bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary care for people with a newly diagnosed dementia in hospital after discharge
Authors: Hegerath Flora‐Marie , Giehl Chantal , Otte Ina , Vollmar Horst Christian
Published: December 2022

Background

Older people with cognitive impairment usually live at home. Possible deficits can be compensated there, often with the help of relatives. Therefore, the diagnosis of dementia is often delayed. It can lead to a first dementia diagnosis being made during an acute hospital stay. As a result, hospital discharge and subsequent care pose challenges for those involved. The aim of this study was to assess existing barriers and facilitating factors in the care of patients with a newly diagnosed dementia after hospitalization in the general practitioner (GP) setting. The study is funded by the German Alzheimer Society.

Method

Sixteen semi‐structured interviews with GPs from Germany were conducted from July to December 2021. Data were analysed according to the qualitative content analysis from Kuckartz.

Result

Theoretical saturation regarding the research question was reached within the qualitative interviews. The analysis showed that GPs identify communication deficits on the part of the hospitals as a barrier to provide adequate care for their patients. A conversation is rarely initiated with the GPs to ensure continued outpatient care.

GPs use different strategies to provide care for their patients. Special importance is given to the communication with people with dementia and their relatives in a first consultation after hospital discharge to obtain detailed information, e.g., about the hospital stay or third‐party anamnesis. This first consultation is focused on organizing the care of patients in their own homes. Managing medication from the hospital is a critical issue for GPs, as patients are often prescribed many new medications.

Conclusion

Since the acute reason for hospitalization is not dementia, there is usually no comprehensive assessment. It is therefore important for those affected that the diagnosis is verified after discharge and that appropriate measures are initiated. Based on the study results, practice‐oriented recommendations for the GP setting are going to be developed, which, for example, highlight the sensitive communication with those involved. For better initial care of their patients, GPs need adequate communication from the side of the hospital. Here, additional professional groups (e.g., care managers) and better digital networking can have a positive impact on care.
Effects of Oral ALZ‐801, an Amyloid Oligomer Inhibitor, on Plasma Biomarkers in APOE4 Carriers with Early Alzheimer’s Disease: Results of Six‐month Interim Analysis from a Phase 2 Biomarker Study
Authors: Abushakra Susan , Hey John , Blennow Kaj , Scheltens Philip , Reiman Eric M. , Hort Jakub , Sheardova Katerina , Rutgers Sterre M. , Prins Niels D. , Dautzenberg Paul , Pazdera Ladislav , Power Aidan , Tolar Martin
Published: December 2022

Background

ALZ‐801, an oral, brain‐penetrant small molecule inhibitor of amyloid oligomer formation is being evaluated as a disease‐modifying treatment in APOLLOE4, a Phase 3 trial in APOE4/4 homozygotes with Early Alzheimer’s disease (AD). A concurrent Phase 2 study is in progress to study its effects on core AD biomarkers, beta‐amyloid (Aβ) and hyperphosphorylated tau (p‐tau) in APOE4 carriers with Early AD.

Method

The Phase 2 study in Czech Republic and Netherlands enrolled APOE4/4 and APOE3/4 subjects with MMSE 22‐30 (CDR‐G 0.5 or 1), who receive ALZ‐801 265 mg tablets BID for 104 weeks. Subjects were amyloid‐PET positive or A+/T+ on CSF assays (ratio of Aβ42/40×10 < 0.61, and p‐tau181 > 61 pg/ml). CSF is evaluated at 52 and 104 weeks, and plasma biomarkers at every visit. Memory tests include the Rey Auditory Verbal Learning Test (RAVLT). Primary outcome is CSF p‐tau181 reduction at 104 weeks; interim analysis on plasma was conducted when all subjects completed 26 weeks. Dr. Blennow’s laboratory (Mölndal, Sweden) performed biomarker analyses blinded to clinical data, using Lumipulse (Fujirebio) for CSF and Simoa assays for plasma. Change from baseline in observed biomarker values at each visit were analyzed with paired t‐tests (2‐sided p‐values).

Result

Of 84 enrolled subjects (mean 69 years, 51% female, MMSE 25.6), 80 completed 26 weeks. Plasma p‐tau181, the interim primary outcome, showed significant 18% and 29% reductions at 13 and 26 weeks (p = 0.038 and p = 0.028). Reductions of p‐tau181/Aβ42 were also significant 21% and 30% at 13 and 26 weeks (p = 0.018 and p = 0.022). RAVLT memory scores (immediate + delayed) improved significantly at 26 weeks (p = 0.002). Most common adverse events were mild nausea with no drug‐ related serious events and no ARIA‐E at 52 weeks.

Conclusion

Interim Phase 2 plasma biomarker results show significant and robust reductions in plasma p‐tau181 and p‐tau181/Aβ42 at 26 weeks with memory improvement at 26 weeks. These ALZ‐801 effects on core biomarkers confirm target engagement in AD brain, and support disease modification potential of ALZ‐801. The biomarker effects, oral formulation, and favorable safety without ARIA‐E, make ALZ‐801 an attractive potential treatment for APOE4 carriers with AD.
Baseline β‐amyloid and tau predict longitudinal tau accumulation at different stages of Alzheimer’s disease
Authors: Cai Yue , Ma Shaohua , Guo Tengfei ,   Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University, Shenzhen, China
Published: December 2022

Background

Previous literatures suggest that β‐amyloid (Aβ) plaques, initial tau levels, age and Klotho‐VS heterozygosity (KL‐VShet) may be related to longitudinal tau accumulation in Alzheimer’s disease (AD), but it is still not fully understood how they predict tau replication in medial temporal cortex and propagations from the medial temporal lobe to inferior/middle temporal cortices at different stages of AD.

Method

We classified 325 Aβ PET positive (A+) ADNI participants into 143 A+/T‐and 182 A+/T+ according to the threshold (≥1.25) of Temporal‐metaROI 18F‐flortaucipir (FTP) standardized uptake value ratio (SUVR). Besides, 162 A‐/T‐ cognitive unimpaired participants without evidence of neurodegeneration were included as the reference group (Ref). We compared baseline and slopes of Aβ Centiloids and FTP SUVRs in 6 regions within Temporal‐metaROI with the Ref, and also investigated the prediction of longitudinal FTP SUVR changes by baseline Aβ Centiloids and FTP SUVRs in A+/T‐ and A+/T+ groups. Furthermore, we determined how age (Age<65 and Age≥65 years) and KL‐VShet haplotype (KL‐VShet+ and KL‐VShet‐) affect these associations.

Result

A+/T‐ showed significantly or marginally higher tau and faster tau increases in amygdala, entorhinal and parahippocampus than the Ref (Figure 1). Both baseline Aβ and entorhinal tau predicted faster rates of FTP SUVR increases in amygdala, entorhinal and parahippocampus in A+/T‐. While entorhinal tau predicted faster FTP SUVR increases in all the cortical regions within Temporal‐metaROI in A+/T+, baseline Aβ predicted faster FTP SUVR increases in fusiform, inferior and middle temporal regions (Figure 2). Additionally, younger ages showed faster baseline Aβ‐related whereas older ages had more tau‐related longitudinal FTP SUVR increases in fusiform and inferior temporal regions (Figure 3). KL‐VShet+ individuals exhibited attenuated entorhinal tau‐related FTP SUVR increases in fusiform and inferior temporal regions than the KL‐VShet‐ individuals (Figure 4).

Conclusion

Aβ plaques and initial tau tangles may play different roles in tau replication and propagation in A+/T‐ and A+/T+ individuals, and may interact differently with age at prediction longitudinal tau accumulation. KL‐VShet may attenuated tau accumulation via modulating entorhinal tau‐related tau propagation. These findings may provide novel insights into understanding how tau tangles replicate and propagate in Temporal‐metaROI region at different stages of AD.
The interplay between functional MRI measures of episodic memory and CSF measures of tau in healthy adults at risk of Alzheimer’s Disease
Authors: Molloy Eóin N. , Binette Alexa Pichet , Marquardt Jonas , Remz Jordana , Kreißl Michael C. , Rosa‐Neto Pedro , Poirier Judes , Rajah Natasha , Villeneuve Sylvia , Maass Anne ,   Pre‐symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer’s Disease (PREVENT‐AD) Research Group
Published: December 2022

Background

Neural changes occur early in Alzheimer’s disease (AD). Longitudinal data on the relationship between AD pathology and brain activity, however, are sparse. Using an established cohort of cognitively unimpaired older adults (PREVENT‐AD) at risk of AD (due to familial incidence), we assessed the relationship between functional magnetic resonance imaging (fMRI) activity during episodic memory retrieval and cerebrospinal fluid (CSF) markers of tau and β‐amyloid. We aimed to test whether baseline fMRI signal predicts changes in CSF markers and vice versa.

Method

Three‐hundred and three participants (64.7±8.3yrs, 82 male) underwent task‐based fMRI of associative episodic memory retrieval at baseline, with longitudinal fMRI data for up to five timepoints with a 3, 12, 24, and 48‐month follow‐up. Region of Interest (ROI) analysis assessed retrieval activity (Fig.1A; t‐contrast differentiating hits for old stimuli from the correct rejection of new stimuli) in the bilateral precuneus and medial temporal lobe (MTL, Fig.1B‐1C). In a subset of participants (n = 117, 30 male), CSF was sampled to quantify t‐tau, p‐tau 181, and the ratio of β‐amyloid 1‐42 to p‐tau 181 (with another measurement 36‐months post‐baseline). Data were analyzed with random‐intercept linear mixed models, assessing changes in ROI activity and CSF markers over time. We tested whether baseline ROI activity predicted change in CSF markers and whether baseline CSF measures predicted change in ROI activity over time.

Result

Results indicate a significant decrease in precuneus activity over time, but not MTL, and an increase in t‐tau and p‐tau 181 (Fig.2A‐2D). No change was observed for β‐amyloid/p‐tau 181 ratio. We also observed a significant time by baseline MTL activity interaction on t‐tau (Fig.3) with higher baseline activity being associated with lower t‐tau in CSF over time. We observed no relationship between baseline CSF markers and functional activity.

Conclusion

While preliminary, these results suggest that baseline MTL retrieval activity may predict t‐tau (a marker of neurodegeneration) accumulation in the CSF of healthy adults at risk of AD. Further analyses of whole‐brain episodic memory responses, episodic memory task‐performance over time, and of positron emission tomography (PET) measures of regional tau and β‐amyloid, are critical to extend these findings further.
Differential brain expression of 3R and 4R Tau isoforms in aging wild‐type and young genetically engineered PSEN1 mutant marmosets
Authors: Rizzo Stacey J Sukoff , Choi Sang‐Ho , Huhe Hasi , Kofler Julia , Schaeffer David , Murai Takeshi , Hachem Stephanie , Karavolis Marlena , Mou Yongshan , Ha Seung‐Kwon , Carter Gregory W , Park Jung Eun , Homanics Gregg E , Strick Peter L , Silva Afonso C
Published: December 2022

Background

The common marmoset (Callithrix jacchus) has emerged as an important model for studying Alzheimer’s disease (AD). Several previous publications reported the natural and spontaneous accumulation of Aβ aggregates in aging marmosets. However, the presentation of tau in aging marmosets has been understudied. A recent report investigated the expression of different tau isoforms and concluded that only 4R tau is expressed throughout adulthood (Sharma et al., J. Biol. Chem. 2019). Here, we investigated the presence of amyloid and tau aggregates in aged wild‐type marmosets and in young adult individuals genetically engineered with knock‐in (KI) point mutations in the PSEN1 gene that cause early‐onset AD.

Method

We used standard IHC protocols and western blotting techniques with validated antibodies for amyloid (NAB228) and tau (RD3, 3T3, PHF‐1) to investigate the presence and localization of AD aggregates in the brains of 5 marmosets (n = 3 wild‐type and 2 PSEN1 KI mutants).

Result

We observed the natural accumulation of amyloid aggregates with the anti‐amyloid antibody NAB228 in a 10‐year male marmoset that confirms this subject’s previous in vivo evaluation with 11C‐PiB PET imaging. Interestingly, this aged marmoset showed positive 3R and 4R tau staining with the anti‐tau antibodies RD3 and 3T3, respectively (Figure 1) in the hippocampus. In agreement with Sharma et al., 2019, tau staining in the hippocampus was much more abundant for the 4R than the 3R tau isoform, with substantial phosphorylation at Ser‐396 and Ser‐404. We detected no tau staining in the entorhinal cortex of this animal and no amyloid nor tau in the brain of a one‐year‐old juvenile. We observed similar results of significant amyloid accumulation and RD3 and 3T3 labeling in the brains of two young (18 months) PSEN1 KI mutants. Separately, we confirmed by western blot 3R and 4R tau isoforms in homogenates from the hippocampus and entorhinal cortex of three individual marmosets (aged 1‐7 years).

Conclusion

Our genetically diverse marmoset population of aging and PSEN1 mutation carriers present both 3R and 4R isoforms across the lifespan. These data further support marmosets as an ideal species for translational studies of AD. Studies in larger sample sizes are ongoing.
The expression levels of pro‐inflammatory and anti‐inflammatory cytokines and chemokines in blood serum of Alzheimer’s dementia patients: report from a pilot study in Kazakhstan
Authors: Kaiyrlykyzy Aiym , Zholdasbekova Gulnaz , Alzhanova Dinara , Olzhayev Farkhad , Baibulatova Aida , Tsoy Andrey , Askarova Sholpan
Published: December 2022

Background

Chronic peripheral inflammation is one of the critical factors contributing significantly to the development and progression of Alzheimer’s disease (AD). Human and animal studies strongly suggest that systemic inflammation, marked by changes in the peripheral profile of blood immune cells and blood levels of circulating pro‐inflammatory and anti‐inflammatory cytokines, can promote or even precede pro‐inflammatory conditions in the CNS. It has been reported that the levels of circulating pro‐inflammatory cytokines are increased while the levels of anti‐inflammatory cytokines are decreased in AD patients. However, despite increasing data supporting the association between abnormal peripheral inflammation and AD, no well‐established inflammatory biomarkers are currently available for AD. In this regards, we have studied an expanded spectrum of pro‐inflammatory and anti‐inflammatory cytokines and chemokines in the serum samples of the patients diagnosed with AD and compared them to those without cognitive impairment matched on age and gender.

Methods

We have simultaneously assayed cytokines and chemokines in the serum of AD patients (n=40) and normal controls (n=46) using MILLIPLEX Map Human Cytokine/Chemokine Magnetic Beas Panel on the Luminex xMAP technology according to the manufacturer’s protocol. The kit included the following 41 human cytokines and chemokines: EGF, IL‐12P70, IL‐13, IL‐15, IL‐17A, IL1RA, IP‐10, MCP‐1, MIP‐1α, MIP‐1β, RANTES, VEGF, FGF‐2, TGF‐α, FIT‐3L, Fractalkine, GRO, MCP‐3, MDC, PDGF‐AA, PDGF‐AB/BB, sCD40L, IL‐1α, IL‐1β, TNFα, G‐CSF, IFNγ, TNFβ, IL‐10, IL‐2, GM‐CSF, IL‐3, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, IL‐9, Eotaxin, IFNα2, and IL‐12P40.

Results

We have found IL‐12P40, IL‐9, IL‐7, GM‐CSF, IL‐10, IFNγ, IL‐1α, MCP‐3, FIT‐3L, IL‐17A, IL‐13, IL‐15, and IL‐12P70 were significantly higher in Alzheimer’s patients compared to controls. At the same time, cognitively healthy controls had higher concentrations of PDGF‐AB/BB, PDGF‐AA, RANTES, and FGF‐2 in the peripheral blood. We observed significant positive correlation between C‐reactive protein and IP‐10 (r=0.5), IL1RA (r=0.3), PDGF‐AA (r=0.3), IL‐10 (r=0.3), GRO (r=0.4), GCSF (r=0.3), PDGF‐AB/BB (r=0.3).

Conclusion

Studying the expression levels of pro‐inflammatory and anti‐inflammatory cytokines and chemokines in the blood serum of Alzheimer’s dementia patients is of considerable interest since it can potentially contribute to the discovery of new blood‐based biomarkers for earlier diagnosis of AD and development of the personalized treatment strategies.
Modeling CNS neuronal‐glial interactions relevant to Alzheimer’s Disease and ADRD with microglia and neurons derived from human induced pluripotent stem cells
Authors: McDonough Patrick M. , Gordon Kara L. , Basa Ranor C. B. , Rines Christine G. , Rohn Troy T. , Price Jeffrey H.
Published: December 2022

Background

CNS neurons and microglia participate in neuroimmune pathways linked to Alzheimer’s Disease (AD) and AD Related Dementias (ADRD). However, CNS neurons and microglia cannot be isolated from living people, and primary microglia harvested post‐mortem rapidly de‐differentiate in culture. hiPSC‐neurons and hiPSC‐MG represent a practical alternative for in vitro research, as they are human‐derived, upscalable, and can be made from people with AD/ADRD‐sensitive or ‐resilient genotypes. We are developing high‐throughput assays utilizing hiPSC‐neurons/‐MG, to explore interactions between these cell types and pathways relevant to AD, and to test compounds for beneficial effects on neuronal health.

Method

hiPSC‐neurons (excitatory) were purchased from Fujifilm CDI or differentiated in‐house (with kits from Elixirgen). hiPSC‐MG were differentiated in‐house from hiPSCs via a protocol in which yolk sac‐like structures are produced as an intermediary step. Mono‐ or cocultures were prepared in 96‐ or 384‐well dishes. Results were obtained via automated digital microscopy, with cellular structures and biomarkers analyzed via high content analysis (HCA) and cell activity (calcium or voltage transients) analyzed via Kinetic Image Cytometry; in certain experiments, LDH release, a general measure of cytotoxicity, was also assayed.

Result

Coculture of hiPSC‐MG with hiPSC‐neurons led to a 2‐fold increase in neurites. hiPSC‐MG also elicited calcium transients in the hiPSC‐neurons via close contact. The APOE‐e4 gene variant confers the greatest risk for late‐onset AD, and proteolysis of ApoE4 may produce neurotoxic fragments. In our hands, a fragment of ApoE4 (ApoECFp17, aa 1‐151) induced LDH release in both hiPSC‐neurons and hiPSC‐MG, indicating cytotoxicity, whereas the corresponding fragment of ApoE3 had no effect; additionally, the toxic effect on hiPSC‐MG was partially blocked by PH002 (an ApoE4 “structure corrector”) and by RAP (a protein that blocks ApoE4 binding to cell‐surface receptors).

Conclusion

Our data demonstrate that hiPSC‐MG alter neurite expression and calcium transient activity in cocultured hiPSC‐neurons, and that the aa 1‐151 fragment of ApoE4 is toxic to human neurons and microglia, which could potentially play a role in AD etiology. Future research will incorporate hiPSC‐astrocytes into the cultures to further model CNS neuronal‐glial interactions and elucidate pathways relevant to AD/ADRD.
Amyloid futures in the expanding pathology of brain aging and dementia
Authors: Thorwald Max A. , Silva Justine , Head Elizabeth , Finch Caleb E.
Published: December 2022

Positron emission tomography (PET) imaging studies of Alzheimer's disease (AD) patients show progressive increases of fibrillar Aβ‐amyloid. Because current PET ligands underestimate nonfibrillar forms, we assayed soluble Aβ in AD and controls. To identify the mechanisms responsible for soluble Aβ in AD brains, we examined lipid rafts (LRs), where amyloid precursor protein (APP) is enzymatically processed. Frontal cortex was compared with cerebellum, which has minimal AD pathology. Compared with cognitively normal controls (CTL; Braak 0‐1), elevations of soluble Aβ40 and Aβ42 were similar for intermediate‐ and later‐stage AD (Braak 2‐3 and 4‐6). Clinical‐grade AD showed a greater increase in soluble Aβ40 than Aβ42 relative to CTL. LR raft yield per gram AD frontal cortex was 20% below that of controls, whereas cerebellar LR did not differ by Braak score. The extensive overlap of soluble Aβ levels in controls with AD contrasts with the PET findings on fibrillar Aβ. These findings further support fibrillar Aβ as a biomarker for AD treatments and show the need for more detailed postmortem analysis of diverse soluble and insoluble Aβ aggregates in relation to PET.
Natural products and extracts from plants as natural UV filters for sunscreens: A review
Authors: Li Liyan , Chong Lan , Huang Tao , Ma Yunge , Li Yingyan , Ding Hui
Published: December 2022

Although solar exposure is necessary for human health, phototoxicology induced by excessive UVB and UVA radiation, which involves sunburns, skin aging and even tumorigenesis, has been widely researched. Sunscreen is one of the most important ways to protect skin from UV phototoxic damage. As well as inorganic and organic UV filters, some natural products or plant extracts with aromatic rings in their structures, such as flavonoids or polyphenols, can absorb UV to reduce sunburn, acting as a natural UV filter; they also show antioxidant or/and anti‐inflammatory activity. This could explain why, although there are no officially approval natural commercial sun‐filters, more and more commercial sunscreen products containing plant extracts are available on the market. Here we summarize articles focusing on natural UV filters from plant published in the last 6 years, selecting the most significant data in order to better understand the photoprotective activity of natural products and extracts from plants, including their major constituents and main biological effects, methods for evaluating UV radiation resistance, anti‐UV radiation experimental models and anti‐UV radiation mechanisms.
A Versatile Strategy for Screening Custom‐Designed Warhead‐Armed Cyclic Peptide Inhibitors
Authors: Kang Deokhee , Kim Do‐Wook , Kim Joo‐Chan , Park Hee‐Sung
Published: December 2022

Demand for peptide‐based pharmaceuticals has been steadily increasing, but only limited success has been achieved to date. To expedite peptide‐based drug discovery, we developed a general scheme for cell‐based screening of cyclic peptide inhibitors armed with a user‐designed warhead. We combined unnatural amino acid incorporation and split intein‐mediated peptide cyclization techniques and integrated a yeast‐based colorimetric screening assay to generate a new scheme that we call the custom‐designed warhead‐armed cyclic peptide screening platform (CWCPS). This strategy successfully discovered a potent inhibitor, CY5‐6Q, that targets human histone deacetylase 8 (HDAC8) with a KD value of 15 nM. This approach can be a versatile and general platform for discovering cyclic peptide inhibitors.
A Dynamic Kinetic Resolution Approach to Axially Chiral Diaryl Ethers by Catalytic Atroposelective Transfer Hydrogenation
Authors: Dai Linlong , Liu Yuheng , Xu Qing , Wang Meifang , Zhu Qiaohong , Yu Peiyuan , Zhong Guofu , Zeng Xiaofei
Published: December 2022

Diaryl ethers are widespread in biologically active compounds, ligands and catalysts. It is known that the diaryl ether skeleton may exhibit atropisomerism when both aryl rings are unsymmetrically substituted with bulky groups. Despite recent advances, only very few catalytic asymmetric methods have been developed to construct such axially chiral compounds. We describe herein a dynamic kinetic resolution approach to axially chiral diaryl ethers via a Brønsted acid catalyzed atroposelective transfer hydrogenation (ATH) reaction of dicarbaldehydes with anilines. The desired diaryl ethers could be obtained in moderate to good chemical yields (up to 79 %) and high enantioselectivities (up to 95 % ee) under standard reaction conditions. Such structural motifs are interesting precursors for further transformations and may have potential applications in the synthesis of chiral ligands or catalysts.
Programming Photodegradability into Vinylic Polymers via Radical Ring‐Opening Polymerization
Authors: Do Phuong T. , Poad Berwyck L. J. , Frisch Hendrik
Published: December 2022

Incorporation of photolabile moieties into the polymer backbone holds promise to remotely‐control polymer degradation. However, suitable synthetic avenues are limited, especially for radical polymerizations. Here we report a strategy to program photodegradability into vinylic polymers by exploiting the wavelength selectivity of photocycloadditions for radical ring‐opening polymerization (rROP). Irradiation of coumarin terminated allylic sulfides with UVA light initiated intramolecular [2+2] photocycloaddition producing cyclic macromonomers. Subsequent RAFT‐mediated rROP with methyl acrylate yielded copolymers that inherited the photoreactivity of the cyclic parent monomer. Irradiation with UVB initiated efficient photocycloreversion of the coumarin dimers, causing polymer degradation within minutes under UVB light or days under sunlight exposure. Our synthetic strategy may pave the way to insert photolabile linkages into vinylic polymers, tuning degradation for specific wavelengths.
Diiron bis‐cyclopentadienyl complexes as transfer hydrogenation catalysts: The key role of the bridging aminocarbyne ligand
Authors: Bresciani Giulio , Biancalana Lorenzo , Zacchini Stefano , Pampaloni Guido , Ciancaleoni Gianluca , Marchetti Fabio
Published: December 2022

The catalytic activity of a series of diiron complexes based on the {Fe2Cp2(CO)x} core (x = 2–3) and containing a bridging aminocarbyne ligand was screened in transfer hydrogenation reaction of cyclohexanone from isopropanol. The series includes cationic tricarbonyl complexes, [1a–d]CF3SO3, and neutral derivatives obtained by substitution of one carbonyl with hydride (2a–c), cyanide (3a–d) or chloride (4a) ligands. The novel compounds 2a–b, 3a–b and 4a were characterized by analytical and spectroscopic techniques, and the single crystal X‐ray structure of one isomer of 4a was determined. In general, diiron complexes exhibited a moderate activity in combination with potassium hydroxide; [Fe2Cp2(CN)(CO)(μ‐CO){μ‐CN (Me)(4‐C6H4OMe)}], 3a, emerged as the best catalyst, and the study of its activity was extended to a range of other ketones. DFT calculations suggest an unusual carbyne‐centred mechanism, and the better performance displayed by 3a is ascribable to the stabilizing effect provided by the cyanide co‐ligand, which is experimentally supported by IR analyses.
The impact of political factors on international student mobility
Authors: Fidler Setenay Dilek , Clarke Linda , Wang Rebecca Yi
Published: December 2022

International student mobility contributes to a knowledge‐based economy and forms an important component of a highly educated migration. This paper aims to identify how far political factors—including political discrimination, restrictions, freedom, UK migration policies and social cultural norms and policies—enhance or inhibit individuals' capabilities to become mobile. It offers a novel conceptualisation of mobility, drawing on structuration theory and the capability approach, to reveal the link between structure, capability and agency in the mobility process. Semi‐structured in‐depth interviews were conducted with 40 PhD students, two professors from Turkey in the United Kingdom and three international education experts. A capability list established shows how mobility occurs when students' capabilities (freedoms) fail to flourish and they lose their power (capacity) to influence society due to the political environment in the home country. ‘Impo‐mobility’, derived from the word ‘imposed’, is proposed to refer to highly educated people having to become mobile as a result of impositions placed upon them by home and host‐government political practices. An appealing political environment is necessary if Turkey is not to lose highly educated individuals and the United Kingdom is to remain a global player in international higher education.
Religion as a barrier to the use of student loans for higher education: A community‐based participatory study with Somalis living in England
Authors: Avdukic Alija , Khaleel Fawad , Abdullah Ahmed , Brawe Abdulbasit H.
Published: December 2022

The unwillingness of the Somali community to finance higher education has largely gone unnoticed within the academic literature and government policy documents. This study explores the role of religion and the influence of Shari'ah scholars on the use of interest‐bearing student loans within the Somali community. In the absence of any theoretical framework on this topic, we explore the multiple socioeconomic factors that may influence the attitude, perception of need, motivation and action of using student loans for higher education, by proposing the UK Somali Muslims Acceptance of Interest‐bearing Student Loan Model. This is also a community‐based participatory study that actively involved Somali community members in exploring and interpreting the results. This was achieved through regular consultations with the sampled Somali Muslim communities within the UK. Our results contribute to the broader debate on the effect of cultural, religious and social values of marginalised communities on inclusion and widening access policies for higher education. The findings reemphasise that people sharing the same location do not necessarily share the same level of opportunities for higher education because of the intersectionality of race, religion, gender and class. The results also show the complexity of the issue of exclusion and the atheoretical nature of student loans as a financial instrument for improving financial inclusion and widening access to higher education among Somali residents in England.
Tackling a lingering infirmity: On the nature and warrant of action research in education
Authors: Hogan Padraig , Malone Anthony
Published: December 2022

The BERA initiative on promoting Close‐to‐Practice (CtP) research raises new challenges for action research, particularly as uncertainties about the standing and rigour of action research were expressed in the report of the education panel for the 2015 Research Excellence Framework (REF) in the United Kingdom. The work of tackling these challenges is essential in advancing CtP research, and it discloses, in turn, new possibilities. In this paper we review some pioneering developments in action research and analyse the difficulties it has experienced in securing parity of standing with other forms of research. We argue that action research is more than, and sometimes other than, a social science. We seek to show that if action research is to be recognised by credentials that are its own, and judged by criteria that are proper to it, not only does it lose any lower standing. Rather, it becomes a major pathway, with deep roots in the critical traditions of Western practical philosophy, through which the defining purposes of education itself, as a distinctive human practice, are ascertained and affirmed, pursued and appraised.
M(other) tongue: An exploration of the impact on power dynamics for the therapist working in English as a second language
Authors: Medlicott Charlotte , Tomicsne‐Wagner Szabina , Griffo Federica
Published: December 2022

This research explores the experiences of bilingual therapists whose first language is not English and who are therefore working in English as a second language, with native‐speaking English clients. Existing literature suggests that the therapeutic relationship is inherently unbalanced, with the therapist constructed as the more powerful. This is particularly true of psychodynamic therapy—the researchers' own modality—in which the therapist withholds self‐revelation. However, the power balance can shift in the client's favour, particularly if they hold knowledge about their therapist. Our research focusses on how bilingualism as an inherent self‐disclosure might result in shifting the power in the therapeutic dyad when the client is perceived as the more competent native speaker. This research aims to contribute an alternative to the prevailing view that linguistic difference is merely challenging. Qualitative semistructured interviews generated narrative transcripts from six participants, which were analysed thematically. Three themes emerged, demonstrating how the therapists experienced their difference in terms of power shifts: my difference is an inherent vulnerability; my difference is a tool; and my difference is unspoken. When experienced as a vulnerability, therapists' bilingualism results in a power struggle. Working with this vulnerability can facilitate the alliance and create a sense of equality. This brings bilingualism as a tool into focus. Almost all participants experienced a lack of recognition of this aspect of their diversity in training and supervision. Most participants acknowledged that it remained unspoken between them and their clients.
Ugi Bis‐Amide Derivatives as Tyrosinase Inhibitor; Synthesis, Biology Assessment, and in Silico Analysis
Authors: Yousefnejad Faeze , Iraji Aida , Sabourian Reyhaneh , Moazzam Ali , Tasharoie Shima , Sara Mirfazli Seyedeh , Zomorodian Kamiar , Alireza Akhlagh Seyed , Hosseini Samensadst , Larijani Bagher , Tehrani Maliheh Barazandeh , Hajimahmoodi Mannan , Mahdavi Mohammad
Published: December 2022

Herein, a straightforward synthetic strategy mediated by Ugi reaction was developed to synthesize novel series of compounds as tyrosinase inhibitors. The structures of all compounds were confirmed by FT‐IR, 1H‐NMR, 13C‐NMR, and CHNOS techniques. The tyrosinase inhibitory activities of all synthesized derivatives 5a–m were determined against mushroom tyrosinase and it was found that derivative 5c possesses the best inhibition with an IC50 value of 69.53±0.042 μM compared to the rest of the synthesized derivatives. Structure–activity relationships (SARs) showed that the presence of 4‐MeO or 4‐NO2 at the R2 position plays a key role in tyrosinase inhibitory activities. The enzyme kinetics studies showed that compound 5c is an noncompetitive inhibitor. For in silico study, the allosteric site detection was first applied to find the appropriate binding site and then molecular docking and molecular dynamic studies were performed to reveal the position and interactions of 5c as the most potent inhibitor within the tyrosinase active site. The results showed that 5c bind well with the proposed binding site and formed a stable complex with the target protein.
Post‐Coronavirus disease syndrome (post‐COVID‐19) syndrome: A case report
Authors: Thapa Rukshar , Pant Prashant , Singh Pragyat , Karki Sagun , Thapa Kriti , Aryal Saman , Shrestha Oshan
Published: December 2022

Post‐COVID syndrome, a cluster of symptoms that develops or persists even after the recovery from COVID‐19 or viral clearance, can have multi‐system manifestations. This entity should be considered in patients who recently tested positive for COVID‐19 after ruling out other possible obvious causes. Its management should involve a multidisciplinary approach.
Design and mechanical properties analysis of heterogeneous porous scaffolds based on bone slice images
Authors: Wang Xiaokang , Chen Jigang , Dong Xuegang , Guan Yabin , Kang Yongxing
Published: December 2022

Bone tissue engineering plays an extremely important role in the clinical treatment of bone defects. Porous scaffold is one of the three essential factors of bone tissue engineering, and its structural design has attracted more and more attention . At present, most of the design methods of porous scaffolds focus on uniform porous scaffolds with periodic and regular pore structures. However, periodic and regular pore structure cannot comprehensively and accurately simulate the microstructures and mechanical properties of natural bone. To address this problem, based on bone slice images and VT (Voronoi‐Tessellation) method, this article proposed a design method of HPS (Heterogeneous Porous Scaffolds) with bionic pore structure and controllable porosity. The FDM (fused deposition modeling) printing technology was applied to fabricate HPS with different porosities, and the mechanical properties of the HPS were analyzed by experiments. The research results illustrate that the HPS constructed by the design method proposed in this article have good controllability, and their internal pore structures are highly similar to those of natural bone, which have biomimetic characteristics. The mechanical property analysis illustrate that the stiffness and compressive strength of HPS decrease with the increase of porosity, in addition, the heterogeneous pore distribution makes HPS have the characteristics of non‐concentrated and discontinuous damage distribution. This study provides a new idea for the design of porous scaffolds and a theoretical basis for the bionic design of HPS.
A Review of the Evolving Landscape of Inclusive Research and Improved Clinical Trial Access
Authors: Mohan Shalini V. , Freedman Jamie
Published: December 2022

Current clinical research does not reflect the diversity of patient populations, despite continued recommendations to increase enrollment of under‐represented racial and ethnic groups. The ramifications of this lack of trial diversity are important because of potential differences between races and ethnicities in response to therapies, which have been observed for drugs across indications. Nonrepresentative research populations limit the generalizability of study results, which may lead to questions about safety and efficacy in certain subgroups of patients and hinder regulators, healthcare providers, and patients in their ability to adequately consider the benefits and risks of a therapeutic treatment across all populations. Renewed efforts to address healthcare disparities and increase diversity in clinical trials have demonstrated that inclusive trials are achievable and can provide scientifically rigorous results, and, thus, should stimulate greater action across all stakeholders. Ensuring that studies throughout the clinical development process include representative populations is a scientific imperative to advance health equity, racial justice, and trust in the safety and efficacy of medical therapies. This article reviews the long‐standing lack of diversity and barriers to enrollment of diverse and representative populations in clinical trials, outlines the current evolving trial landscape and the efforts of stakeholders, and provides examples from scientifically rigorous inclusive trials. The goal is to share learnings in a wider context of opportunities to enhance diversity, equity, and inclusion in clinical development while ensuring the safety and efficacy of medical therapies in all populations of patients, and in doing so, provide wider patient access to therapeutic treatments.
Carrier‐Free Immobilization of Multi‐Enzyme Complex Facilitates In Vitro Synthetic Enzymatic Biosystem for Biomanufacturing
Authors: Liu Miaomiao , Song Yunhong , Zhang Yi‐Heng P. Job , You Chun
Published: December 2022

A method is developed for carrier‐free immobilization of multi‐enzyme complexes with more than four enzymes by utilization of polypeptide interactions (SpyCatcher‐SpyTag and dockerin‐cohesin) and enzyme component self‐oligomerization. Two pairs of scaffoldins with different arrangements of SpyCatcher‐SpyTag and cohesins are prepared to recruit the four dockerin‐containing cascade enzymes (i. e., alpha‐glucan phosphorylase, phosphoglucomutase, inositol 1‐phosphate synthase, and inositol 1‐phosphatase) that can convert starch into inositol, forming multi‐enzyme complexes. These self‐assembled enzyme complexes show higher initial reaction rates than the four‐enzyme cocktail. Moreover, water‐insoluble self‐assembled multi‐enzyme complexes are observed, being the carrier‐free immobilized multi‐enzyme complex aggregates. These immobilized enzyme complexes can be recycled easily by simple centrifuging followed by resuspension for another round of reaction. Not only can these immobilized enzyme complexes be obtained by mixing the purified enzyme components, but also by the mixing of crude cell extracts. Therefore, the strategy for the carrier‐free immobilization of enzyme complex sheds light on improving the catalytic capability of in vitro synthetic enzymatic biosystems.
Decoupled Water Electrolysis Driven by 1 cm2 Single Perovskite Solar Cell Yielding a Solar‐to‐Hydrogen Efficiency of 14.4 %
Authors: Lv Fei , Qin Zhixiao , Wu Jiazhe , Pan Lixia , Liu Longjie , Chen Yubin , Zhao Yixin
Published: December 2022

Invited for this month's cover is the group of Yubin Chen at Xi'an Jiaotong University as well as collaborators at Shanghai Jiao Tong University. The image shows a decoupled water electrolysis system driven by a single perovskite solar cell (PSC) to produce separated hydrogen and oxygen. The Research Article itself is available at 10.1002/cssc.202201689.
Time‐modulated multi‐tone antenna array for wireless information and power transfer
Authors: Suneel Varma D. , Ram Gopi , Arun Kumar G.
Published: December 2022

This paper aims to design a multi‐tone radiator exploiting harmonic radiation characteristic of time‐modulated antenna array for wireless information and power transmission (WIPT) and multi‐operational WIPT receiver. The time‐modulated linear antenna array (TMLAA) radiating simultaneously at modulating and harmonic frequencies separated in multiple switching periods is utilized as a multi‐tone radiating system. TMLAA with suitable power in harmonic bands generates multi‐tone radiation by employing an optimized switching sequence. The ON and OFF time instants of the TMLAA are optimized to suppress sidelobe level and enhance sideband level. A population‐based optimization algorithm, teaching learning based optimization (TLBO), is employed to optimize the ON and OFF instants of the TMLAA to suppress sidelobe level and enhance sideband level. TLBO is utilized for a 16‐element TMLAA with minimizing cost function to achieve the above objectives. The 16‐element TMLAA with optimized switching radiates multi‐tone beams with a minimum of 5 dB peak power difference exploited as WIPT. The purpose of multi‐operation is accomplished by utilizing the Wilkinson power divider in the receiver system; its power dividing capability is analyzed using applied wave research (AWR). A voltage doubler type rectifier is modeled for DC generation and is tested using AWR. The DC generating capability is tested for fixed power available at various frequencies, and the fixed desired frequency with various available power levels is tested. The results show that the designed circuitry provides a maximum of 80% power conversion efficiency (PCE).
Hyperphenylalaninemias genotyping: Results of over 60 years of history in Lombardy, Italy
Authors: Rovelli Valentina , Cefalo Graziella , Ercoli Vittoria , Zuvadelli Juri , Olivia Turri , Graziani Daniela , Luisella Alberti , Bassi Davide , Re Dionigi Alice , Selmi Raed , Paci Sabrina , Salvatici Elisabetta , Banderali Giuseppe
Published: December 2022

Background

Hyperphenylalaninemias (HPA) are due to several gene mutations, of which the PAH gene is the most frequently involved. Prevalence and incidence of disease vary between populations, with genotype/phenotype correlations not always capable to correctly predict disease severity. The aim of this study was to give an overview of PAH mutations among one of the largest cohort of patients among Europe, born in Lombardy (Italy) starting from late 1970 s and including over a 60 years of activity; furthermore, to evaluate and discuss identified genotype/phenotype correlations and related reliability.

Patients/Methods

Eight hundred and twenty‐six HPA patients in current follow‐up at the San Paolo Hospital in Milan (Italy) were retrospectively reviewed, including molecular results and allelic phenotype and genotype values (attributed on the basis of the APV/GPV system) to verify genotype–phenotype correlations.

Results

A total of 166 different PAH variants were reviewed; of those, seven variants were identified as not previously described in literature. Most frequently reported variant was p.Ala403Val, followed by p.Arg261Gln, p.Val245Ala, IVS10‐11 g>a, p.Tyr414Cys and p.Leu48Ser. Phenotype prediction, based on APV/GPV, matched the actual phenotype in most cases, but not always.

Conclusion/Discussion

The cohort of patients included in this study constitute a representative sample of the HPA population worldwide. Studies on this sample may allow to improve clinical and genetic evaluation performances for affected patients, consequently to develop personalized medicine interventions and provide more precise indications on the correct treatment approach based on the accumulated evidence, also in light of a prognostically reliable but not always conclusive APV/GPV system.
Electronic Configuration Regulation by N‐Doped MXenes Boosting Electrocatalytic Performance of Cobalt Phthalocyanine
Authors: Zhang Wenlin , He Tingting , Liu Shimeng , Zhang Lu‐Hua , Yu Fengshou
Published: December 2022

The precise control of electronic configurations of catalytic sites via molecular engineering is significantly desirable for boosting electrocatalytic activity. We reported a new‐type composite electrocatalyst with cobalt phthalocyanine supported on N‐doped MXene nanosheets (N‐MXene/CoPc) through a self‐assembly process. Beneficial from the joint action of N sites participation and axial coordination, N‐MXene/CoPc exhibits a high ORR activity with positive onset potential (Eonset=0.98 V vs. RHE) and half‐wave potential (E1/2=0.863 V), which is superior over the pristine CoPc (E1/2=0.72 V) and the composite with undoped MXene as support (MXene/CoPc, E1/2=0.771 V). Additionally, N‐MXene/CoPc exhibits an excellent durability with only 8.5 % attenuation after 25000 s of continuous i‐t test, while a more obvious decay 18.6 % for 20 wt.% Pt/C. This work not merely reported a robust ORR catalyst, but more provides a reasonable design strategy for nonnoble‐metal catalysts through catalyst‐support interactions.
Chronic demyelination of rabbit lesions is attributable to failed oligodendrocyte progenitor cell repopulation
Authors: Cooper James J. M. , Polanco Jessie J. , Saraswat Darpan , Peirick Jennifer J. , Seidl Anna , Li Yi , Ma Dan , Sim Fraser J.
Published: December 2022

The failure of remyelination in the human CNS contributes to axonal injury and disease progression in multiple sclerosis (MS). In contrast to regions of chronic demyelination in the human brain, remyelination in murine models is preceded by abundant oligodendrocyte progenitor cell (OPC) repopulation, such that OPC density within regions of demyelination far exceeds that of normal white matter (NWM). As such, we hypothesized that efficient OPC repopulation was a prerequisite of successful remyelination, and that increased lesion volume may contribute to the failure of OPC repopulation in human brain. In this study, we characterized the pattern of OPC activation and proliferation following induction of lysolecithin‐induced chronic demyelination in adult rabbits. The density of OPCs never exceeded that of NWM and oligodendrocyte density did not recover even at 6 months post‐injection. Rabbit OPC recruitment in large lesions was further characterized by chronic Sox2 expression in OPCs located in the lesion core and upregulation of quiescence‐associated Prrx1 mRNA at the lesion border. Surprisingly, when small rabbit lesions of equivalent size to mouse were induced, they too exhibited reduced OPC repopulation. However, small lesions were distinct from large lesions as they displayed an almost complete lack of OPC proliferation following demyelination. These differences in the response to demyelination suggest that both volume dependent and species‐specific mechanisms are critical in the regulation of OPC proliferation and lesion repopulation and suggest that alternate models will be necessary to fully understand the mechanisms that contribute to failed remyelination in MS.