bluuebunny/crossref_metadata_2025 huggingface dataset:
A glimpse into the structural properties of α‐synuclein oligomers
Authors: Santos Jaime , Pallarès Irantzu , Ventura Salvador
Published: December 2023

α‐Synuclein (αS) aggregation is the main neurological hallmark of a group of debilitating neurodegenerative disorders, collectively referred to as synucleinopathies, of which Parkinson's disease is the most prevalent. αS oligomers formed during the initial stages of aggregation are considered key pathogenic drivers of disease onset and progression, standing as privileged targets for therapeutic intervention and diagnosis. However, the structure of αS oligomers and the mechanistic basis of oligomer to fibril conversion are yet poorly understood, thereby precluding the rational formulation of strategies aimed at targeting oligomeric species. In this review, we delve into the recent advances in the structural and mechanistic characterization of αS oligomers. We also discuss how these advances are transforming our understanding of these elusive species and paving the way for oligomer‐targeting therapeutics and diagnosis.
Glycosaminoglycan dermatan sulfate supplementation decreases diet‐induced obesity and metabolic dysfunction in mice
Authors: Stojnić Bojan , Galmés Sebastiá , Serrano Alba , Sulli Maria , Sušak Lana , Seye Ndioba , Palou Andreu , Diretto Gianfranco , Bonet M. Luisa , Ribot Joan
Published: December 2023

Glycosaminoglycans are complex carbohydrates used as nutraceuticals for diverse applications. We studied the potential of the glycosaminoglycan dermatan sulfate (DS) to counteract the development of diet‐induced obesity (DIO) using obesity‐prone mice fed a high‐fat diet (HFD) as a model. Oral DS supplementation protected the animals against HFD‐induced increases in whole‐body adiposity, visceral fat mass, adipocyte size, blood glucose levels, insulin resistance, and pro‐inflammatory lipids levels in brown adipose tissue (BAT) and the liver, where it largely counteracted the HFD‐induced changes in the nonpolar metabolome. Protection against DIO in the DS‐supplemented mice occurred despite higher energy intake and appeared to be associated with increased energy expenditure, higher uncoupling protein 1 expression in BAT, decreased BAT “whitening,” and an enhanced channeling of fuel substrates toward skeletal muscle. This work is the first preclinical study to examine the anti‐obesity activity of DS tested individually in vivo. The results support possible uses of DS as an active component in functional foods/supplements to manage obesity and associated metabolic diseases.
Hypoxia is correlated with the tumor immune microenvironment: Potential application of immunotherapy in bladder cancer
Authors: Chen Haotian , Zhang Yao , Chen Xingyu , Xu Runshi , Zhu Yuxing , He Dong , Cheng YaXin , Wang Zhanwang , Qing Xiang , Cao Ke
Published: December 2023

Objective

Hypoxia, which can considerably affect the tumor microenvironment, hinders the use of immunotherapy in bladder cancer (BLCA). Therefore, we aimed to identify reliable hypoxia‐related biomarkers to guide clinical immunotherapy in BLCA.

Methods

Using data downloaded from TCGA‐BLCA cohort, we determined BLCA subtypes which divide 408 samples into different subtypes. Tumor immune infiltration levels of two clusters were quantified using ssGSEA, MCPcounter, EPIC, ESTIMATE, and TIMER algorithms. Next, we constructed a hypoxia score based on the expression of hypoxia‐related genes. The IMvigor210 cohort and SubMap analysis were used to predict immunotherapeutic responses in patients with different hypoxia scores. Hub genes were screened using cytoscape, immunohistochemistry (IHC), and multispectral immunofluorescence were used to detect the spatial distribution of immune markers.

Results

Patients with BLCA were categorized into cluster1 (n = 227) and Cluster2 (n = 181). Immune infiltration and expression of immune markers were higher in Cluster1. Immune infiltration was also more obvious in the high‐hypoxia score group which related to a better predicted response to immunotherapy. IHC, and multispectral immunofluorescence confirmed the importance of TLR8 in immune infiltration and immune phenotype.

Conclusions

BLCA subtype can evaluate the infiltration of immune cells in the tumor microenvironment of different patients. Hypoxia score in this study could effectively predict immunotherapeutic responses in patients with BLCA. TLR8 may be a potential target for clinical immunotherapy.
Clinical characteristics and prognostic factors analysis of core binding factor acute myeloid leukemia in real world
Authors: Zhai Yamei , Wang Qingya , Ji Li , Ren Hanyun , Dong Yujun , Yang Fan , Yin Yue , Liang Zeyin , Wang Qian , Liu Wei , Mei Yan , Zhang Lu , Li Yuan
Published: December 2023

Background

Chromosomal translocations involving core binding factor (CBF) genes account for 15% of adult acute myeloid leukemia (AML) cases in China. Despite being classified as favorable‐risk by European Leukemia Net (ELN), CBF‐AML patients have a 40% relapse rate. This study aims to analyze clinical characteristics and prognosis of CBF‐AML, compare its subtypes (inv(16) and t(8;21)), and validate prognostic factors.

Methods

Retrospective analysis of 149 AML patients (75 CBF‐AML, 74 non‐CBF) at Peking University First Hospital (March 2012–March 2022).

Results

CBF‐AML patients have significantly lower disease‐free survival (DFS) (p = 0.005) and higher non‐relapse mortality (NRM) (p = 0.028) compared to non‐CBF AML. inv (16) and t(8;21) show distinct co‐occurring gene mutation patterns, with inv(16) being prone to central nervous system (CNS) leukemia. Multivariate analysis identifies age as a risk factor for overall survival (OS) and disease free survival (DFS), kinase mutation as a risk factor for DFS and Recurrence, while WT1 mutation as a risk factor for OS and non relapse mortality (NRM) risk in t(8;21) AML. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) improves prognosis in low‐risk t(8;21).

Conclusion

Prognosis of CBF‐AML is poorer than ELN guidelines suggest. inv(16) and (8;21) are separate entities with relatively poor prognoses, requiring rational risk stratification strategies. Allo‐HSCT may benefit low‐risk t(8;21), but further research is needed for conclusive evidence.
Diagnosis, testing, treatment, and outcomes among patients with advanced non‐small cell lung cancer in the United States
Authors: Yang Mo , MacEwan Joanna P. , Boppudi Sai Sriteja , McClain Monica R. , O'Hara Richard M. , Paik Paul K.
Published: December 2023

Introduction

Characteristics of patients in clinical trials may differ from those of real‐world patients. Our objective was to describe biomarker testing and outcomes among patients with advanced non‐small cell lung cancer (aNSCLC) in a real‐world setting.

Methods

This retrospective cohort study included patients ≥18 years old, diagnosed with stage IIIB/C or IV NSCLC, and in the TEMPUS oncology dataset from January 1, 2012, to December 31, 2020. Patient characteristics associated with biomarker testing were evaluated in patients with positive biomarkers using univariate logistic regression models. Cox proportional hazard models were used to estimate median survival.

Results

Of 9540 patients included, 41.7% had biomarker testing, and 2158 had a positive biomarker result. Men (vs women; odds ratio [OR], 0.82; 95% CI: 0.74–0.91), Black patients (vs White; OR, 0.83; 95% CI: 0.72–0.97), patients with squamous (OR, 0.22; 95% CI: 0.19–0.25) or unknown histology (OR, 0.53; 95% CI: 0.45–0.61) (vs non‐squamous histology), and patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 2+ (OR, 0.69; 95% CI: 0.57–0.84) or missing (OR, 0.56; 95% CI: 0.48–0.66) (vs ECOG PS of 0) were less likely to undergo biomarker testing. Patients with positive biomarkers who received NCCN‐recommended treatment options (55.7%) had significantly longer median overall survival (OS) (hazard ratio [HR], 0.84; 95% CI: 0.75–0.95) and real‐world progression‐free survival (rwPFS) (HR, 0.68; 95% CI: 0.62–0.75).

Conclusion

More than 50% of patients were untested for biomarkers. Patients who were less likely to be tested included men, Black patients, current smokers, patients with squamous aNSCLC, and patients with an ECOG PS of 2+. Patients with positive biomarkers who received NCCN‐recommended treatment options had significantly longer OS and PFS.
Beyond the horizon: Neutrophils leading the way in the evolution of immunotherapy
Authors: Rajgopal Sanjana , Nakano Kosuke , Cook Leah M.
Published: December 2023

Cancer is a complex and dynamic disease, initiated by a multitude of intrinsic mutations and progressed with the assistance of the tissue microenvironment, encompassed by stromal cells including immune cell infiltration. The novel finding that tumors can evade anti‐cancer immune functions shaped the field of immunotherapy, which has been a revolutionary approach for the treatment of cancers. However, the development of predominantly T cell‐targeted immunotherapy approaches, such as immune checkpoint inhibition, also brought about an accumulation of evidence demonstrating other immune cell drivers of tumor progression, such as innate immune cells and notably, neutrophils. In the past decade, neutrophils have emerged to be primary mediators of multiple cancer types and even in recent years, are gaining attention for their potential use in the next generation of immunotherapies. Here, we review current immunotherapy strategies and thoroughly discuss the roles of neutrophils in cancer and novel neutrophil‐targeted methods for treating cancer.
COVID‐19 in cancer patients: The impact of vaccination on outcomes early in the pandemic
Authors: Khawaja Fareed , Angelidakis Georgios , Feldman Adina , Ravi Vinod , Woodman Eric , Bhatti Micah , Ariza‐Heredia Ella , Elhajj Peter , Spallone Amy , Jiang Ying , Chemaly Roy F.
Published: December 2023

Background

With the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, the development of effective and safe vaccines was of utmost importance to protect vulnerable individuals, including cancer patients. Studies comparing the clinical outcomes of cancer patients with or without vaccination against coronavirus disease 2019 (COVID‐19) have not demonstrated clear benefit. We aimed to determine the protective effects of COVID‐19 vaccination by comparing vaccinated and unvaccinated cancer patients after the initial phase of vaccine roll‐out and to identify risk factors associated with hospitalization, severe COVID‐19, and 30‐day COVID‐19 attributable mortality.

Methods

We performed a retrospective cohort study of cancer patients with COVID‐19 diagnosed by polymerase chain reaction on nasal swabs between January 1, 2021 and July 30, 2021. Outcomes of interest included hospitalization, severe COVID‐19, and 30‐day COVID‐19 attributable mortality. Univariate and multivariate analyses were performed to identify factors associated with clinical outcomes, using vaccination status as a variable of interest in all models.

Results

Key risk factors, such as age ≥ 60 years; comorbidities including diabetes mellitus, heart failure, and lung diseases; and specific cancer types (leukemia and lymphoma) were independently associated with hospital admission for COVID‐19, severe COVID‐19, and 30‐day COVID‐19 attributable mortality in cancer patients regardless of their vaccination status. Vaccinated patients were protected against severe COVID‐19 but with no impact on hospitalization or mortality due to COVID‐19.

Conclusion

Our study highlights a significant benefit of COVID‐19 vaccination for cancer patients—specifically its protection against severe COVID‐19.
Efficacy and safety of fruquintinib dose‐escalation strategy for elderly patients with refractory metastatic colorectal cancer: A single‐arm, multicenter, phase II study
Authors: Tan Sirui , Zhang Shunyu , Zhou Nan , Cai Xiaohong , Yi Cheng , Gou Hongfeng
Published: December 2023

Background

Fruquintinib has demonstrated significant improvement in overall survival (OS) among previously treated metastatic colorectal cancer (mCRC) patients. However, the utilization of fruquintinib has been constrained by various toxicities, such as hand‐foot skin reaction (HFSR) and hypertension, particularly in elderly patients with reduced tolerance to the standard dosage. This study aims to investigate the efficacy and safety of fruquintinib dose‐escalation strategy for elderly refractory mCRC patients.

Patients and Methods

This open‐label, single‐arm, phase II trial included patients aged 65 years or over with mCRC who had progressed after two or more lines of chemotherapy. Fruquintinib was administered for 21 consecutive days of a 28‐day treatment cycle. The starting dose of fruquintinib was 3 mg/day and escalated to 4 mg/day in Week 2 and 5 mg/day in Week 3 if no significant drug‐related toxicity was observed. The highest tolerated dose from Cycle 1 would be administered in Cycle 2 and all subsequent cycles. Before commencing treatment, all enrolled patients underwent a G8 questionnaire and comprehensive geriatric assessments. The primary endpoint of the study was progression‐free survival (PFS).

Results

A total of 29 patients were enrolled and all started fruquintinib at 3 mg/day. Fifteen patients (51.7%) were subsequently escalated to 4 mg/day and 4 (13.8%) to 5 mg/day. Only four (13.8%) patients discontinued treatment due to adverse events (AEs). The median PFS was 3.8 months (95% CI, 2.7–4.9), and the median OS was 7.6 months (95% CI, 6.5–8.7). Treatment‐related adverse events (TRAEs) were observed in all 29 patients (100%). The most frequently occurring (>10%) TRAEs greater than Grade 3 were HFSR (20.7%), hypertension (20.7%), and diarrhea (10.3%).

Conclusion

Our study indicated that a dose of 4 mg/day was well tolerated by most elderly patients, suggesting that fruquintinib dose‐escalation strategy during the first cycle could serve as a viable alternative to the standard 5 mg/day dosing.
Synthesis of azide‐modified glycerophospholipid precursor analogs for detection of enzymatic reactions
Authors: Ueshima Rina , Kikuma Takashi , Sano Kanae , Toda Nahoko , Greimel Peter , Takeda Yoichi
Published: December 2023

Glycerophospholipids (GPLs) are major cell membrane components. Although various phosphorylated molecules are attached to lipid moieties as their headgroups, GPLs are biosynthesized from phosphatidic acid (PA) via its derivatives, diacylglycerol (DAG) or cytidine diphosphate diacylglycerol (CDP‐DAG). A variety of molecular probes capable of introducing detection tags have been developed to investigate biological events involved in GPLs. In this study, we report the design, synthesis, and evaluation of novel analytical tools suitable to monitor the activity of GPL biosynthetic enzymes in vitro. Our synthetic targets, namely, azide‐modified PA, azide‐modified DAG, and azide‐modified CDP‐DAG, were successfully obtained from solketal as their common starting material. Moreover, using CDP‐diacylglycerol‐inositol 3‐phosphatidyltransferase (CDIPT), an enzyme that catalyzed the final reaction step in synthesizing phosphatidylinositol, we demonstrated that azide‐modified CDP‐DAG worked as a substrate for CDIPT.
Comparison of MANTA versus Perclose Prostyle large‐bore vascular closure devices during transcatheter aortic valve implantation
Authors: Barbash Israel M. , Wasserstrum Yishay , Erlebach Magdalena , Guetta Victor , Ziegelmüller Johannes , Segev Amit , Fefer Paul , Maor Elad , Lange Rüdiger , Ruge Hendrik
Published: December 2023

Background

New vascular closure devices (VCD) are being introduced for achieving hemostasis after transcatheter aortic valve implantation (TAVI). However, no safety or efficacy data have been published compared to other contemporary VCD.

Aim

To compare the safety and efficacy of suture‐based Perclose Prostyle as compared to plug‐based MANTA device.

Methods

A total of 408 consecutive TAVI patients from two high volume TAVI centers were included in the present study. Patients were grouped according to VCD: Prostyle versus MANTA. Propensity score matching (PSM) and multivariable analysis were utilized to compare clinical endpoints between the two groups. The primary endpoint was any vascular complication (VC) according to VARC‐3 criteria.

Results

After PSM, a total of 264 patients were analyzed, of them 132 in each group. Overall baseline characteristics of the two groups were comparable. Primary end‐point was similar between MANTA as compared to Prostyle (16.7% vs. 15.3% respectively, p = 0.888). The main driver for VC among MANTA group were minor vascular complications (15.2%). Conversely, minor and major VC contributed equally to the primary endpoint among Prostyle group (7.6%) (p = 0.013). No outcome predictors were identified in multivariate analysis.

Conclusions

VCD for transfemoral TAVI using the new‐generation Prostyle device or the MANTA device achieved comparable VARC‐3 VC rates.
Cyclometalated gold(III)‐hydride under oriented external electric fields: a new strategy to modulate its reactivity?
Authors: Li Yin‐Qi , Cheng Xin , Jiang Shan , Song Wen‐Xuan , Chen Jing‐Hua , Sun Wei‐Ming
Published: December 2023

Selected gold complexes have been regarded as promising anti‐cancer agents because they can bind with protein targets containing thiol or selenol moieties, but their clinical applications were hindered by the unbiased binding towards off‐target thiol‐proteins. Recently, a novel gold(III)‐hydride complex (abbreviated as 1) with visible light‐induced thiol reactivity has been reported as potent photo‐activated anticancer agents (Angew. Chem. Int. Ed., 2020, 132, 11139). To explore new strategies to stimuli this potential antitumor drug, the effect of oriented external electric fields (OEEFs) on its geometric structure, electronic properties, and chemical reactivity was systematically investigated. Results reveal that imposing external electric fields along the Au−H bond of 1 can effectively activate this bond, which is conducive to its dissociation and the binding of Au site to potential targets. Hence, this study provides a new OEEF‐strategy to activate this reported gold(III)‐hydride, revealing its potential application in electrochemical therapy. We anticipate this work could promote the development of more electric field‐activated anticancer agents. However, further experimental research should be conducted to verify the conclusions obtained in this work.
Comprehensive evaluation of benign and malignant etiologies of different serous effusions with the International System for Reporting Serous Fluid Cytopathology: A multi‐institutional study in Taiwan
Authors: Lu Chun‐Han , Liu Chih‐Yi , Jhuang Jie‐Yang , Chen Chien‐Chin
Published: December 2023

Background

The International System for Reporting Serous Fluid Cytopathology (ISRSFC) was introduced globally in 2019 in response to the absence of a standardized reporting system for serous fluid cytology. This study presents experiences implementing this system across three distinct hospitals in Taiwan.

Methods

A total of 6177 serous fluid specimens in three hospitals in Taiwan between 2018 and 2020 were retrospectively reviewed and reclassified according to the ISRSFC. Cytohistological correlation and chart review were further performed to investigate etiologies and risks of malignancy (ROMs).

Results

Reclassification showed that 34 (0.7%) of 4838 pleural effusions were nondiagnostic (ND), 4086 (84.5%) were negative for malignancy (NFM), 201 (4.2%) were atypia of undetermined significance (AUS), 92 (1.9%) were suspicious for malignancy (SFM), and 425 (8.8%) were malignant (MAL). The 1231 ascites cases contained 13 (1.1%) ND, 1004 (81.6%) NFM, 53 (4.3%) AUS, 31 (2.5%) SFM, and 130 (10.6%) MAL specimens. In pleural effusions, the ROM was 2.9% for ND, 14.0% for NFM, 52.2% for AUS, 85.9% for SFM, and 95.1% for MAL. In ascites, it was 15.4% for ND, 19.1% for NFM, 52.8% for AUS, 83.9% for SFM, and 92.3% for MAL. In pericardial effusions, it was 0.0% for ND, 11.6% for NFM, 30.8% for AUS, 100.0% for SFM, and 95.2% for MAL. Different effusions' most common benign and malignant etiologies were also disclosed.

Conclusions

These multi‐institutional data have determined the diagnostic usefulness of the ISRSFC, which provides pathologists and physicians with invaluable assistance in correctly classifying effusions for further management.
Comparison of monkey and human retrosplenial neurocytology
Authors: Vogt Brent A. , Rosene Douglas L.
Published: December 2023

Retrosplenial cortex (RSC) has unique problems for human neuroimaging studies as its divisions are small, at the lower end of functional scanner spatial resolution, and it is buried in the callosal sulcus. The present study sought to define the cytoarchitecture of RSC in human and monkey brains along its entire anteroposterior extent. The results show anterior extensions, a newly defined dichotomy of area 30, a new area p30, and an area p29v in monkey that differentiates into three divisions in human. Accordingly, anterior (a), intermediate (i), and posterior (p) divisions of areas 29l, 29m, 30l, and 30m were identified. Posterior area 29 has higher neuron packing in the granular layer than anterior and intermediate divisions of area 29. A newly detected dysgranular area p30 has larger neurons in layers II–IIIab than a30 and i30 and with substantially higher NFP expression  in layer IIIab of posterior areas than areas a30 and i30. Medial area 30 has larger pyramids and higher NFP expression in all layers than area 30l. The new area p30 was seen between areas p29m and p30I in both species. Finally, a ventral area p29v is present in monkeys. This latter area appears to differentiate into three divisions in human with the most extensive granular layer adjacent to layer I in p29vm and p29vl. Functional imaging has identified pRSC as part of a cognitive map which is engaged in spatial navigation and localization of personally relevant objects.
Shrinking Devices: Shape‐Memory Polymer Fabrication of Micro‐and Nanostructured Electrodes
Authors: González‐Martínez Eduardo , Moran‐Mirabal Jose
Published: December 2023

Since their discovery in the 1940s, shape memory polymers (SMPs) have been used in a broad spectrum of applications for research and industry.[1] SMPs can adopt a temporary shape and promptly return to their original form when submitted to an external stimulus. They have proven useful in fields such as wearable and stretchable electronics,[2] biomedicine,[3] and aerospace..[4] These materials are attractive and unique due to their ability to “remember” a shape after being submitted to elastic deformation. By combining the properties of SMPs with the advantages of electrochemistry, opportunities have emerged to develop structured sensing devices through simple and inexpensive fabrication approaches. The use of electrochemistry for signal transduction provides several advantages, including the translation into inexpensive sensing devices that are relatively easy to miniaturize, extremely low concentration requirements for detection, rapid sensing, and multiplexed detection. Thus, electrochemistry has been used in biosensing,[5] pollutant detection,[6] and pharmacological[7] applications, among others. To date, there is no review that summarizes the literature addressing the use of SMPs in the fabrication of structured electrodes for electrochemical sensing. This review aims to fill this gap by compiling the research that has been done on this topic over the last decade.
Exploring the Reactivity of Flavins with Nucleophiles Using a Theoretical and Experimental Approach
Authors: Zubova Ekaterina , Pokluda Adam , Dvořáková Hana , Krupička Martin , Cibulka Radek
Published: December 2023

Covalent adducts of flavin cofactors with nucleophiles play an important role in non‐canonical function of flavoenzymes as well as in flavin‐based catalysis. Herein, the interaction of flavin derivatives including substituted flavins (isoalloxazines), 1,10‐ethylene‐bridged flavinium salts, and non‐substituted alloxazine and deazaflavin with selected nucleophiles was investigated using an experimental and computational approach. Triphenylphosphine or trimethylphosphine, 1‐nitroethan‐1‐ide, and methoxide were selected as representatives of neutral soft, anionic soft, and hard nucleophiles, respectively. The interactions were investigated using UV/Vis and 1H NMR spectroscopy as well as by DFT calculations. The position of nucleophilic attack estimated using the calculated Gibbs free energy values was found to correspond with the experimental data, favouring the addition of phosphine and 1‐nitroethan‐1‐ide into position N(5) and methoxide into position C(10a) of 1,10‐ethylene‐bridged flavinium salts. The calculated Gibbs free energy values were found to correlate with the experimental redox potentials of the flavin derivatives tested. These findings can be utilized as valuable tools for the design of artificial flavin‐based catalytic systems or investigating the mechanism of flavoenzymes.
Biophysical factors and agronomic practices associated with Fusarium ear rot and fumonisin contamination of maize in multiple agroecosystems in Ethiopia
Authors: Deressa Temesgen , Adugna Girma , Suresh L. M. , Bekeko Zelalem , Opoku Joseph , Vaughan Martha , Proctor Robert H. , Busman Mark , Burgueño Juan , Prasanna B. M.
Published: December 2023

In Ethiopia, Fusarium ear rot (FER) reduces yield, quality, and safety of maize and negatively impacts the economics of maize growers. However, there is almost no published information on geographic distribution, severity, or causal agents of FER in Ethiopia or levels of preharvest fumonisin contamination, biophysical factors, and agronomic practices associated with FER. Therefore, we surveyed 480 agricultural fields located in 10 Ethiopian zones to assess the incidence and severity of FER as well as agricultural practices and biophysical factors associated with each field. We also determined the concentration of fumonisin in samples taken from the fields. Results revealed that FER was prevalent with varied disease intensity and yield loss levels among the assessed zones. The highest percent severity index (PSI) was recorded in Mirab Wellega (33.2%), with a correspondingly maximum estimated mean grain yield loss of 13.6%, while the minimum disease severity 11.3% and yield loss 5.4% were recorded from the Ilubabor zone. Fumonisins (FB1, FB2, FB3, and FB4) were detected in 98% of the samples, and the levels ranged from 5 to 7517 μg kg−1 (mean, 540 μg kg−1 and median 82.4 μg kg−1). The mean fumonisin contamination of 1524.4, 1316.8, 744.5, and 742.6 μg kg−1 was recorded for Mirab Welega, Misraq Wellega, Assosa, and Hawassa zones, respectively. In total, about 11.3% of the maize samples exceeded the maximum tolerable total fumonisin limit set by the European Union in maize flour (>1000 μg kg−1) and are not suitable for human consumption. Disease severity highly significantly (p < 0.0001) correlated with biophysical factors such as insect infestation (r = 0.60, p < 0.0001) and weed infestation (r = 0.64, p < 0.0001) and agronomic practices such as nitrogen phosphorus sulfur fertilizer application rate (r = −0.39, p < 0.0001) and insecticide spray frequency (r = −0.55, p < 0.0001). Other agronomic practices such as earlier or later sowing date and inter‐cropping systems significantly reduced (p < 0.001) FER incidence, PSI, and the associated grain yield loss. There was significant (p < 0.0001) variation among maize cultivars currently under production in reaction against FER disease intensity. Moreover, the result of the present study attests a strong positive association (p < 0.001) between disease intensity and maize fumonisin concentrations. Generally, the study revealed a wider distribution of FER and fumonisin contamination of maize in the southwest major maize‐growing belts of Ethiopia. Thus, appropriate integrated pre‐harvest ear rot management strategies including the use of resistant cultivars and suitable agronomic practices are recommended for the management of FER and the associated mycotoxins in Ethiopia.
Axial ratio bandwidth improvement of compact planar monopole antenna with dual‐band and dual‐sense
Authors: Mondal Kalyan , Bag Biplab , Sarkar Partha Pratim
Published: December 2023

A small size, dual‐band and dual‐sense monopole antenna is proposed to improve the axial ratio bandwidth (ARBW). The proposed antenna is considered on a low‐cost lossy FR4 substrate with parasitic strips (PSs) and partial ground plane of half guided wavelength dimensions. The dimension of the antenna in terms of wavelength is
, where
is the wavelength at the lowest resonant frequency. The circularly polarized (CP) mode is created for strong orthogonal electric fields
and
. The obtained phase difference (PD) between two electric fields
and
is varied from
to
under ARBW. The achieved ARBW is 3.68–3.8 GHz, 4.84–12.58 GHz, and impedance bandwidth (IBW) is 3.51–3.82 GHz and 4.28–15 GHz. The applications of the proposed antenna are International Telecommunication Union (ITU) for 5G, C‐band IEEE 802.11a wireless local area network (WLAN) at 5 GHz (5.15–5.825 GHz) and X‐band wireless systems.
The WHO system versus the Papanicolaou society of cytopathology system for reporting pancreaticobiliary cytology for risk stratification—which is better?
Authors: Kundu Reetu , Kollabathula Arpitha , Gupta Nalini , Rohilla Manish , Rana Surinder Singh , Nada Ritambhra , Kalra Naveen , Basher Rajender Kumar , Gupta Parikshaa , Dey Pranab , Gupta Rajesh , Dutta Usha , Srinivasan Radhika
Published: December 2023

Background

Recently, the World Health Organization (WHO) has proposed a reporting system for pancreaticobiliary cytopathology. We applied this classification for pancreatic lesion samples by fine needle aspiration (FNA) and compared the results to the previous classification of the Papanicolaou Society of Cytopathology (PSC) system for risk stratification.

Methods

The computerized database was searched for all pancreatic endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) and transabdominal ultrasound‐guided FNA (TUS‐FNA) samples from 2016 to 2020 and cases were reassigned as per the PSC and the WHO diagnostic categories. Cases with follow‐up, clinicoradiological, and/or histopathology were included in the study. The risk of malignancy (ROM) was calculated across all diagnostic categories based on clinical data, imaging data, and histopathology wherever available.

Results

There were a total of 625 pancreatic FNA. In 230 cases, follow‐up information was available which included 116 EUS and 114 TUS‐FNA samples. The ROM for PSC categories I–VI was 40%, 19.7%, 28.6%, 57.1%, 94.7%, and 97.9% and for the WHO categories (I–VII), it was 60%, 21.3%, and 35.7%, not representative, not applicable, 94.7% and 94.9%. The overall sensitivity and specificity of PSC was 68.2% and 96.2% when categories V and VI were taken as positive and 78.9% and 93.3% for WHO when categories VI and VII were taken as positive.

Conclusions

Pancreatic FNA samples reported as per the WHO system showed better sensitivity as compared to the PSC system resulting in better risk stratification and consequently better patient management. The overall high specificity and moderate sensitivity reaffirm the utility of FNA in pancreatic lesions.
Bilateral intra‐lymph node Warthin's tumor as a potential diagnostic pitfall mimicking metastatic carcinoma
Authors: Santos‐Sousa Ana Lívia , Camilo‐Júnior Deolino João , Conrado‐Neto Sebastião , Bernabé Daniel Galera , Xavier‐Júnior Jose Candido C.
Published: December 2023

Warthin's tumor (WT) is a benign and frequent salivary gland tumor primarily affecting the parotid gland. In some cases, this tumor can involve the extra parotid region and affect cervical lymph nodes. Fine‐needle aspiration can be the first step in the diagnostic approach to lymphadenopathy; however, specimens from intra‐nodal WT can present a potential pitfall, leading to a misdiagnosis of metastasis. Here, we report an unusual case of a patient with bilateral WT in parotid lymph nodes misdiagnosed as metastases. In addition, we highlight the cytopathological aspects of WT to alert cytopathologists about this challenging diagnosis.
Opportunistic microsporidiosis unveiled by fine‐needle aspiration cytology of cervical lymph node with literature review
Authors: Singh Brijdeep , Kundu Reetu , Sharma Chayan , Khurana Sumeeta , Bhujade Harish , Singla Neeraj , Rudramurthy Shivaprakash M.
Published: December 2023

Microsporidia are highly specialized obligate intracellular organisms closely related to fungi, traditionally linked to diarrheal diseases in acquired immunodeficiency syndrome patients. Over the past two decades, an increasing incidence of extraintestinal infections affecting various organ systems, especially in immunocompromised individuals, has been observed. The report presents a unique case of lymph node microsporidiosis in a 38‐year‐old male, positive for human immunodeficiency virus, with coinfections of hepatitis B and C. Fine‐needle aspiration cytology (FNAC) from cervical lymph node yielded pus‐like, necrotic material with periodic acid‐Schiff stained smear uncovering small round to oval spores on microscopy suspicious for microsporidia. Based on polymerase chain reaction and sequencing done with aspiration material, the causative agent was identified as Vittaforma corneae. This rare encounter highlights the significance of recognizing unique morphological characteristics of infectious organisms and employing appropriate ancillary techniques for precise identification. The case underscores the crucial role of FNAC in diagnosing opportunistic infections involving the lymph nodes and the growing significance of molecular tests for specific pathogen confirmation.
Qualitative study of the impact on recovery of peer relationships between female inpatients during treatment for anorexia nervosa in the United Kingdom
Authors: Lotery Elizabeth , Bell Rebecca , Combe Gillian , Biddle Lucy , Bould Helen
Published: December 2023

Objective

Admissions to hospitals for people with anorexia nervosa (AN) often last over 2 months, during which significant time is often spent with other patients, but there is little qualitative research on the impact on recovery of the inter‐patient relationships. Our aim was to conduct qualitative interviews with people with a history of inpatient treatment for AN, focusing on the impact of interactions and relationships between patients during hospital admission on recovery, including short‐term and long‐term effects.

Method

We conducted nine semi‐structured, one‐to‐one interviews, specifically exploring the helpful and unhelpful aspects of inter‐patient relationships during inpatient treatment for AN. No type of relationship was either included or excluded. Participants were recruited as volunteers in response to an online advertisement; all who met the eligibility criteria were selected. Interviews were transcribed and analyzed using thematic analysis.

Results

Thematic analysis identified five themes: (1) comparison and justification, (2) learnt unhelpful behaviors, (3) dealing with distress, (4) compassion, and (5) role‐modeling. All participants expressed conflicting feelings about their relationships with other patients, but generally described developing more resilience to negative effects as they got closer to recovery. Positive effects, such as compassion, appeared to hold significance long term in participants' recovered lives.

Discussion

The detailed exploration of themes in this study provides a deeper understanding of inter‐patient relationships during inpatient treatment for AN. This could aid clinical decision‐making when choosing appropriate treatment settings for individual patients as well as informing clinical practice in hospital.

Public Significance

This study closely examines the effect on recovery of relationships with other patients during hospital treatment for AN, a severe eating disorder. Findings might help hospital staff to understand the feelings of those they look after and develop ways to protect patients from the negative effects of peer relationships and enhance the positive ones, to support recovery in hospital.
How to Set the “Chirality” of Polyhedral Small Molecule Hydrocarbons: Decoration and Editing of Cubane Skeleton
Authors: Takebe Hiyori , Matsubara Seijiro
Published: December 2023

Small polyhedral hydrocarbons represented by cubane have attracted attention as potential molecular scaffolds for pharmaceuticals as benzene bioisoster. Cubane is also expected to be used as a chiral scaffold, but due to its high symmetry, it is necessary to introduce chirality by sequential site‐selective introduction of substituents. Furthermore, polyhedral desymmetrized isomers of cubane, such as cuneane and semibullvalene, and extended cage compounds, such as bishomocubane and homocuneane, exhibit chirality and are also expected to be used as new optically active scaffolds. In this concept, we would like to explain the synthetic routes we have planned, specifically, the decoration and editing of the cubane skeleton.
Trifluoromethyl Ketone Galactose Catalyst for Asymmetric Epoxidation: Experimental and Theoretical Model
Authors: Imperio Daniela , Casali Emanuele , Del Grosso Erika , Caprioglio Diego , Minassi Alberto , Panza Luigi
Published: December 2023

Since the introduction of the Shi catalyst, the organocatalytic epoxidation of olefins has become an area of continued research interest. To explore the possibility of enhancing the efficiency and stability of the catalyst, the synthesis of a galactose‐derived trifluoromethyl ketone, and its use for stereoselective epoxidation reaction that exploits a transitory dioxirane as active species are herein reported. The trifluoromethyl ketone was built on the C6 of a protected d‐galactopyranose. The organocatalyst was obtained smoothly in a few steps, and when utilized for stereoselective epoxidation exhibited excellent stability as no chemical alterations were observed during the reaction. The stereoselectivity, although sometimes moderate, appears surprisingly high considering the conformational freedom of the trifluoromethyl ketone moiety.

DFT calculations were performed to investigate the interactions involved in regulating the observed selectivities. Moreover, a new mnemonic model has been developed to serve as a fast‐predicting tool for epoxidation of new substrates.
Biological recovery of phosphorus (BioP‐Rec) from wastewater streams using brewer's yeast on pilot‐scale
Authors: Vučić Vedran , Harms Hauke , Müller Susann
Published: December 2023

Most recent advances for phosphorus (P) recovery using brewery yeast on laboratory scale were used to scale up to a pilot‐scale process (BioP‐Rec module) and applied in a full‐scale wastewater treatment plant (WWTP). A P balance was established for WWTP Markranstädt according to two thresholds: (1) the economic feasibility threshold for P recovery of 0.05 kg/m3 of free P, and (2) the German Sewage Sludge Ordinance (GSSO) threshold, which demands that all WWTPs with a P content in dry matter (DM) of biosolids of 20 gP/kgDM or higher in the coming years must perform mandatory P recovery. In terms of defined thresholds, return and excess sludges were identified as the most feasible WWTP process streams for P recovery. In a 1 m3 BioP‐Rec module a 3 stage process was established. From the P‐rich water‐phase of the return sludge produced in stage 1, which contained 0.051 kg/m3 of free P, 77.56% was taken up by P‐depleted brewer's yeast Saccharomyces pastorianus in 3 h in stage 2. In stage 3, the yeast was concentrated in 1 h to produce yeast sludge as a fertilizer product. We demonstrated a novel pilot‐scale process for the production of bio‐based P‐rich fertilizer.
Analysis of hygroscopicity and pyrolysis behaviour of propanediol esters synthesized by the enzymatic method
Authors: Gao Ziting , Chu Wenjuan , Han Lu , Wan Jiqiang , Li Mengxue , Yang Xiaopeng , Guo Qi , Lu Hongliang , Ji Xiaoming , Tian Haiying , Lai Miao
Published: December 2023

In order to develop food or tobacco usable flavour precursors, compounds 2‐hydroxypropyl benzoate (3a), propane‐1,2‐diyl dibenzoate (4a), 2‐hydroxypropyl cinnamate (3b) and propane‐1,2‐diyl (2E,2′ E)‐bis(3‐hydroxypropyl cinnamate) (4b) were synthesized by transesterification propanediol with vinyl benzoate and vinyl cinnamate under the biological enzyme Novozym435. The structures of the propanediol esters were characterized using nuclear magnetic resonance (1H NMR, 13C NMR), infrared spectroscopy (IR) and high‐resolution mass spectrometry (HRMS). The hygroscopicity and moisture retention capacity of reconstituted tobacco shreds with the synthesized propanediol were explored by 100 h hygroscopic desorption assay, model validation and low‐field nuclear magnetic resonance imaging (LF‐NMR). The results showed that the bound water content of 3a and 3b was lower than that of propanediol and higher than that of the control under both low (RH = 32%) and high (RH = 84%) humidity conditions. In addition, pyrolysis‐gas chromatography/mass spectrometry (Py‐GC/MS) technique was applied to investigate the thermal behaviour of 3a and 3b. Four and five pyrolysis products were formed by pyrolysis of 3a and 3b, respectively. The main pyrolysis products benzoic acid and cinnamic acid could be used as flavouring agents in food and tobacco. 3a and 3b had good moisture and humidity retention effects as well as uniform and sustained flavour release. The results of the study not only effectively improve the water absorbency of reconstituted tobacco and enhance the flavour, which is suitable for the storage and smoking process, but also provide a reference for the further development of new flavour moisturizers in the tobacco industry.
Effects of spices mixture and cooking on phytochemical content in Ethiopian spicy hot red pepper products
Authors: Medalcho Tadewos Hadero , Ali Kebede Abegaz , Augchew Engeda Dessalegn , Mate Juan Ignacio
Published: December 2023

Spicy hot red pepper, the most popular spice in Ethiopia, is also locally known as berbere, which is highly valued for its pungency, flavor, and color. The spicy hot red pepper powder is used to flavor shiro and other stews, as well as different forms of condiments. The aim of this study was to measure the phytochemical content of raw spices (black cumin, garlic, ginger, and cardamom) and control hot red pepper (HRP), as well as the raw and cooked experimental and commercial spicy hot red pepper products. The samples were analyzed for phytochemical content using a spectrophotometer. Compared to raw experimental spicy hot red pepper, raw spices, and HRP, raw commercial spicy hot red pepper exhibited the highest bioactive phytochemicals. The cooked commercial spicy hot red pepper or sauté had the highest total flavonoid content (TFC) and total carotenoid content (TCC). Similarly, cooked experimental spicy hot red pepper contained the highest levels of total phenolic content (TPC) and β‐carotene. With r values ranging from 0.24 to 0.65, the TPC and TFC of raw spices were correlated with antioxidant activity. There was a significant correlation between TCC and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) (r = .71), 2, 2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) (r = .95), and ferric ion reducing antioxidant power (FRAP) (r = .76), as well as between β‐carotene and DPPH (r = .69), FRAP (r = .69), and ferrous ion chelating activity (FICA) (r = .78). This study verified that raw spices and their mix with hot red pepper are good sources of bioactive phytochemicals with radicals scavenging abilities in Ethiopian diets.
Epigenetic age in African American adolescents with type 2 diabetes: A cross‐sectional case–control study protocol
Authors: Foster Christy , Mamaeva Olga , Shrestha Sadeep , Hidalgo Bertha
Published: December 2023

Background and Aims

Type 2 diabetes (T2D) is a disease caused by a relative insulin deficiency compared to the significant insulin requirement needed by the body to achieve glycemic control. T2D in adolescence appears to be increasing in prevalence over the past several decades, necessitating studies to understand for the onset of the disease to occur early in the lifespan. Given the high burden of disease, specifically in young African American adolescents, our study chose to focus initially on feasibility of recruitment of this population.

Methods

Data was collected at a single study center at Children's of Alabama. The protocol was completed as part of routine care or at a study visit. The study team was able to leverage the Electronic Medical Record to prescreen eligible patients to discuss the study. A variety of times of day were utilized to improve likely of success with reaching potential participants. Inclusion criteria for patients with T2D was focused on the adolescent population (ages 12–18 years), with no history of an obesity syndrome. DNA methylation age will be calculated using the EPIC 850K array. Statistical analysis will be done using linear regression analysis, adjusting for covariates.

Conclusions

This study's aim was to screen and enroll young African American adolescents for a study investigating epigenetic aging and T2D. Our study found that more direct contact (face‐to‐face‐ or phone call) improve success of recruitment. Leveraging the electronic medical record also helped improve success with pre‐screening participants. Challenges included recruiting participants who might come from long distances to a tertiary care center. Consolidating appointments helped improve the success of reaching these participants. Other challenges included frequent address changes and changed phone numbers. Close attention to the barriers as well as the successes will aid in understanding effective strategies for this important population.
SSRIs in the course of COVID‐19 pneumonia: Evidence of effectiveness of antidepressants on acute inflammation. A retrospective study
Authors: Fei Leonardo , Bozza Bernardo , Melani Giulia , Righi Lorenzo , Santarelli Gabriele , Boy Ottone Baccaredda , Benedetti Davide , Falone Andrea , Flaccomio Dario , Giuranno Gabriele , Martelli Michela , Merola Pierpaolo , Moretti Sandra , Ndoci Endrit , Pecoraro Vincenzo , Siviglia Serena , Berni Andrea , Fanelli Alessandra , Giovagnini Eleonora , Morettini Alessandro , Nozzoli Carlo , Para Ombretta , Rostagno Carlo , Tozzetti Camilla
Published: December 2023

Introduction

Relationships between inflammation and mood have been observed in terms of pro‐inflammatory effects induced by depressive conditions and, in parallel, by an antidepressant‐induced favorable effect on the recovery of inflammatory states. Selective serotonin reuptake inhibitor (SSRI) drugs were hypothesized to improve the prognosis of COVID‐19 pneumonia, a typical acute inflammation, in terms of decreased mortality rate and pro‐inflammatory cytokine serum levels.

Methods

The medical records of COVID‐19 pneumonia inpatients at Careggi University Hospital (Florence) were analyzed for prognosis and Interleukin 6 (IL‐6) after admission for over a period of 22 months. Medical records of patients treated at admission and not discontinued until discharge with an SSRI or with vortioxetine were identified. Two groups, one treated with antidepressants, the other not treated, were evaluated according to the mentioned parameters. Multiple linear regression and logistic regression were performed.

Results

The entire sample composed of 1236 records (recovered patients 77.1%, deceased patients 22.9%). The treated group (n = 107) had a better prognosis than the untreated group in spite of age and comorbidity both being greater than in the untreated group. Correspondingly, IL‐6 levels in the treated group were significantly lower (p < 0.01) than the levels in the untreated group, in every comparison.

Conclusions

Outcomes of this study support the hypothesis of the favorable influence of some antidepressants on the prognosis of COVID‐19, possibly mediated by IL‐6 modulation. Reduction in acute inflammation induced by the action of antidepressants was confirmed.
Inherited episodic ataxia type 2 in pregnancy: A case report
Authors: Mascherpa Margaret , Fichera Anna , Orabona Rossana , Recupero Daniela , Borroni Barbara , Odicino Franco Edoardo , Prefumo Federico
Published: December 2023

Synopsis

An optimal materno‐neonatal outcome was obtained in a pregnancy with inherited episodic ataxia through a multidisciplinary team handling timing and mode of delivery.