bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased recombinant adeno‐associated virus production by HEK293 cells using small molecule chemical additives
Authors: Scarrott Joseph M. , Johari Yusuf B. , Pohle Thilo H. , Liu Ping , Mayer Ayda , James David C.
Published: December 2022

Recombinant adeno‐associated virus (rAAV) has established itself as a highly efficacious gene delivery vector with a well characterised safety profile allowing broad clinical application. Recent successes in rAAV‐mediated gene therapy clinical trials will continue to drive demand for improved rAAV production processes to reduce costs. Here, we demonstrate that small molecule bioactive chemical additives can significantly increase recombinant AAV vector production by human embryonic kidney (HEK) cells up to three‐fold. Nocodazole (an anti‐mitotic agent) and M344 (a selective histone deacetylase inhibitor) were identified as positive regulators of rAAV8 genome titre in a microplate screening assay. Addition of nocodazole to triple‐transfected HEK293 suspension cells producing rAAV arrested cells in G2/M phase, increased average cell volume and reduced viable cell density relative to untreated rAAV producing cells at harvest. Final crude genome vector titre from nocodazole treated cultures was >2‐fold higher compared to non‐treated cultures. Further investigation showed nocodazole addition to cultures to be time critical. Genome titre improvement was found to be scalable and serotype independent across two distinct rAAV serotypes, rAAV8 and rAAV9. Furthermore, a combination of M344 and nocodazole produced a positive additive effect on rAAV8 genome titre, resulting in a three‐fold increase in genome titre compared to untreated cells.
An idea to explore: How an interdisciplinary undergraduate course exploring a global health challenge in molecular detail enabled science communication and collaboration in diverse audiences
Authors: Dutta Shuchismita , Jiang Jennifer , Ghosh Sutapa , Patel Shriya , Bhikadiya Charmi , Lowe Robert , Voigt Maria , Goodsell David , Zardecki Christine , Burley Stephen K.
Published: December 2022

Communication and collaboration are key science competencies that support sharing of scientific knowledge with experts and non‐experts alike. On the one hand, they facilitate interdisciplinary conversations between students, educators, and researchers, while on the other they improve public awareness, enable informed choices, and impact policy decisions. Herein, we describe an interdisciplinary undergraduate course focused on using data from various bioinformatics data resources to explore the molecular underpinnings of diabetes mellitus (Types 1 and 2) and introducing students to science communication. Building on course materials and original student‐generated artifacts, a series of collaborative activities engaged students, educators, researchers, healthcare professionals and community members in exploring, learning about, and discussing the molecular bases of diabetes. These collaborations generated novel educational materials and approaches to learning and presenting complex ideas about major global health challenges in formats accessible to diverse audiences.
Factors associated with cognitive impairment at 3, 6, and 12 months after the first stroke among Lebanese survivors
Authors: Boutros Celina F. , Khazaal Walaa , Taliani Maram , Sadier Najwane Said , Salameh Pascale , Hosseini Hassan
Published: December 2022

Introduction

This study aimed to calculate the rate of post‐stroke cognitive impairment (PSCI) by evaluating the cognitive domains among Lebanese stroke survivors at 3, 6, and 12 months post‐stroke, and to identify the contributing factors including pre‐ and post‐stroke related factors.

Methods

A multicenter longitudinal prospective study was conducted in 10 hospitals from Beirut and Mount Lebanon for a 15‐month period. Mini‐Mental State Examination (MMSE), modified Rankin Scale (mRS), Short Form Health Survey (SF12), National Institutes of Health Stroke Scale (NIHSS), and Hospital Anxiety and Depression Scale (HADS) were used to assess cognitive function, disability degree, Quality of Life (QoL), stroke severity, and levels of anxiety and depression, respectively. Then, univariate and multivariable analyses were performed to identify the predictors of PSCI.

Results

Low MMSE scores were found among survivors during the first 3 months post‐stroke (74.8%) of whom 53.7% presented with an MMSE ≤ 17, followed by 46.7% in the 6 months, and 37.6% at 12 months post‐stroke. Follow‐up comparisons showed a significant increase of MMSE scores over time (p < .001), indicating a 37% improvement of the cognitive function over time. The most affected cognitive domain was the attention and concentration at the three time points. Independent factors that were positively associated with low MMSE scores were as follows: sedentary behavior ≥ 12 h/day (AOR = 3.062, p = .033), involvement of the left hemisphere (AOR = 2.710, p = .006), HADS ≥ 11 (AOR = 2.536, p = .049), and high NIHSS scores (AOR = 3, p = .009). Age was the main predictor in the three time periods (AOR ≈ 3, p < .05). Inversely, female gender (AOR = 0.09, p = .027), high educational level (AOR = 0.2, p < .02), employment post‐stroke (AOR = 0.3, p = .023), high Physical Component Summary (PCS) of Quality of Life (QoL) (AOR = 0.8, p < .001), and the use of anti‐diabetic treatment post‐stroke (AOR = 0.17, p = .016) improved MMSE scores to > 23.

Conclusion

The risk of PSCI among Lebanese stroke survivors was high especially in the acute phase, depending on various determinants. Health care providers are invited to implement an emergency rehabilitation program for an appropriate successful management of the risk factors in order to reduce stroke burden and to improve overall cognitive performance.
Association of sex and age with in‐hospital mortality and complications of patients with intracerebral hemorrhage: A study from the Chinese Stroke Center Alliance
Authors: Lu Ping , Cao Zhentang , Gu Hongqiu , Li Zixiao , Wang Yu , Cui Lingyun , Wang Yongjun , Zhao Xingquan
Published: December 2022

Background and purpose

The impact of sex and age on prognosis in patients with intracerebral hemorrhage (ICH) in the Chinese population remains unclear. Our study aimed to investigate the relationship between sex and age of Chinese ICH patients and adverse prognosis.

Methods

We used the Chinese Stroke Center Alliance database with in‐hospital mortality as the primary outcome and hospital complications as the secondary outcome. Patients were divided into four groups by sex and age. Logistic regression analyses were performed to assess the association between sex and age and the prognosis of ICH patients.

Results

We enrolled 60,911 ICH patients, including 22,284 young and middle‐aged males, 15,651 older males, 11,948 young and middle‐aged females, and 11,028 older females. After adjusting for variables, older male patients had a higher mortality rate (OR = 1.21, 95% CI 1.01–1.45), combined with more frequent hematoma expansion (OR = 1.14, 95% CI 1.03–1.26), pneumonia (OR = 1.91, 95% CI 1.81–2.03), and hydrocephalus (OR = 1.28, 95% CI 1.04–1.59). Young and middle‐aged female patients had a lower mortality rate (OR = 0.74, 95% CI 0.58–0.95) and less frequent combined pneumonia (OR = 0.81, 95% CI 0.75–0.87). In‐hospital mortality was not significantly different in older females compared with young and middle‐aged males, but the odds of deep vein thrombosis, swallowing disorders, urinary tract infections, and gastrointestinal bleeding were significantly higher.

Conclusion

Among young and middle‐aged patients, females are related to a lower in‐hospital mortality rate from ICH. Older patients are at an increased risk of ICH complications, with higher in‐hospital mortality in older men.
TAT‐LBD‐Ngn2‐improved cognitive functions after global cerebral ischemia by enhancing neurogenesis
Authors: Feng Bin , Jia Sansan , Li Liya , Wang Jiajia , Zhou Fang , Gou Xingchun , Wang Qiang , Xiong Lize , Zeng Yi , Zhong Haixing
Published: December 2022

Background

Stroke is the major cause of adult neurocognitive disorders (NCDs), and presents a significant burden on both of the families and society. To improve the cerebral injury, we generated a blood–brain barrier penetrating peptide TAT‐LBD‐Ngn2, in which Ngn2 (Neurogenin2) is a classical preneural gene that enhances neurogenesis, and neural precursor cells survival and differentiation. We previously demonstrated that it has a short‐term protective effect against cerebral ischemia‐reperfusion injury. However, it is uncertain if TAT‐LBD‐Ngn2 could promote neurogenesis to exhibit long‐term therapeutic impact.

Methods and results

In present study, TAT‐LBD‐Ngn2 was administered for 14 or 28 days following bilateral common carotid arteries occlusion (BCCAO). After confirming that TAT‐LBD‐Ngn2 could cross the brain blood barrier and aggregate in the hippocampus, we conducted open field test, Morris water maze and contextual fear conditioning to examine the long‐term effect of TAT‐LBD‐Ngn2 on cognition. We discovered that TAT‐LBD‐Ngn2 significantly improved the spatial and contextual learning and memory on both days 14 and 28 after BCCAO, while TAT‐LBD‐Ngn2 exhibited anxiolytic effect only on day 14, but had no effect on locomotion. Using western blot and immunofluorescence, TAT‐LBD‐Ngn2 was also shown to promote neurogenesis, as evidenced by increased BrdU+ and DCX+ neurons in dentate gyrus. Meanwhile, TAT‐LBD‐Ngn2 elevated the expression of brain derived neurotrophic factor rather than nerve growth factor compared to the control group.

Conclusions

Our findings revealed that TAT‐LBD‐Ngn2 could dramatically promote learning and memory in long term by facilitating neurogenesis in the hippocampus after global cerebral ischemia, indicating that TAT‐LBD‐Ngn2 may be an appealing candidate for treating poststroke NCD.
Rh‐endostatin plus camrelizumab and chemotherapy in first‐line treatment of advanced non‐small cell lung cancer: A multicenter retrospective study
Authors: Pu Xingxiang , Wang QianZhi , Liu Liyu , Chen Bolin , Li Kang , Zhou Yu , Sheng Zengmei , Liu Ping , Tang Yucheng , Xu Li , Li Jia , Kong Yi , Xu Fang , Xu Yan , Wu Lin
Published: December 2022

Background

Clinical evidence of immune checkpoint inhibitors combined with antiangiogenic drugs in patients with advanced non‐small cell lung cancer (NSCLC) was limited. Recombinant human endostatin (rh‐endostatin), an antiangiogenic drug, and camrelizumab, an anti‐PD‐1 antibody, have been approved for the treatment of advanced NSCLC in China. This study aimed to investigate the efficacy and safety of rh‐endostatin plus camrelizumab and chemotherapy in the treatment of advanced NSCLC.

Methods

Eligible patients were enrolled and received camrelizumab (200 mg, day 1) every 3 weeks and continuous intravenous infusion of rh‐endostatin (70 mg/day, days 1–3) and cisplatin combined with pemetrexed (for adenocarcinoma) or paclitaxel (for NSCLC other than adenocarcinoma) every 3 weeks. Primary endpoint was progression‐free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles.

Results

Overall, 27 patients were included, and 25 patients were eligible for efficacy evaluation. For these 25 patients, ORR was 48.15% (13/27) and DCR was 85.19% (23/27). With a median follow‐up of 10.37 months, the median PFS was 8.9 (95% CI: 4.23–13.57) months. Median OS was not reached. Overall, 96.3% of patients experienced at least one treatment‐related adverse event, and grade 3 TRAEs occurred in 9 (33.3%) patients. No unexpected AEs were observed.

Conclusion

Rh‐endostatin plus camrelizumab and chemotherapy showed favorable efficacy and safety profile in patients with advanced NSCLC, representing a promising treatment regimen for these patients.
Anaphylaxis induced by intra‐articular injection of chitosan: A case report and literature review
Authors: Peng Shengxin , Liang Yuanhao , Xiao Wenshan , Liu Yang , Yu Mengya , Liu Lei
Published: December 2022

Generally, we consider chitosan being a safe, nontoxic natural polymer with wide clinical applications. However, allergic reactions caused by chitosan have been reported on rare occasions. We report here a case of allergy and perform a literature review.
Management of an extensive form of verrucous hemangioma with staged skin grafting: A case report
Authors: Sharma Samit , Rayamajhi Aadesh , Chapagain Abhishek , Shrestha Jayan Man
Published: December 2022

A 20‐year‐old male presented with large and extensive lesions of verrucous hemangioma involving the left lower extremity. The lesions were excised in the supra‐fascial plane. After 10 days, the split‐thickness skin graft was applied over the raw area resulting in good graft take.
One‐Electron Injection‐triggered Radical Reaction of Alkyl Benzoates Promoted by 1,4‐Bis(diphenylamino)benzene Photocatalysis
Authors: Koike Takashi , Okumura Ryo , Kato Tomoki , Abe Manabu , Akita Munetaka
Published: December 2022

The ester group is one of the most ubiquitous functional groups in natural products and synthetic organic molecules. Herein, we describe the photocatalytic generation of alkyl radicals from readily accessible alkyl benzoate esters. The excited organic photocatalyst 1,4‐bis(diphenylamino)benzene (BDB) plays a vital role as a one‐electron injector. The present photoredox‐catalytic system realizes the hydroxy‐1,1‐dialkylfluoroethylation of aromatic alkenes. Finally, a strategy is developed for generation of fluoroalkyl radicals from the corresponding readily available 2‐fluorinated 1,1‐dialkylethanols.
Three Sides of the Same Coin: Combining Microbial, Enzymatic, and Organometallic Catalysis for Integrated Conversion of Renewable Carbon Sources
Authors: Mengers Hendrik G. , Guntermann Nils , Graf von Westarp William , Jupke Andreas , Klankermayer Jürgen , Blank Lars M. , Leitner Walter , Rother Dörte
Published: December 2022

All catalysts have unique abilities. This is especially true for microbial, enzymatic, and organometallic catalysis, which are often seen as competitive approaches preventing the exploitation of their complementarity. An increasing number of examples show, how using the complete catalytic spectrum can open roads from new substrates to new products. C1‐compounds such as formate, formaldehyde, methanol, or methane from CO2 in combination with green H2 are likely to be future sources of carbon feedstock. This short review highlights how combinations of different catalyst types can facilitate integrated reaction sequences with biogenic substrates to form “bio‐hybrid” fuels and products.
Schutzschild für die Puppe
Authors: Tetsch Larissa
Published: December 2022

Um sich von einer Raupe zum erwachsenen Insekt zu entwickeln, müssen sich Käfer verpuppen. Da sich die Puppe nicht mehr bewegen kann, ist sie besonders durch Räuber gefährdet. Der Schildkäfer Chelymorpha alternans geht deshalb eine Schutzsymbiose mit einem Pilz ein.
Tetramethylammonium Iodide Additive for Enhancing the Charge Carrier Mobilities of Diketopyrrolopyrrole‐Based Conjugated Polymer in Ambipolar Organic Field‐Effect Transistors†
Authors: He Waner , Liu Qian , Otep Sultan , Matsumoto Hidetoshi , Manzhos Sergei , Sonar Prashant , Kyaw Aung Ko Ko , Michinobu Tsuyoshi
Published: December 2022

Comprehensive Summary

Diketopyrrolopyrrole (DPP) is one of the most promising building blocks for constructing polymer semiconductors with high charge‐carrier mobilities in organic field‐effect transistors (OFETs). In this study, a novel DPP‐based conjugated polymer, PDPPy‐BDD, was designed and synthesized. The ambipolar field‐effect transistor characteristics were realized with the average hole and electron mobilities of 3.5 × 10–3 and 3.07 × 10–2 cm2 V−1 s−1, respectively. Both the hole and electron mobilities could be successfully enhanced by using a tetramethylammonium iodide (NMe4I) additive. Such an enhancement was attributed to the formation of stronger interchain π–π stackings, the weakening of the face‐on packing orientation in the thin film state, and the higher channel conductivities in the OFETs.
Trans‐spatial Structure Additive Passivated Sn(II) for High‐efficiency CsSnI3 Perovskite Solar Cells Fabricated in Humid Air
Authors: Li Xinrui , Zhou Huanyi , Zhang Junfang , Sang Kaihang , Fan Hua , Lu Jiangying , Pang Qi , Chen Peican , Zhou Liya , Li Lei , Yang Yunfan
Published: December 2022

Black crystalline γ‐CsSnI3 is an ideal light absorption material to replace lead‐based perovskite due to its low biotoxicity and excellent photoelectric properties. However, CsSnI3 is usually prepared in a low humidity inert atmosphere because of its oxidation in air. The severe preparation environment, on the other hand, will surely raise the economic cost of mass production. Therefore, a kind of additive engineering is proposed to introduce (1R, 2R)‐(−)‐1,2‐diaminocyclohexane (transDACH), a small nitrogen‐containing ligand with trans‐spatial structure, into the perovskite layer, which can stabilize Sn2+ in the preparation process, allowing for the preparation of efficient and stable perovskite solar cells under high humidity conditions. The forward scan maximum power conversion efficiency (PCE) of the CsSnI3‐transDACH device reaches 5.49%, the highest for hole‐free carbon‐based CsSnI3 PSCs prepared in humid air conditions. Furthermore, the transDACH‐modified devices retain 73.7% of their original PCEs after 160 hours of storage in ambient air conditions.
Is whole‐body magnetic resonance imaging a source of anxiety in oncological patients?
Authors: Mazzocco Ketti , Busacchio Derna , Summers Paul Eugene , Marzorati Chiara , Pricolo Paola , Petralia Giuseppe , Pravettoni Gabriella
Published: December 2022

Objective

Magnetic resonance often produces feelings of anxiety before, or during, the examination. The aim of this study was to assess anxiety and potential causes of anxiety in cancer patients undergoing whole‐body magnetic resonance imaging (WB‐MRI).

Methods

This monocentric study recruited 70 cancer patients who were scheduled to undergo WB‐MRI for detection, staging or therapy monitoring. At baseline (prior to the WB‐MRI), assessments were performed using the State–Trait Anxiety Inventory (STAI‐Y 1), Illness Perception Questionnaire (IPQ‐R), Big Five Inventory (BIF‐10) and Revised Life Orientation Test (LOT‐R), while at the end of the WB‐MRI examination the patients repeated the STAI‐Y 1 questionnaire and were asked to indicate their preference between WB‐MRI and computed tomography.

Results

We found a positive correlation between pre‐ and post‐examination STAI‐Y 1 scores (r = 0.536, p < .0001), with no significant difference between them. Pre‐examination STAI‐Y 1 scores had a negative correlation with the emotional stability in the BIF‐10 questionnaire (r = −0.47, p = .001) and a positive correlation with emotional representation (r = 0.57, p = .001) in IPQ‐R. The post‐examination STAI‐Y 1 had a negative correlation with optimistic orientation (r = −0.59, p = .001).

Conclusions

The anxiety associated with a WB‐MRI examination was only in small part associated with the examination itself, and in fact, most patients preferred WB‐MRI to computed tomography. Concern with the outcome of the examination was likely a greater source of anxiety.
Prognostic factors of toxicity of immune checkpoint inhibitors in nonsmall cell lung cancer and small cell lung cancer patients: The ToxImmune study
Authors: Difoum Francoise , Schernberg Antoine , Vanquaethem Hélène , Picchi Hugo , Roy Audrey Le , Vuagnat Perrine , Helissey Carole
Published: December 2022

Background

Immunotherapy alone or in combination has clearly improved the survival of patients with lung cancer. However, it may also be responsible for adverse events impacting these patients' quality of life. The ToxImmune study aims to identify prognostic factors that can help to predict immune‐related adverse events.

Methods

We included all patients aged 18 years and older who had received at least one dose of immune checkpoint inhibitors, with or without other therapy, between June 2015 and December 2020 and were diagnosed with nonsmall cell lung cancer or small‐cell lung cancer. Patients' baseline demographic characteristics, biological blood markers, and imaging by PET‐scanner were collected from electronic medical records. All adverse events (AEs) and immune‐related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Events V.5.0).

Results

Sixty‐four patients were included, of whom 60 (94%) presented at least one irAE. The incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 and grade 3–4 was 34% and 8% respectively.

Female sex, Primitive Tumor Standardized Uptake Value Max (SUVmax) <5, number of metastases ≥3 and immunotherapy received after the first line were found to be significant risk factors for immune‐related adverse events. Based on the number of risk factors, the ToxImmune score predicts the risk of having a grade ≥2 adverse event (primitive tumor SUV ≥ 5 = 0 vs. primitive tumor SUV <5 = 1, number of metastases <3 = 0 vs. number of metastases ≥3 = 1 and L1 = 0 vs. L1 ≥ 1). The incidence of grade ≥2 adverse events was 20%, 55% and 90% with ToxImmune scores 0, 1 and = 2 respectively (p = .003). Median progression‐free survival (PFS) times were 19.2 months, 6.64 months and 2.63 months for ToxImmune scores 0, 1 and = 2 respectively, p = .13. Median overall survival times were 22.6 months, 16.4 months and 9.8 months for ToxImmune scores 0, 1 and ≥2 respectively, p = .24. The disease control rate (DRR) was 78% in ToxIummune score 0 group, and 50% in ToxImmune score 1 and ≥2 groups (p = .363).

Conclusion

The ToxImmune score, which is grounded on objective clinical parameters, indicates that cases with a high score had an advanced threat of severe adverse events. The ToxImmune score could therefore be used in clinical practice to identify patients treated for lung cancer with immunotherapy and at risk of severe AE.
“Struck down by cancer with no old life to fall back on” a clinical study of illness experiences among Norwegian adolescent and young adult cancer survivors investigating the ethical implications of their illness narratives
Authors: Hjulstad Kristine , Bondevik Hilde , Hem Marit Helene , Nortvedt Per
Published: December 2022

Background

Cancer is a leading cause of death among people 15–24 years of age. Increasing numbers of cancer patients survive. Extensive cancer therapy may cause wide‐ranging somatic and psychosocial challenges in the lives of the survivors.

Research indicates adolescent and young adult cancer (AYA) survivors need to be seen as a distinctive group of survivors having unique health care needs. The existing literature suggests the need for specific follow‐up care programs addressing the challenges of AYAs and providing them access to specialized after care, as well as a need to explore AYA cancer survivors' own illness experiences.

Aims

Through the theoretical lens of narrative medicine and care ethics, our purpose was to investigate the particular challenges encountered by the AYA cancer survivors, and how they view themselves in light of their illness experiences. We ask how AYA cancer survivors are met and understood by their medical professionals?

Methods

This study applied a qualitative method using a narrative research design by collecting self‐stories of illness in order to conceptualize human experiences of illness among AYA cancer survivors. Eight in‐depth interviews were conducted using a narrative analysis according to the narrative plots ofrestitution,chaosandquest,as suggested by Arthur Frank.

Results

Hopelessness and a struggle to take part in the activities of daily life as survivors of cancer were revealed. Too ill to fully take part in the society, the AYA cancer survivors strive to be understood for what they are, namely young survivors.

Conclusion

The survivors'stories reveal a moral imperative that needs to be honored by medical professionals in order to improve cancer care. Cancer survivorship may be a lifelong process necessitating long‐term follow‐up care. With the lack of specific care programs for AYA cancer survivors, follow‐up care is provided by general practitioners or other medical professionals, who often lack expertise in the unique challenges faced by AYA survivors. Because they feel their needs are unmet and their stories not understood, the AYA survivors might experience a sense of abandonment. By adopting a care ethics and narrative medicine approach we provide medical professionals a theoretical framework to better understand and care for AYA cancer survivors. Clinical trial number is 2012/1141.
Outcomes in patients with non‐invasive breast carcinoma
Authors: Kim Ryungsa , Kawai Ami , Wakisaka Megumi , Shimoyama Mika , Yasuda Naomi , Ito Mitsuya , Kin Takanori , Arihiro Koji
Published: December 2022

Background and Aim

Non‐invasive breast carcinoma is considered to be localized disease and is distinguished from invasive ductal and lobular carcinomas. The local recurrence of non‐invasive carcinoma after surgery may lead to development of invasive carcinoma and promote distant metastasis, which worsens the prognosis for breast cancer mortality. The distant metastasis of non‐invasive carcinoma may involve the ductal microvasculature without invasion. The outcomes of non‐invasive breast carcinoma were examined in this retrospective cohort study.

Methods and Results

Of 872 primary breast cancers diagnosed at a single center between May 2008 and March 2022, 93 (10.6%) were found to be non‐invasive carcinomas and were examined in this study. The breast cancer recurrence and survival rates of patients with non‐invasive carcinoma were analyzed retrospectively. The median follow‐up period was 1891 (range, 5–4804) days. All patients underwent surgical treatment [mastectomy with sentinel lymph node biopsy (SLNB) and partial mastectomy with or without SLNB, tumorectomy, and microdochectomy]. Postoperatively, radiation therapy was administered to 73 (78.4%) of the patients and endocrine therapy was administered to 64 (81.0%) of 79 patients with hormone‐receptor positivity. Of 26 patients who underwent partial mastectomy with SLNB, 24 (92.3%) showed isolated tumor cells in the SLNs on one‐step nucleic acid amplification. Local recurrence was observed in three (0.3%) patients; no distant metastasis was observed. One patient died of a noncancerous disease. The overall survival rate was 98.0% and the breast cancer‐specific survival rate was 100.0%.

Conclusions

Non‐invasive breast carcinoma, like invasive breast carcinoma, causes local recurrence, but has a good prognosis without distant metastasis. The clinical significance of isolated tumor cells in the SLNs as a systemic component of non‐invasive breast carcinoma remains to be elucidated.
A Study to Evaluate Relative Bioavailability, Food Effect, and Pharmacodynamics of Tropifexor, a Farnesoid X Receptor Agonist, in Healthy Participants
Authors: Stringer Rowan , Chen Jin , Shah Bharti , Gu Jessie , Zhang Yiming , Prince William , Klickstein Lloyd B. , Woessner Ralph
Published: December 2022

This open‐label, randomized, 3‐treatment, 3‐period, 6‐sequence, crossover study in healthy subjects compared the pharmacokinetic and pharmacodynamic properties of a lipid‐based (soft gelatin capsule) prototype final market image (pFMI) formulation of tropifexor (90‐µg) to its clinical service form (CSF) and assessed the food effect for the pFMI formulation. In the fasted state, drug exposure was higher for the pFMI. The geometric mean ratios for pFMI versus CSF of peak concentration and area under the concentration–time curve were 2.0 and 1.5, respectively. No food effect was apparent for the pFMI formulation, and the geometric mean ratios for pFMI fed versus pFMI fasted of peak concentration and area under concentration–time curve were 1.0 and 1.0 respectively. Despite having lower systemic exposure, the CSF formulation provided a higher pharmacological response for the gut biomarker fibroblast growth factor 19. Under fasted conditions, fibroblast growth factor 19 maximum change from baseline serum concentration after drug administration and area under the change from baseline serum concentration–time curve from time 0 to 24 hours were 36% for CSF and 12% for FMI. For a second biomarker, serum 7‐alpha hydroxy‐4‐cholest‐3‐one, the pharmacological activity was comparable between CSF (fasted) and pFMI (both fasted and fed states). The pFMI offers advantages over the CSF in terms of insensitivity to food effect, lower intersubject variability, and overcoming solubility limitations.
Internet of Things‐based root disease classification in alfalfa plants using hybrid optimization‐enabled deep convolutional neural network
Authors: Jayapalan Daniel Francis Selvaraj , Ananth John Patrick
Published: December 2022

In this article, water cycle spider monkey optimization‐based deep convolutional neural network (WCSMO‐based deep CNN) is designed to classify root diseases in alfalfa plants. In the proposed method, the alfalfa plant root images are accessed remotely using a camera and transferred to the sink node to classify the disease. The proposed water cycle spider monkey optimization (WCSMO) algorithm performs the routing. Once the root images are received at base station or sink node, the images undergo preprocessing, segmentation, and classification. In the preprocessing module, a median filter is utilized to reduce the image noise. The preprocessed output is subjected to the segmentation phase, which is carried out using enhanced fuzzy C‐means clustering. The segmented results are passed to the classification step, where the deep convolutional neural network (deep CNN) is employed to categorize the root illness after being trained by the proposed WCSMO algorithm, which combines the water cycle algorithm and spider monkey optimization. The developed method achieved effective performance in terms of the metrics like sensitivity, accuracy, and specificity with the value of 0.9169, 0.9198, and 0.92. Moreover, the proposed WCSMO algorithm obtained the average energy and average throughput of 0.26641 J, and 91.483%, respectively.
Secured information sharing for supply chain management based on blockchain technology and optimal key generation process
Authors: Lahane Priti S. , Sharma Manish
Published: December 2022

Supply Chain Management (SCM) is one of the biggest important focal areas in most corporate environments. However, some difficulties are presented in the structure like high cost, privacy issues and distortions. Thus, new secured information sharing for SCM is proposed in this work and deals with the introduction of privacy preservation of data transfers among supply chains. Initially, a supply chain is constructed and the data transfer among the diverse levels takes place via blockchain technology. In the blockchain, security being a crucial factor, a new privacy preservation method is introduced. The initial information is converted to a sanitization procedure prior to transmission via blockchain technology, in which the information is turned into sanitized data. Similarly, the sanitized data is restored on the receiving end to obtain the original data. More importantly, key generation has a significant role in both processes, and it must be ideally chosen. The key is optimally chosen for this study using a new optimization algorithm called Fitness‐based Self‐adaptive Sea lion Optimization (FSA‐SLnO), which is a better variant of the conventional Sealion Optimization technique (SLnO). In terms of security, the proposed protected information sharing in SCM using block chain technology is evaluated by comparing it with traditional approaches.
Shuffled shepherd social optimization based deep learning for rice leaf disease classification and severity percentage prediction
Authors: Daniya Thavasilingam , Srinivasan Vigneshwari
Published: December 2022

The earlier diagnosis and classification of plant diseases has the ability to control the spread of illnesses on a variety of crops with the aim of improving crop quality and yield. The automatic system effectively recognizes the plant diseases at less error and cost without the interpretation of farm specialists. In this article, shuffled shepherd social optimization‐based deep learning (SSSO‐based deep learning) technique is developed to classify rice leaf disease and severity percentage prediction. The classification is carried out using deep maxout network and the severity percentage prediction is performed using deep LSTM. The training of both deep learning techniques is achieved using developed SSSO algorithm, which is the combination of shuffled shepherd optimization algorithm (SSOA) and social optimization algorithm. The proposed technique achieved maximum accuracy, sensitivity, specificity of 0.926, 0.935, 0.892, and minimum mean square error, and root mean square error of 0.106, and 0.326. The accuracy of the implemented approach is 7.24%, 5.29%, 4%, and 2.81% improved than the existing techniques, like bacterial leaf streak‐based UNet (BLSNet), multilayer maxout, resistance spot welding‐based deep recurrent neural network (RSW‐based deep RNN), and rider Henry gas solubility optimization_deep neuro fuzzy network (RHGSO_DNFN) + deep LSTM.
Fractional Artificial Bee Chicken Swarm Optimization technique for QoS aware virtual machine placement in cloud
Authors: Pushpa Ramaiah , Siddappa Maadappa
Published: December 2022

Cloud computing provides different constructive services in order to share huge scale information, computing resources, storage resources, and offer research knowledge. Cloud Service Providers (CSPs) afforded its services to cloud customers, usually in structure of Virtual Machines (VMs). In this paper, Fractional Artificial Bee Chicken Swarm Optimization (Fractional ABCSO) is introduced for VM placement in the cloud. The Fractional ABCSO is obtained by integrating the Fractional concept (FC), Chicken Swarm Optimization (CSO), and Artificial Bee Colony (ABC). Here, the cloud simulation is performed by means of VM and physical machine (PM). At first, VM placement is carried out using different system factors, such as Central Processing Unit (CPU), Million Instructions per Second (MIPS), bandwidth, migration cost, memory, frequency, power, along with Quality of Service (QoS). The developed Fractional ABCSO algorithm outperformed other existing techniques with regard to load, migration cost, and power consumption of 0.1614, 0.0535, and 0.0408.
Intelligent skin cancer diagnosis using adaptive k‐means segmentation and deep learning models
Authors: Enturi Bala Krishna Manash , Suhasini A. , Satyala Narayana
Published: December 2022

Since melanoma spreads swiftly throughout the body, it is typically a deadly form of skin cancer. Only when skin cancer is discovered early on is it usually treatable. In order to do this, this work proposes a unique melanoma detection model that has five main phases, including (i) pre‐processing, (ii) segmentation, (iii) feature extraction, (iv) suggested HKPCA based dimensionality reduction, and (v) classification. Pre‐processing is done first, and segmentation is done using a new adaptive k‐means methodology after that. After that, features from the gray‐level co‐occurrence matrix (GLCM), deviation relevance based local binary pattern (DRLBP), and gray‐level run‐length matrix (GLRM) is extracted. Extracted features were subjected for dimensionality reduction via hybrid kernel proposed principal component analysis (HKPCA). These dimension reduced features are then classified using deep belief network (DBN) framework, where the weights will be optimized by means of improved elephant herding optimization (IEHO). Finally, a comparison of the proposed and existing models' convergent performance is conducted.
Dynamics of Citrate Coordination on Gold Nanoparticles Under Low Specific Power Laser‐Induced Heating
Authors: Oliveira de Souza Danilo , Girardon Jean‐Sébastien , Hoffmann David J. , Berrier Elise
Published: December 2022

SERS evolution recorded over a drop‐coated coffee‐ring pattern of citrate‐capped gold colloids was investigated as a function of time under low‐specific laser power. Spectral changes caused by plasmon‐induced reaction could not be detected, but a long‐term transient original spectral profile showing additional lines was observed. We performed deep qualitative and quantitative SERS intensity variation analysis based on the complementary use of extreme deviation and cross‐correlation statistics, which provided further insights on the behavior of citrate‐capping layers of gold nanoparticles upon laser illumination. More precisely, the cross‐correlation analysis made possible to follow the so‐called individual events denoting particular resonance structures, in which groups of modes were assigned to an evolution of citrate coordination on gold surface driven by photo‐activation. As a consequence, the detection limit was increased and new lines were related to the presence of a very low amount of dicarboxy‐acetone (DCA), which was already present in the system.
Metacognitive training for negative symptoms: Support for the cognitive model
Authors: Swanson Linda , Griffiths Helen , Moritz Steffen , Cervenka Simon
Published: December 2022

Developing effective treatment options for negative symptoms of psychotic disorders remains a major unmet treatment need and area for further research. In a recent uncontrolled study by the main author, Metacognition Training (MCT) for negative symptoms was found to lead to fewer negative symptoms, less stigma and increased self‐rated reflective ability. As the analysis examined negative symptoms as a whole, we here performed an additional analysis on individual negative symptom items as recent research has suggested that negative symptoms are best conceptualized through a five‐factor model. It was found that the intervention led to changes specifically on sociality and blunted affect (with large effect sizes), which might reflect changes in both intrapersonal and interpersonal (meta)cognitive processes.
Clinical Trial Site Perspectives and Practices on Study Participant Diversity and Inclusion
Authors: MacLennan Demi L. , Plahovinsak Jennifer L. , MacLennan Rob J. , Jones Carolynn T.
Published: December 2022

Clinical trial participant populations fail to adequately represent target populations that drugs are intended to serve. Improving racial and ethnic diversity of clinical trial participants is essential for generalizable, quality clinical research results and ensuring social and medical equity. Site‐level clinical research professionals (CRPs) have unique insights on diversity improvement strategies for clinical trial enrollment. A survey was distributed to current CRPs working at clinical research sites in the United States to describe current practices and perceptions of the impact these practices have on participant diversity. Subsequently, descriptive quantitative analysis and inductive content analysis were performed. For the practices surveyed, there are discrepancies between frequency of use and perceived impact on diversity enrollment. Common current practices include phone‐based or telemedicine study visits, electronic/digital data collection, and participant compensation. However, we report travel reimbursement and services, translated documents and translator services, and adequate participant compensation as most impactful on diverse enrollment. A multistakeholder approach is necessary to enhance diversity and inclusion (D&I) of study participants. Besides large‐scale solutions such as countering community distrust, actionable steps are needed by sponsors and study sites to improve D&I of trial participants. Study leadership at the sponsor, contract research organization (CRO), and site‐level should create diversity plans prior to study start, and CRO and sponsor budgets should consider D&I strategies during study planning. Planning should incorporate strategies to improve D&I including adequate participant compensation, translated documents and translator services, and travel reimbursements.
Amphiphilic Graphene Quantum Dots: Metal‐Free Photocatalyst for Hydrogen Evolution via Encapsulation of Organic Thermally Activated Delayed Fluorescence Photosensitizers
Authors: Park Hyunho , Serdiuk Illia E. , Park Soo Young
Published: December 2022

Designing a metal‐free photocatalyst for the photocatalytic hydrogen evolution reaction (HER) is a very important research goal. Although graphene quantum dots (GQDs) have already been demonstrated as HER photocatalysts, it is necessary to address the poor visible light absorption of GQDs to achieve higher efficiency in the hydrogen evolution reaction (HER) rate. We have synthesized amphiphilic GQD by hexylamine (HA) functionalization through an amide bond formation reaction. We confirmed that HA functionalized GQD (GQD‐HA) is amphiphilic and can act as the photocatalyst and templating surfactant at the same time. GQD‐HA can form much more stable composite nanoparticles with thermally activated delayed fluorescence (TADF) photosensitizers than bare GQD. Importantly, the HER performance and the stability of the composite systems are remarkably enhanced after HA functionalization. Through electrochemical analyses, it was verified that composite photosensitizer nanoparticles with GQD‐HA have efficient charge separation and fast charge transfer properties.
Maternal use of substances while pregnant does not affect ADHD symptoms in offspring
Authors: Knopf Alison
Published: December 2022

A recent study has found that in contrast to some previously published studies, maternal prenatal substance use with legal substances is not associated with offspring attention‐deficit hyperactivity disorder (ADHD). For the study, researchers measured associations between prenatal smoking, alcohol, and caffeine consumption with childhood ADHD symptoms. They took into consideration shared familial factors.
Ultrafast PEDOT:PSS/H2SO4 Electrical Double Layer Capacitors: Comparison with Polyaniline Pseudocapacitors
Authors: Kim Kein , Park Jinwoo , Lee Junyoung , Suh Soomin , Kim Woong
Published: December 2022

Poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) is one of the most widely studied conductive polymers, owing to its excellent electrical, optical, and mechanical properties, with various applications such as organic electrochemical transistors, electrochromics, and flexible/stretchable supercapacitors. The charging mechanism of PEDOT:PSS supercapacitors has been traditionally believed to be faradaic, which involves the transfer of charge across the electrode/electrolyte interface. In the present work, however, robust experimental evidence suggests that the PEDOT:PSS supercapacitors mainly store and deliver charge nonfaradaically. The various electrochemical properties of PEDOT:PSS electrical double layer capacitors (EDLCs) are clearly distinguishable from those of polyaniline (PANI) pseudocapacitors, which store charge faradaically. Owing to the nonfaradaic mechanism, the frequency response of PEDOT:PSS supercapacitors is comparable to that of state‐of‐the‐art ultrafast EDLCs with carbon‐based electrodes, making them suitable for high‐frequency applications such as 60 Hz AC line filtering. This result is of great importance for the fundamental understanding of the charging mechanism of mixed ionic‐electronic conducting polymers, such as PEDOT:PSS, and is expected to contribute to the development of various electrochemical devices based on this type of material.
On checking dissipativity of parameterized linear and time‐invariant circuits and systems
Authors: Zanco Alessandro , Grivet‐Talocia Stefano
Published: December 2022

A novel dissipativity characterization is proposed for linear time‐invariant circuits and systems whose dynamic behavior depends on one external parameter. The proposed formulation extends to the parameterized case standard Hamiltonian‐based algebraic dissipativity characterizations and is structured as an underdetermined multiparameter eigenvalue problem. Resulting from a polynomial parameterization, the proposed characterization leads to an effective set of algorithms that are able to determine the regions of local dissipativity and local activity in the frequency‐parameter plane, which in turn can be exploited by dissipativity enforcement algorithms to produce uniformly passive models. The reference application of proposed technique is behavioral modeling of complex circuits or systems, whose dynamic behavior can be compressed into a low‐order system through dedicated model order‐reduction processes. Various examples ranging from integrated components to microstrip filters and networks are used to illustrate the proposed characterization.
Clustered regularly interspaced short palindromic repeats screens in pediatric tumours: A review
Authors: van Mackelenbergh Madelaine G. , Metselaar Dennis S. , Meel Michaël H. , Hulleman Esther
Published: December 2022

In recent years, the discovery and development of clustered regularly interspaced short palindromic repeats (CRISPR) technology has revolutionized and accelerated functional genetic screening in cancer research. In this review, we discuss different methods of executing CRISPR screens, with a focus on pediatric tumour entities. Historically, these tumours were thought to resemble their adult counterparts. However, the new era of genomic research and the extensive use of gene editing has identified pediatric tumours as distinct entities with drastically different development and presentation. Here we provide an overview of CRISPR screens performed in pediatric tumour models and highlight unique considerations for pediatric tumour screens. In particular, the results from CRISPR screens combining treatment with genetic knockouts can push treatment for pediatric patients. We conclude by discussing the potential of CRISPR genetic screening to unravel pediatric tumour biology and identify new treatment options.
Prefrontal activation in preschool children is associated with maternal adversity and child temperament: A preliminary fNIRS study of inhibitory control
Authors: Miller Jonas G. , Hyat Mahnoor , Perlman Susan B. , Wong Ronald J. , Shaw Gary M. , Stevenson David K. , Gotlib Ian H.
Published: December 2022

Exposure to adversity is a well‐documented risk factor for cognitive, behavioral, and mental health problems. In fact, the consequences of adversity may be intergenerational. A growing body of research suggests that maternal exposures to adversity, including those prior to childbirth, are associated with offspring biobehavioral development. In a sample of 36 mothers and their preschool‐age children (mean child age = 4.21 ± 0.92 years), we used functional near‐infrared spectroscopy to replicate and extend this work to include brain activation during inhibitory control in young children. We found that measures of maternal exposure to adversity, including cumulative, childhood, and preconception exposures, were significantly and positively associated with activation in the right frontopolar prefrontal cortex (PFC) and in the left temporal and parietal clusters during inhibitory control. In addition, and consistent with previous findings, children's increased negative affect and decreased effortful control were associated with increased right PFC activation during inhibitory control. These findings provide preliminary evidence that maternal and dispositional risk factors are linked to alterations in PFC functioning during the preschool years. Children of mothers with a history of exposure to adversity, as well as children who are less temperamentally regulated, may require increased neural resources to meet the cognitive demands of inhibitory control.