bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrophysiological markers of early Alzheimer’s Disease proteinopathy in the human brain
Authors: Rudolf Jonathan E Gallego , Wiesman Alex I , Binette Alexa Pichet , Villeneuve Sylvia , Baillet Sylvain
Published: December 2022

Background

Alzheimer's Disease (AD) is characterized by the pathological accumulation of amyloid‐beta (Aβ) and hyperphosphorylated tau proteins in the brain. Animal models have demonstrated that early Aβ accumulation induces neuronal hyperexcitability (Stargardt et al., 2015), whereas later additive effects of Aβ and tau lead to suppression of neuronal activity that parallels disease severity (Busche et al., 2020). Although neural hypo‐excitability has been reported in the later stages of AD, it remains unknow if such a shift from hyper‐ to hypo‐excitability exists at the macroscopic level in the human brain of asymptomatic individuals (Figure 1).

Methods

We used Positron Emission Tomography to measure the deposition of whole‐brain Aβ ([18F] NAV4694) and medial temporal tau ([18F] Flortaucipir) and resting‐state Magnetoencephalography (MEG) to capture the neurophysiological changes related to AD pathology in a group of clinically unimpaired older adults with family history of AD (PREVENT‐AD cohort; McSweeney et al., 2020). We used linear mixed effects models to test the association between MEG spectral power and Aβ across cortical regions, and the interactive effect of tau accumulation on this relationship. We then used linear regressions to test if the observed associations between MEG spectral power and AD pathology related to longitudinal cognitive performance, evaluated annually using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Results

Aβ deposition was associated with neural hyper‐activity, as reflected by a positive association between Aβ SUVR values and MEG spectral power in higher frequencies (alpha [8 ‐ 12 Hz]) and a negative association in slow frequencies (delta [2 – 4 Hz]; Figure 2). The accumulation of medial temporal tau predicted a shift in these associations towards a hypo‐activation pattern (increased neural slowing), which was related to longitudinal decreases in attention scores (Figure 3).

Conclusion

Our results support the hypothesis that Aβ induces neural hyper‐activity in asymptomatic individuals, while the additive effects of Aβ and tau accumulation lead to a shift towards neural slowing that relates to cognitive deficits. These early detectable electrophysiological changes may represent novel non‐invasive biomarkers of the preclinical stages of AD and may potentially help predicting cognitive trajectories and disease progression in the AD continuum.
Comparison of lipidomic profiling and spatial distribution in brain of a genetic mouse model of Alzheimer’s disease using DESI Imaging Mass Spectrometry: regional lipid dyshomeostasis in AD.
Authors: Lazarian Artur , Costa Ana Paula , Fowler Brandon , Zandkarimi Fereshteh , McIntire Laura Beth
Published: December 2022

Background

Alzheimer’s disease (AD) is one of the biggest health challenges worldwide. It is culpable for millions of deaths annually, the annual associated costs reach many billions, and these trends are expected to increase dramatically over the next decades. Yet, the underlying cause of AD is not yet understood and therefore no effective treatment is available to date.

Lipidomic data from autopsy brain, human plasma and animal models highlight severe lipid dyshomeostasis in AD. Specifically, previous studies have shown that the loss of polyunsaturated fatty acids among multiple phospholipid classes is common in AD affected human brain and mouse models. Thus, the disruption of lipid metabolism and the homeostasis are thought to play a crucial role in the development of AD pathology. It is likely then, that specific pathways in lipid metabolism underlie AD disease mechanisms leading to clinical impairment.

Therefore, in order to understand the full etiology and progression of disease, it is critical to identify specific and regionally dysregulated lipid species in both healthy and AD affected brain tissues.

Method

In order to interrogate differences in the lipid species between brains from WT and a genetic mouse model of AD across aging, DESI Imaging Mass Spectrometry (IMS) was used to detect regional composition of brain tissue with the Synapt G2‐Si (Waters). We have successfully developed a workflow for quantitative and qualitative lipidomics profiling for mouse brains by using 10µm coronal‐cut brain slices at 60µm resolution.

Result

In this study, we compared the brains of WT and AD mice of different ages, namely 8, 12 and 22 years old. By applying DESI IMS, we have shown regional dysregulation of specific lipid species in different brain areas including specific early changes in the hypothalamus region of the mouse brain.

Conclusion

We have shown that certain ions, such as m/z 327.233 which corresponds with the polyunsaturated fatty acid DHA, is highly abundant in the putative hypothalamus region of AD mouse brains of various ages compared to that of the wild type. This suggests early and persistent dysregulation of polyunsaturated lipid content associated with genetic drivers of AD in a mouse model.
Bacillus Calmette‐Guérin (BCG) treatment of bladder cancer protects against Alzheimer’s Disease in older adults: The Massachusetts General Brigham cohort
Authors: Weinberg Marc S. , Magdamo Colin G. , Zafar Affan , Chung Sunny , Arnold Steven E. , Das Sudeshna
Published: December 2022

Background

Retraining the immune system offers a potential means of preventing or treating Alzheimer’s disease (AD). Vaccines can confer non‐specific beneficial effects (NSBEs), impacting diseases far afield from the original target. The Bacillus Calmette‐Guérin (BCG) vaccine, used worldwide in the prevention of tuberculosis, causes NSBE on non‐TB respiratory infections, type 1 diabetes, and multiple sclerosis. BCG is the gold‐standard therapy for non–muscle‐invasive bladder cancer. Recently, several retrospective studies have associated intravesicular BCG treatment of bladder cancer with lowered risk of AD (Gofrit et al., 2019, Klinger et al., 2021, Kim et al., 2021). We sought to replicate the retrospective study in a large cohort of patients in the Massachusetts General Brigham (MGB) System.

Method

We retrieved 30y of electronic health records from MGB, consisting of 17,920 subjects with new bladder cancer diagnoses. We limited records to patients aged >50y, without a previous dementia diagnosis, and with at least one year MGB follow‐up after diagnosis. Using natural language processing (NLP), we identified and assigned pathological stages to each patient’s first transurethral resection of bladder tumor (TURBT) surgical pathology report. The study population consisted of non‐muscle‐invasive bladder cancer (NMIBC) patients (n = 6467). The intervention group was patients who had any exposure to intravesical BCG, determined by semiautomated methods using NLP and manual validation. The control group was NMIBC patients without exposure to intravesical BCG.

Result

We found a protective effect of BCG on the risk of dementia. Cox analysis of time to AD: HR 0.84, CI (0.7‐0.99), p = 0.049, age and sex‐adjusted. In a stratified analysis by age, the effect of BCG treatment on patients 70 or older was more pronounced (HR 0.77, CI 0.63‐0.95, p = 0.017), whereas there was no effect on patients younger than 70 (HR 0.98, CI 0.72 ‐ 1.36, p = 0.98).

Conclusion

Findings from our large retrospective study suggest an overall protective effect of BCG treatment on the subsequent incidence of Alzheimer’s Disease, with the effect largely drawing from patients 70yo or older. Further survival and competing risk analyses will be provided to contextualize the basis for these apparently beneficial effects of BCG.
Plasma pTau markers correlate with an imaging surrogate marker of hyperphosphorylation in mouse models of Alzheimers disease
Authors: Parekh Parag A , Badachhape Andrew , Menon Renuka , Bhavane Rohan , Srivastava Mayank , Bhandari Prajwal , Devkota Laxman , Sun Xianwei , Tanifum Eric , Ghaghada Ketan , Devaraj Sridevi , Annapragada Ananth
Published: December 2022

Background

We previously reported Cell surface vimentin (CSV) as a surrogate marker for cells in a hyperphosphorylative state, leading to pathological tau deposits in mouse models. Here were investigate the correlation between a Magnetic Resonance Imaging (MRI) marker of CSV and changes in the plasma pTau biomarkers at early stages of tau pathology. We studied total tau, ptau181 and ptau 231 in the plasma of mice at 2 and 5months of age prior to the formation of frank pathology, and with emerging pathology respectively, and compared them to the signal from the MRI marker of CSV.

Method

Transgenic P301S and APP/PSEN1 mice and their wild‐type littermates were injected intravenously with liposomal nanoparticles bearing small molecule Withaferin (WNP) as a targeting ligand, and Gd/DOTA as an MRI readout, at 2‐ and 5‐ months of age. Animals (n=10 each) underwent magnetic resonance imaging (MRI) using T1 weighted sequences to visualize brain localization of CSV‐targeted liposomes. Blood was collected in EDTA tubes by puncture of facial vein post‐MRI scan. Plasma samples were centrifuged at 1000xg for 10mins at 4⁰C within 30mins of collection and stored at ‐80⁰C. Plasma concentrations of tau species were measured using the multiplex xMAP Luminex platform with kit‐based reagents, Milliplex for ptau181, total tau and Procartaplex for ptau231.

Result

MRI signal enhancement was observed in 2‐month old transgenic mice but not in WT mice in both P301S and APP/PSEN1 AD models. Concurrently, we observed higher expression of ptau 181 in the TG mice over WT littermates. Similar results were also observed in the 5‐month old mice.

Conclusion

MRI with CSV targeted nanoparticles demonstrates brain signal that correlates with pTau181, consistent with the cell surface marker of hyperphosphorylation marking the same process that results in hyperphosphorylated tau species being formed in the transgenic mice. The results strengthen the mechanistic basis of a cell‐surface vimentin targeted agent being a suitable marker of very early‐stage development of tau pathology and furthermore demonstrates localization of the pathology. The use of readily available and relatively inexpensive MRI for this purpose has huge advantages over existing methods for the identification of early stage tau pathology.
Single cell analysis of the peripheral immune landscape in Alzheimer reveals a distinct adaptive immune signature
Authors: van Olst Lynn
Published: December 2022

Background

Alzheimer’s disease (AD) is the most frequent cause of dementia. Recent evidence suggests involvement of peripheral immune cells in the disease, but the underlying mechanisms remain unclear.

Method

We comprehensively mapped systemic immune changes in AD patients from the Amsterdam Dementia Cohort with mild cognitive impairment (MCI; n = 21; 65y±6; 52% female) or dementia (n = 59; 63y±8; 53% female) compared to controls (n = 35; age 61y±6; 46% female), using high‐dimensional single‐cell characterization.

Result

We found an adaptive immune signature in AD, and specifically highlight the accumulation of PD1+ CD57+ CD8+ T effector memory re‐expressing CD45RA (TEMRA) cells in the MCI stage of AD. This subset formed unique, dynamic networks with subsets of CD4+ T cells. In addition, several innate and adaptive immune subsets correlated to cerebrospinal fluid (CSF) levels of amyloid‐β and phosphorylated tau, and measures for cognitive decline. Specifically, subsets of memory B cells were negatively associated with CSF biomarker levels of neurodegeneration and neuroinflammation in AD patients.

Conclusion

Together, these findings highlight substantial adaptive immune changes in AD and signify the demand for a greater understanding of how these cells contribute to underlying brain pathology.
Association between reproductive factors in women and risk of brain ageing and dementia
Authors: McGrath Emer R , Scott Matthew R , Buckley Rachel , Satizabal Claudia L , DeCarli Charles S. , Bhasin Shalender , Vasan Ramachandran S , Murabito Joanne M , Beiser Alexa S , Seshadri Sudha
Published: December 2022

Background

Women have a higher prevalence of dementia than men. We determined the association between female reproductive factors and risk of cognitive outcomes, including incident dementia, in a community‐based sample of cognitively healthy individuals.

Method

Lifetime reproductive factors including age of menarche, age of menopause, reproductive lifespan (age of menopause minus age of menarche), number of live births, post‐menopausal hormone replacement therapy use, and serum estradiol and estrone concentrations were measured in 796 dementia‐free women [mean age 68.4 (SD 5.7) yr] from the Framingham Heart Study Offspring cohort at examination cycle seven (1998‐2001). We related reproductive factors to subsequent risk of incident dementia. Structural MRI brain measures and neurocognitive test performance were included as secondary outcomes.

Result

During a median 10 [Q1‐Q3, 8.04‐10.0] year follow‐up, 138 participants developed dementia. On Cox proportional‐hazards analysis adjusting for age and education, a longer reproductive lifespan was associated with a reduced risk of incident dementia (HR 0.94, 95% CI 0.91‐0.98, p = 0.004) while earlier age of menopause of ≤49 vs 50‐51 years was associated with an increased dementia risk (HR 2.56, 95% CI 1.12‐5.88, p = 0.027). Earlier menopause (≤49 versus 50‐51 years) was cross‐sectionally associated with lower hippocampal volume (β±SE, ‐0.123±0.057, p = 0.03). Compared to no live births, 1‐2 live births (5.85±2.03, p = 0.004) and ≥3 live births (5.17±2.06, p = 0.01) were associated with greater total cerebral brain volume. Use of post‐menopausal HRT (0.15±0.055, p = 0.007) and elevated serum estradiol (0.058±0.027, p = 0.03) and estrone concentrations (0.078±0.029, p = 0.006) were cross‐sectionally associated with improved abstract reasoning (Similarities test). Compared to no live births, 1‐2 live births (0.20±0.08, p = 0.018) and ≥3 live births (0.25±0.08, p = 0.003) were also associated with superior visuospatial performance.

Conclusion

Greater exposure to estrogen throughout a woman’s reproductive life was associated with a lower risk of incident dementia and cross‐sectionally associated with larger brain volumes and enhanced cognitive performance. Our results suggest positive cognitive benefits of greater lifetime estrogen exposure and highlight the potential role of estrogen exposure in modifying the risk of dementia.
The trans‐entorhinal cortex differential depends on retromer‐mediated endosomal recycling
Authors: Simoes Sabrina
Published: December 2022

Anatomical studies have pinpointed the trans‐entorhinal cortex (TEC) as the subregion of the brain selectively vulnerable to Alzheimer’s disease. Additional molecular studies have identified endosomal trafficking defects as a cytopathological driver of the disease. However, whether and how endosomal trafficking is linked to anatomical vulnerability still remains unknown. Here, in addressing these questions, we begin by showing that neurons are enriched with a functional distinct retromer core organized around VPS26b, differentially dedicated to endosomal recycling. Using fMRI imaging, and in contrast to its paralog VPS26a, we further demonstrated that depleting VPS26b in mice caused preferential age‐dependent dysfunction in the trans‐entorhinal cortex, a finding further validated by electrophysiology, immunocytochemistry, and behavior. Surprisingly, repletion of VPS26b, both in vitro and in vivo, rescued all phenotypes seen upon VPS26b depletion. We then turned to humans to find VPS26b highly enriched in the TEC region, where both VPS26b and the retromer‐related receptor SORL1 were found deficient in Alzheimer’s brains. Finally, by regulating glutamate receptor and SORL1 recycling and its levels, VPS26b was shown to mediate regionally‐selective synaptic dysfunction, as well as AD‐associated amyloid‐precursor protein misprocessing and tau secretion. Together with the trans‐entorhinal’s unique network properties, hypothesized to impose a heavy demand on endosomal recycling, these results suggest a general mechanism that can explain AD’s regional vulnerability.
Gut microbiome alterations in Alzheimer’s disease
Authors: Bendlin Barbara B.
Published: December 2022

This presentation will provide an update on research linking gut microbiome to Alzheimer’s disease and discuss potential mechanisms linking gut microbiome to ADRD and how these mechanisms can be tested in humans.
AAV‐mediated delivery of an anti‐BACE1 VHH alleviates pathology in an Alzheimer’s disease model
Authors: Holt Matthew G
Published: December 2022

Background

Single domain antibodies (VHH) are potentially disruptive therapeutics, with important biological value for treatment of several diseases, including neurological disorders. However, VHH have not been widely used in the central nervous system (CNS), largely because of their restricted blood‐brain barrier (BBB) penetration. To overcome this restriction, we designed a gene transfer strategy using BBB‐crossing adeno‐associated virus (AAV)‐based vectors to deliver VHH directly into the CNS. As a proof‐of‐concept, we explored the potential of AAV‐delivered VHH to inhibit BACE1, given its well‐characterized and central role in Alzheimer’s disease.

Method

In a first step, we generated a panel of novel VHHs targeting BACE1: one of these, VHH‐B9, demonstrates high selectivity for BACE1 and appears to specifically inhibit APP‐cleavage in vitro. On the basis that a substrate‐selective inhibition of BACE1 may overcome the mechanism‐based adverse effects commonly reported in BACE1 inhibitor trials, we selected VHH‐B9 for incorporation into a BBB‐crossing vector.

Result

A single systemic dose of AAV‐VHH‐B9 produces positive long‐term (12 months plus) effects on amyloid load, neuroinflammation, synaptic function and cognitive performance, in the AppNL‐G‐F
Alzheimer’s mouse model, without any overt signs of toxicity.

Conclusion

These results suggest that long‐term BACE1 inhibition, with a selective APP‐cleavage inhibitor, may constitute a novel therapeutic approach for Alzheimer’s disease. More broadly, we propose that AAV‐mediated VHH delivery will be a useful tool for the treatment of a range of CNS disorders.
Identification of an Inherent Bioenergetic and Metabolic Phenotype in Late‐Onset Alzheimer’s Disease Using the Induced Pluripotent Stem Cell Paradigm
Authors: Sonntag Kai‐Christian
Published: December 2022

Background

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Method

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Result

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Conclusion

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The synthesis of Fe3O4@SiO2@Pr‐N (CH2CH2OH)3 and Fe3O4@SiO2@Pr‐N (CH2CH2‐ OBuSO3H)3 as nanomagnetic catalysts and their application in the synthesis of tetrahydroacenaphtho[1,2‐b]indolones and docking studies
Authors: Kheilkordi Zohreh , Mohammadi Ziarani Ghodsi , Mohajer Fatemeh , Badiei Alireza , Gaikwad Sunil , Luque Rafael
Published: December 2022

The Fe3O4@SiO2@Pr‐N (CH2CH2‐OBuSO3H)3 as magnetic nanocatalyst with Fe3O4 core has been synthesized and used in the synthesis of tetrahydroacenaphtho[1,2‐b]indolones, which was accomplished through the one‐pot four‐component reaction of 5,5‐dimethyl cyclohexane‐1,3‐dione, acenaphthoquinone, arylamines, and active methylenes under solvent‐free conditions at 80°C. Fe3O4@SiO2@Pr‐N (CH2CH2‐OBuSO3H)3 with high magnetical and nontoxic properties has a core‐shell structure. The molecular docking was performed against the cancer target like the crystal structure of the motor protein kinesin spindle protein in complex with adenosine‐5'‐diphosphate and monastrol (pdb: 1Q0B) (2) and crystal structure of Mcl‐1 in complex with compound 7‐(4‐carboxyphenyl)‐3‐[3‐(naphthalen‐1‐yloxy)propyl]pyrazolo[1,5‐a]pyridine‐2‐carboxylic acid (pdb: 3WIX) (3).
Strengthening and toughening 3D printing of photocured resins by thermal expansion microspheres
Authors: Kang Xiaoqing , Li Xiaogang , Li Yuexuan , Duan Yugang
Published: December 2022

High cross‐linking density thermally cured epoxy resin typically results in brittle nature. 3D printing technology of a photocurable resin modified by thermally expandable microspheres is proposed in this paper to overcome these limitations. The addition of appropriate amounts of thermally expandable microspheres into the UV‐cured epoxy resin can improve the tensile strength, bending strength, elongation at break, and impact strength. Therefore, thermally expandable microspheres can strengthen and toughen the epoxy resin. In addition, the effects of different amounts of UV‐cured resins modified with thermally expandable microspheres on various mechanical properties are systematically analyzed. Moreover, the toughening mechanism of thermally expandable microspheres and their influence on thermal performance are also studied.
Isolation and screening of microorganisms for high yield of succinic acid production
Authors: Nagime Pooja Vilas , Upaichit Apichat , Cheirsilp Benjamas , Boonsawang Piyarat
Published: December 2022

This study involves the isolation of succinic acid (SA)‐producing microorganisms from different samples, including the rumen, sludge, soil, and wastewater. For primary screening, 29 isolates exhibited a zone of clearance around the colony, indicating acid production. For secondary screening using thin‐layer chromatography, only two isolates symbolized SA production according to their Rf values. These two isolates were further identified as Bacillus velezensis and Enterococcus gallinarum by phylogenetic analysis using the neighbor‐joining method. The high SA concentrations of 50.2 and 66.9 g/L were produced by B. velezensis and E. gallinarum with an SA yield of 0.836 and 1.12 g/g glucose, respectively. The high SA concentration from these newly isolated strains was achieved with a low formation of unwanted acids compared with those from Actinobacillus succinogenes ATCC 55618. Moreover, E. gallinarum was cultured in palm oil mill wastewater (POMW) and molasses, which were cheap substrates. The high SA production of 73.9 g/L with low other acids (the ratio of SA to total acids = 0.917) was achieved using POMW and molasses (80:20) as substrates.
Food Waste: Reflecting on Our Current Habits to Benefit the Future
Authors: Greer Mitchell J. , Howell Brittany J. , Weisenborn Gregory
Published: December 2022

Creating a college experience that is impactful to students is a challenge for every professor. Current research shows that inclusion of High Impact Teaching Practices (HITP) is one way to achieve these desired outcomes. One form of a HITP is Experiential Learning (EL), which is defined as “learning that begins with experience and transforms it into knowledge, skills, attitudes, emotions, values, beliefs, and senses. Our in‐class activity “The Food Waste Challenge” utilizes experiential learning and reflection on the experience to demonstrate the issues associated with food waste at the local and global scales. The number of food waste related activities is plentiful when you search the World Wide Web. However, in reviewing these activities we have found very few that are as inclusive or versatile as ours. Our activity requires a 3‐week period of food collection and for students to bring their waste to class each week. The length of time and physically bringing the waste to class creates a vital visualization of how much food waste one course can generate. We scale the food waste generated by one course up to what would be produced by the population of the university or of the town/city the university is in. Again, this highlights the magnitude of the food waste problem. Our activity also utilizes a food waste log where students keep track of why they threw out the food and asks them to estimate what the cost of the discarded items might be. Finally, we conduct a composting demonstration for the class. This helps to show students an alternative to throwing food in the trash and highlights a disconnect in what “can” be composted and what people “think” can be recycled. Our activity is well received by the students and in many cases, students have mentioned that it was one of the most memorable activities they conducted during their college careers.
Interrelationships among platelet‐activating factor and lipoprotein‐associated phospholipase A2 activity and traditional cardiovascular risk factors
Authors: English Carolyn J. , Lohning Anna E. , Mayr Hannah L. , Jones Mark , Reidlinger Dianne P.
Published: December 2022

Traditionally cardiovascular disease (CVD) risk has been assessed through blood lipids and inflammatory marker C‐reactive protein (hsCRP). Recent clinical interest in novel pro‐inflammatory markers platelet‐activating factor (PAF) and lipoprotein‐associated phospholipase A2 (Lp‐PLA2) recognizes that vascular damage can exist in the absence of traditional risk factors. This cross‐sectional study investigated the potential relationship between circulating PAF, Lp‐PLA2, hsCRP, and traditional risk factors for CVD. One hundred adults (49 ± 13 years, 31% male) with variable CVD risk were recruited. Fasting inflammatory markers PAF, Lp‐PLA2 and hsCRP and total, high‐density lipoprotein (HDL), low‐density lipoprotein (LDL) cholesterol, and triglycerides were measured. Blood pressure, body mass index, and waist circumference were measured. Medical and physical activity data were self‐reported. Linear and multiple regressions were performed. PAF, Lp‐PLA2, and hsCRP independently correlated with several CVD risk factors. PAF was correlated significantly with risk factors in an unexpected way; there was a medium positive correlation between PAF and HDL cholesterol (r = 0.394, p < 0.001) and medium negative correlations with Total:HDL cholesterol; (r = −0.436, p < 0.001) systolic blood pressure; (r = −0.307, p = 0.001); BMI (r = −0.381, p < 0.001); and waist circumference (r = −0.404, p < 0.001). There were large positive correlations between Lp‐PLA2 and LDL (r = 0.525, p < 0.001) and non‐HDL cholesterol (r = 0.508, p < 0.001). There were large positive correlations between hsCRP and Total:HDL cholesterol (r = 0.524, p < 0.001); BMI (r = 0.668, p < 0.001); and waist circumference (r = 0.676, p < 0.001). PAF, Lp‐PLA2, and hsCRP are implicated in the pathophysiology of inflammation in CVD; however, the relationships between each marker and traditional risk factors were different suggesting they may be involved in different atherogenic pathways.
A case of knuckle pad syndrome in a middle‐aged man
Authors: Chandler Zachary , Seamon Kimberly , Ramsubeik Karishma , Kaeley Gurjit
Published: December 2022

Knuckle pads are benign papules, nodules, or plaques overlying joints and typically manifest at the proximal interphalangeal joints (PIPs). They may be confused with other dermatologic or rheumatologic diseases. Treatment options for primary knuckle pads are limited and acquired knuckle pads typically improve with withdrawal of the offending insult.
Severe thrombocytopenia and anemia as an initial presentation of breast cancer: A case report
Authors: Otsubo Ryota , Yano Hiroshi , Itonaga Hidehiro , Iwasaki Keisuke , Segawa Keiko , Nagayasu Takeshi
Published: December 2022

Breast cancer patients with bone marrow metastasis (BMM) having profound thrombocytopenia and anemia are rare and there is no definitive treatment guideline. We present a case of successful initial treatment with anti‐disseminated intravascular coagulation therapy and endocrine therapy, followed by chemotherapy to avoid deterioration of severe thrombocytopenia and anemia.
Peristalsis in an unusual place—The diagnostic utility of point‐of‐care ultrasound: A case report
Authors: Twohig Patrick A. , Pile James C.
Published: December 2022

Complications related to inguinal hernias are commonly encountered in medicine. Clinical presentation can vary, and although diagnosis can often be made during physical examination, point‐of‐care ultrasound (POCUS) can be useful in cases where the diagnosis is unclear. Our case underscores to clinicians the utility of POCUS in diagnosing inguinal hernias.
DNA Nanomaterial‐Based Optical Probes for Exosomal miRNA Detection
Authors: Tang Jianpu , Li Qian , Yao Chi , Yang Dayong
Published: December 2022

Micro ribonucleic acids (miRNAs) in exosomes have been proven as reliable biomarkers to detect disease progression. In recent years, deoxyribonucleic acid (DNA)‐based nanomaterials show great potential in the field of diagnosis due to the programmable sequence, various molecule recognition and predictable assembly/disassembly of DNA. In this review, we focus on the molecular design and detection mechanism of DNA nanomaterials, and the developed DNA nanomaterial‐based optical probes for exosomal miRNA detection are summarized and discussed. The rationally‐designed DNA sequences endows these probes with low background signal and high sensitivity in exosomal miRNA detection, and the detection mechanisms based on different DNA nanomaterials are detailly introduced. At the end, the challenges and future opportunities of DNA nanomaterial‐based optical probes in exosomal miRNA detection are discussed. We envision that DNA nanomaterial‐based optical probes will be promising in precise biomedicine.
Long‐term programs helped boost applications, spur enrollment
Authors: D'Orio Wayne
Published: December 2022

When Scott Verzyl joined the University of South Carolina in 2004, the school's goals were clear but wide ranging. The public university wanted to grow its enrollment, increase both in‐state and out‐of‐state applicants, and improve the profile of the student body.
N, B codoped graphite felt for high‐performance 1,8‐dihydroxyanthraquinone redox flow battery
Authors: Deng Jianxiang , Cai Xinghua , Huang Chengde
Published: December 2022

In this article, a graphite felt electrode was modified by NS double‐element and NB double‐element codoping. The surface morphology, crystal structure, element content, and surface chemical state of the modified electrode were characterized by scanning electron microscopy, X‐ray powder diffraction (XRD), Raman spectroscopy, and X‐ray photoelectron spectroscopy. The electrochemical performance of the modified electrode was evaluated by cyclic voltammetry, electrochemical impedance spectra, and a single cell. The results show that nitrogen (N) and boron (B) double‐element codoping can enhance the catalytic activity of graphite felt and create abundant defect sites, which increases the electrocatalytic activity by approximately a factor of 2. The reason why the doped graphite felt can obtain higher electrocatalytic activity may be related to the synergy between N and B atoms, especially the synergy between pyridine‐N and BC3, and the resistance of the first charge transfer reaction of 1,8‐dihydroxyanthraquinone on the doped graphite felt electrode is then reduced.
Bond behaviour of rebar in concrete at elevated temperatures: A soft computing approach
Authors: Al Hamd Rwayda Kh. S. , Alzabeebee Saif , Cunningham Lee S. , Gales John
Published: December 2022

This paper assesses the capability of using a new data‐driven approach to predict the bond strength between steel rebar and concrete subjected to high temperatures. The analysis has been conducted using a novel evolutionary polynomial regression analysis (EPR‐MOGA) that employs soft computing techniques, and new correlations have been proposed. The proposed correlations provide better predictions and enhanced accuracy than existing approaches, such as classical regression analysis. Based on this novel approach, the resulting correlations have achieved a lower mean absolute error (), and root mean square error (), a mean () close to the optimum value (1.0) and a higher coefficient of determination (R2) compared to available correlations, which use classical regression analysis. Based on their enhanced performance, the proposed correlations can be used to obtain better optimised and more robust design calculations.
Evaluation of resistance and determination of stability of different sugar beet (Beta vulgaris L.) genotypes in rhizomania‐infected conditions
Authors: Rajabi Abazar , Ahmadi Masoud , Bazrafshan Mohsen , Hassani Mehdi , Saremirad Ali
Published: December 2022

Plant diseases are considered one of the main factors reducing yield and quality of crops, which are constantly developing and creating more virulent races and cause the resistance of more genes to break. Identifying resistance sources and including them in breeding programs will improve resistant genotypes. Rhizomania is the most common, widespread, and devastating disease of sugar beet in Iran and worldwide. Breeding genotypes with disease resistance genes is one of the most important ways to deal with this destructive disease. Twenty sugar beet genotypes along with five controls were evaluated in a randomized complete block design with four replications in rhizomania‐infected conditions in four regions of Mashhad, Shiraz, Miandoab, and Hamedan for 2 years. The results of genotypic reaction to rhizomania showed that the genotypes with resistance reaction were much more frequent than those with susceptibility reaction. The analysis of multiplicative effects of the AMMI model showed that the first six components were significant and explained 98.80% of the interaction variations. The biplot obtained from the mean white sugar yield and the first interaction principal component confirmed the superiority of the RM5 genotype due to its high white sugar yield and stability in infected conditions. The results obtained from the first three principal components biplot showed that the RM9 genotype with a mean white sugar yield of 11.91 t. ha−1 was a genotype with vast general stability in all disease‐infected environments. Based on the results of the MTSI index, RM3, RM17, RM9, RM13, and RM15 are introduced as stable genotypes under rhizomania‐infected conditions. In conclusion, it seems that the studied genotypes have valuable and useful genes inherited from their parents to deal with rhizomania disease. Applying these genotypes in sugar beet breeding programs can effectively prevent the threat of rhizomania.
Rethinking Decision Quality: Measures, Meaning, and Bioethics
Authors: Schwartz Peter H. , Sachs Greg A.
Published: December 2022

Studies of patient decision‐making use many different measures to evaluate the quality of decisions and the decision‐making process, partly to determine whether the ethical goals of informed consent, patient autonomy, and shared decision‐making have been achieved. We describe these measures, grouped under three main approaches, and review their limitations, leading to three conclusions. First, no measure or combination of measures can provide a complete assessment of decision quality. Second, the quality of a decision is best characterized vaguely, for instance as “good,” “satisfactory,” or “poor,” and these categorizations depend on qualitative judgments that go beyond quantitative measures. Third, bioethicists should focus on identifying and addressing poor or problematic decisions, rather than trying to incrementally increase decision quality, quantified by a measure. Decision‐quality measures can be useful in research and in advancing important goals of bioethics, as long as the challenges of defining and measuring decision quality are recognized.
Evolution of health sector strategic planning in Tanzania: What have we learnt and how can we improve?
Authors: Nabyonga‐Orem Juliet , Asamani James Avoka
Published: December 2022

Progressive realization of Universal Health Coverage is inevitable given resource constraints. The incremental approach must be reflected in health sector strategic plans which serve as roadmaps. Using a matrix based on the health systems building blocks to extract data, we reviewed three successive sector strategies to assess priority issues addressed. We undertook a thematic synthesis to draw lessons and conclusion reported in this paper.

Our review shows good practice as well as areas desiring attention if health sector strategic plans are to serve the intended purpose. Although all strategies were aligned to global and national development aspirations, were developed in a participatory manner they did not reflect the required incremental approach. The challenges to be addressed and the priorities remained largely the same over a 15‐year period. The strategies and key results areas to be implemented in the different strategies were numerous with funding gaps.

Improving the utility of strategic plans requires improving both the process and content. Implied in this approach is the need for prioritised and affordable strategic plans that reflect incremental efforts to attaining long term targets coupled with strong trend analysis and monitoring. Additionally, we advocate for strategic plan with a longer timeframe perhaps 10 years with adjustments at regular intervals.
The HR ecosystem: Emerging trends and a future research agenda
Authors: Snell Scott A. , Swart Juani , Morris Shad , Boon Corine
Published: December 2022

Human resource leaders are experimenting with new approaches to organizing and utilizing workers that are not limited to the traditional boundaries of the firm, but rather expand to an ecosystem of work and organization. This special issue introduction article introduces a set of papers from management scholars discussing the ecosystem of work and organization and offers a roadmap for future research on HR ecosystems. An ecosystem perspective invites us to rethink our current frameworks to better link theory to practice. It also challenges us to shift our level of analysis from the organization to the ecosystem, asking: how is work organized and conducted within this complex and evolving context? These papers uncover trends related to (1) technological mediation, (2) impermanence and adaptation, and (3) shared governance. Our hope is that by framing these trends found within the research in this special issue that scholars will be provided a better road map in moving forward with their own research on the role of HR within the ecosystem of work and organization.
Association of screening status, polygenic risk score and environmental risk factors with colorectal cancer incidence and mortality risks
Authors: Ren Jiaojiao , Zhang Peidong , Li Zhihao , Zhang Xiru , Shen Dong , Chen Peiliang , Huang Qingmei , Gao Pingming , Mao Chen
Published: December 2022

Whether screening can attenuate the influence of genetic risk and environmental risk factors for colorectal cancer (CRC) mortality risk remains unknown. Our study is to investigate the association of the screening history, genetic risk and environmental risk factors with CRC incidence and mortality risks using UK Biobank data. Screening history was associated with lower CRC incidence (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.58‐0.69) and mortality risk (HR: 0.56, 95% CI: 0.49‐0.63). Compared to the HRs of participants with a low genetic risk, low environmental risk and no screening history, the HRs of participants with a high genetic risk, high environmental risk and no screening history were 3.42 (95% CI: 2.76‐4.24) for CRC incidence and 3.36 (95% CI: 2.48‐4.56) for CRC mortality. In contrast, the HRs of participants with a high genetic risk and no screening history, but a low environmental risk, were 1.92 (95% CI: 1.55‐2.36) for CRC incidence and 1.88 (95% CI: 1.39‐2.53) for CRC mortality. Furthermore, the HRs of participants with a high genetic risk and a low environmental risk, but a screening history were 1.62 (95% CI: 1.15‐2.28) for CRC incidence and 1.77 (95% CI: 1.08‐2.89) for CRC mortality. Participants benefited more substantially from screenings for CRC mortality than for CRC incidence risk. A higher environmental risk was associated with higher risk of CRC incidence and mortality within each category of genetic risk. These findings emphasize the importance of CRC screening and identifying environmental factors to reduce CRC incidence and mortality risks.
Examining polymer‐protein biophysical interactions with small‐angle x‐ray scattering and quartz crystal microbalance with dissipation
Authors: Upadhya Rahul , Di Mare Elena , Tamasi Matthew J. , Kosuri Shashank , Murthy N. Sanjeeva , Gormley Adam J.
Published: December 2022

Polymer‐protein hybrids can be deployed to improve protein solubility and stability in denaturing environments. While previous work used robotics and active machine learning to inform new designs, further biophysical information is required to ascertain structure–function behavior. Here, we show the value of tandem small‐angle x‐ray scattering (SAXS) and quartz crystal microbalance with dissipation (QCMD) experiments to reveal detailed polymer‐protein interactions with horseradish peroxidase (HRP) as a test case. Of particular interest was the process of polymer‐protein complex formation under thermal stress whereby SAXS monitors formation in solution while QCMD follows these dynamics at an interface. The radius of gyration (Rg) of the protein as measured by SAXS does not change significantly in the presence of polymer under denaturing conditions, but thickness and dissipation changes were observed in QCMD data. SAXS data with and without thermal stress were utilized to create bead models of the potential complexes and denatured enzyme, and each model fit provided insight into the degree of interactions. Additionally, QCMD data demonstrated that HRP deforms by spreading upon surface adsorption at low concentration as shown by longer adsorption times and smaller frequency shifts. In contrast, thermally stressed and highly inactive HRP had faster adsorption kinetics. The combination of SAXS and QCMD serves as a framework for biophysical characterization of interactions between proteins and polymers which could be useful in designing polymer‐protein hybrids.
Post‐COVID‐19 fatal Aspergillus endocarditis: A case report
Authors: Najafi Narges , Moslemi Azam , Ghafari Rahman , Shayesteh Azar Shadi , Nabati Maryam , Faeli Leila , Salimi Maryam , Mirzakhani Roghayeh , Shokohi Tahereh
Published: December 2022

Background

Aspergillus endocarditis (AE) is a rare fatal infection. The infection is often reported in patients with prosthetic heart valves, immunosuppressed, broad‐spectrum antimicrobial use regimens, and drug abusers.

Methods

Herein, we report a rare case of native mitral valve AE in a 63‐year‐old man, with a probable COVID‐19‐associated invasive pulmonary aspergillosis nine months ago treated with antifungals.

Results

In the last admission, the lethargy, neurological deficit, and septic‐embolic brain abscess in brain MRI led to suspicion of infective endocarditis. Transesophageal two‐dimensional echocardiography and color Doppler flow velocity mapping showed a large highly mobile mass destroying leaflet and severe mitral regurgitation. The Surgical valve replacement is performed. The surgical valve replacement is performed. Direct microscopic examination and culture of the explanted and vegetative mass revealed Aspergillus section Fumiagati confirmed by molecular method. Despite the administration of voriconazole and transient improvement the patient expired.

Conclusion

As AE is a late consequence of COVID‐19‐associated invasive pulmonary aspergillosis, therefore, long‐term follow‐up of invasive aspergillosis, and prompt diagnosis of surgical and systemic antifungal therapy treatment, are warranted to provide robust management.
Post‐radiotherapy cribriform‐morular thyroid carcinoma
Authors: Or Koca Arzu , Güler Şimşek Gülçin
Published: December 2022

Background

According to the new 2022 World Health Organization classification of endocrine tumors, thyroid malignancy, formerly known as the cribriform‐morular variant of papillary thyroid carcinoma, is now categorized as differentiated thyroid malignancy; it is, at present, called cribriform‐morular thyroid carcinoma and classified as a tumor of unknown histogenesis.

Case Report

In this case report, we report on a 15‐year‐old patient who underwent external radiotherapy to the neck for Hodgkin's disease and developed cribriform‐morular thyroid carcinoma 5 years after radiotherapy.

Conclusions

We believe that cribriform‐morular thyroid carcinoma with diffuse nuclear beta‐catenin expression has exciting and unresolved uncertainties that may affect disease prognosis and follow‐up for cytopathologists and endocrinologists.
Variations on a theme by Rachlin: Probability discounting
Authors: Killeen Peter R.
Published: December 2022

Rachlin and colleagues laid the groundwork for treating the discounting of probabilistic goods as a variant of the discounting of delayed goods. This approach was seminal for a large body of subsequent research. The present paper finds the original development problematic: In converting probability to delay, the authors incorrectly dropped trial duration. The subsumption of probability by delay is also empirically questionable, as those are different functions of variables such as magnitude of outcome and commodity versus money. A variant of Rachlin's theme treats human discounting studies as psychophysical matching experiments, in which one compound stimulus is adjusted to equal another. It is assumed that a function of amount (its utility) is multiplied by a function of probability (its weight). Conjoint measurement establishes the nature of these functions, yielding a logarithmic transform on amount, and a Prelec function on probability. This model provides a good and parsimonious account of probability discounting in diverse data sets. Variant representations of the data are explored. By inserting the probabilistically discounted utility into the additive utility theory of delay discounting, a general theory of probabilistic intertemporal choice is achieved.
A new method for Raman spectral analysis: Decision fusion‐based transfer learning model
Authors: Chen Chen , Ma Yuhua , Zhu Min , Yan Ziwei , Lv Xiaoyi , Chen Cheng , Tian Feng
Published: December 2022

As an emerging technology for artificial intelligence‐aided medical diagnosis, deep learning combined with Raman spectroscopy has great potential. The technology still has some problems in the actual medical diagnosis research process. The differences in spectrometers, experimental conditions, and experimental operations can result in non‐uniform and universally applicable data standards, which in turn lead to low data utilization. At the same time, it is still necessary to retrain the models when building diagnostic models for different diseases, which is time‐consuming and laborious. In this paper, a more complete transfer learning model for multiple types of serum Raman spectra is established for the first time, and a decision fusion strategy is applied to this diagnostic model. The Raman spectral data of serum from hepatitis B patients/control group, serum from abnormal thyroid function patients/control group, and serum from glioma patients/control group were selected as the source domains, and the Raman spectral data of tissue from hepatitis C patients/control group, serum from esophageal cancer patients/control group, and tissue from cervical cancer and cervical inflammation (patients/control) group were selected as the target domains. Three deep neural network models, ResNet, GoogLeNet, and CNN‐LSTM were trained in the source domain data for disease diagnosis, and the trained models were transfer to the target domain. The model is fine‐tuned by freezing different layers and then combined with logistic regression algorithms to construct a decision fusion model, which further improves the model effect. The results show that the proposed method can effectively improve the accuracy of transfer learning models. At the same time, this experiment extends the application of transfer learning in Raman spectroscopy and demonstrates that unrelated and scale‐different Raman datasets are still intrinsically connected, which also lays the foundation for us to build more stable and data‐inclusive spectral transfer learning fusion models in the future.