bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlling Threshold and Resistive Switch Functionalities in Ag‐Incorporated Organometallic Halide Perovskites for Memristive Crossbar Array
Authors: Im In Hyuk , Kim Seung Ju , Baek Ji Hyun , Kwak Kyung Ju , Lee Tae Hyung , Yang Jin Wook , Lee Da Eun , Kim Jae Young , Kwon Hee Ryeong , Heo Do Yeon , Kim Soo Young , Jang Ho Won
Published: December 2022

Halide perovskites (HPs) can be the effective functional materials for the sneak‐path current issue in the memristive crossbar array. Herein, an efficient strategy is proposed to integrate the HPs‐based bidirectional threshold and bipolar resistive switches (TS and RS). The resistance change characteristics from volatile threshold to nonvolatile resistive switching are modulated by controlling Ag doping concentration in the MAPbI3. HPs provide the diffusive condition and the quantity of Ag regulates the radius of its network. A low amount of Ag contributes to weak network with a short lifetime. However, when the amount of Ag increases, the conductive filament becomes more robust, showing a long lifetime. A MAPbI3:Ag TS with a low Ag content is developed, showing a steep switching slope (1 mV per decade), fast switching speed (< 80 ns), and low off‐current (10 nA). And, a MAPbI3:Ag RS with a high Ag content is developed, showing multilevel storage capability and long retention time (1400 s). Finally, these TS and RS coupled into the 1S‐1R integrated component, resulting the development of the maximum crossbar array size to 1.4 × 1012. This study offers an efficient methodology for tailoring the resistance change characteristics and a promising strategy for practical HPs‐based memristive crossbar application.
Functionalized Collagen/Elastin‐like Polypeptide Hydrogels for Craniofacial Bone Regeneration
Authors: Pal Pallabi , Tucci Michelle A. , Fan Lir‐Wan , Bollavarapu Ratna , Lee Jonathan W. , Salazar Marocho Susana M. , Janorkar Amol V.
Published: December 2022

Critical‐sized cranial bone defects fail to re‐ossify and require the surgical intervention of cranioplasty. To achieve superior bone healing in such cases, a hydrogel consisting of an interpenetrating network of collagen and elastin‐like polypeptide to encapsulate bone morphogenetic protein‐2 (BMP‐2), doxycycline, and 45S5 Bioglass is developed. This hydrogel has an appropriate elastic modulus of 39 ± 2.2 kPa to allow proper handling during implantation. The hydrogel promotes human adipose‐derived stem attachment, proliferation, and differentiation toward the osteogenic lineage, including the deposition of hydroxyapatite particles embedded within a collagenous fibrillar structure after 21 days of in vitro culture. After eight weeks of implantation of the acellular hydrogel in a critical‐sized rat cranial defect model, only a small quantity of various pro‐inflammatory (< 20 pg mg−1) and anti‐inflammatory (< 10 pg mg−1) factors in the adjacent cranial tissue is noticed, indicating the overall biocompatibility of the hydrogel. Scanning electron microscopy evidenced the presence of new fibrous extracellular matrix and mineral aggregates at the defect site, with calcium/phosphorus ratio of 0.5 and 2.0 by eight and twelve weeks, respectively. Microcomputed tomography (Micro‐CT) and histological analyses showed formation of mature mineralized tissue that bridged with the surrounding bone. Taken together, the acellular composite hydrogel shows great promise for superior bone healing after cranioplasty.
Inverse Design of Energy‐Absorbing Metamaterials by Topology Optimization
Authors: Zeng Qingliang , Duan Shengyu , Zhao Zeang , Wang Panding , Lei Hongshuai
Published: December 2022

Compared with the forward design method through the control of geometric parameters and material types, the inverse design method based on the target stress‐strain curve is helpful for the discovery of new structures. This study proposes an optimization strategy for mechanical metamaterials based on a genetic algorithm and establishes a topology optimization method for energy‐absorbing structures with the desired stress‐strain curves. A series of structural mutation algorithms and design‐domain‐independent mesh generation method are developed to improve the efficiency of finite element analysis and optimization iteration. The algorithm realizes the design of ideal energy‐absorbing structures, which are verified by additive manufacturing and experimental characterization. The error between the stress‐strain curve of the designed structure and the target curve is less than 5%, and the densification strain reaches 0.6. Furthermore, special attention is paid to passive pedestrian protection and occupant protection, and a reasonable solution is given through the design of a multiplatform energy‐absorbing structure. The proposed topology optimization framework provides a new solution path for the elastic‐plastic large deformation problem that is unable to be resolved by using classical gradient algorithms or genetic algorithms, and simplifies the design process of energy‐absorbing mechanical metamaterials.
Wearable E‐Skin Microgrid with Battery‐Based, Self‐Regulated Bioenergy Module for Epidermal Sweat Sensing
Authors: Yin Lu , Sandhu Samar S. , Liu Ruixiao , Khan Muhammad Inam , Wicker Connor , Garcia‐Gradilla Victor , Zhou Jiachi , Chang An‐Yi , Wu Shixuan , Moon Jong‐Min , Chen Chuanrui , Ding Shichao , Wang Joseph
Published: December 2022

Energy‐autonomous wearable systems and wearable microgrids have been a focus of developing the next‐generation wearable electronics due to their ability to harvest energy and to fully support the sustainable operation of wearable electronics. However, existing bioenergy harvesters require complex and low‐efficiency voltage regulation circuitry and have not achieved reliable extended operation and energy storage. In this work, the first example of integrating sweat lactate biofuel cells with a rechargeable Zn–AgCl battery into a bioenergy module for regulation‐free, high‐efficiency, extended biochemical energy harvesting and storage is demonstrated. The integrated bioenergy module is able to operate at its best efficiency due to their matching operating potentials and is characterized by robust mechanical durability enduring over 1000 cycles of repeated tensile deformation, as well as the outstanding long‐term autonomous operation that harvest 2.9 J of energy overnight from 20 min of exercise without measurable self‐discharge. A fully integrated wearable electronic skin patch, powered by two such bioenergy modules, is developed to wirelessly perform continuous sweat pH, ascorbic acid, and lactate sensing. The presented bioenergy module, adapting the wearable microgrid design considerations, delivers a practical, high‐efficiency, and reliable solution for next‐generation wearable electronics that features compatible form factors, commensurate performance, and complementary characteristics.
Dissection of genotype‐by‐environment interaction and simultaneous selection for grain yield and stability in faba bean (Vicia faba L.)
Authors: Gela Tadesse S. , Khazaei Hamid , Podder Rajib , Vandenberg Albert
Published: December 2022

Increasing faba bean production is indispensable to supply the growing demand for plant‐based protein on the global scale. A thorough understanding of genotype (G) × environment (E) interaction (GEI) patterns is critical to developing high‐yielding varieties with wider adaptation. Thirteen faba bean genotypes were evaluated in 15 environments during 2019–2020 in western Canada to estimate their yield stability using different stability statistics. The combined analysis of variance and additive main effects and multiplicative interaction (AMMI) analysis revealed that G, E, and GEI effects were highly significant (p < 0.001), indicating differential responses of the genotypes across the environments, enabling the stability analysis. The result of the model comparison found the best linear unbiased prediction (BLUP) to outperform AMMI models. The BLUP‐based biplot of the weighted average of absolute scores (WAASB) stability and mean grain yield (GY) identified AO 1155 (Navi), 1089‐1‐2, 1310‐5, DL Tesoro, and 1239‐1 as high‐yielding and stable genotypes. The correlation analysis revealed that most of the stability parameters had a strong association with GY and with each other, indicating that they should be used in combination with one another to select genotypes with high yield. Overall, the WAASB superiority index and the average sum of ranks of all stability statistics identified the same genotypes in terms of high‐yielding and stability, and genotype AO 1155 is considered the most stable and highest yielding among the tested genotypes. Genotypes with stable yields across environments would be beneficial for faba bean genetic improvement programs globally.
Selecting maize cultivars to regulate canopy structure and light interception for high yield
Authors: Liu Na , Li Lu , Li Haotian , Liu Zimeng , Lu Yang , Shao Liwei
Published: December 2022

Under climate change background, long shady days during the summer maize growing season reduce the yield potential of this crop in the North China Plain. Optimizing the canopy structure can increase light interception to mitigate the negative effects of climate change. The spatial arrangement of each leaf along the stem affects the light interception that was influenced by cultivar characteristics. Field studies were carried out to select cultivars to optimize canopy structure in maize (Zea mays L.). Results indicated that the middle‐upper canopy above the ear and two leaves below the ear position play a more important role than that of the lower canopy below the ear in deciding the final grain yield. The middle‐upper canopy layer had larger leaf photosynthetic potential decided by the larger net photosynthesis rate and leaf area, as compared with the lower canopy. Larger FIPAR (the fraction of the photosynthetically active radiation) and less PAR (the photosynthetically active radiation) observed below the ear position were beneficial for yield improvement. Therefore, optimizing the middle‐upper canopy structure by selecting cultivars to construct an ideotype plant in maize should be adopted for higher grain production.
Prognostic impact of preoperative skeletal muscle change from diagnosis to surgery in patients with perihilar cholangiocarcinoma
Authors: Hayashi Koki , Abe Yuta , Kitago Minoru , Yagi Hiroshi , Hasegawa Yasushi , Hori Shutaro , Tanaka Masayuki , Nakano Yutaka , Kitagawa Yuko
Published: December 2022

Background

Loss of skeletal muscle mass is a prognostic factor after surgery for gastrointestinal cancers. The treatment for perihilar cholangiocarcinoma (PHC) is a highly invasive surgery. Biliary drainage and portal vein embolization, which can prolong the preoperative waiting time (PWT), are often required before surgery. Assuming that the skeletal muscle mass can change during PWT, we investigated the clinical effect of skeletal muscle change on surgical outcomes of PHC.

Methods

We retrospectively reviewed the medical records of 89 patients who underwent curative surgery for PHC from January 2013 to December 2019. We defined the psoas muscle area (PMA) at the third lumbar vertebra as the skeletal muscle mass. The PMA just before surgery was divided by that at the time of diagnosis, and we defined it as the rate of change of PMA (CPMA). Patients were divided into two groups according to CPMA: wasting (n = 44, below the median CPMA) and no‐change (n = 45, above the median CPMA).

Results

The median PWT was 63 d, and CPMA was 96.1%. The median recurrence‐free survival and overall survival were significantly shorter in the wasting group than in the no‐change group (8.0 vs 33.2 mo, P = 0.001 and 14.2 vs 48.7 mo, P < 0.001, respectively). Multivariate analysis revealed that histological differentiation, R1 resection, lymph node metastasis, and preoperative skeletal muscle wasting were independent prognostic factors of PHC.

Conclusion

This study suggests that preoperative skeletal muscle wasting in patients with PHC has a negative effect on survival outcomes.
Maternal stress and hair cortisol among pregnant women following hurricane Florence
Authors: Howells Michaela , Wander Katherine , Rivera Latisha , Arfouni Chahra , Benhelal Ouassila , Galeano M. Alicia Overstreet , Schultz Laura , Flock Naomi , Dancause Kelsey
Published: December 2022

Natural disasters represent major stressors, resulting in psychological distress and physiological responses such as increased cortisol. During pregnancy, this impacts not only maternal well‐being, but also fetal development. In 2018, Hurricane Florence caused extensive damage across the eastern United States. Studies indicated that compared to married pregnant women, unmarried pregnant women had higher risk of distress. Here we assess hair cortisol among a subsample of participants, and variations based on marital status.

Methods

We analyzed multiple stress measures among 37 participants who were pregnant during Hurricane Florence. We used questionnaires modeled on previous studies to assess hardship associated with the hurricane, psychological distress, sociodemographic characteristics, social support, and food security. We analyzed cortisol concentrations in proximal and distal hair sections, representing stress around the time of the disaster (distal) and 3–4 months following the disaster (proximal). We used linear regression to test relationships between hair cortisol and self‐report stress measures, and variations based on marital status.

Results

Self‐report measures of distress and hardship were similar among married and unmarried participants. Mean cortisol levels in distal and proximal sections were higher among unmarried participants. Controlling for confounding variables, hardship was not associated with hair cortisol. Distress predicted cortisol in distal sections (β = .482,p = .018), with a trend for proximal sections (β = .368,p = .055). Marital status was a significant predictor of distal (β = .388,p = .027) and proximal (β = .333,p = .047) hair cortisol, explaining 8.6%–11.7% of unique variance.

Conclusions

Preexisting and intersecting risk factors likely place unmarried pregnant individuals at risk of stress during and following a disaster.
Achievements, Challenges, and Perspectives on Nitrogen Electrochemistry for Carbon‐Neutral Energy Technologies
Authors: Yang Xiaoxuan , Mukherjee Shreya , O'Carroll Thomas , Hou Yang , Singh Meenesh R. , Gauthier Joseph A. , Wu Gang
Published: December 2022

Unrestrained anthropogenic activities have severely disrupted the global natural nitrogen cycle, causing numerous energy and environmental issues. Electrocatalytic nitrogen transformation is a feasible and promising strategy for achieving a sustainable nitrogen economy. Synergistically combining multiple nitrogen reactions can realize efficient renewable energy storage and conversion, restore the global nitrogen balance, and remediate environmental crises. Here, we provide a unique aspect to discuss the intriguing nitrogen electrochemistry by linking three essential nitrogen‐containing compounds (i.e., N2, NH3, and NO3−) and integrating four essential electrochemical reactions, i.e., the nitrogen reduction reaction (N2RR), nitrogen oxidation reaction (N2OR), nitrate reduction reaction (NO3RR), and ammonia oxidation reaction (NH3OR). This minireview also summarizes the acquired knowledge of rational catalyst design and underlying reaction mechanisms for these interlinked nitrogen reactions. We further underscore the associated clean energy technologies and a sustainable nitrogen‐based economy.
A systematic review and meta‐analysis of associations between primarily non‐autistic people's characteristics and attitudes toward autistic people
Authors: Kim So Yoon , Song Da‐Yea , Bottema‐Beutel Kristen , Gillespie‐Lynch Kristen , Cage Eilidh
Published: December 2022

This systematic review includes a narrative synthesis and meta‐analysis of research on the associations between primarily non‐autistic people's characteristics and their attitudes toward autistic people. Of 47 studies included in the narrative synthesis, White undergraduate students were surveyed most frequently. Demographic characteristics were the factors most frequently tested for associations with attitudes, followed by contact‐related factors (i.e., quantity and quality), knowledge about autism, trait and personality factors, and other factors that did not fit into a single category. Internal consistency was not reported for some instruments assessing raters' characteristics; some instruments had alpha levels lower than 0.70, and many characteristics of raters were measured using one‐item measures. Moreover, theoretical motivations for investigating the raters' characteristics were rarely provided. A total of 36 studies were included in the meta‐analysis, which showed that attitudes toward autistic people were significantly associated with participants' gender, knowledge about autism, and quality and quantity of their previous contact with autistic people, but not with their age or autistic traits. These findings indicate a need for more studies that focus on context‐related characteristics (e.g., institutional variables such as support/commitment to inclusion), use reliable instruments to measure non‐autistic people's characteristics, and situate their investigation in a theoretical framework.
Differentially expressed messenger RNA/proteins can distinguish teratoma from necrosis in postchemotherapy retroperitoneal lymph node dissection tissue
Authors: Nestler Tim , Kremer Lara , von Brandenstein Melanie , Wittersheim Maike , Paffenholz Pia , Wagener‐Ryczek Svenja , Quaas Alexander , Hellmich Martin , Müller Stefan , Pfister David , Odenthal Margarete , Heidenreich Axel
Published: December 2022

Background

Before postchemotherapy retroperitoneal lymph node dissection (pcRPLND), in patients with metastasized germ cell tumors (GCTs), those harboring necrosis (NEC) cannot be distinguished from those who have teratoma (TER), resulting in relevant overtreatment, whereas microRNA‐371a‐3p may be predictive for viable GCT. The purpose of this study was to explore messenger RNA (mRNA) and proteins to distinguish TER from NEC in pcRPLND tissue.

Methods

The discovery cohort consisted in total of 48 patients, including 16 each with TER, viable GCT, and NEC. Representative areas were microdissected. A NanoString panel and proteomics were used to analyze 770 genes and >5000 proteins. The most significantly and differentially expressed combination of both parameters, mRNA and its associated protein, between TER and NEC was validated using immunohistochemistry (IHC) in an independent validation cohort comprising 66 patients who were not part of the discovery cohort.

Results

The authors observed that anterior gradient protein 2 homolog (AGR2) and keratin, type I cytoskeletal 19 (KRT19) were significantly differentially expressed in TER versus NEC in mRNA and protein analyses (proteomics). The technical validation using IHC was successful in the same patients. These proteins were further validated by IHC in the independent patient cohort and exhibited significantly higher levels in TER versus NEC (p < .0001; area under the curve, 1.0; sensitivity and specificity, 100% each).

Conclusions

The current study demonstrated that KRT19 and AGR2 mRNA and protein are overexpressed in TER versus NEC in pcRPLND tissue and might serve as a future diagnostic target to detect TER, for instance, by functional imaging, to avoid overtreatment.

Plain language summary

The proteins and the corresponding genes called AGR2 and KRT19 can differentiate between teratoma and necrosis in remaining tumor masses after chemotherapy in patients who have metastasized testicular cancer.

This may be a way to improve presurgical diagnostics and to reduce the current overtreatment of patients with necrosis only, who could be treated sufficiently by surveillance.
Patterns of failure in pediatric medulloblastoma and implications for hippocampal sparing
Authors: Baliga Sujith , Adams Judith A. , Bajaj Benjamin V. M. , Van Benthuysen Liam , Daartz Juliane , Gallotto Sara L. , Lewy Jacqueline R. , DeNunzio Nicholas , Weyman Elizabeth A. , Lawell Miranda P. , Palmer Joshua D. , Yeap Beow Y. , Ebb David H. , Huang Mary S. , Perry Alisa F. , MacDonald Shannon M. , Jones Robin M. , Tarbell Nancy J. , Yock Torunn I.
Published: December 2022

Background

Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole‐brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri‐hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri‐hippocampal relapse in pediatric patients with medulloblastoma (MB).

Methods and materials

We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri‐hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ‐1), 6 to 10 mm (HZ‐2), and >10 mm (HZ‐3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard‐risk patients with MB were planned using either volumetric‐modulated arc therapy (VMAT) or intensity‐modulated proton therapy (IMPT) plans.

Results

Thirty‐eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ‐1. The crude incidence of peri‐hippocampal failure was 8%. Both HA‐VMAT and HA‐IMPT plans were associated with significantly reduced mean dose to the hippocampi (p < .05). HA‐VMAT and HA‐IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy.

Conclusions

Peri‐hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB.

Plain Language Summary

In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial.
Annual report to the nation on the status of cancer
Authors: Nierengarten Mary Beth
Published: December 2022

This news section offers Cancer readers timely information on events, public policy analysis, topical issues, and personalities. In this issue, we present findings from part one of the Annual Report to the Nation on the Status of Cancer, which provides statistics on incidence and mortality rates across cancer types and demographics. In addition, a new study shows that combining metastasis‐directed radiation therapy with intermittent hormone therapy improves progression‐free survival for advanced prostate cancer and updated American Society of Clinical Oncology guidelines on HER2‐positive breast cancer provide new recommendations based on a systematic evaluation of the best evidence to date by a panel of experts.
Effects of Tablet Formulation, Food, or Gastric pH on the Bioavailability of Asundexian
Authors: Kanefendt Friederike , Brase Christine , Unger Sigrun , Kubitza Dagmar
Published: December 2022

Absolute bioavailability (F) and the impact of gastric pH, tablet formulation, and food on the pharmacokinetics and safety of asundexian, an oral factor XIa inhibitor, was assessed in healthy White men aged 18–45 years in 4 studies. For F, fasted participants received 50 μg of [13C7,15N]‐labeled asundexian intravenously 2 hours after 25 mg of asundexian orally. Tablet formulation (50‐mg immediate release [IR], and different amorphous solid dispersion [ASD] IR 25‐mg and 50‐mg ASD IR tablets) and food effects were explored in 2 studies. Formulation was compared using 50‐mg IR versus 25‐mg ASD IR and 25‐mg ASD IR versus 50‐mg ASD IR (fasted); food effect using 25‐mg ASD IR and 50‐mg ASD IR. Gastric pH modulation was assessed using omeprazole or antacid coadministration with asundexian in the fasted state. Pharmacokinetic parameters included area under the concentration‐time curve (AUC; and AUC/dose [D]) and maximum observed concentration (Cmax and Cmax/D) data were evaluable for 59 participants. F was 103.9%. Relative bioavailability with 25‐mg ASD IR and 50‐mg ASD IR tablets, respectively, was marginally affected by formulation (AUC/D ratios, 94.3% and 95.1%; Cmax/D ratios, 95.5% and 88.7%), food (AUC[/D] ratios, 91.1% and 96.9%; Cmax[/D] ratios: 78.3% and 95.1%), and gastric pH (omeprazole, no effect; antacid, AUC ratio, 89.9% and Cmax ratio, 83.7%). No serious adverse events or deaths occurred; most adverse events were mild or moderate. In summary, oral asundexian was well tolerated and demonstrated complete bioavailability irrespective of tablet formulation, food, or gastric pH.
Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants
Authors: Holze Friederike , Becker Anna M. , Kolaczynska Karolina E. , Duthaler Urs , Liechti Matthias E.
Published: December 2022

Psilocybin is being investigated as a potential treatment for psychiatric and neurological disorders. Only a few studies have evaluated the pharmacokinetics (PKs) of psilocybin and have used body weight‐adjusted dosing. Data on PKs and the PK‐pharmacodynamic (PD) relationship of fixed doses that are commonly used are unavailable. The present study characterized the PKs and PK‐PD relationship of 15, 25, and 30 mg of orally administered psilocybin in 28, 23, and 28 healthy subjects, respectively. Plasma levels of unconjugated psilocin (the psychoactive metabolite of psilocybin) and corresponding subjective effects were repeatedly assessed up to 24 hours. PK parameters were determined using compartmental modeling. Concentration‐subjective effect relationships were described using PK‐PD modeling. Mean (95% confidence interval) maximal psilocin concentrations were 11 ng/mL (10‐13), 17 ng/mL (16‐19), and 21 ng/mL (19‐24) after the administration of 15, 25, and 30 mg psilocybin, respectively. Maximal concentrations were reached after an average of 2 hours. Elimination half‐lives were 1.8 hours (1.7–2.0), 1.4 hours (1.2–1.7), and 1.8 hours (1.6–1.9) for 15, 25, and 30 mg psilocybin, respectively. Mean (± SD) durations of subjective effects were 5.6 ± 2.2 hours, 5.5 ± 1.6 hours, and 6.4 ± 2.2 hours, and maximal effects (“any drug” effects) were 58% ± 25%, 73% ± 27%, and 80% ± 18% after 15, 25, and 30 mg psilocybin, respectively. Psilocin exhibited dose‐proportional PKs. The duration and intensity of subjective effects were dose‐dependent. Body weight did not influence pharmacokinetics or the response to psilocybin. These data may serve as a reference for future clinical trials.
Differential expression of CD8 defines phenotypically distinct cytotoxic T cells in cancer and multiple sclerosis
Authors: Burkard Tobias , Herrero San Juan Martina , Dreis Caroline , Kiprina Anastasiia , Namgaladze Dmitry , Siebenbrodt Kai , Luger Sebastian , Foerch Christian , Pfeilschifter Josef M. , Weigert Andreas , Radeke Heinfried H.
Published: December 2022

Background

Cytotoxic T lymphocytes take on a leading role in many immune‐related diseases. They function as key effector immune cells fighting cancer cells, but they are also considerably involved in autoimmune diseases. Common to both situations, CD8+ T cells need to adapt their metabolism and effector function to the harsh and nutrient‐deprived conditions of the disease‐associated microenvironment.

Methods

We used an in vitro starvation as well as rapamycin treatment protocol mimicking nutrient deprivation to generate CD8Low versus CD8High T cells and performed FACS‐Sorting followed by transcriptomic profiling of the cytotoxic T cell subsets. Prominent markers identified in the CD8Low versus the CD8High T cells were then used to investigate the presence of these cell subsets in immune‐related human diseases. Employing cancer tissue microarrays and PhenOptics multispectral imaging as well as flow cytometry, we studied these CD8+ T cell subsets in cancer and relapsing‐remitting multiple sclerosis patients.

Results

Starvation induced a decreased expression of CD8, yielding a CD8Low T cell subpopulation with an altered transcriptomic signature and reduced effector function. CD8Low T cell showed enhanced ST2L and IL6ST (CD130) expression compared to CD8High T cells which expressed elevated KLRD1 (CD94) and granzyme B levels within the tumour microenvironment (TME). Spatial analysis revealed the presence of CD8High T cells in close proximity to tumour cells, while the CD8Low T cells resided at the tumour boundaries. Importantly, the number of tumour‐infiltrating CD8Low T lymphocytes correlated with a poor prognosis as well as with enhanced cancer progression in human mammary carcinoma. We also found a reduced frequency of CD8Low T lymphocytes in a cohort of relapse (disease active) multiple sclerosis patients compared to healthy subjects during immune cell starvation in vitro.

Conclusions

In summary, our data show that functionally distinct cytotoxic T lymphocytes can be identified based on their expression of CD8. Indicating a more general role in CD8 T cell immunity, these cells may play opposing roles in the TME, and also in the pathophysiology of autoimmune diseases such as multiple sclerosis.
Solvent‐Polarity‐Induced Assembly of Calixarene‐Capped Titanium‐Oxo Clusters with Catalytic Activity in the Oxygenation of Sulfides
Authors: Wang Yanyan , Zheng Haifeng , Zhang Guoshuai , Wang Hao , Xiong Ying , Liao Wuping
Published: December 2022

Four calixarene‐coordinated titanium‐oxo clusters, namely, [Ti4(C6A)2(μ3‐O)2(DMF)2] (CIAC‐258), [Ti8(H3C6A)4(C6H5PO3)8(μ2‐O)4]4− (CIAC‐259), [Ti6(TC4A)3(μ2‐O)3 (OiPr)6] (CIAC‐260) and [Ti6(H2TC4A)4(C6H5PO3)4(μ2‐O)5(DMF)2]2− (CIAC‐261) were obtained, which feature sandwich‐like, windmill‐like, triangular, and tetrahedral structures, respectively. The polarity of the solvent determines the involvement of the auxiliary ligand phenylphosphonic acid in the formation of the products and their structures. Compounds CIAC‐258 and CIAC‐261 exhibit good catalytic performance in the selective oxidation of sulfides to sulfoxides with H2O2 as the oxidant, which can be attributed to the Ti active sites coordinated by exchangeable DMF molecules. Moreover, density functional theory (DFT) calculations revealed that the Ti‐hydroperoxo species formed by the interaction of the Ti active site in CIAC‐258 or CIAC‐261 and H2O2 is the most likely catalytic active component during the catalytic sulfoxidation process.
Photocatalyzed Synthesis of 3‐Substituted Phthalides: A Key Access to (±)‐Herbaric Acid
Authors: Fortier Lucas , Gosset Cyrille , Lefebvre Corentin , Pellegrini Sylvain , Pélinski Lydie , Bousquet Till
Published: December 2022

An efficient organophotocatalyzed protocol was developed for the preparation of 3‐substituted phthalides. The presented transformation was performed under particularly mild conditions within 6 h and was ultimately applied to a precursor of the herbaric acid.
Evaluation of antioxidant properties of nanoencapsulated sage (Salvia officinalis L.) extract in biopolymer coating based on whey protein isolate and Qodumeh Shahri (Lepidium perfoliatum) seed gum to increase the oxidative stability of sunflower oil
Authors: Safarpour Behnaz , Kenari Reza E. , Farmani Jamshid
Published: December 2022

Sage leaf extract (SLE) is considered an excellent source of bioactive compounds mainly because of its high content of phenolics, widely known as natural antioxidants. This study aimed to compare the performance of free/encapsulated SLE by different coatings in protecting sunflower oil against oxidative deterioration. The coating materials were whey protein isolate and qodumeh seed gum at different ratios (1:0, 1:1, and 0:1). Each nanocapsule was analyzed for particle size, zeta potential, encapsulation efficiency, phenolics release, and SEM images. The total phenolic compounds of SLE were 31.12 mg GA/g. The antioxidant activity of SLE was increased in both DPPH and FRAP assays by increasing extract concentration from 50 to 250 ppm. All nanoparticles exhibited nanometric size, negative zeta potential, encapsulation efficiency higher than 60%, and gradual release during storage. The oxidative stability of sunflower oil with or without the incorporation of 250 ppm of free/encapsulated SLE was evaluated during 24 days of storage at 60°C. Peroxide value (PV), thiobarbituric acid value (TBA), oxidative stability index (OSI), color index (CI), and conjugated dienes (CD) were determined. COPM nanoparticles showed the lowest PV, TBA, CI, and CD but both SGUM and WHEY were more effective in delaying oil oxidation than TBHQ and free extract. Higher OSI was observed in oil‐containing nanoparticles with composite coating. Results obtained reinforce the use of whey protein isolate and qodumeh seed gum as a coating for encapsulating SLE to increase the shelf life of sunflower oil as a natural antioxidant.
Impact of the hemostatic approach after laparoscopic endometrioma excision on ovarian reserve: Systematic review and network meta‐analysis of randomized controlled trials
Authors: Riemma Gaetano , De Franciscis Pasquale , La Verde Marco , Ravo Mariangela , Fumiento Pietro , Fasulo Diego Domenico , Della Corte Luigi , Ronsini Carlo , Torella Marco , Cobellis Luigi
Published: December 2022

Background

Laparoscopic excision of endometrioma and subsequent hemostasis have detrimental effects on ovarian reserve.

Objectives

To evaluate which hemostatic approach after stripping cystectomy shows less damage on ovarian reserve.

Search Strategy

Embase, MEDLINE, Scopus, Scielo.br, LILACS, Cochrane Library at the CENTRAL Register of Controlled Trials, Clinicaltrials.gov, CINAHL, conference abstracts, and International Clinical Trials Registry Platform were searched from inception until April 2022.

Selection Criteria

Randomized controlled trials of women undergoing laparoscopic endometrioma excision that compared at least two hemostatic approaches.

Data Collection and Analysis

Relevant data were extracted and tabulated. Network meta‐analysis based on random‐effects model for mixed multiple treatment to rank hemostatic strategies using the surface under the cumulative ranking curve area (SUCRA) was performed. Quality assessment was performed using Cochrane criteria. The primary outcome was serum antimullerian hormone levels 3 months after surgery.

Main Results

Ten studies, including 748 women, were selected. Suturing the ovary with barbed suture (SUCRA, 82.80%) seem the most effective strategy to avoid antimullerian hormone reduction. Similarly, for ultrasonographic antral follicular count, barbed (SUCRA, 30.70%) and simple suture (SUCRA, 30.70%) were ranked the best choices. Ovarian suturing with simple suture demonstrated lower follicle‐stimulating hormone levels (SUCRA, 88.70%).

Conclusions

Suturing the ovary, with simple or barbed suture, seems the most effective approach to keep ovarian reserve higher.
“Never ‘Because of’, Always ‘In Spite Of’”: Implications of the Culturally Relevant Leadership Learning Model for Student Social Justice Activists
Authors: Owen Julie E. , McCarron Graziella Pagliarulo , Chen Cher Weixia
Published: December 2022

Social justice activism can both precede and be the byproduct of collegiate leadership education. As leaders and participants in these social movements, college student activists can catalyze national and global change (Boren, 2019). However, this change can occur at the expense of the activists’ well‐being, especially when they engage in identity work or aim to address daunting structural problems (Chen & Gorski, 2015; Linder et al., 2019). The current article presents results from a constructivist, qualitative study grounded in individual interviews with 17 college student activists representing eight universities in the mid‐Atlantic region. Themes include identity as a catalyst for action, costs of activism, linking leadership and self‐care, and the need for collective approaches to leadership efficacy and well‐being.
Response of seasonal variation in soil detachment capacity to straw incorporation in sloping farmland on the Loess Plateau
Authors: Yao Chong , Zhang Qingwei , Chen Kebing , Liu Liting , Wang Hao , Wang Chenfeng , Wu Faqi
Published: December 2022

Soil detachment capacity by rill flow (Dc) is sensitive to changes in topsoil properties generated by crop straw incorporation. In the present study, we investigated the effect of crop straw incorporation on the seasonal variation in Dc, the knowledge regarding which is limited currently, and identified the key influencing factors. Three typical crop straw types (wheat, soybean, and maize) were selected for this study. Soil samples incorporated with crop straw and without crop straw were collected over 375 days (from October 1, 2020 to October 10, 2021) and were subjected to a hydraulic flume (length, 4.0 m; width, 0.2 m) to determine Dc. The topsoil properties soil bulk density (BD), soil cohesion (Coh), soil penetration resistance (PR), soil organic matter content (SOM), mean weight diameter (MWD), and straw decomposition rate (SDR) were measured to explain the seasonal variation in Dc. The results showed that crop straw incorporation effectively reduced Dc, and the Dc for the soil incorporated with straw decreased by 25.92%–38.76% compared with that without straw incorporation. Dc exhibited a significant decreasing trend over time, and the Dc at the end stage decreased by 83.00%–88.31%, compared with the initial stage. Seasonal variation in Dc was significantly correlated with BD, Coh, PR, SOM, MWD, and SDR. The measured Dc decreased with BD and Coh as a power function and with SOM and MWD as an exponential function. The influence of straw incorporation on Dc is time‐dependent and can be divided into short‐term and long‐term effects. Natural soil consolidation gradually masked the effect of straw residue with the decomposition of the incorporated straw. The comprehensive response of seasonal variation in Dc to straw incorporation was described by a power combination equation (Dc = 1.23 τ1.65 BD−2.63 Coh−1.33 SOM−0.70; R2 = 0.96). Thus, the seasonal variations in Dc with straw incorporation were mainly controlled by the changes in soil properties triggered by the decomposition of incorporated straw and natural soil consolidation. The results of this study provided a scientific reference for soil erosion prediction and control in sloping farmlands.
Cerebrospinal FluidBiomarkers of Synaptic Dysfunction are Altered in Parkinson's Disease and Related Disorders
Authors: Nilsson Johanna , Constantinescu Julius , Nellgård Bengt , Jakobsson Protik , Brum Wagner S. , Gobom Johan , Forsgren Lars , Dalla Keti , Constantinescu Radu , Zetterberg Henrik , Hansson Oskar , Blennow Kaj , Bäckström David , Brinkmalm Ann
Published: December 2022

Background

Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects.

Objective

To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders.

Methods

Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n1 = 51, n2 = 101), corticobasal degeneration (CBD) (n1 = 11, n2 = 3), progressive supranuclear palsy (PSP) (n1 = 22, n2 = 21), multiple system atrophy (MSA) (n1 = 31, n2 = 26), and healthy control (HC) (n1 = 48, n2 = 30) participants, as well as Alzheimer's disease (AD) (n2 = 23) patients in the second cohort.

Results

Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin‐2 levels compared with HC were observed. In AD, levels of 14‐3‐3 zeta/delta, beta‐ and gamma‐synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini‐Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32,P < 0.05) and reduced dopaminergic pre‐synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29,P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β‐estimate = −0.025 to −0.038,P < 0.05) and cognitive decline (NPTX2; β‐estimate = 0.32,P = 0.021).

Conclusions

These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. © 2022 The Authors.Movement Disorderspublished by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Edge detection from X‐ray tomographic data for geometric image registration
Authors: Lajili Mohamed , Rjaibi Badreddine , Auroux Didier , Moakher Maher
Published: December 2022

In this paper, we propose new variational model for image registration from tomographic data. First, we employ the topological gradient approach for a tomographic reconstruction that uses the first‐ and the second‐order discontinuities in order to detect important objects of a given observed X‐ray tomographic data (sinograms). Second, we use this geometric information furnished by a high‐order operator in order to define an appropriate fidelity measure for the image registration process. A theoretical study of the proposed model is provided; Gauss–Newton method and multilevel technique are used for its numerical implementation. The performed numerical experiments show the efficiency and effectiveness of our model.
Student‐focused, career‐driven exploration in natural history museums through experiential education and mentorship: A model to intentionally increase the racial and ethnic diversity of students
Authors: Flemming Adania D. C.
Published: December 2022

Being immersed in the processes of research can develop undergraduate students’ science identities and support their persistence in pursuing science careers. However, it can be difficult for students to find opportunities for engaging in authentic scientific research. The professional staff and scientific objects in natural history museums provide such an opportunity that can create relationships through which both undergraduate students and museums benefit. Students require authentic practical experiences to better understand their academic fields and career trajectories, and museums require assistance curating and managing collections. This can be accomplished through mentorship, training, and research experience in a formal course. At the University of Florida, I developed and taught a course titled “Introduction to Natural History” that engaged students in projects in museum collections. Discussion sessions replaced lectures by introducing topics such as the concept of research, distinction between predictions and hypotheses, understanding of the nature of science, and how to conduct literature reviews. In 2019 and 2020, students completed a pre‐ and postcourse survey to gauge their understanding of science and their anticipated career trajectory. My results demonstrate that mentorship and authentic experiential science opportunities using museum collections enable students to realize a passion, sense of purpose, and better understanding of science and careers in science.
Dual and Sequential Locked/Unlocked Photochromic Effects on FRET Controlled Singlet Oxygen Processes by Contracted/Extended Forms of Diarylethene‐Based [1]Rotaxane Nanoparticles
Authors: Khang Trang Manh , Nhien Pham Quoc , Cuc Tu Thi Kim , Weng Chang‐Ching , Wu Chia‐Hua , Wu Judy I. , Hue Bui Thi Buu , Li Yaw‐Kuen , Lin Hong‐Cheu
Published: December 2022

Manipulations of singlet oxygen (1O2) generations by the integration of both aggregation‐induced emission luminogen (AIEgen) photosensitizer and photochromic moieties have diversified features in photodynamic therapy applications. Through Förster resonance energy transfer (FRET) pathway to induce red PL emissions (at 595 nm) for 1O2 productions, [1]rotaxane containing photosensitive tetraphenylethylene (TPE) donor and photochromic diarylethene (DAE) acceptor is introduced to achieve dual and sequential locked/unlocked photoswitching effects by pH‐controlled shuttling of its contracted/extended forms. Interestingly, the UV‐enabled DAE ring closure speeds follow the reversed trend of DAE self‐constraint degree as: contracted < extended < noninterlocked forms in [1]rotaxane analogues, thus FRET processes can be adjusted in contracted/extended forms of [1]rotaxane upon UV irradiations. Accordingly, the contracted form of [1]rotaxane is FRET‐OFF locked and inert to UV exposure due to the larger bending conformation of DAE parallel (p‐)conformer, compared with its extended and noninterlocked analogues possessing switchable FRET‐OFF/ON behaviors activated by dual and sequential pH‐ and photoswitching. Owing to the advantages of 1O2 productions tuned by multistimuli inputs (pH, UV, and blue light), an useful logic circuit for toxicity outputs of the surface modified [1]rotaxane nanoparticles (NPs) has been demonstrated to offer promising 1O2 productions and managements based on mechanically interlocked molecules for future bioapplications.
Cascade‐Gates Guarded Asymmetrical Nanochannel Membrane: An Interference‐Free Device for Straightforward Detection of Trace Biomarker in Undiluted Serum
Authors: Jian Xiaoxia , Xu Jing , Guo Junli , Zhao Junjian , Shen Tian , Gao Zhida , Song Yan‐Yan
Published: December 2022

Accurate detection of trace biomarkers in biological samples is a key task in diagnostic testing, but it remains challenging due to the high concentration of other physiologically relevant interferences. This work presents a new electrochemiluminescence (ECL) sensing device based on a bio‐inspired nanochannel membrane (NM) guarded with two differential gates. The recognition event at the aptamer gate is followed by the permitting of stimulator transport toward the metal‐organic framework (MOF) gate. Proof of concept application is evaluated using cytochrome C (Cytc) as the analyte, and glucose, a commonly existing nutriment as the stimulator. The oxidase‐mimic plasmonic nanoparticles induce an effective release of ECL luminophore from the MOF gate. This cascade‐gates guarded NM can effectively separate biological matrices from the detection cell. Consequently, the proposed system can achieve direct sensing of 1.0 nm Cytc in undiluted serum within the threshold concentrations of leukemia and lymphoma, making it attractive for point‐of‐care applications.