bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular Origins of EGFR‐Driven Lung Cancer Cells Determine Sensitivity to Therapy
Authors: Chen Fan , Liu Jinpeng , Flight Robert M. , Naughton Kassandra J. , Lukyanchuk Alexsandr , Edgin Abigail R. , Song Xiulong , Zhang Haikuo , Wong Kwok‐Kin , Moseley Hunter N. B. , Wang Chi , Brainson Christine F.
Published: October 2021

Targeting the epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKIs) is one of the major precision medicine treatment options for lung adenocarcinoma. Due to common development of drug resistance to first‐ and second‐generation TKIs, third‐generation inhibitors, including osimertinib and rociletinib, have been developed. A model of EGFR‐driven lung cancer and a method to develop tumors of distinct epigenetic states through 3D organotypic cultures are described here. It is discovered that activation of the EGFR T790M/L858R mutation in lung epithelial cells can drive lung cancers with alveolar or bronchiolar features, which can originate from alveolar type 2 (AT2) cells or bronchioalveolar stem cells, but not basal cells or club cells of the trachea. It is also demonstrated that these clones are able to retain their epigenetic differences through passaging orthotopically in mice and crucially that they have distinct drug vulnerabilities. This work serves as a blueprint for exploring how epigenetics can be used to stratify patients for precision medicine decisions.
Multiband Photoresponding Field‐Effect Transistor Memory Using Conjugated Block Copolymers with Pendent Isoindigo Coils as a Polymer Electret
Authors: Lin Chen‐Fu , Lin Yan‐Cheng , Yang Wei‐Chen , Hsu Li‐Che , Ercan Ender , Hung Chih‐Chien , Yu Yang‐Yen , Chen Wen‐Chang
Published: October 2021

In this study, the authors report a series of conjugated block copolymers, PF‐b‐Piso comprising poly[2,7‐(9,9‐dihexylfluorene)] (PF), and poly(pendent isoindigo) (Piso) for polymer electret in the photonic field‐effect transistor (FET) memory device. The optical properties, surface morphology, and molecular organization of these BCPs are investigated systematically. Accordingly, Piso with absorption in the Ultraviolet C range (UVC, 200–280 nm) possibly rendered the device with a multiband photoresponse, and a good memory performance is achieved by optimizing the polymer composition. Therefore, the memory device comprising PF‐b‐Piso could perform a high current contrast of 106 to 405 nm light and 105 to 254 nm light over 104 s. In addition, a current contrast of 104 and 102 is achieved in response to 650 and 530 nm light, and this phenomenon can be attributed to the charge transfer between channel and memory layers. The experimental results indicate that the block copolymer design not only conduces to forming a self‐assembled microphase separation to stabilize the trapped charge in the polymer electret, but also triggers multiband photoresponding of the photonic FET memory.
Large‐Area Endohedral Metallofullerene Single‐Crystal Arrays for High‐Performance Field‐Effect Transistors and Photodetectors
Authors: Su Mingming , Hu Yajing , Yang Shaoting , Yu Ao , Peng Ping , Yang Le , Jin Peng , Su Bin , Li Fang‐Fang
Published: October 2021

A structure with high crystallinity and orderly molecular packing is a requirement for high‐performance optoelectronic devices. However, growing large‐area, long‐range order, highly crystalline micro or nanostructures remains a challenge. Endohedral metallofullerenes (EMFs) are spherical π‐conjugated molecules with unique electronic structures, hence they can be easily assembled into highly ordered crystals through intermolecular π–π interactions. In this work, large‐area single‐crystal microwire arrays of M3N@Ih‐C80 (M = Sc, Lu) are prepared with the assistance of a pillar‐structured template, and the microwire diameter can be tuned via the fullerene concentration. A field‐effect transistor is fabricated using Sc3N@Ih‐C80 microwire arrays, exhibiting a record‐high charge carrier mobility (6.16 cm2 V−1 s−1) among EMF‐based devices. Further, microwire‐based photodetectors are developed, with a response time as low as 0.1 s. The precise arrangement of the M3N@Ih‐C80 molecules helps improve the electron transportation channels, thereby enhancing the device performance.
From Flower‐Like to Spherical Deposition: A GCNT Aerogel Scaffold for Fast‐Charging Lithium Metal Batteries
Authors: Yang Tianyu , Li Li , Zhao Teng , Ye Yusheng , Ye Zhengqing , Xu Sainan , Wu Feng , Chen Renjie
Published: October 2021

Lithium metal anode has attracted the attention of both academic and industrial community for its high specific capacity and lowest redox potential. However, uncontrollable growth of lithium dendrite and low Coulombic efficiency (CE) exclude it from real world applications, especially in the fast‐charging area. Herein, a graphene/carbon nanotube composite (GCNT) aerogel as a stable host for a lithium metal anode is proposed. The porous aerogel with large surface area and high conductivity can significantly decrease the local current density to enable spherical and uniform lithium deposition. The GCNT aerogel electrode can maintain a high CE of 97.7% for 430 cycles at a current of 1 mA cm−2 under a capacity of 1 mAh cm−2 while symmetric cells can sustain a high current up to 8 mA cm−2. The composite anode paired with a LiFePO4 cathode shows ultrahigh‐rate capability of 18 C and ultrahigh capacity retention of 97.6% and average CE of 99.1% in the subsequent 570 cyclings at 4 C. When paired with the LiNi0.8Co0.1Mn0.1O2 cathode, the composite anode can also demonstrate a high rate of 10 C and achieve a high capacity retention of 83.2% and an average CE of 99.8% for the subsequent 470 cycles at 2 C.
Dual‐Salt Electrolyte Additives Enabled Stable Lithium Metal Anode/Lithium–Manganese‐Rich Cathode Batteries
Authors: Zhou Junhua , Lian Xueyu , Shi Qitao , Liu Yu , Yang Xiaoqin , Bachmatiuk Alicja , Liu Lijun , Sun Jingyu , Yang Ruizhi , Choi Jin-Ho , Rummeli Mark H.
Published: October 2021

Although lithium (Li) metal anode/lithium–manganese‐rich (LMR) cathode batteries have an ultrahigh energy density, the highly active Li metal and structural deterioration of LMR can make the usage of these batteries difficult. Herein, a multifunctional electrolyte containing LiBF4 and LiFSI dual‐salt additives is designed, which enables the superior cyclability of Li/LMR cells with capacity retentions of ≈83.4%, 80.4%, and 76.6% after 400 cycles at 0.5, 1, and 2 C, respectively. The dual‐salt electrolyte can form a thin, uniform, and inorganic species‐rich solid electrolyte interphase (SEI) and cathode electrolyte interphase (CEI). In addition, it alleviates the bulk Li corrosion and enhances the structural sustainability of LMR cathode. Moreover, the electrolyte design strategy provides insights to develop other high‐voltage lithium metal batteries (HVLMBs) to enhance the cycle stability.
Randomized controlled trial comparing an open surgical technique and a Seldinger technique for cricothyrotomy performed on a simulated airway
Authors: Mallows James L. , Tyler Perry A.
Published: October 2021

Objectives

Emergency cricothyrotomy is a lifesaving procedure performed when intubation fails and oxygenation cannot occur. There are multiple techniques and kits to perform this procedure. However, current evidence does not provide a definitive answer as to which method is superior. Two techniques in common use are a surgical technique and a percutaneous Seldinger‐based cricothyrotomy kit. The objective was to determine which of these two methods was quickest to perform and to determine which was most preferred by participants.

Methods

A prospective randomized controlled crossover trial was conducted involving emergency physicians and trainees. Each participant performed both cricothyrotomy techniques in succession on an airway model, with the technique performed first being randomized for each participant. The primary outcome was time to first insufflation of the artificial lung. A survey was completed by participants asking their comfort with each technique on a 5‐point scale from 1 (not at all comfortable) to 5 (very comfortable) and which technique they preferred.

Results

Twenty‐one emergency physicians and nine emergency medicine trainees were recruited. The surgical technique was performed the fastest, with a mean (±SD) time of 51.6 (±16.3) s versus 66.6 (±14.9) s for the Seldinger technique, with a statistically significant difference of 15.0 s (95% confidence interval = 8.5 to 21.5, p < 0.001). The surgical technique was rated the most comfortable to perform, with a median rating of 5 (interquartile range [IQR] = 4–5) versus 4 (IQR = 3–5) for the Seldinger technique. The surgical technique was most preferred by participants (80% vs 20%).

Conclusion

The surgical technique was the fastest to perform and was rated the most comfortable to perform and the most preferred technique.
Solar node and gateway wireless system functions in record breaking polar vortex outbreak of February 2021
Authors: Evett Steven R. , Thompson Alondra I. , Schomberg Harry H. , Andrade Manuel A. , Anderson John
Published: October 2021

Advances in environmental and agricultural management are increasingly enabled by unattended data acquisition using internet‐of‐things (IOT) approaches. These approaches combine advanced sensors and wireless data transmission to automatically convey field data to the internet. Users, either human or machine, then can access and act upon the data from nearly anywhere in the world. Particularly in the case of machines automatically acting on the data, robustness, reliability and accuracy of data are crucial to preventing unintended outcomes of machine operations and continued supply of key services. Low‐cost, low‐power, and solar‐powered systems are important to enable market entry of advanced decision support systems based on IOT data acquisition approaches. The polar vortex outbreak of February 2021 in the central United States provided an extreme test of such a node and gateway system for automatic data acquisition and telemetry to the internet over the cellular telephone network. The system, codesigned by USDA‐ARS and Acclima, performed admirably despite air temperatures reaching a minimum of −24 °C, temperatures < 0 °C for 8 d and < −7 °C for 6 d, two snowstorms, and overcast conditions. The six nodes, gateway, and 36 sensors continued to function reliably with a data transmission failure rate of <2 in 10,000 even though the Li‐ion batteries could not be recharged for 7 d due to temperatures <5 °C. The system reports geographic position of each node and gateway, model numbers and firmware versions of all equipment, including sensors, date, and time of sensor readings, and individual sensor elevations relative to a reference surface, affording data self‐identification for unfettered use by remote systems.
Artificial intelligence‐based computer vision in surgery: Recent advances and future perspectives
Authors: Kitaguchi Daichi , Takeshita Nobuyoshi , Hasegawa Hiro , Ito Masaaki
Published: October 2021

Technology has advanced surgery, especially minimally invasive surgery (MIS), including laparoscopic surgery and robotic surgery. It has led to an increase in the number of technologies in the operating room. They can provide further information about a surgical procedure, e.g. instrument usage and trajectories. Among these surgery‐related technologies, the amount of information extracted from a surgical video captured by an endoscope is especially great. Therefore, the automation of data analysis is essential in surgery to reduce the complexity of the data while maximizing its utility to enable new opportunities for research and development. Computer vision (CV) is the field of study that deals with how computers can understand digital images or videos and seeks to automate tasks that can be performed by the human visual system. Because this field deals with all the processes of real‐world information acquisition by computers, the terminology “CV” is extensive, and ranges from hardware for image sensing to AI‐based image recognition. AI‐based image recognition for simple tasks, such as recognizing snapshots, has advanced and is comparable to humans in recent years. Although surgical video recognition is a more complex and challenging task, if we can effectively apply it to MIS, it leads to future surgical advancements, such as intraoperative decision‐making support and image navigation surgery. Ultimately, automated surgery might be realized. In this article, we summarize the recent advances and future perspectives of AI‐related research and development in the field of surgery.
Comparison of endoscopic papillary large‐balloon dilatation with endoscopic sphincterotomy in clearing large common bile duct stones: A systematic review and meta‐analysis of randomized controlled trials
Authors: Cheng Chao‐Ling , Tang Kung‐Pei , Cheng Sheng‐Wei , Fang Hua‐Chen , Shiue Sheng‐Jie , Suk Fat‐Moon , Lien Gi‐Shih , Wu Ming‐Shun
Published: October 2021

There are three methods to retrieve large common bile duct stones, the first is endoscopic sphincterotomy (EST), the second is endoscopic papillary large‐balloon dilatation (EPLBD), and the third is limited EST plus EPLBD. Although EST is the most popularly used method, it has higher risk of bleeding complication and basket stuck. EPLBD alone without EST demonstrated safe and quick in the clinical practice, but there were only few studies focused on comparing EST or EPLBD alone. Thus, this study aims to compare the efficacy and safety of EPLBD with EST. We searched for PubMed, Embase, and Cochrane Library databases to collect relevant articles until August 31st, 2019. We included randomized controlled trials, common bile duct stones > 10 mm, comparison of endoscopic papillary large‐balloon dilatation with endoscopic sphincterotomy, and patients older than 18. We compare endoscopic papillary large‐balloon dilatation with endoscopic sphincterotomy on the clearance of large common bile duct stones, the adverse events, and the need for mechanical lithotripsy. This systematic review and meta‐analysis was registered on PROSPERO and the registration number is CRD42020150485. Total six studies met inclusion criteria and 762 participants were enrolled. The data revealed that endoscopic papillary large‐balloon dilatation alone was comparable to endoscopic sphincterotomy on the clearance of large common bile duct stones (RR = 1.02, 95% CI: 0.93‐1.12), the adverse events (RR = 1.01, 95% CI: 0.71‐1.43) and the need for mechanical lithotripsy. In the subgroup analysis, the requirement of mechanical lithotripsy decreased in the non‐Chinese group (RR = 0.58, 95% CI: 0.41‐0.84). The efficacy and safety to clean large common bile duct stones are comparable in either EPLBD or EST. In addition, EPLBD alone not only saves the operation time but also reduces the chance of mechanical lithotripsy in the subgroup analysis.
D‐bifunctional protein deficiency caused by splicing variants in a neonate with severe peroxisomal dysfunction and persistent hypoglycemia
Authors: Werner Kelly M. , Cox Allison J. , Qian Emily , Jain Preti , Ji Weizhen , Tikhonova Irina , Castaldi Christopher , Bilguvar Kaya , Knight James , Ferdinandusse Sacha , Fawaz Rima , Jiang Yong‐Hui , Gallagher Patrick G. , Bizzarro Matthew , Gruen Jeffrey R. , Bale Allen , Zhang Hui
Published: October 2021

D‐bifunctional protein (DBP) deficiency is a rare, autosomal recessive peroxisomal enzyme deficiency resulting in a high burden of morbidity and early mortality. Patients with DBP deficiency resemble those with a severe Zellweger phenotype, with neonatal hypotonia, seizures, craniofacial dysmorphisms, psychomotor delay, deafness, blindness, and death typically within the first 2 years of life, although patients with residual enzyme function can survive longer. The clinical severity of the disease depends on the degree of enzyme deficiency. Loss‐of‐function variants typically result in no residual enzyme activity; however, splice variants may result in protein with residual function. We describe a full‐term newborn presenting with hypotonia, seizures, and unexplained hypoglycemia, who was later found to have rickets at follow up. Rapid whole genome sequencing identified two HSD17B4 variants in trans; one likely pathogenic variant and one variant of uncertain significance (VUS) located in the polypyrimidine tract of intron 13. To determine the functional consequence of the VUS, we analyzed RNA from the patient's father with RNA‐seq which showed skipping of Exon 14, resulting in a frameshift mutation three amino acids from the new reading frame. This RNA‐seq analysis was correlated with virtually absent enzyme activity, elevated very‐long‐chain fatty acids in fibroblasts, and a clinically severe phenotype. Both variants are reclassified as pathogenic. Due to the clinical spectrum of DBP deficiency, this provides important prognostic information, including early mortality. Furthermore, we add persistent hypoglycemia to the clinical spectrum of the disease, and advocate for the early management of fat‐soluble vitamin deficiencies to reduce complications.
Non‐native marine species risk screening and vector analysis to inform conservation management in the southern Caribbean
Authors: Tidbury Hannah J. , Copp Gordon H. , Davison Phil I. , Olsson Karin , Graham Jennifer A. , Hill Tom W. , Vilizzi Lorenzo , Stebbing Paul D.
Published: October 2021

Marine protected areas of the Caribbean islands are at high risk of non‐native species (NNS) introductions and impacts that may threaten conservation goals. To inform conservation management of these protected areas, the present study identified potentially‐invasive NNS as well as introduction vectors and pathways for the southern Caribbean islands of Grenada, and St Vincent and the Grenadines.

The activities associated with the introduction vectors and pathways relevant to priority NNS were assessed to highlight locations within the risk assessment area at elevated risk of NNS introduction and spread.

The preliminary NNS list comprised 223 species of which 10 were screened using the Aquatic Species Invasiveness Screening Kit, which generated scores indicating moderate‐to‐high risk (18–51) of being invasive in the risk assessment area, based on generalized global threshold scores. The ports of Kingston (St Vincent) and St George’s (Grenada) were associated with the greatest shipping and boating activity, indicating elevated risk of NNS introductions by way of these vectors. Coastal areas in the south of the risk assessment area were associated with highest risk of introduction of NNS by natural dispersal.

The evidence presented in this study provides a strong basis upon which to develop and implement risk‐based biosecurity and monitoring programmes to protect and conserve this region’s marine protected areas.
Effects of transcutaneous auricular vagus nerve stimulation on brain functional connectivity of medial prefrontal cortex in patients with primary insomnia
Authors: Zhang Shuai , He Jia‐Kai , Meng Hong , Zhao Bin , Zhao Ya‐Nan , Wang Yu , Li Shao‐Yuan , Wang Lei , Wu Mo‐Zheng , Chen Yu , Xiao Xue , Hou Li‐Wei , Fang Ji‐Liang , Rong Pei‐Jing
Published: October 2021

As a representative of acupuncture and nonpharmaceutical therapy, auricular acupuncture has been widely for the treatment of insomnia. Transcutaneous auricular vagus nerve stimulation (taVNS) is a combination of auricular point stimulation and vagus nerve stimulation. It can not only treat primary insomnia effectively, but also is noninvasive, painless, portable and economical. The medial prefrontal cortex (mPFC) is a core region of default mode network (DMN), which is important for maintenance of sleep. However, the mechanism of taVNS in alleviating primary insomnia (PI) remains to be clarified. In this study, we found that taVNS could not only effectively reduce the score of Pittsburgh Sleep Quality Index, but also decreased functional connection (FC) between the left mPFC and bilateral dorsal anterior cingulate gyrus as well as FC between the right mPFC and the occipital cortex in patients with PI. Furthermore, the decrease in FC was positively correlated with the decline of sleep index score. Therefore, we proposed that treatment with taVNS can improve sleep quality and prolong sleep duration in patients with PI by reducing FC within DMN, FC between DMN and salience network, as well as FC between DMN and the occipital cortex. This may be one of mechanisms of taVNS in treating PI.
Discovering emerging topics in textual corpora of galleries, libraries, archives, and museums institutions
Authors: Candela Gustavo , Carrasco Rafael C.
Published: October 2021

For some decades now, galleries, libraries, archives, and museums (GLAM) institutions have provided access to information resources in digital format. Although some datasets are openly available, they are often not used to their full potential. Recently, approaches such as the so‐called Labs within GLAM institutions promote the reuse of digital collections in innovative and inspiring ways. In this article, we explore a straightforward computational procedure to identify emerging topics in periodical materials such as newspapers, bibliographies, and journals. The method is illustrated in three use cases based on public digital collections. This type of tools are expected to promote further usage by researchers of the digital collections.
Job loss predicts worsening depressive symptoms for young adults with autism: A COVID‐19 natural experiment
Authors: Taylor Julie Lounds , Adams Ryan E. , Pezzimenti Florencia , Zheng Shuting , Bishop Somer L.
Published: October 2021

Adults with autism spectrum disorder (ASD) experience high rates of both unemployment and depression. Though job loss predicts increased risk of depression in the general population, studies have yet to directly examine this relationship among individuals with ASD. With the backdrop of rising unemployment due to COVID‐19, we used a longitudinal design to examine whether employment changes predicted increasing depressive symptoms among young adults with ASD. Online surveys were collected from young adults with ASD at two times: just before widespread social distancing measures were adopted in the United States, and again 10 weeks later. Both time points included measurement of depressive symptoms (Beck Depression Inventory‐2). At Time 2, COVID‐related employment changes and the perceived impact of those changes on well‐being were collected. Of the young adults who were employed at Time 1 (n = 144), over one‐third (37.5%) reported employment changes during the first 2 months of COVID‐19. Most of this change was job loss or reductions in hours or pay (“job loss/reduction”). Controlling for Time 1 depressive symptoms, young adults who experienced job loss/reduction had significantly higher depressive symptoms at Time 2 than those without an employment change. Individuals' perceived impact of employment change also predicted depressive symptoms. These findings suggest that losing a job or experiencing reductions in hours or pay leads to worsening depressive symptoms among adults with ASD. Better supporting autistic adults in the workplace may not only decrease the likelihood of job loss, but also combat the exceedingly high rates of depression in this group.

Lay Summary

Though unemployment has been linked to mental health problems in the general population, this relationship is seldom considered among adults with autism. In this study, we found that adults on the autism spectrum who lost their jobs or experienced reductions in pay or hours during the first 2 months of COVID‐19 had worsening depression compared to adults who did not have job changes. Our findings suggest that increasing access to employment may help alleviate poor mental health among autistic adults.
Strategies for leveraging media to improve leadership within nonprofits
Authors: Scranton Annie Pace
Published: October 2021

When thinking about media exposure in the nonprofit world, more times than not, the end goal is to raise awareness to attract potential donors. We've seen this strategy work time and time again. In fact, one of our nonprofit clients, Concern Worldwide US, saw a $1 million donation come in after its CEO gave an appearance on Bloomberg television.
Prognostic impact of eligibility for adjuvant immunotherapy in locally advanced urothelial cancer
Authors: Miura Yuki , Hatakeyama Shingo , Tanaka Toshikazu , Fujita Naoki , Horiguchi Hirotaka , Okuyama Yoshiharu , Kojima Yuta , Noro Daisuke , Tokui Noriko , Okamoto Teppei , Yamamoto Hayato , Ito Hiroyuki , Yoneyama Takahiro , Hashimoto Yasuhiro , Ohyama Chikara
Published: October 2021

Objective

To evaluate the effect of postoperative pathological findings related to the eligibility of adjuvant immunotherapy on oncologic outcomes in patients with localized and locally advanced muscle‐invasive bladder carcinoma (MIBC) and upper tract urothelial carcinoma (UTUC).

Patients and methods

We retrospectively evaluated 1082 patients treated with radical cystectomy (n = 597) and nephroureterectomy (n = 485) between January 2000 and April 2021. Patients were divided into two groups: pT3‐4 or pN+ without neoadjuvant chemotherapy and ypT2‐4 or pN+ treated with neoadjuvant chemotherapy (trial‐eligible group) or others (trial‐ineligible group). The primary outcome was the effect of trial eligibility for adjuvant immunotherapy on disease‐free survival (DFS) and overall survival (OS). Secondary outcomes included the additional effect of lymphovascular invasion (LVI) status to the clinical trial criteria on prognosis and a risk model development.

Results

The median ages of the patients were 69 and 72 years in the MIBC and UTUC groups, respectively. Fifty‐two percent of patients met the trial inclusion criteria. Trial eligibility was significantly associated with poor DFS and OS among patients with MIBC and UTUC. LVI‐positive status was significantly associated with poor prognosis among patients in the trial‐eligible group. A very high risk (LVI+ or pN+ among the pT3‐4 or ypT2‐4) was significantly associated with poor prognosis.

Conclusion

A total of 52% of patients were eligible for adjuvant immunotherapy. Trial eligibility was significantly associated with a poor prognosis. LVI+ and pN+ may play a key role in candidate selection for adjuvant immunotherapy.
A student led computational screening of peptide inhibitors against main protease of SARS‐CoV‐2
Authors: Khan Anika Tajrian , Chowdhury Golam Mahmud , Hafsah Juwairiyah , Maruf Md , Raihan Md Riyad Hossen , Chowdhury Md Talha , Nawal Nafisa , Tasnim Nishat , Saha Pranto , Roy Prottoy , Tabassum Raya , Rodrigues Souvick Patrick , Hasan Walid , Samanta Zarin Tasnim , Kamal Suprio , Nazir Md Shahoriar , Ali Md Ackas , Halim Mohammad A.
Published: October 2021

The main protease of SARS‐CoV‐2 is a promising drug target due to its functional role as a catalytic dyad in mediating proteolysis during the viral life cycle. In this study, experimentally proven 14 HIV protease peptides were screened against the main protease of SARS‐CoV‐2. Fourteen middle and high school “student researchers” were trained on relevant computational tools, provided with necessary biological and chemical background and scientific article writing. They performed the primary screening via molecular docking and the best performing complexes were subjected to molecular dynamics simulations. Molecular docking revealed that HIP82 and HIP1079 can bind with the catalytic residues, however after molecular dynamics simulation only HIP1079 retained its interaction with the catalytic sites. The student researchers were also trained to write scientific article and were involved with drafting of the manuscript. This project provided the student researchers an insight into multi‐disciplinary research in biology and chemistry, inspired them about practical approaches of computational chemistry in solving a real‐world problem like a global pandemic. This project also serves as an example to introduce scientific inquiry, research methodology, critical thinking, scientific writing, and communication for high school students.
Diminished culpability in fetal alcohol spectrum disorders (FASD)
Authors: Novick Brown Natalie , Greenspan Stephen
Published: October 2021

There is a biological basis for diminished criminal responsibility in offenders with fetal alcohol spectrum disorders (FASD) just as there is in those with intellectual disability. Functional limitations affecting cognition in both neurodevelopmental conditions stem directly from structural brain damage at a gross and molecular level, which usually impairs executive functioning among other cognitive skills. Executive functioning, which includes reasoning and impulse control, is the only neural system in the brain that involves consciousthought. With respect to the law, impaired reasoning or rationality is an aspect of mens rea (“guilty mind”). When rationality is impaired by prenatal alcohol exposure, acts driven by strong emotion and urges can occur, which has obvious implications regarding criminal responsibility. TheAtkinsdecision by the U.S. Supreme Court reflects the rationale that organically based brain dysfunction in executive skills reduces criminal culpability. We argue that people with FASD who have similar brain dysfunction likewise have reduced criminal responsibility.
Positive electrostatic therapy of metastatic tumors: selective induction of apoptosis in cancer cells by pure charges
Authors: Zandi Ashkan , Rafizadeh‐Tafti Saeid , Shojaeian Fatemeh , Ali Khayamian Mohammad , Abbasvandi Fereshteh , Faranoush Mohammad , Anbiaee Robab , Najafikhoshnoo Sahar , Hoseinpour Parisa , Assadi Sepanta , Katebi Pouyan , Davari sh. Zahra , Shalileh Shahriar , Salemizadeh Parizi Mohammad , Vanaei Shohreh , Ghaderinia Mohammadreza , Abadijoo Hamed , Taheri Payam , Reza Esmailinejad Mohammad , Sanati Hassan , Reza Rostami Mohammad , Sadeghian Reza , Kordehlachin Yasin , Sadegh Mousavi‐kiasary S. M. , Mamdouh Amir , Hossein Miraghaie Seyyed , Baharvand Hossein , Abdolahad Mohammad
Published: October 2021

Background

We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues.

Methods

We interacted normal and cancer cell lines and animal tumors with PECs by connecting a charged patch to cancer cells and animal tumors. many biochemical, molecular and radiological assays were carried out on PEC treated and control samples.

Results

Correlative interactions between electrostatic charges and cancer cells contain critical unknown factors that influence cancer diagnosis and treatment. Different types of cell analyses prove PEC‐based apoptosis induction in malignant cell lines. Flowcytometry and viability assay depict selective destructive effects of PEC on malignant breast cancer cells. Additionally, strong patterns of pyknotic apoptosis, as well as downregulation of proliferative‐associated proteins (Ki67, CD31, and HIF‐1α), were observed in histopathological and immunohistochemical patterns of treated mouse malignant tumors, respectively. Quantitative real‐time polymerase chain reaction results demonstrate up/down‐regulated apoptotic/proliferative transcriptomes (P21, P27, P53/CD34, integrin α5, vascular endothelial growth factor, and vascular endothelial growth factor receptor) in treated animal tumors. Expression of propidium iodide in confocal microscopy images of treated malignant tissues was another indication of the destructive effects of PECs on such cells. Significant tumor size reduction and prognosis improvement were seen in over 95% of treated mouse models with no adverse effects on normal tissues.

Conclusion

We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. The findings were statistically and observationally significant when compared to radio/chemotherapy‐treated mouse models. As a result, this nonionizing radiation may be used as a practical complementary approach with no discernible side effects after passing future human model studies.
Development and validation of pretreatment nomogram for disease‐specific mortality in gastric cancer‐A competing risk analysis
Authors: Bando Etsuro , Ji Xinge , Kattan Michael W. , Bencivenga Maria , de Manzoni Giovanni , Terashima Masanori
Published: October 2021

Background

In several reports, gastric cancer nomograms for predicting overall or disease‐specific survival have been described. The American Joint Committee on Cancer (AJCC) introduced the attractiveness of disease‐specific mortality (DSM) as an endpoint of risk model. This study aimed to develop the first pretreatment gastric cancer nomogram for predicting DSM that considers competing risks (CRs).

Methods

The prediction model was developed using data for 5231 gastric cancer patients. Fifteen prognosticators, which were registered at diagnosis, were evaluated. The nomogram for DSM was created as visualizations of the multivariable Fine and Gray regression model. An independent cohort for external validation consisted of 389 gastric cancer patients from a different institution. The performance of the model was assessed by discrimination (Harrell's concordance (C)‐index), calibration, and decision curve analysis. DSM and CRs were evaluated, paying special attention to host‐related factors such as age and Eastern Cooperative Oncology Group performance status (ECOG PS), by using Gray's univariable method.

Results

Fourteen prognostic factors were selected to develop the nomogram. The new nomogram for DSM exhibited good discrimination. Its C‐index of 0.887 surpassed that of the American Joint Committee on Cancer (AJCC) clinical staging (0.794). The C‐index was 0.713 (AJCC, 0.582) for the external validation cohort. The nomogram showed good performance internally and externally, in the calibration and decision curve analysis. Host‐related factors including age and ECOG PS, were strongly correlated with competing risks.

Conclusions

The newly developed nomogram accurately predicts DSM, which can be used for patient counseling in clinical practice.
Lymph node metastases >5 and metastatic lymph node ratio >0.30 of differentiated thyroid cancer predict response to radioactive iodine
Authors: Yun Canhua , Xiao Juan , Cao Jingjia , Shao Chunchun , Wang Lihua , Zhang Wei , Jia Hongying
Published: October 2021

Purpose

The study was designed to elucidate the predictive value of the number of lymph node metastases (LNMs) and lymph node ratio (LNR) for response to therapy restratification system (RTRS).

Methods

From December 2015 to December 2019, 1228 patients who accepted radioactive iodine (RAI) were collected in the study. After 6–8 months, response to RAI was evaluated as complete response (excellent response) and incomplete response (indeterminate, biochemical, and structural incomplete response). The study developed classification tree to determine the optimum LNMs and LNR that predicted response to RAI. Multivariate logistic regression analyses were further analyzed to find independent factors of response to RAI.

Result

The mean age of patients was 44 ± 12 and 71.09% (873/1228) were females. The best cutoff value of LNMs to affect RAI treatment response determined by classification tree was 5. Further in 388 patients with LNMs >5, the best cutoff value of LNR to affect RAI treatment response determined by classification tree was 0.30. With multivariate analysis, the study found that LNMs (>5), gender, lymph node dissection, and American Thyroid Association (ATA) risk classification were independent predictors of response to RAI for all 1228 patients; and LNR (>0.30), gender, and ATA risk classification for 388 patients with LNMs >5. The sensitivity analysis indicated that whether patients with LNM or not were included, the multivariate logistic regression model was kept stable. On subgroup analysis, no significant interactions were observed between the effect of LNMs/LNR and gender, N stage, ATA risk classification, lymph node dissection, or T stage.

Conclusions

With classification tree, the study found that LNMs and LNR could predict initial response to RAI, and their optimal cutoff values were 5 and 0.30, separately.
Recombinant activated factor VII in a patient with intracranial hemorrhage and severe thrombocytopenia
Authors: Ansari Amir M. , Khorasanchi Adam , Faghihimehr Armaghan , Toor Amir
Published: October 2021

Hemorrhage in patients with hematologic malignancies is often difficult to manage as many of these patients also have coagulopathy and thrombocytopenia of varying severity. Recombinant factor VIIa is a FDA‐approved agent for management of bleeding in hemophilia patients with inhibitors. Use of recombinant FVIIa has also been used as a last resort in various clinical settings such as trauma, alveolar hemorrhage, gastrointestinal bleeding, and intracranial hemorrhage for control of bleeding with variable outcomes. This paper presents a case of recombinant FVIIa administration in a patient with multiple myeloma and profound transfusion refractory thrombocytopenia suffering from traumatic subdural hematoma.
Lidocaine‐induced systemic toxicity complicating radiofrequency ablation of benign thyroid nodule procedure: A case report and review of literature
Authors: Nguyen Van Bang , Nguyen Van Vy Hau , Tuyen Linh Pham Nguyen , Le Chi Van
Published: October 2021

The systemic toxicity of lidocaine is an extremely rare complication of thyroid RFA procedure, and it can be life‐threatening. The quick recognization of its symptoms and intravenous use of lipid emulsion are essential to preventing mortality.
Systemic lupus erythematous as an unusual cause of intussusception in Sudanese woman: A case report
Authors: Salih Mohammadeen Salwa Dafa Allah , F. Eldow Ahmed Amar , Abdelmutalib Mohamed Rania Eisa , Osman Hamza Sara Galal , Mohammed Elagib Elnour , H. Awadalla Huyam , Hassan Abubkar , Ahmed Abdelkareem A. , Adam Essa Mohammed Elmujtba
Published: October 2021

Abdominal pain does have a wide differential diagnosis, however, gastrointestinal involvement is not unusual in SLE, and this report is to describe an unusual case of intussusception due to SLE in a Sudanese woman.
Buried bumper syndrome: A late complication of PEG tube insertion
Authors: Mohamad Ali Norliana Dalila , Johari Bushra , Mohd Aripin Yahya
Published: October 2021

The identification of BBS is crucial to avoid serious complications including sepsis and peritonitis. The diagnosis can be made clinically or from endoscopy. The exact site of the migrated PEG internal bumper can be demonstrated on imaging study.
Trichorrhexis invaginata and ichthyosiform erythroderma in netherton syndrome
Authors: Ahmadian Heris Javad , Nouri‐Vaskeh Masoud , Soroureddin Zahra , Noroozi Guilandehi Sama
Published: October 2021

Trichorrhexis invaginata and ichthyosiform erythroderma are pathognomic for Netherton Syndrome.
Was Menschen bewegt, die etwas bewegen
Authors: Subiranas Alba Mena
Published: October 2021

Im Profil: Frau Dr. Alba Mena Subiranas, Vice President Europe Operations Resins & Additives bei BASF und stellvertretende Vorsitzende des VDI‐Fachbereichs GVC03 Betriebsingenieure.
Rising drug cost impacts on cost‐effectiveness of 2 chemotherapy regimens for intermediate‐risk rhabdomyosarcoma: A report from the Children's Oncology Group
Authors: Russell Heidi V. , Chi Yueh‐Yun , Okcu M. Fatih , Bernhardt M. Brooke , Rodriguez‐Galindo Carlos , Gupta Abha A. , Hawkins Douglas S.
Published: October 2021

Background

The Children's Oncology Group clinical trial for intermediate risk rhabdomyosarcoma randomized participants to a combination of vincristine, dactinomycin, and cyclophosphamide (VAC) alone or VAC alternating with vincristine plus irinotecan (VAC/VI). Clinical outcomes were similar, but toxicity profiles differed. This study estimates the cost differences between arms from the health care system's perspective.

Methods

A decision‐analytic model was used to estimate the incremental cost‐effectiveness ratio (ICER) of VAC versus VAC/VI. Protocol‐required or recommended medications and laboratory studies were included. Costs were obtained from national databases or supporting literature and inflated to 2019 US dollars. Demographic and outcome data were obtained from the clinical trial and directed chart reviews. Life‐years (LY) were estimated from life‐expectancy tables and discounted by 3% annually. Probabilistic sensitivity analyses and alternative clinical scenarios identified factors driving costs.

Results

Mean direct medical costs of VAC and VAC/VI were $164,757 and $102,303, respectively. VAC was associated with an additional 0.97 LY and an ICER of $64,386/LY compared with VAC/VI. The ICER was sensitive to survival estimations and to alternative clinical scenarios including outpatient cyclophosphamide delivery (ICER $49,037/LY) or substitution of alternative hematopoietic growth factor schedules (ICER $73,191‐$91,579/LY). Applying drug prices from 2012 decreased the total costs of VAC by 20% and VAC/VI by 15% because of changes in dactinomycin and pegfilgrastim prices.

Conclusions

Neither arm was clearly more cost‐effective. Pharmaceutical pricing and location of treatment drove costs and may inform future treatment decisions. Rising pharmaceutical costs added $30,000 per patient, a finding important for future drug‐pricing policy decisions.

Lay Summary

Two chemotherapy regimens recently tested side‐by‐side for rhabdomyosarcoma had similar tumor outcomes, but different side effects.

The health care costs of each regimen were compared; neither was clearly more cost‐effective.

However, the costs of each treatment changed dramatically with choices of supportive medicines and location of treatment.

Costs of treatment rose by 15% to 20% because of rising US drug costs not associated with the clinical trial.
Impact of including second and later cancers in cause‐specific survival estimates using population‐based registry data
Authors: Forjaz Gonçalo , Howlader Nadia , Scoppa Steve , Johnson Christopher J. , Mariotto Angela B.
Published: October 2021

Background

Second or later primary cancers account for approximately 20% of incident cases in the United States. Currently, cause‐specific survival (CSS) analyses exclude these cancers because the cause of death (COD) classification algorithm was available only for first cancers. The authors added rules for later cancers to the Surveillance, Epidemiology, and End Results cause‐specific death classification algorithm and evaluated CSS to include individuals with prior tumors.

Methods

The authors constructed 2 cohorts: 1) the first ever primary cohort, including patients whose first cancer was diagnosed during 2000 through 2016) and 2) the earliest matching primary cohort, including patients with any cancer who matched the selection criteria irrespective of whether it was the first or a later cancer diagnosed during 2000 through 2016. The cohorts' CSS estimates were compared using follow‐up through December 31, 2017. The new rules were used in the second cohort for patients whose first cancers during 2000 through 2016 were their second or later cancers.

Results

Overall, there were no statistically significant differences in CSS estimates between the 2 cohorts. Estimates were similar by age, stage, race, and time since diagnosis, except for patients with leukemia and those aged 65 to 74 years (3.4 percentage point absolute difference).

Conclusions

The absolute difference in CSS estimates for the first cancer ever cohort versus earliest of any cancers cohort in the study period was small for most cancer types. As the number of newly diagnosed patients with prior cancers increases, the algorithm will make CSS more inclusive and enable estimating survival for a group of patients with cancer for whom life tables are not available or life tables are available but do not capture other‐cause mortality appropriately.
Risk of malignancy associated with diagnostic categories of the proposed World Health Organization International System for Reporting Pancreatobiliary Cytopathology
Authors: Centeno Barbara A.
Published: October 2021

In 2014, the Papanicolaou Society of Cytopathology (PSC) published terminology guidelines for reporting pancreatobiliary cytology. Recently, a group of international experts convened to update the PSC system for reporting pancreatobiliary cytology. The proposed new system will be named the World Health Organization (WHO) International System. This study retrospectively assesses the risk of malignancy in a previously studied cohort of patients using the proposed WHO International System for reporting pancreatobiliary cytology.
ESL curriculum with a heuristic anchorage: Tokenist discourses and the epistemology of community service education
Authors: Chandrasoma Ranamukalage
Published: October 2021

Community service education (CSE) in developing countries still remains under‐represented in research. Addressing this gap, this article reports a study that investigated a CSE activity at a secondary school in Sri Lanka. The participants of this study comprised 10 English as a second language (ESL) teachers from four secondary schools, 68 Grade 10 students from a secondary school located in a semi‐urban area and the author as participant observer. Based on this qualitative case study in the context of ESL writing pedagogy, the article conceptualises the epistemology of CSE in terms of four dimensions: experiential learning, knowledge/skills application, community participation and critical judgement. It also emphasises the futility of tokenist discourses and suggests that an ESL curriculum needs to have a heuristic orientation in CSE not as a mere extra‐curricular exercise but as a mandatory component of social interaction where mutually constitutive benefits for students, teachers and the community are foregrounded. This article highlights how the student writer participants in this study were disadvantaged as a result of tokenist discourses and their teachers demoralised due to an inadequate grasp of the epistemology of CSE, curricular deficiencies, politically driven constraints and poorly resourced classrooms.
Behavioral reinforcement of pathological exercise in anorexia nervosa
Authors: Coniglio Kathryn A. , Cooper Marita , Selby Edward A.
Published: October 2021

Pathological exercise in anorexia nervosa (AN) is a harmful behavior associated with a chronic course and poor prognosis. To date, no comprehensive theoretical model exists to describe pathological exercise in the context of AN, and as such, few treatments are effective at promoting direct and sustained pathological exercise extinction. Using a framework put forth by Wise & Koob (2014), debating the relative importance of positive and negative reinforcement in substance use, we present three hypotheses of behavioral reinforcement of exercise, encompassing biological, psychological, and environmental influences. Specifically, we argue that exercise is positively reinforced through receipt of biological and behavioral rewards, negatively reinforced through avoidance of aversive emotions, and that these two systems work in tandem over time to engrain pathological exercise as a habit. We then present suggestions for testing each of these hypotheses as future directions for the field.