bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Alzheimer’s disease drug development landscape
Authors: van Bokhoven Pieter , de Wilde Arno , Vermunt Lisa , Leferink Prisca S. , Heetveld Sasja , Cummings Jeffrey , Scheltens Philip , Vijverberg Everard G. B. 
Published: November 2021

AbstractBackgroundAlzheimer’s disease (AD) is a devastating neurodegenerative disease leading to dementia. The field has made significant progress over the last 15 years. AD diagnosis has shifted from syndromal, based on signs and symptoms, to a biomarker construct based on the pathological hallmarks of the disease: amyloid β deposition, pathologic tau, and neurodegeneration. Numerous genetic risk factors for sporadic AD have been identified, providing further insight into the molecular underpinnings of the disease. For the last two decades, however, drug development for AD has been proven to be particularly challenging. Here, we provide a unique overview of the drug development landscape for AD. By comparing preclinical and clinical drug development pipelines, we aim to describe trends and differences regarding target classes and therapeutic modalities in preclinical and clinical development.MethodsWe analyzed proprietary and public databases and company websites for drugs in preclinical development for AD by the pharmaceutical industry and major clinical trial registries for drugs in clinical development for AD. Drugs were categorized by target class and treatment modality.ResultsWe found a higher proportion of preclinical interventions targeting molecular pathways associated with sporadic AD genetic risk variants, compared to clinical stage interventions. These include apolipoprotein E (ApoE) and lipids, lysosomal/endosomal targets, and proteostasis. Further, we observed a trend suggesting that more traditional therapeutic modalities are developed for these novel targets, while more novel treatment modalities such as gene therapies and enzyme treatments are in development for more traditional targets such as amyloid β and tau. Interestingly, the percentage of amyloid β targeting therapies in preclinical development (19.2%) is even higher than the percentage in clinical development (10.7%), indicating that diversification away from interventions targeting amyloid-beta has not materialized. Inflammation is the second most popular target class in both preclinical and clinical development.ConclusionsOur observations show that the AD drug development pipeline is diversifying in terms of targets and treatment modalities, while amyloid-targeting therapies remain a prominent avenue of development as well. To further advance AD drug development, novel companion diagnostics are needed that are directed at disease mechanisms related to genetic risk factors of AD, both for patient stratification and assessment of therapeutic efficacy in clinical trials.
A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites
Authors: Shi Hongli , Ge Xing , Ma Xi , Zheng Mingxuan , Cui Xiaoying , Pan Wei , Zheng Peng , Yang Xiaoying , Zhang Peng , Hu Minmin , Hu Tao , Tang Renxian , Zheng Kuiyang , Huang Xu-Feng , Yu Yinghua 
Published: November 2021

Abstract
Background
Cognitive impairment, an increasing mental health issue, is a core feature of the aging brain and neurodegenerative diseases. Industrialized nations especially, have experienced a marked decrease in dietary fiber intake, but the potential mechanism linking low fiber intake and cognitive impairment is poorly understood. Emerging research reported that the diversity of gut microbiota in Western populations is significantly reduced. However, it is unknown whether a fiber-deficient diet (which alters gut microbiota) could impair cognition and brain functional elements through the gut-brain axis.

Results
In this study, a mouse model of long-term (15 weeks) dietary fiber deficiency (FD) was used to mimic a sustained low fiber intake in humans. We found that FD mice showed impaired cognition, including deficits in object location memory, temporal order memory, and the ability to perform daily living activities. The hippocampal synaptic ultrastructure was damaged in FD mice, characterized by widened synaptic clefts and thinned postsynaptic densities. A hippocampal proteomic analysis further identified a deficit of CaMKIId and its associated synaptic proteins (including GAP43 and SV2C) in the FD mice, along with neuroinflammation and microglial engulfment of synapses. The FD mice also exhibited gut microbiota dysbiosis (decreased Bacteroidetes and increased Proteobacteria), which was significantly associated with the cognitive deficits. Of note, a rapid differentiating microbiota change was observed in the mice with a short-term FD diet (7 days) before cognitive impairment, highlighting a possible causal impact of the gut microbiota profile on cognitive outcomes. Moreover, the FD diet compromised the intestinal barrier and reduced short-chain fatty acid (SCFA) production. We exploit these findings for SCFA receptor knockout mice and oral SCFA supplementation that verified SCFA playing a critical role linking the altered gut microbiota and cognitive impairment.

Conclusions
This study, for the first time, reports that a fiber-deprived diet leads to cognitive impairment through altering the gut microbiota-hippocampal axis, which is pathologically distinct from normal brain aging. These findings alert the adverse impact of dietary fiber deficiency on brain function, and highlight an increase in fiber intake as a nutritional strategy to reduce the risk of developing diet-associated cognitive decline and neurodegenerative diseases.
Heavy metal contamination and health risk assessment of mechanically milled delicacy called fufu
Authors: Nkansah Marian Asantewah , Agorsor Patrica-Ivy , Opoku Francis 
Published: November 2021

AbstractContamination of food by heavy metals is a concern as consumption of contaminated food is one of the most likely human exposure routes to metals. Fufu is a delicacy in Ghana consumed mainly by the Akans. Human exposure to some heavy metals (Cr, Fe, Zn, Mn and Ni) through mechanically processed fufu consumption was analysed by atomic absorption spectrophotometer and ascertaining consumer awareness of potential exposure by questionnaire administration. A total of 30 milled and un-milled fufu samples (cassava and plantain) were sampled from Bomso, Kotei, Ayeduase, Ayigya and Kentikrono, all within Kumasi. The results showed that Fe and Zn levels after milling were elevated in the range: 2.816–7.297 and 0.753–7.529 mg/kg, respectively. The concentrations of Fe and Zn were below the Food and Agriculture Organization/World Health Organization (FAO/WHO) permissible limits except Zn concentration at Bomso. Cr, Mn and Ni were below the detection limit (0.05). Hazard quotients and indices were less than the US Environmental Protection Agency’s permitted level of one, indicating no possible harm to consumers. Findings from the questionnaire administration indicated a complete lack of knowledge on consumer exposure due to the food processing method.
An investigation of latent fingerprinting techniques
Authors: Dhaneshwar Ritika , Kaur Mandeep , Kaur Manvjeet 
Published: November 2021

Abstract
Background
Latent fingerprints are the unintentional impressions that are left at crime scenes, which are considered to be highly significant in forensic analysis and authenticity verification. It is an extremely crucial tool used by law enforcement and forensic agencies for the conviction of criminals. However, due to the accidental nature of these impressions, the quality of prints uplifted is generally inferior.

Main body
In order to improve the overall fingerprint recognition performance, there is an insistent need to design novel methods to improve the reliability and robustness of the existing techniques. Therefore, a systematic review is presented to study the existing methods for latent fingerprint acquisition, enhancement, reconstruction, and matching, along with various benchmark datasets available for research purposes.

Conclusion
The paper highlights multiple challenges and research gaps using comparative analysis of existing enhancement, reconstruction and matching approaches in order to augment the research in this direction that has become imperative in this digital era.
(Trans) Sex Sells
Authors: Goldberg RL 
Published: November 2021

Abstract
In this article the author considers the vexed relationship that Star Distributors' trans sleaze had with taxonomy. The author argues that linguistic slippage and the inability to define a precise trans identity as object speaks not only, or exclusively, to a sloppiness on the part of sleaze writers but is also a deliberate illumination of the degree to which white trans is not reducible to something known or necessarily stable. Because it is irreducible to knowledge and finality, these texts delight in the possibilities of plurality, in teaching, and in learning to work one's gender in excess of cis practice. Finally, this article explores the bifurcated way these novels depict pedagogy for white and Black trans characters.
A method for selective stimulation of leg chemoreceptors in whole crustaceans
Authors: Solari Paolo , Sollai Giorgia , Palmas Francesco , Sabatini Andrea , Crnjar Roberto 
Published: November 2021

ABSTRACT
The integration of sensory information with adequate motor outputs is critical for animal survival. Here, we present an innovative technique based on a non-invasive closed-circuit device consisting of a perfusion/stimulation chamber chronically applied on a single leg of the crayfish Procambarus clarkii. Using this technique, we focally stimulated the leg inside the chamber and studied the leg-dependent sensory–motor integration involving other sensory appendages, such as antennules and maxillipeds, which remain unstimulated outside the chamber. Results show that the stimulation of a single leg with chemicals, such as disaccharides, is sufficient to trigger a complex search behaviour involving locomotion coupled with the reflex activation of antennules and maxillipeds. This technique can be easily adapted to other decapods and/or other sensory appendages. Thus, it has opened possibilities for studying sensory–motor integration evoked by leg stimulation in whole aquatic animals under natural conditions to complement, with a direct approach, current ablation or silencing techniques.
Tumour-to-normal tissue (T/N) dosimetry ratios role in assessment of 90Y selective internal radiation therapy (SIRT)
Authors: Knešaurek Karin , Martinez Ricardo Bello , Ghesani Munir 
Published: November 2021

Objective:
The purpose of our work is to assess the role of tumour-to-normal tissue (T/N) dosimetry ratios for predicting response in patients undergoing locoregional therapy to the liver with 90Y microspheres.

Methods:
A total of 39 patients (7 female:32 male, mean age 68.3 ± 7.6 years), underwent positron emission tomography (PET)/CT imaging after treatment with 90Y microspheres. For attenuation correction and localization of the 90Y microspheres, the low-dose, non-diagnostic CT images from PET/CT were used. The acquisition took 15 min and the reconstruction matrix size was 200 × 200 × 75 mm and voxel size of 4.07 × 4.07 × 3.00 mm. For dosimetry calculations, the local deposition method with known activity of 90Y was used. For each patient, regions of interest for tumour(s) and whole liver were manually created; the normal tissue region of interest was created automatically. mRECIST criteria on MRI done at 1 month post-treatment and subsequently every 3 months after 90Y treatment, were used to assess response.

Results:
For 39 patients, the mean liver, tumour and normal tissue doses (mean ± SD) were, 55.17 ± 26.04 Gy, 911.87 ± 866.54 Gy and 47.79 ± 20.47 Gy, respectively. Among these patients, 31 (79%) showed complete response (CR) and 8 (21%) showed progression of disease (PD). For patients with CR, the mean T/N dose ratio obtained was 24.91 (range 3.09–80.12) and for patients with PD, the mean T/N dose ratio was significantly lower, at 6.69 (range 0.36–14.75).

Conclusion:
Our data show that patients with CR have a statistically higher T/N dose ratio than those with PD. Because, the number of PD cases was limited and partial volume effect was not considered, further investigation is warranted.

Advances in knowledge:
T/N dosimetry ratios can be used for assessing response in patients undergoing locoregional therapy to the liver with 90Y microspheres.
Radiopaque drug-eluting embolisation beads as fiducial markers for stereotactic liver radiotherapy
Authors: Beaton Laura , Daly Mairead , Tregidgo Henry FJ , Grimes Helen , Moinuddin Syed , Stacey Chris , Znati Sami , Hague Julian , Bascal Zainab A , Wilde Paul E , Cooper Sarah , Bandula Steven , Lewis Andrew L , Clarkson Matthew J , Sharma Ricky A 
Published: November 2021

Objective:
To determine the feasibility of using radiopaque (RO) beads as direct tumour surrogates for image-guided radiotherapy (IGRT) in patients with liver tumours after transarterial chemoembolisation (TACE).

Methods:
A novel vandetanib-eluting RO bead was delivered via TACE as part of a first-in-human clinical trial in patients with either hepatocellular carcinoma or liver metastases from colorectal cancer. Following TACE, patients underwent simulated radiotherapy imaging with four-dimensional computed tomography (4D-CT) and cone-beam CT (CBCT) imaging. RO beads were contoured using automated thresholding, and feasibility of matching between the simulated radiotherapy planning dataset (AVE-IP image from 4D data) and CBCT scans assessed. Additional kV, MV, helical CT and CBCT images of RO beads were obtained using an in-house phantom. Stability of RO bead position was assessed by comparing 4D-CT imaging to CT scans taken 6–20 days following TACE.

Results:
Eight patients were treated and 4D-CT and CBCT images acquired. RO beads were visible on 4D-CT and CBCT images in all cases and matching successfully performed. Differences in centre of mass of RO beads between CBCT and simulated radiotherapy planning scans (AVE-IP dataset) were 2.0 mm mediolaterally, 1.7 mm anteroposteriorally and 3.5 mm craniocaudally. RO beads in the phantom were visible on all imaging modalities assessed. RO bead position remained stable up to 29 days post TACE.

Conclusion:
RO beads are visible on IGRT imaging modalities, showing minimal artefact. They can be used for on-set matching with CBCT and remain stable over time.

Advances in knowledge:
The role of RO beads as fiducial markers for stereotactic liver radiotherapy is feasible and warrants further exploration as a combination therapy approach.
Assessment of body composition and association with clinical outcomes in patients with lung and colorectal cancer
Authors: Sakai Naomi S , Bhagwanani Anisha , Bray Timothy JP , Hall-Craggs Margaret A , Taylor Stuart Andrew 
Published: November 2021

Objectives:
To assess body composition in patients with non-small cell lung cancer (NSCLC) and colorectal cancer using whole-body MRI and relate this to clinical outcomes.

Methods:
53 patients with NSCLC (28 males, 25 females; mean age 66.9) and 74 patients with colorectal cancer (42 males, 32 females; mean age 62.9) underwent staging whole-body MRI scans, which were post-processed to derive fat mass (FM), fat free mass (FFM) and skeletal muscle (SM) indices and SM fat fraction (FF). These were compared between the two cancer cohorts using two-sided t-tests and the chi-squared test. Measurements of body composition were correlated with outcomes including length of hospital stay, metastatic status and mortality.

Results:
Patients with NSCLC had significantly lower FFM (p = 0.0071) and SM (p = 0.0084) indices. Mean SM FF was greater in patients with NSCLC (p = 0.0124) and was associated with longer hospital stay (p = 0.035). There was no significant relationship between FM, FFM and SM indices and length of hospital stay, metastatic status or mortality.

Conclusions:
Patients with NSCLC had lower FFM and SM indices than patients with colorectal cancer and greater SMFF, indicating lower SM mass with fatty infiltration. These findings reflect differences in the phenotype of the two groups and suggest patients with lung cancer are more likely to require additional nutritional support.

Advances in knowledge:
Body composition differs between NSCLC and colorectal cancer. Patients with NSCLC have both a reduced SM mass and greater SM FF suggesting that they are more nutritionally deplete than patients with colorectal cancer.
Case Report: The resiliency journey of a Vietnamese female sexual abuse survivor: an exploration in life history
Authors: Giang Thien-Vu , Le Duy-Hung , Nguyen Thanh-Huan , Huynh Van-Son , Nguyen-Thi Diem-My 
Published: November 2021

Currently, the studies on sexual abuse trauma, and resilience in Confucian survivors are still limited. The purpose of this study is to explore the resilience of Confucian women after sexual abuse trauma to provide evidence to support in counseling and psychotherapy practices. The article describes the resiliency story of a Vietnamese Confucian female survivor who was abused by her brother from the age of 8 to 16. The life history approach used in qualitative narrative research was applied in this study. The researcher identified two factors that strongly influence the survivor’s resilience: (1) the effectiveness of passive education in the general education curriculum is oriented to both competence and quality development; and (2) an authentic understanding of the core Confucian philosophical doctrine: the neutrality and the self-nurture. Based on the findings, we propose a 7-stage flow diagram of a Confucian women's resilience following sexual abuse. These findings provide a new approach to psychological counseling for female survivors of any religion by using Confucian philosophy and contribute to the impact of studies on religious and spiritual factors affecting the resilience of sexual abuse survivors.
Efficacy, safety, and immunogenicity of rurioctocog alfa pegol for prophylactic treatment in previously treated patients with severe hemophilia A: a systematic review and meta-analysis of clinical trials
Authors: Witarto Bendix Samarta , Visuddho Visuddho , Witarto Andro Pramana , Sutanto Henry , Wiratama Bayu Satria , Wungu Citrawati Dyah Kencono 
Published: November 2021

Background: Patients with severe hemophilia often present with painful joint and soft tissue bleeding which may restrict them from their daily activities. The current standard of care still relies on a regular prophylactic factor VIII (FVIII), which has a high daily treatment burden. Recently, rurioctocog alfa pegol, a third-generation recombinant FVIII with a modification in its polyethylene glycol (PEG) component, has been developed. Several trials have studied this synthetic drug as bleeding prophylaxis in severe hemophilia A. This study aims to evaluate the efficacy, safety, and immunogenicity of rurioctocog alfa pegol for previously treated patients with severe hemophilia A. Methods: This study was conducted in conformity with the PRISMA guidelines. Data were retrieved from PubMed, Scopus, Cochrane Library, Wiley Online Library, and CINAHL (via EBSCOhost). Study qualities were assessed using the Methodological Index for Non-Randomized Studies (MINORS) and Modified Jadad scales. Results: Four studies involving 517 previously treated severe hemophilia A patients were included in this study. The pooled mean of total annualized bleeding rate (ABR) and hemostatic efficacy was 2.59 (95% CI = 2.04–3.14) and 92% (95% CI = 85%–97%), respectively. Only 30 (2.3%) non-serious and one (1.4%) serious adverse events were considered related to rurioctocog alfa pegol treatment. At the end of the studies, no development of FVIII inhibitory antibodies was observed. None of the developed binding antibodies to FVIII, PEG-FVIII, or PEG was correlated to the treatment efficacy and safety. Conclusions: Despite the limited availability of direct comparison studies, our analyses indicate that rurioctocog alfa pegol could serve as a safe and effective alternative for bleeding prophylaxis in previously treated hemophilia A patients. Moreover, it appears to have low immunogenicity, which further increases the safety profile of the drug in such clinical conditions.
CONSTRUCTION MARKET OF SMOLENSK REGION DURING THE PERIOD FINANCIAL CRISIS AND PANDEMIC IMPACT
Authors: Sapozhnikova Svetlana M. 
Published: November 2021

The study examines the features of the development of the construction industry at the regional level, defines the main parameters of the state and the prospects for its further functioning.
The factors influencing the current trends in the development of the construction industry, threats and main problems, especially in the context of the global economic crisis and pandemic, are identified. A survey of the state of the material and technical base of construction companies and the level of their competition was carried out, as well as a survey of industry entrepreneurs on changes in the level of their economic activity and the prospects for the formation of a construction portfolio.
On the basis of this, measures were proposed to improve the regulation of the construction market in the context of the economic crisis and pandemic. The main conclusion of the study is that the only condition for effective development and recovery to the pre-crisis level of the economy of the regions and its industries, including construction, in a lockdown is full government regulation, financing, nationalization and financial, legal, diplomatic, information protection from external negative impact globalization and crisis.
Purpose. The goal is to assess the state of the construction market in the region, identify problems and threats and propose measures to regulate it in the face of a lockdown, sanctions, economic crisis and pandemic.
Methodology: the article used methods of comparison, survey, index, graphic, methods of statistical and factor analysis.
Results: the main problems and threats to the construction market were identified, recommendations were given for their neutralization in the context of the economic crisis and pandemic.
Practical implications: the results obtained should be applied to select the optimal management solution when working out a development strategy for a regional construction company.