of seven recruited) participants completed the study, which was temporarily suspended due to COVID-19 restrictions. At 1 month, in-game data showed a positive trend, but pain scores showed no clear trends. Functioning scores improved for 1 participant.

Conclusions

Mr. MAPP is feasible and has the potential to improve pain and function in patients with phantom pain.

Trial registration

Clinical Trials Registration, NCT04529083
Targeted thrombolysis by magnetoacoustic particles in photothrombotic stroke model
Authors: Choi Wonseok , Cho Hyeyoun , Kim Gahee , Youn Inchan , Key Jaehong , Han Sungmin
Published: October 2022

Background

Recombinant tissue plasminogen activator (rtPA) has a short half-life, and additional hemorrhagic transformation (HT) can occur when treatment is delayed. Here, we report the design and thrombolytic performance of 3

μ

m discoidal polymeric particles loaded with rtPA and superparamagnetic iron oxide nanoparticles (SPIONs), referred to as rmDPPs, to address the HT issues of rtPA.

Methods

The rmDPPs consisted of a biodegradable polymeric matrix, rtPA, and SPIONs and were synthesized
via
a top-down fabrication.

Results

The rmDPPs could be concentrated at the target site with magnetic attraction, and then the rtPA could be released under acoustic stimulus. Therefore, we named that the particles had magnetoacoustic properties. For the
in vitro
blood clot lysis, the rmDPPs with magnetoacoustic stimuli could not enhance the lytic potential compared to the rmDPPs without stimulation. Furthermore, although the reduction of the infarcts
in vivo
was observed along with the magnetoacoustic stimuli in the rmDPPs, more enhancement was not achieved in comparison with the rtPA. A notable advantage of rmDPPs was shown in delayed administration of rmDPPs at poststroke. The late treatment of rmDPPs with magnetoacoustic stimuli could reduce the infarcts and lead to no additional HT issues, while rtPA alone could not show any favorable prognosis.

Conclusion

The rmDPPs may be advantageous in delayed treatment of thrombotic patients.
A health promotion intervention to address youth violence among students in a technical college in Sri Lanka guided by the participatory action research approach: a study protocol
Authors: Rathnayake Nadeeka , Abhayasinghe Kalpani , De Silva Jayamal , Guruge G. N. Duminda
Published: October 2022

Background

Youth violence is a global public health issue and the highest rates are reported in Low and Middle-Income Countries (LMICs). Higher rates of youth violence are reported in Sri Lanka as well. Students who fail to continue higher studies in schools or enter the universities in Sri Lanka, enroll in technical colleges and are associated with a higher number of risk factors of violence. This study aims to empower youth (15–29 years old) of a technical college in Matale district, Sri Lanka, to carry out activities among themselves to improve their knowledge, change perceptions, and violence-related behaviours.

Methods

The Participatory Action Research (PAR) approach will be used. The study participants will be eighty students in a technical college in Matale district, Sri Lanka. The study period will be three years. Study participants will also be collaborators and they will involve actively in all stages of the study. A health promotion intervention will be implemented to identify determinants of youth violence and to design and implement actions while monitoring the changes. The data will be collected mainly through focus group discussions and key informant interviews both before and after the health promotion intervention. Additionally, a self-administered questionnaire will be used and the principal investigator will maintain a reflective diary. The qualitative data will be analysed thematically whereas quantitative data will be analysed using descriptive statistics. Data will be triangulated to increase the rigour of the study.

Discussion

According to literature, PAR is not widely used in health promotion. The enabling and empowerment goals of health promotion are fulfilled in PAR. Thus, this will be a novel experience for researchers and this will stimulate discussion on the combination of PAR and health promotion. This study design itself promotes active participant involvement and it may generate effective youth-led, culturally appropriate actions to address youth violence. The findings will describe what works and why it works and will help Sri Lanka and similar LMICs to create safe environments for youth in educational institutes or training colleges.
Good practices for 68Ga radiopharmaceutical production
Authors: Nelson Bryce J. B. , Andersson Jan D. , Wuest Frank , Spreckelmeyer Sarah
Published: October 2022

Background

The radiometal gallium-68 (68Ga) is increasingly used in diagnostic positron emission tomography (PET), with 68Ga-labeled radiopharmaceuticals developed as potential higher-resolution imaging alternatives to traditional 99mTc agents. In precision medicine, PET applications of 68Ga are widespread, with 68Ga radiolabeled to a variety of radiotracers that evaluate perfusion and organ function, and target specific biomarkers found on tumor lesions such as prostate-specific membrane antigen, somatostatin, fibroblast activation protein, bombesin, and melanocortin.

Main body

These 68Ga radiopharmaceuticals include agents such as [68Ga]Ga-macroaggregated albumin for myocardial perfusion evaluation, [68Ga]Ga-PLED for assessing renal function, [68Ga]Ga-t-butyl-HBED for assessing liver function, and [68Ga]Ga-PSMA for tumor imaging. The short half-life, favourable nuclear decay properties, ease of radiolabeling, and convenient availability through germanium-68 (68Ge) generators and cyclotron production routes strongly positions 68Ga for continued growth in clinical deployment. This progress motivates the development of a set of common guidelines and standards for the 68Ga radiopharmaceutical community, and recommendations for centers interested in establishing 68Ga radiopharmaceutical production.

Conclusion

This review outlines important aspects of 68Ga radiopharmacy, including 68Ga production routes using a 68Ge/68Ga generator or medical cyclotron, standardized 68Ga radiolabeling methods, quality control procedures for clinical 68Ga radiopharmaceuticals, and suggested best practices for centers with established or upcoming 68Ga radiopharmaceutical production. Finally, an outlook on 68Ga radiopharmaceuticals is presented to highlight potential challenges and opportunities facing the community.
Using objective measures to examine the effect of suspect-filler similarity on eyewitness identification performance
Authors: McKinley Geoffrey L. , Peterson Daniel J.
Published: October 2022

When selecting fillers to include in a police lineup, one must consider the level of similarity between the suspect and potential fillers. In order to reduce misidentifications, an innocent suspect should not stand out. Therefore, it is important that the fillers share some degree of similarity. Importantly, increasing suspect-filler similarity too much will render the task too difficult reducing correct identifications of a guilty suspect. Determining how much similarity yields optimal identification performance is the focus of the proposed study. Extant research on lineup construction has provided somewhat mixed results. In part, this is likely because similarity is often defined in relative terms due to the subjective nature of similarity. In the current study, we propose an experiment in which we manipulate suspect-filler similarity via a multidimensional scaling model constructed using objective facial measurements. In doing so, we test the “propitious heterogeneity” and the diagnostic-feature-detection hypotheses which predict an advantage of lineups with low similarity fillers in terms of discriminability.
Anti-high mobility group box protein 1 monoclonal antibody downregulating P-glycoprotein as novel epilepsy therapeutics
Authors: de Liyis Bryan Gervais , Tandy Sevinna Geshie , Endira Joana Fourta , Putri Komang Andjani , Utami Desak Ketut Indrasari
Published: October 2022

Epilepsy, a neurological illness, is characterized by recurrent uncontrolled seizures. There are many treatments of options that can be used as the therapy of epilepsy. However, anti-seizure medications as the primary treatment choice for epilepsy show many possible adverse effects and even pharmacoresistance to the therapy. High Mobility Group Box 1 (HMGB1) as an initiator and amplifier of the neuroinflammation is responsible for the onset and progression of epilepsy by overexpressing P-glycoprotein on the blood brain barrier. HMGB1 proteins then activate TLR4 in neurons and astrocytes, in which proinflammatory cytokines are produced. Anti-HMGB1 mAb works by blocking the HMGB1, reducing inflammatory activity in the brain that may affect epileptogenesis. Through the process, anti-HMGB1 mAb reduces the TLR4 activity and other receptors that may involve in promote signal of epilepsy such as RAGE. Several studies have shown that anti-HMGB1 has the potential to inhibit the increase in serum HMGB1 in plasma and brain tissue. Further research is needed to identify the mechanism of the inhibiting of overexpression of P-glycoprotein through anti-HMGB1 mAb.
Horner syndrome secondary to edema of the longus colli muscle: a case report
Authors: Zhou Avery , Nichols Cory , Paul Janda , Vickers Aroucha
Published: October 2022

Background

Horner syndrome is caused by disruption to any part of the oculosympathetic nerve supply, and is classically characterized by the triad of ptosis, miosis, and facial anhidrosis. Two cases of Horner syndrome secondary to longus colli edema have previously been reported in the literature; however, this is the first case of bilateral asymmetric longus colli inflammation causing unilateral Horner syndrome.

Case presentation

An 18-year-old male was found unresponsive in his car after a motor vehicle accident and was found to have new onset anisocoria with a miotic left pupil and left-sided ptosis consistent with Horner syndrome. Imaging was unremarkable except for the MRI neck soft tissues, which revealed abnormal increased signal intensity consistent with extensive edema in the left longus colli muscle and a shorter segment of edema in the right longus colli muscle.

Conclusion

The patient’s presentation and imaging results suggest Horner syndrome secondary to edema of the longus colli muscle, as the second-order sympathetic innervation to the eye runs under the longus colli. Traumatic Horner syndrome from longus colli contusion is a rare and benign entity that may self-resolve as inflammation and compression decrease. Imaging of the soft tissues of the neck is vital in assessing this rare occurrence. More common and concerning etiologies should be excluded with proper vascular, cerebral and spinal imaging before attributing Horner syndrome to a benign cause.
Major concerns of surface water quality in south-west coastal regions of Vietnamese Mekong Delta
Authors: Nguyen Thanh Giao , Phan Kim Anh , Huynh Thi Hong Nhien
Published: October 2022

This study aimed to appraise seasonal variations in surface water quality on the coasts of Southwestern Vietnam using entropy-weighted water quality index (EWQI) and multivariate statistics: cluster analysis (CA), principal component analysis (PCA), and discriminant analysis (DA). Forty-nine samples monitored in Kien Giang province during the rainy and dry seasons were analysed for 16 physiochemical and biological parameters. Compared to the Vietnamese standard, surface water quality in the study areas was contaminated with organic matter (high biological oxygen demand and chemical oxygen demand), nutrients (high ammonium (NH4+), nitrite, and orthophosphate), total suspended solids (TSS), iron (Fe), and coliform. Seasonal variations in surface water quality in the coastal regions were observed. TSS, organic matter and microbial problems in water bodies tend to be more serious in the rainy seasons due to an increase in water flow containing pollutants from upstream and wastes from regional human activities. Meanwhile, the salinity in the dry season (0–32‰) was greatly higher, which caused only 10% of samples to be suitable for irrigation. CA extracted 11 and 13 clusters from 49 locations in the dry and rainy seasons, respectively. Five principal components obtained from PCA can explain 74 and 70% of total water quality variations in dry and rainy seasons, respectively. Moreover, the results of PCA suggested that natural factors (hydrological regimes, temperature, rainfall, sea-level rise) and human sources (domestic, agriculture, industry, and tourism) are accountable for these fluctuations. DA extracted 7 parameters (pH, TSS, salinity, Fe, nitrate, NH4+, and chloride) for leading the difference in water quality, with 88% of correct assignation. EWQI revealed that about 66% of total samples were classified as a very bad quality for drinking in the dry season. However, this ratio declined to 59% in the rainy season. Although the surface water quality was slightly improved during the rainy season, organic matter and microbial pollution need to be concerned. The findings of this study can provide insights into seasonal variations in surface water with the application of multivariate statistics and EWQI, which could support policymakers in developing water management strategies.