bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of CT‐based regional Centiloid pipeline and application in Alzheimer’s disease cohort
Authors: Kim Soo‐Jong , Kim Young Ju , Seo Sang Won
Published: February 2022

Background

Standard CL prosess was suggested to standardized measurement of amyloid deposition in amyloid PET imaging. In the present study, we aimed to develop CT based regional Centiloid scales using head to head comparison cohort of FMM and FBB PET. We also explored the clinical implications of our new CT based regional Centiloid scales investigating the effects of regional increased Aβ uptakes and striatal involvements of Aβ on brain structural and neuropsychological changes.

Method

Head‐to‐head comparison dataset was included from 25 Alzheimer’s disease dementia (ADD) patients, 18 old controls (OC), and 20 young controls (YC) for FBB and FMM PET. We used direct comparison of FBB‐FMM CL (dcCL) method using MRI and CT images to define a common target region and six regional VOIs for all tracers. Clinical characteristics were compared to 2245 independent subjects in cognitive normal (CN), aMCI, and ADD. We also classified four stages using Centiloid cutoffs determined by machine learning technique. Among the subjects, regional Centiloid cutoffs were applied to classify four stages. The four stages were defined into focal (‐) and global (‐), F(‐)G(‐), F(‐)G(+), global (+) and striatum (‐), G(+)Str(‐), and G(+)Str(+) using determined Centiloid cutoffs. We also explored between the stages and clinical scores for cognition, structural changes.

Result

High reliability and precision between MRI based and CT based Centiloid pipeline in quantification and Centiloid scales were found by head to head cohort. Those correlation of Centiloid scales were R2 = 0.91∼0.97 for paired PET tracers as head to head comparison and R2 = 0.95∼0.99 for same PET ligands between MRI based and CT based pipelines. In classified stages, F(‐)G(‐) stage was significantly different in comparison to G(+)Str(+) stage in CDR SOB, SVLT Delayed recall, hippocampal volume, and global cortical thickness (p<0.05).

Conclusion

Our proposed CT based Centiloid pipeline was validated by MRI based Centiloid pipeline, globally and regionally. Those applications into independent cohort were also validated by comparing cognitive scores and structural changes. Therefore, we demonstrated the new CT based regional Centiloid scales and the four stages by comparing cognitive score and structural changes in our independent cohort.
The effect of mindfulness‐based interventions on cognitive deficits from mild cognitive impairment
Authors: Mahabir‐Walston Dianna , Noblitt James R , Graves James
Published: February 2022

Background

Mild cognitive impairment (MCI) involves an objective and subjective decline in cognitive functions unrelated to aging and does not meet the diagnostic criteria for dementia. The deficits experienced with MCI can result in diminished cognitive and neural resources, and subsequently, functional impairment as well as heightened susceptibility for developing Alzheimer’s disease. Significantly, compensation can result in cognitive restructuring and neuroplasticity, which may provide a window for interventions that may assist with slowing the progression to dementia. Namely, across the literature to date, mindfulness‐based interventions (MBI)s has been shown to affect cognitive deficits across pathologies in the aging population as well as areas of the brain (e.g., increase grey and white matter volume, as well as cerebral blood flow). Therefore, further investigation into the effect of MBIs on cognitive deficits associated with MCI is warranted.

Method

The information from the current literature and consultations with professionals working directly with individuals diagnosed with MCI was synthesized to discover if MBI’s improve cognitive functioning. For this review, MBI’s included mindfulness‐based stress reduction, mindfulness‐based cognitive therapy, acceptance and commitment therapy, dialectical behavior therapy, yoga, meditation, mindfulness‐awareness practices, integrated mind‐body training, and metacognitive therapy, as well as multi‐component treatment modalities that incorporate mindfulness.

Results

Fifteen studies showed various mindfulness‐based interventions improved cognitive function in individuals diagnosed with MCI. Comparatively, five studies showed no improvement in cognitive function. Results were reported with neurological tests and cognitive screeners such as the mini‐mental status exam. Cognitive improvements included memory, executive functioning, verbal recognition, attention, concentration, problem‐solving, cognitive processing speed, psychomotor speed, as well as subjective improvements. Significantly, the studies that showed no improvement did not describe any deterioration in cognitive functioning. Additionally, field experts predominately utilized mindfulness as part of a multi‐component treatment plan and reported subjective improvements in cognitive functioning.

Conclusion

Results of this analysis suggest that mindfulness‐based interventions do improve cognitive functioning as well as other symptoms influenced by MCI. Moreover, there are significant beneficial outcomes with multi‐component interventions that include mindfulness. However, these results should be considered preliminary, and further investigation is required because there was substantial variably between studies.
Factors contributing to person‐centered care provisioning for people with dementia in Dutch long‐term care facilities
Authors: van der Roest Henriëtte G , van der Kuil Milan , Overbeek Anouk , Hartstra Egbert
Published: February 2022

Background

Person‐centered care provisioning (PCC) is seen as the golden standard for dementia care. Positive evidence has been found for PCC, the level of person‐centeredness of care is positively associated with residents’ quality of life, quality of care an wellbeing. When providing PCC, care and support are provided in line with the needs, preferences and capacities of people with dementia.

In long‐term care facilities, needs and preferences of people with dementia are not always obvious, due to the relatively high levels of cognitive impairment. This, and amongst others time constraints might hinder high PCC by care professionals. However, there is some evidence that certain organizational and environmental conditions, such as satisfactory leadership, interdisciplinary collaboration, and continuing education, lead to higher PCC. In order to facilitate care professionals as much as possible in providing PCC, more insight is desirable.

This study aims to provide more insight into the modifiable factors that contribute to person‐centered care for people with dementia in Dutch long‐term care facilities.

Method

A cross‐sectional design was applied. Data were collected during the fifth assessment of the Living Arrangements for people with Dementia (LAD)‐study from April 2019 until February 2020. Care professionals working in psychogeriatric units in long‐term care facilities filled in an online survey. Organizational characteristics of participating long‐term care facilities were inventoried.

The Dutch version of the ‘Person‐centred care questionnaire’ (PCCq) was used to assess the degree of person‐centred care provided in a long term care unit/location. Modifiable factors potentially impacting the level of provided person‐centred care with regard to staff characteristics (e.g. autonomy, education), organizational features (size, involvement of family in care), and culture (e.g. learning climate) were included in multiple regression analyses.

Result

In total 58 long‐term facilities were included in the study, and 814 care professionals completed the survey. Average PCCq score was 3.2 (range 0 to 4, higher scores indicating higher PCC).

Conclusion

Factors with regard to staff, and organizations that contribute to PPC will be presented. The outcomes of the study will provide input for optimalization of the organization of dementia care in long‐term care facilities.
Communication during Covid‐19: Use of video conferencing technology by people living with dementia
Authors: Agustus Jennifer L , Volkmer Anna , Jeong Tina Hyerim , Jiang Jessica , Brotherhood Emilie V , Dobson Lucianne , Harding Emma , Gonzalez Aida Suarez , Crutch Sebastian J , Warren Jason D , Hardy Chris JD
Published: February 2022

Background

The use of videoconferencing technology has increased as an alternative communication method for people to retain social and clinical contact during Covid‐19 restrictions. This study investigated the uptake, limitations and benefits of videoconferencing for people living with dementia (PLWD).

Method

Twenty‐three PLWD, 87 caregivers (on behalf of PLWD) and 39 healthy control participants anonymously reported their experiences of using videoconferencing technology during the Covid‐19 pandemic (PLWD: 38‐90 years; controls: 32‐100 years). The online survey ran between December 2020 and April 2021. Respondents represented experiences of people living with Alzheimer’s Disease (AD; 27), Frontotemporal Dementia (FTD; 23), Primary Progressive Aphasia (PPA; 24), Posterior Cortical Atrophy (PCA; 22), Lewy Body Dementia (LDB; 7). Mann‐Whitney U tests were used to compare Likert ratings of videoconferencing experiences between PLWD or diagnostic subgroups and controls.

Result

The majority of survey respondents that use videoconferencing technology reported an increased usage during the Covid‐19 pandemic than before (85%). However, 28% of PLWD did not use videoconferencing at all, compared to 3% of healthy controls. Only 53% of PLWD reported they liked using videoconferencing technology compared to 67% of controls, and this was lowest for people with LBD (33%) or PCA (40%). Interestingly, 64% of people with FTD liked videoconferencing and rated it more engaging than traditional telephone calls compared to healthy controls (p=0.045). People with AD, PCA and FTD found online meetings with multiple people more difficult than controls (p=0.036; p<0.001; p=0.030). Qualitative responses to questions on telemedicine were mixed, with PLWD three times more likely to report overall negative consequences (e.g. “communication better face‐to‐face”) than positive benefits (e.g. “less tiring”) for cognitive clinic and dementia‐related GP appointments, compared to face‐to‐face visits.

Conclusion

The use of videoconferencing by PLWD and healthy controls has increased during the Covid‐19 pandemic. However, a significant proportion of PLWD surveyed are not able to use these technologies, with different profiles of uptake and enthusiasm across dementia subtypes. Our findings suggest that whilst representing a helpful alternative to face‐to‐face communication during the pandemic, videoconferencing (particularly in clinical settings) may be a significant barrier to communication for some people with cognitive impairment.
Associations between cortical microinfarcts and MRI markers of neurodegeneration and cerebrovascular disease in aging
Authors: Sadaghiani Shokufeh , Dolui Sudipto , Tisdall Dylan M. , Tackett William , Wolk David A. , Detre John A.
Published: February 2022

Background

Cortical microinfarcts (CMI) are associated with cognitive impairment in both healthy aging and dementia, though the mechanisms underlying CMIs remain uncertain. Here we assessed correlations between CMIs and medial temporal lobe (MTL) cortical thickness, white matter hyperintensity (WMH) volume, and cerebral blood flow (CBF) in older subjects.

Method

Neuroimaging data from 55 cognitively intact older subjects scanned using a hybrid 7T/3T protocol were analyzed. CMIs were manually identified on T1‐weighted MP2RAGE data (0.7mm isotropic resolution) obtained at 7T (Figure 1). Cortical thickness, WMH volume and whole brain CBF were obtained with T1‐weighted, FLAIR and 3D background suppressed arterial spin labeling (ASL) imaging, all acquired at 3T and were available from N=39, 49 and 48 subjects of the N=55 subjects respectively. Spearman’s bivariate nonparametric test was used for statistical analyses.

Result

Cohort demographics and imaging results are summarized in Table 1. 111 CMIs were detected in 43 of 55 (78%) of 7T T1‐weighted and FLAIR MRI scans (range:0‐6, 56% multiple CMIs). Age and sex were not significantly correlated with the number of CMIs. A negative correlation between the number of CMIs and mean BA36 cortical thickness was observed (r(37)= ‐0.348, p=0.03) (Figure 2). A similar trend was also observed in entorhinal and parahippocampal cortices. No significant correlation was seen between the number of CMIs and WMH volume. No significant correlation was observed between the number of CMIs and CBF in whole brain, gray matter, or white matter.

Conclusion

The percentage of subjects showing CMIs is higher than previous 3T studies suggesting improved sensitivity of high‐resolution 7T MRI for detection of CMIs. Contrary to prior reports the lack of correlation between the number of CMIs and either WMH volume or CBF suggests that cerebrovascular insufficiency and small vessel ischemic disease may not be the underlying pathologic mechanisms causing CMIs, at least in cognitively intact older subjects. However, the negative correlation between CMIs and MTL cortical thickness supports the possibility of a mutual underlying pathway for Alzheimer’s disease and CMIs that may be mediated by cerebral amyloid angiopathy.
Managing responsive behaviours of care home residents with dementia during the COVID‐19 pandemic
Authors: O'Donnell Elizabeth A
Published: February 2022

Background

Most care home residents with dementia exhibit responsive behaviours including aggression, agitation and wandering (Cerejeira et al., 2012). Psychotropic drugs are often prescribed to manage responsive behaviours but contravene guidance as they increase the rate of strokes and death in people with dementia (Gustafsson et al., 2013). However, the use of psychotropic drugs for behaviour management may potentially increase during the COVID‐19 pandemic (Howard et al., 2020). Therefore, it is imperative to understand how responsive behaviours are managed to identify facilitators and barriers to implementing non‐pharmacological approaches.

Method

During the Covid‐19 pandemic, 25 interviews were conducted with managers, nurses and care assistants from 21 care homes across Ireland. All participants provided written informed consent. Themes emerging from thematic analysis (Braun & Clarke, 2006) conceptualised understanding of how care home staff managed responsive behaviours during the COVID‐19 pandemic. Ethics approval was obtained from Lancaster University Faculty of Health and Medicine Research Ethics Committee (FHMREC20099).

Result

Residents with dementia were perceived to be more depressed during the COVID‐19 pandemic due to the absence of family visits. However, care home staff reported that psychotropic drugs were not used more frequently for behaviour management than before the pandemic and that a person‐centred care approach was taken which involved supporting residents to participate in activities in smaller groups. Maintaining adequate staffing levels was challenging due to recruitment of nurses and care assistants from private care homes to acute public hospitals during the pandemic. Moreover, psychiatry and mental health support were difficult to access in rural regions of Ireland during COVID‐19 restrictions. Another emerging theme demonstrated that care assistants rarely contributed to equitable decision‐making, posing a barrier to implementing non‐pharmacological strategies to manage responsive behaviours.

Conclusion

This study recommends that care homes should be prioritised in public health planning for Covid‐19, particularly to ensure optimal staffing levels and access to mental health support. In addition, care assistants should be provided with opportunities to contribute to decision‐making including case conferences. These recommendations will inform development of Department of Health policy and dementia care guidelines to facilitate implementation of non‐pharmacological strategies to manage responsive behaviours in dementia.
Impact of COVID‐19 and imposed lockdown on presenting complaints of persons with dementia and challenges faced by caregivers in India
Authors: Natarajan Nirupama , Vaitheswaran Sridhar
Published: February 2022

Background

A diagnosis of dementia increases the vulnerability of an already vulnerable older adult population. COVID‐19 infection and the imposed lockdown have both had a huge impact on the lives of persons with dementia and their caregivers. The aim of this study is to evaluate presenting complaints provided by caregivers in the COVID‐19‐context in India.

Method

We examined the case records of persons with dementia who presented at theDementia Care in SCARF (DEMCARES), an outpatient clinic in Chennai between May 2020 and April 2021 during the COVID‐19 pandemic. We reviewed their presenting complaints to look for ones specific to the COVID‐19 context and identified caregiver challenges.

Result

COVID‐19 infection was reported by caregivers to affect the cognition and functioning of their relatives with dementia. The impact of imposed lockdown was observed through reports of caregivers noticing initial signs of dementia following the increased social isolation experienced by their loved ones during the pandemic. Some of the challenges faced by caregivers included their relative with dementia’s inability to understand the gravity of the COVID‐19 situation, wanting to step out of the house and inability to do so contributing to restlessness, agitation and aggression.

Conclusion

Caregivers are increasingly facing challenges posed by behavioral and psychological symptoms of dementia stemming from the imposed lockdown restrictions. Teleconsultation and virtual delivery of dementia‐specific interventions could potentially help caregivers overcome some of these challenges. Older persons at risk for social isolation and those recovering from COVID‐19 should be screened for dementia. General and primary care physicians should actively watch out for signs of cognitive impairment and make necessary referrals as early detection of dementia in elderly persons recovering from COVID‐19 may improve outcomes.
Humans and horses: Therapeutic interventions for people living with early‐stage dementia and care partners
Authors: Anzelmo Nancy A Schier
Published: February 2022

Background

Human‐equine interaction research started 2015 for recently diagnosed (PWD)/ (CP). Therapy animals reduce agitated behavior, irritability, anxiety, sleep disturbances, increase social interactions, positive engagement and communication (Richardson 2003; Dabelko‐Schoeny et al.:2014, Kogan, 2001: Sellers & Smith, 2002, Richeson, 2003; Filan & Llewellyn‐Jones, 2006) Workshops provided equine guided engagement to activate the dyad. Sessions taught participants stress reduction techniques for quality of life, identified coping mechanisms and reflection debriefing discussions. Booster sessions focused on the experiences of the dyad 6 months after initial workshop.

Method

Study designed as a comparative booster from initial study at Stanford/ UC Davis ( n=88) with six month follow up; 3 consecutive weeks, 15 hour intervention. Pre/post‐test design, with standardized measures of stress, burden, mood, sleep, social support for dyad. Research was conducted over 3 years through UC Davis School of Medicine, ADRC & School of Veterinary Medicine. Booster sessions followed ( n= 44) with (n=18) Pre/post data on (CP)/(PWD) within 3‐ week sessions. 14/18 dyads completed pre/post‐booster assessment comparison with post‐intervention scores.

Result

Study findings supported changes in (CP) / (PWD) evaluated results confirmed using rank tests for deviations from normality. Initial study data validated previous findings (CP). Booster session data within 6‐months for (CP)/ ( PWD) pre/post sessions. Prior analyses indicated significant reduction in BDI‐II, PSS / PSQI total scores after intervention. There was no significant difference between pre‐booster BDI‐II / PSS total scores and post‐intervention assessment (p>0.1). However, pre‐booster session PSQI scores were higher than the post‐intervention scores.

Conclusion

Booster session results indicate initial (CP) benefit of reduced feelings of depression remained stable between initial session/ booster. Though not conclusive, t data raised interesting questions regarding benefits of equine therapeutic interventions. Study results are encouraging for exploring further for (CP) as alternative approaches to enhancing quality of life. Booster session sample was small and more information is required in sample. Ultimately the connection and learning between dyads and horses in a brief period, provides opportunities to benefit persons with immediate needs from varying backgrounds.
Quantifying longitudinal cognitive resilience to Alzheimer's disease and other neuropathologies
Authors: Wagner Maude , Wilson Robert S. , Leurgans Sue E. , Boyle Patricia A. , Bennett David A. , Grodstein Francine , Capuano Ana W.
Published: February 2022

Introduction

Cognitive resilience (CR) has been defined as the continuum of better (or worse) than expected cognition, given the degree of neuropathology. To quantify this concept, existing approaches focus on either cognitive level at a single time point or slopes of cognitive decline.

Methods

In a prospective study of 1215 participants, we created a continuous measure of CR defined as the mean of differences between estimated person‐specific and marginal cognitive levels over time, after accounting for neuropathologies.

Results

Neuroticism and depressive symptoms were associated with all CR measures (P‐values < .012); as expected, cognitive activity and education were only associated with the cognitive‐level approaches (P‐values < .0002). However, compared with the existing CR measures focusing on a single measure or slopes of cognition, our new measure yielded stronger relations with risk factors.

Discussion

Defining CR based on the longitudinal differences between person‐specific and marginal cognitive levels is a novel and complementary way to quantify CR.
Rewritable Macromolecular Data Storage with Automated Read‐out
Authors: Soete Matthieu , De Bruycker Kevin , Du Prez Filip
Published: February 2022

Rewriting data stored on synthetic macromolecules is an interesting feature, even though it is considered as being quite challenging within the area of digital macromolecules. In this context, we initially studied a strategy for modifying the position tag of sequence‐encoded macromolecules in a reversible manner. The efficiency of this method, which relies on the orthogonal cleavage of a thioester moiety via aminolysis, was demonstrated by modifying parts of an exemplary sentence. Simultaneously, a novel algorithm was developed to ease the read‐out of macromolecular information by means of MS/MS techniques. This program, Oligoreader, can identify potential information‐containing macromolecules from a series of MS1 spectra, analyze the corresponding MS2 spectra, and finally decode the data. Consequently, the algorithm simplifies the entire read‐out process by avoiding any interference from the operator, which increases the potential for blind sequencing of uniform macromolecules.
Cyclic Solid‐State Multiple Phase Changes with Tuned Photoemission in a Gold Thiolate Coordination Polymer
Authors: Veselska Oleksandra , Vaidya Shefali , Das Chinmoy , Guillou Nathalie , Bordet Pierre , Fateeva Alexandra , Toche François , Chiriac Rodica , Ledoux Gilles , Wuttke Stefan , Horike Satoshi , Demessence Aude
Published: February 2022

The discovery of a universal memory that exhibits fast access speed, high‐density storage, and non‐volatility has fuelled research into phase‐change materials over the past decades. In spite of the efficiency of the inorganic chalcogenides for phase‐change random access memory (PCRAM), they still have some inherent drawbacks, such as high temperature required for phase change and difficulty to control the domain size of the phase change, because of their brittleness. Here we present a AuI–thiolate coordination polymer which undergoes two successive phase changes on application of mild heating (<200 °C) from amorphous‐to‐crystalline1‐to‐crystalline2 phases. These transitions are reversible upon soft hand grinding. More importantly, each phase exhibits different photoluminescent properties for an efficient optical read‐out. We believe that the ability of the AuI–thiolate coordination polymer to have reversible phase changes under soft conditions and at the same time to display distinct optical signals, can pave the way for the next generation of PCRAM.
Design Strategies for High‐Energy‐Density Aqueous Zinc Batteries
Authors: Ruan Pengchao , Liang Shuquan , Lu Bingan , Fan Hong Jin , Zhou Jiang
Published: February 2022

In recent years, the increasing demand for high‐capacity and safe energy storage has focused attention on zinc batteries featuring high voltage, high capacity, or both. Despite extensive research progress, achieving high‐energy‐density zinc batteries remains challenging and requires the synergistic regulation of multiple factors including reaction mechanisms, electrodes, and electrolytes. In this Review, we comprehensively summarize the rational design strategies of high‐energy‐density zinc batteries and critically analyze the positive effects and potential issues of these strategies in optimizing the electrochemistry, cathode materials, electrolytes, and device architecture. Finally, the challenges and perspectives for the further development of high‐energy‐density zinc batteries are outlined to guide research towards new‐generation batteries for household appliances, low‐speed electric vehicles, and large‐scale energy storage systems.
Novel substituted 5‐methyl‐4‐acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cells
Authors: Sadovnikov Kirill S. , Vasilenko Dmitry A. , Gracheva Yulia A. , Zefirov Nikolay A. , Radchenko Eugene V. , Palyulin Vladimir A. , Grishin Yuri K. , Vasilichin Vladislav A. , Shtil Alexander A. , Shevtsov Pavel N. , Shevtsova Elena F. , Kuznetsova Tamara S. , Kuznetsov Sergei A. , Bunev Alexander S. , Zefirova Olga N. , Milaeva Elena R. , Averina Elena B.
Published: February 2022

A series of novel antimitotic agents was designed using the replacement of heterocyclic cores in two tubulin‐targeting lead molecules with the acylated 4‐aminoisoxazole moiety. Target compounds were synthesized via heterocyclization of β‐aryl‐substituted vinylketones by tert‐butyl nitrite in the presence of water as a key step. 4‐Methyl‐N‐[5‐methyl‐3‐(3,4,5‐trimethoxyphenyl)isoxazol‐4‐yl]benzamide (1aa) was found to stimulate partial depolymerization of microtubules of human lung carcinoma A549 cells at a high concentration of 100 µM and to totally inhibit cell growth (IC50 = 0.99 µM) and cell viability (IC50 = 0.271 µM) in the nanomolar to submicromolar concentration range. These data provide evidence of the multitarget profile of the cytotoxic action of compound 1aa. The SAR study demonstrated that the 3,4,5‐trimethoxyphenyl residue is the key structural parameter determining the efficiency both towards tubulin and other molecular targets. The cytotoxicity of 3‐methyl‐N‐[5‐methyl‐3‐(3,4,5‐trimethoxyphenyl)isoxazol‐4‐yl]benzamide (1ab) to the androgen‐sensitive human prostate adenocarcinoma cancer cell line LNCaP (IC50 = 0.301 µM) was approximately one order of magnitude higher than that to the conditionally normal cells lines WI‐26 VA4 (IC50 = 2.26 µM) and human umbilical vein endothelial cells (IC50 = 5.58 µM) and significantly higher than that to primary fibroblasts (IC50 > 75 µM).
Antibacterial and anticancer profiling of new benzocaine derivatives: Design, synthesis, and molecular mechanism of action
Authors: El‐Zahabi Heba S. A. , Nossier Eman S. , Mousa Safya M. , Hassan Heba , Shalaby AL Shimaa G. , Arafa Reem K.
Published: February 2022

The need for new chemotherapeutics to overcome development of resistance merits research to discover new agents. Benzocaine derivatives are essential compounds in medicinal chemistry due to their various biological activities including antibacterial and anticancer activities. Therefore, this study focuses on the synthesis of new benzocaine derivatives 3a–e, 6, 7a and 7b, 8, 10–14, and 16a–d and their in vitro evaluation as antibacterial agents against gram +ve and –ve strains and as anticancer agents against HepG‐2, HCT‐116, and MCF‐7 human cancer cell lines. The obtained results demonstrated that thiazolidines 6 and 7b showed higher antibacterial and anticancer activity in comparison with the reference drugs. In addition, 6 and 7b showed high potency as inhibitors toward their biological targets, that is DNA gyrase and human topoisomerase IIα, as compared to the reference standard drugs novobiocin and etoposide, respectively. Molecular docking demonstrated that both compounds could identify the active site of their target enzymes and develop effective binding interactions. Absorption, distribution, metabolism and elimination (ADME) and drug‐likeness predictions of both compounds showed that they both have good ADME profiles and no structural alerts that might cause toxicity. Based on this, 6 and 7b could serve as lead compounds for the design of more potent antibacterial and anticancer agents.
Bovine serum albumin functionalized blue emitting Ti3C2 MXene quantum dots as a sensitive fluorescence probe for Fe3+ ion detection and its toxicity analysis
Authors: Al‐Duais Mohammed Ali , Mohammedsaleh Zuhair M. , Al‐Shehri Hamza S. , Al‐Awthan Yahya S. , Bani‐Atta Suhair A. , Keshk Ali A. , Mustafa Syed Khalid , Althaqafy Adel D. , Al‐Tweher Jozaa N. , Al‐Aoh Hatem A. , Panneerselvam Chellasamy
Published: February 2022

In the present work, an improved class of protein functionalized fluorescent 2D Ti3C2 MXene quantum dots (MXene QDs) was prepared using a hydrothermal method. Exfoliated 2D Ti3C2 sheets were used as the starting precursor and transport protein bovine serum albumin (BSA) was used to functionalize the MXene QDs. BSA‐functionalized MXene QDs exhibited excellent photophysical property and stability at various physiological parameters. High‐resolution transmission electron microscopy analysis showed that the BSA@MXene QDs were quasispherical in shape with a size of ~2 nm. The fluorescence intensity of BSA@MXene QDs was selectively quenched in the presence of Fe3+ ions. The mechanism of fluorescence quenching was further substantiated using time‐resolved fluorescence and Stern–Volmer analysis. The sensing assay showed a linear response within the concentration range 0–150 μM of Fe3+ ions with excellent limit of detection. BSA@MXene QDs probe showed good selectivity toward ferric ions even in the presence of other potential interferences. The practical applicability of BSA@MXene QDs was further tested in real samples for Fe3+ ion quantification and the sensor had good recovery rates. The cytotoxicity studies of the BSA@MXene QDs toward the human glioblastoma cells revealed that BSA@MXene QDs are biocompatible at lower doses and showed significant cytotoxicity at higher dosages.
NMR Data‐Driven Docking of HDM2‐Inhibitor Complexes
Authors: Fradera Xavier , Reutershan Michael H. , Machacek Michelle R. , Trotter B. Wesley , McCoy Mark A.
Published: February 2022

We present an automated NMR‐guided docking workflow that can be used to generate models of protein‐ligand complexes based on data from NOE NMR experiments. The first step is to generate a number of intermolecular distance constraints from experimental NOE data. Then, the ligand is docked on an ensemble of receptor structures to account for protein flexibility, and multiple poses are generated. Finally, we use the NOE‐based constraints to filter and score docking poses based on the percentage of NOE constraints that are consistent with protein‐ligand interatomic distances. This workflow was successfully used during a lead optimization project to generate models of synthetic protein‐protein interaction (PPI) inhibitors bound to the HDM2 protein.
Synthetic Neoglycoconjugates of Hepta‐ and Nonamannoside Ligands for Eliciting Oligomannose‐Specific HIV‐1‐Neutralizing Antibodies
Authors: Cattin Matteo , Bruxelle Jean‐François , Ng Kurtis , Blaukopf Markus , Pantophlet Ralph , Kosma Paul
Published: February 2022

Oligomannose‐type glycans on the spike protein of HIV‐1 constitute relevant epitopes to elicit broadly neutralizing antibodies (bnAbs). Herein we describe an improved synthesis of α‐ and β‐linked hepta‐ and nonamannosyl ligands that were subsequently converted into BSA and CRM197 neoglycoconjugates. We assembled the ligands from anomeric 3‐azidopropyl spacer glycosides from select 3‐O‐protected thiocresyl mannoside donors. Chain extensions were achieved using [4+3] or [4+5] block synthesis of thiocresyl and trichloroacetimidate glycosyl donors. Subsequent global deprotection generated the 3‐aminopropyl oligosaccharide ligands. ELISA binding data obtained with the β‐anomeric hepta‐ and nonamannosyl conjugates with a selection of HIV‐1 bnAbs showed comparable binding of both mannosyl ligands by Fab fragments yet lesser binding of the nonasaccharide conjugate by the corresponding IgG antibodies. These results support previous observations that a complete Man9 structure might not be the preferred antigenic binding motif for some oligomannose‐specific antibodies, and have implications for glycoside designs to elicit oligomannose‐targeted HIV‐1‐neutralizing antibodies.
In‐situ Synthesis of the Thinnest In2Se3/In2S3/In2Se3 Sandwich‐Like Heterojunction for Photoelectrocatalytic Water Splitting
Authors: Jin Lin , Wu Yu , Zhang Huijuan , Wang Yu
Published: February 2022

The efficient utilization of solar energy for photoelectrocatalytic (PEC) water splitting is a feasible solution for developing clean energy and alleviating environmental issues. However, as the core of PEC technology, the existing photoanode catalysts have disadvantages such as poor photoelectrocatalytic conversion efficiency, low conductivity of photogenerated carriers, and instability. Here, we report the ultrathin two‐dimensional sandwich‐like (SW) heterojunction of In2Se3/In2S3/In2Se3 (SW In2S3@In2Se3) for the first time for PEC water splitting. Our findings identify the efficient separation of electrons and holes by constructing SW In2S3@In2Se3 heterojunction. The in situ synthesis of ultrathin nanosheet arrays by using surface substitution of Se atom to epitaxially grow cell In2Se3 maximizes the contact area of heterogeneous interface and accelerates the transmission of charge carrier. Benefitting from the unique structure and composition characteristic, SW In2S3@In2Se3 displays excellent performance in PEC water splitting. The photocurrent density of SW In2S3@In2Se3 reaches 8.43 mA cm−2 at 1.23 VRHE. Compared with In2S3, the SW In2S3@In2Se3 photoanode has nearly 12 times higher PEC performance, which represents the best performance among the In2S3‐based photoanode heterojunction reported so far. The evolution rate of O2 reaches 78.8 μmol cm−2 h−1, and the photocurrent has no apparent variety within 24 h.
Stereochemical Behavior of Pairs of P‐stereogenic Phosphanyl Groups at the Dimethylxanthene Backbone
Authors: Škoch Karel , Daniliuc Constantin G. , Müller Marcel , Grimme Stefan , Kehr Gerald , Erker Gerhard
Published: February 2022

The P‐stereogenic bis(phosphanes) 7 and 9, featuring pairs of P(Mes)‐ethynyl or vinyl substituents at the dimethyl xanthene backbone show rather low barriers of stereochemical inversion at phosphorus. π‐Conjugative effects are probably causing these low inversion barriers. Compound 7 reacted with B(C6F5)3 to form the nine‐membered heterocyclic product 10, featuring a [P]−C≡C−B(C6F5)3 substituent. Compound 7 was converted to the bis[P(Mes)vinyl] xanthene derivative 9, which gave the zwitterionic P(H)(Mes)−CH=CH−B(C6F5)3 containing product 16 upon treatment with B(C6F5)3. Thermally induced epimerization barriers at phosphorus of ca. 20 to 27 kcal mol−1 were calculated by DFT for the alkenyl‐ and alkynyl‐P derived systems 6 to 9, 15 and 16 and experimentally determined for the examples 7 and 16.
Retrospective survey for clinical course and aggravating factors of adolescent atopic dermatitis in two years' cohort study on first‐year university students
Authors: Nakano‐Tahara Mayuko , Matsumoto Mai , Yamauchi‐Takihara Keiko , Iso Hiroyasu , Katayama Ichiro , Murota Hiroyuki
Published: February 2022

Background

Recent epidemiological studies have revealed increased numbers of adolescent subjects with atopic dermatitis, most of who experienced chronic symptoms since childhood. However, the complete clinical nature of atopic dermatitis in Japanese adolescents is poorly understood. We conducted this study to accumulate knowledge of factors contributing to protracted atopic dermatitis symptoms in adolescent subjects to avoid an unfavorable clinical outcome in these patients.

Methods

On 2013 and 2014, first‐year students at our university answered a retrospective self‐questionnaire about their demographic characteristics and past history of allergies. Answers from 6105 respondents were analyzed. Subjects with atopic dermatitis were divided into four groups according to their clinical courses, and factors potentially influencing their clinical courses were identified.

Results

Nearly 16% of the students had a history of diagnosed atopic dermatitis, many of who had experienced symptoms since childhood (protracted course). Other respondents had experienced remission (32%), adolescent onset (14%), or recurrence (6%). Logistic regression analysis found that psychological stress and air dryness were apparent exacerbating factors that increased the risk of the protracted, recurrent, and adolescence courses. Furthermore, sleep loss, house dust, pollen, high temperature, and sweat were the aggravating factors associated with the protracted course alone.

Conclusions

We found that a high proportion of Japanese adolescent subjects with atopic dermatitis had experienced protracted symptoms and further identified factors that may have led to this unfavorable course. We expect that limiting these factors in this population might alleviate the subjects' chronic symptoms.
Water‐Soluble Well‐Defined Bifunctional Ferrocenyl Dendrimer with Anti‐Cancer Activity
Authors: Bertuzzi Diego L. , Braga Carolyne B. , Perli Gabriel , Ornelas Catia
Published: February 2022

Combination of advantages of ferrocenyl compounds and multifunctional dendrimer scaffold afforded a water‐soluble well‐defined bifunctional dendrimer with polyamide backbone and thirty two termini: eighteen carboxylic acid groups and eighteen triazolylferrocenyl moieties. The structure of the new dendrimer was thoroughly characterized by nuclear magnetic resonance (NMR) spectroscopy, absorbance spectroscopy in the UV‐vis, and MALDI‐TOF mass spectrometry. The MALDI‐TOF spectrum of the final dendrimer showed the [M]2+ ion peak at 4820.1 m/z unambiguously confirming the successful synthesis of the water‐soluble well‐defined bifunctional dendrimer. The cytotoxicity of the well‐defined bifunctional triazolylferrocenyl dendrimer 4 was evaluated against MCF‐7 (breast adenocarcinoma), HeLa (cervical cancer), PC3 (prostate adenocarcinoma), Caco‐2 (colorectal cancer), and PNT2 (normal prostate cells) cell lines. The cytotoxicity assays showed that the dendrimer exhibits moderate anticancer activity and targets cancer cells selectively over normal cells.
Chemo‐Enzymatic One‐Pot Two‐Step Functionalization of 1,2,3,4‐Tetrahydroisoquinolines by Monoamine Oxidase‐Ugi‐Joullié Reaction Sequence
Authors: Barna Bence , Gáti Tamás , Kotschy András , Tasnádi Gábor
Published: February 2022

A one‐pot two‐step chemo‐enzymatic approach for the functionalization of substituted 1,2,3,4‐tetrahydroisoquinolines (THIQs) was developed. The system combines monoamine oxidase (MAO)‐catalyzed imine formation with Ugi‐type three‐component reaction in an aqueous buffer without intermediate isolation. The two steps were separately optimized for buffer and pH to obtain the expected products. MAOs enabled the functionalization of fifteen THIQs by oxidation to imines, while the Ugi‐Joullié‐reaction was successfully carried out with eight carboxylic acids and eight isonitriles. 41 products were isolated giving access to valuable building blocks for medicinal chemistry applications. Gram‐scale transformation demonstrated the utility of the described protocol for organic synthesis.
High‐Temperature Solid‐State Synthesis and Electrochemical Properties of Transition Metal Sulfides for Thermal Batteries
Authors: Hu Jing , Wang Xin-Liang , Guo Hao , Yang Ming , Yuan Jin-Xiu , Chu Ying , Zhao Li-Li
Published: February 2022

Transition metal sulfide is the most widely used cathode material for thermal batteries. The development of modern weapons requires higher quality and output of transition metal sulfide cathode materials. However, the current synthesis processes have some limitations for large‐scale industrial production due to the long production cycle and low production efficiency. Herein, by controlling the synthesis temperature and adopting a high‐temperature solid‐state method, sulfide FeS2, CoS2, and NiS2 with single‐phase and good crystalline structure are synthesized. This method with a simple production process, short production cycle, and high single output is suitable for engineering production. Hence, guidance for large‐scale industrial synthesis of pure phase FeS2, NiS2, and CoS2 is provided, embodying important scientific significance and application value.
Selection of natural biomaterials for micro‐tissue and organ‐on‐chip models
Authors: Cecen Berivan , Bal‐Ozturk Ayca , Yasayan Gokcen , Alarcin Emine , Kocak Polen , Tutar Rumeysa , Kozaci Leyla Didem , Shin Su Ryon , Miri Amir K.
Published: February 2022

The desired organ in micro‐tissue models of organ‐on‐a‐chip (OoC) devices dictates the optimum biomaterials, divided into natural and synthetic biomaterials. They can resemble biological tissues' biological functions and architectures by constructing bioactivity of macromolecules, cells, nanoparticles, and other biological agents. The inclusion of such components in OoCs allows them having biological processes, such as basic biorecognition, enzymatic cleavage, and regulated drug release. In this report, we review natural‐based biomaterials that are used in OoCs and their main characteristics. We address the preparation, modification, and characterization methods of natural‐based biomaterials and summarize recent reports on their applications in the design and fabrication of micro‐tissue models. This article will help bioengineers select the proper biomaterials based on developing new technologies to meet clinical expectations and improve patient outcomes fusing disease modeling.
Exploring civic behaviors amongst college students in a year of national unrest
Authors: Kornbluh Mariah , Davis Amanda L. , Hoyt Lindsay T. , Simpson Savannah B. , Cohen Alison K. , Ballard Parissa J.
Published: February 2022

This study examined the role of demographics, civic beliefs, and the impact of the COVID‐19 pandemic in association with distinct forms of civic participation. College students were recruited across 10 institutions of higher education to complete an online survey. Bivariate, multivariable linear, and logistic regressions were performed. Findings indicated that participants from traditionally marginalized backgrounds were more likely to engage in systemchallenging forms of civic participation and community engagement than those from more privileged backgrounds. Participants who rated high in critical reflection, viewed racism as a key issue, and were heavily impacted by the COVID‐19 pandemic were also more likely to engage in system‐challenging forms of civic participation. Participants who endorsed beliefs supporting current systems of power were more likely to report they intended to vote. Results highlight implications for antiracist activism, community engagement, and traditional political civic behaviors.
Broadband all‐metal Vivaldi antenna with Rexolite inserted slot edge
Authors: Ari Onur , Kizilay Ahmet
Published: February 2022

In this study, broadband, with a reconfigurable pattern, a slot edge all‐metal Vivaldi antenna (SEMVA) is proposed. The designed antenna is fabricated from an aluminum plate. Then the antenna is measured in an anechoic chamber using a spherical near field measurement system. In the first step, the metal Vivaldi antenna without slots is designed as a reference model. The scattering parameters and the radiation pattern results show that the antenna exhibits poor vswr and deteriorated radiation patterns at the lower operating band. In order to overcome these performance problems, the slot edge technique is successfully adapted to the metal Vivaldi antenna. This technique provides wider bandwidth with vswr <2 and a directive radiation pattern at lower operating frequencies. The dielectric material (Rexolite) can also be inserted into the slots of the designed antenna to improve bandwidth and beamwidth. The proposed antennas with and without dielectric insertion are measured and compared. The measurement results show that using slots increase the bandwidth of the designed antenna from 6:1 to 10:1. The proposed antenna operates between 1.38 and 13.8 GHz with a proper end‐fire radiation pattern. In addition, the power handling capacity of the SEMVA is calculated and compared with PCB antennas.
Impact of COVID‐19 on glycaemic control in a Spanish cohort of patients with type 2 diabetes
Authors: Enguix David Martín , Cambronero María Sánchez , Rodríguez Juan Carlos Aguirre , Rodríguez Abraham Hidalgo
Published: February 2022

The purpose of this study was to investigate the impact of COVID‐19 lockdown on monitoring and glycaemic control of people with type 2 diabetes (T2DM) in a Spanish population.

This prospective cohort study focused on patients with T2DM from a Spanish cohort followed since 2017, with at least one HbA1c determination since the start of the pandemic.

A total of 246 patients was included; 45.9% (113) had at least one HbA1c measurement during the pandemic and, in this case, we used the most recent one. The HbA1c mean value increased from 7.37% before the pandemic to 7.43% (p = 0.63). Those patients with previous HbA1c ≥ 8.5% were the ones whose glycaemic controlled worsened: uncontrolled patients increased from 10.5% to 28.6% (p < 0.05), relative risk 1.65.

In conclusion, nine months after the pandemic start, less than a half of the T2DM patients in our Spanish cohort had at least one HbA1c measurement. Glycaemic control was similar when comparing before versus after the pandemic start, although those patients who were previously poorly controlled had a 1.65 higher risk of worsening their glycaemic control compared to the rest. Copyright © 2022 John Wiley & Sons.