bluuebunny/crossref_metadata_2025 huggingface dataset:
Analyzing the Potential of Feature Groups for Misinformation Detection in WhatsApp
Authors: Angeli Patrick De , Reis Julio C. S.
Published: October 2022

The new mass media (e.g., social networks, and instant messaging applications) have drastically changed how users generate, propagate, and consume information. Given this scenario, an emerging problem is the abuse of these platforms for the propagation of disinformation that, consequently, affects the credibility of the news ecosystem in these environments. The dissemination of misinformation on these platforms has become a worldwide phenomenon, and scalable strategies to contain or mitigate the problem are scarce. Thus, using automated approaches to detect disinformation on digital media can help journalists and fact-check teams identify content that needs to be verified. In this context, in this work, we investigate the potential of feature groups for automatic misinformation detection shared on digital platforms. Our results reveal that using a set of features from some groups, can be useful to build models with satisfactory performance, which can make the application of the model viable in a practical scenario.
NextGISSA, um Sistema Inteligente para Monitoramento e Predição de Hipertensão Arterial em uma Plataforma de Saúde Digital
Authors: Junior Francisco , Quintino Joyce , Freitas Renato , Monteiro Odorico , Cristina Ivana , Oliveira Mauro
Published: October 2022

This paper presents NextGISSA, an intelligent system for the prediction of Arterial Hypertension (AH) by monitoring the patient's vital signs, clinical history and contextual information in real time. A wearable device (smartwatch) is used to collect the patient's vital signs, and for the context of AH prediction, possible intelligent solutions that meet clinical requirements are investigated, such as the classic Machine Learning algorithm supported by ontologies in helping the cognitive processes developed in decision making. It was concluded that NextGISSA responds to the scarcity of studies with a practical proposition that bring together IoT and intelligent systems aimed at hypertensive patients.
Uma ferramenta para a customização de ambientes virtuais para práticas de Orientação e Mobilidade
Authors: M. Júnior José Martônio L. de , Araújo Mariana da C. Carneiro , Façanha Agebson R. , Viana Windson , Sánchez Jaime
Published: October 2022

People who are blind (PwBs) can encounter barriers when doing tasks that require spatial representation (e.g., discerning the spot they are in, establishing the position of people and objects in a physical space, determining a direction to follow). Orientation and Mobility (O&M) is a special education area in which teachers nurture the development of PwBs’ abilities such as space recognition, self-protection, and mind maps building about their surroundings. Following researchers that include virtual environments in the O&M learning process, this paper brings a report about the research and development of a map editor and a mobile application. Together, these tools allow teachers to model and customize experiences for teaching O&M in indoor locations.
Investigation of Soft Impacts in Elements of Pipe Robots
Authors: RAGULSKIS Kazimieras , SPRUOGIS Bronislovas , BOGDEVIČIUS Marijonas , MATULIAUSKAS Arvydas , MIŠTINAS Vygantas , RAGULSKIS Liutauras
Published: October 2022

Vibrators with deformable impact support under harmonic excitation are especially useful in the case when their stationary regimes of motion are stable. This is useful in practice by applying those vibrators to single direction manipulators and various robots of space type.

For practical application it is necessary to reveal dynamical qualities of the system from where it would be possible to determine optimal regimes. For this purpose investigations of dynamics of the system by numerical methods were performed.

Investigation of dynamics of impact interactions in elements of robots is an important engineering problem. Dynamics of soft impacts in elements of manipulators and robots is investigated. The model of the investigated system is described. Numerical investigations for various parameters of the system are performed. Free and forced vibrations are investigated.

From the presented results it can be noted that for the smaller values of the coefficient of stiffness of the support period of steady state motion coincides with the period of the exciting force, while for the higher values of the coefficient of stiffness of the support period of steady state motion is equal to two periods of the exciting force. Thus it is concluded that with the increase of the coefficient of stiffness of the support behavior of the investigated vibro impact system with soft impacts experiences essential changes.

Main characteristics of steady state motion as functions of frequency of excitation are investigated. From the presented results the minimum and maximum inter impact intervals as functions of frequency of excitation, minimum and maximum velocities before impact as functions of frequency of excitation, minimum and maximum minimum displacements in inter impact intervals as functions of frequency of excitation are seen. Three resonant zones of expected single valued motions are observed in the presented results. They correspond to optimal regions of operation of the vibro impact system with soft impacts.

Results of the performed analysis of dynamic interactions with soft impacts in the elements of manipulators and robots are used in the process of design of pipe robots of advanced type.
Antifungal Activity of Propolis against Candida Species: Propolis and Antifungal Action
Authors: Kucukates Emine
Published: October 2022

Candida species live as commensal in humans and cause candidiasis in the presence of some predisposing factors. They are the most common among systemic mycosis agents. Currently, existing drugs used in the treatment of Candida infections may develop resistance, especially azole group compounds, and may lead to serious side effects and problems that may occur in therapy. Therefore, alternative natural treatment methods with very low side effects or no side effects should be considered. Propolis is one of the most natural products which has been used as a natural drug in traditional medicine for the treatment of various diseases for thousands of years. Propolis is a sticky resinous substance collected and deposited by bees from plant buds, leaves, and stems. Propolis has a wide spectrum of biological activities such as antibacterial, antifungal, antiviral, antiparasitic, anti-inflammatory, immunomodulatory, and antioxidant. The compounds responsible for the biological activity of propolis are thought to be flavonoids, caffeic acid and esters, phenolic compounds, aromatic acid and esters. In this chapter, I aimed to investigate the antifungal activity of propolis against Candida species. Considering the safety, low cost, and usefulness of propolis, it should be considered as an alternative natural treatment method.
The Acceleration of Digital Maturity during the COVID-19 Pandemic in the Retail Industry in Sri Lanka
Authors: Hemachandra Sankhani , Sharkasi Nora
Published: October 2022

The recent saying is that COVID-19 pandemic had the most exerted influence in the world after the Second World War. Developing countries, such as Sri Lanka, are no exception. The pandemic brought various digital initiatives to cope with limitations that lead to a much-accelerated digital transformation. The retail sector continued to undergo digital transformation in Sri Lanka with a particular focus on advancing the customer experience by digitally creating, delivering, and capturing value. We interviewed top management in various areas in the retail industry in Sri Lanka and followed a hybrid research methodology for analysis combining the grounded theory and the framework-based approach. We described the gap between the focus of the literature’s digital maturity models in the past 10 years and the top management’s needs throughout the accelerated digital transformation during the pandemic as follows: the difference in the percentage of the expression of common dimensions in digital transformation and maturity models and the percentage of the expression of dimensions in the managers’ interviews. Our findings call for the attention of academic research to dedicate more attention to further integrate more dimensions related to technology, cloud and data, digital marketing, and products into the digital transformation and maturity models.
Fused Pyridine Derivatives: Synthesis and Biological Activities
Authors: Istanbullu Huseyin , Bayraktar Gulsah , Saylam Merve
Published: October 2022

Five-membered heteroaromatic ring fused pyridine derivatives are of increasing interest in drug design and medicinal chemistry. The structural similarity of many drugs (especially antiviral and anticancer ones) with DNA bases such as adenine and guanine is a key factor to explain their effectiveness. Apart from these, it is also found in the structures of substances with antituberculosis, antibacterial, antifungal, anti-inflammatory, and antimalarial activities. Another advantage of this group of compounds is their positive contribution to solubility, polarity, lipophilicity, and hydrogen bonding capacity properties of the compounds they are incorporated into. In this chapter, various bioactivities of fused pyridine derivatives will be categorized and summarized.
The State and the Coronavirus Pandemic: Missed Opportunities for Social and Economic Progress
Authors: Vaslavskiy Yan , Vaslavskaya Irina , Bilyalova Albina
Published: October 2022

The unique feature of the problem field studied is linked to the fact that during the COVID-19 pandemic representatives of almost all societies witnessed failures of the state. These failures included lockdowns and social distancing in the first stage of the pandemic as well as the fast growth of the number of infected and lethal cases in the second stage. This chapter shows that waves of the pandemic which followed each other accompanied by the inability of the countries to prevent them aggravated the problems of economic growth and social instability. The chapter proves that the coronavirus pandemic unveiled the state’s failures both in economic and social policies. The deepening societal crisis caused by citizens’ impoverishment, unemployment growth and absence of a clear perspective of when the pandemic would end and the new post-COVID reality would take shape, made theorists and practitioners return to the phenomenon of the modern state which seemed unexplored by the early 2020s. The author proposed a theoretical basis for prioritizing the functions of the state, which assumes that two of the three groups of state functions related to the distribution of resources and economic stabilization mutually determine each other, albeit with a certain amount of contradictions.
Upsurge of Online Shopping in Malaysia during COVID-19 Pandemic
Authors: Moorthy Krishna , Nian Ci Te , Amalina Kamarudin Aufa , S. Govindarajo Normala , Chun Ting Loh
Published: October 2022

The aim of this study is to assess the factors, perceived usefulness (PU), perceived ease of use (PEOU), subjective norms (SN), perceived risk (PR) and situational influences (SI)) that influence the consumers’ behavioral intention to use online shopping during the Coronavirus time. This research has adopted the Technology Acceptance Model (TAM) as its theoretical base. This research is a quantitative research wherein data were collected through online questionnaire using convenience sampling method. A total of 203 valid samples were collected from Malaysian respondents from selected States. Then, single and multiple linear regression analysis were conducted to test the hypotheses. The results concluded that perceived usefulness, perceived ease of use and situational influences have significant influence on Malaysian consumers’ behavioral intention to adopt online shopping during pandemic times. However, subjective norms and perceived risk have showed an insignificant relationship with consumers’ behavioral intention. The findings have implications for Malaysian government and SME companies in Malaysia in promoting online business.
Splitting the (In)Difference
Authors: Dorst Chris , Dorst Kevin ,   Philosophy Documentation Center
Published: October 2022

Given the laws of our universe, the initial conditions and cosmological constants had to be “fine-tuned” to result in life. Is this evidence for design? We argue that we should be uncertain whether an ideal agent would take it to be so—but that given such uncertainty, we should react to fine-tuning by boosting our confidence in design. The degree to which we should do so depends on our credences in controversial metaphysical issues.
Agenda-Setting invertida: Ciudadanía juvenil (in)formada en redes sociales
Authors: Prejo-Cuéllar Macarena , Vizcaíno-Verdú Arantxa , De-Casas-Moreno Patricia
Published: October 2022

La convergencia digital y la plataformización han transformado los procesos tradicionales de interacción en medios de comunicación. Con jóvenes prosumidores cada vez más activos en redes sociales, la conformación del modelo convencional de agenda mediática ha experimentado alteraciones bajo una supuesta brecha entre la fijación de noticias y contenidos informativos. Este estudio trata de comprender si las redes sociales contribuyen a la ruptura de la Agenda-Setting convencional por otra práctica juvenil informal, paralela e inversa. Para dar respuesta a este planteamiento, se realizaron entrevistas en profundidad a jóvenes españoles, cuyas perspectivas facilitaron, mediante un proceso analítico inductivo-abductivo, la identificación de 21 códigos. Los resultados mostraron una preocupación juvenil por los modos en que se seleccionan y difunden actualmente las noticias en medios convencionales y digitales, con reflexiones morales sobre sus oportunidades e inconvenientes. Este segmento poblacional, considerado tradicionalmente vulnerable ante la influencia de los productos informativos, aboga por una Agenda-Setting invertida, construida sobre la base de la pluralidad ciudadana en la que se amplíe la información que, actualmente, ya se propaga fugazmente por las redes sociales en contenidos que se extienden en escasos minutos.
Correlation of preparation conditions of SrRuO3 ultrathin films with topological Hall effect
Authors: Zhang Jing-Xian , Bao Ming-Rui , Ye Fei , Liu Jia , Cheng Long , Zhai Xiao-Fang ,   Department of Materials Science and Engineering, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China,   School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China
Published: October 2022

As one of the magnetic transition metal oxides, SrRuO3 (SRO) has received much attention in recent years, which is mainly due to its unique itinerate ferromagnetism and the unusual electrical transport properties–behaving as Fermi liquid at low temperature and bad metal at high temperature. In the growth of SRO thin films, there are many factors that can affect the quality of thin films. In this work, we study various factors affecting the growth and quality of SRO thin films by using laser molecular beam epitaxy (laser MBE), including laser energy density, substrate temperature and target surface conditions, and explore their influences on the topological Hall effect (THE) in SRO. For thin films grown at high laser energy density and high temperature, we found that there are large trenches at the edge of steps, which deteriorate the transport properties of the thin films. When using low laser energy density, extra SrO may exist in the films, which also suppresses the conductivity. Films grown at low temperature tend to have poor crystallinity while films grown at high temperature exhibit island structures. The ablation degree of the target surface increases the decomposition of SRO to SrO, Ru and volatile RuO4, resulting in Ru defects in the grown thin film. The SRO thin film grown under the optimal conditions (1.75 J·cm–2, 670 ℃, fresh target surface) exhibits the optimal conductivity and the strongest THE. For non-optimal growth conditions that favors thickness inhomogeneity or Ru defects in the film, THE becomes weaker or even disappears. Therefore, we believe that the THE is due to the Dzyaloshinskii-Moriya interaction (DMI) resulting from the interfacial inversion asymmetry and the associated chiral spin structures.
KAT2-mediated acetylation switches the mode of PALB2 chromatin association to safeguard genome integrity
Authors: Fournier Marjorie , Rodrigue Amélie , Milano Larissa , Bleuyard Jean-Yves , Couturier Anthony M , Wall Jacob , Ellins Jessica , Hester Svenja , Smerdon Stephen J , Tora László , Masson Jean-Yves , Esashi Fumiko
Published: October 2022

The tumour suppressor PALB2 stimulates RAD51-mediated homologous recombination (HR) repair of DNA damage, whilst its steady-state association with active genes protects these loci from replication stress. Here, we report that the lysine acetyltransferases 2A and 2B (KAT2A/2B, also called GCN5/PCAF), two well-known transcriptional regulators, acetylate a cluster of seven lysine residues (7K-patch) within the PALB2 chromatin association motif (ChAM) and, in this way, regulate context-dependent PALB2 binding to chromatin. In unperturbed cells, the 7K-patch is targeted for KAT2A/2B-mediated acetylation, which in turn enhances the direct association of PALB2 with nucleosomes. Importantly, DNA damage triggers a rapid deacetylation of ChAM and increases the overall mobility of PALB2. Distinct missense mutations of the 7K-patch render the mode of PALB2 chromatin binding, making it either unstably chromatin-bound (7Q) or randomly bound with a reduced capacity for mobilisation (7R). Significantly, both of these mutations confer a deficiency in RAD51 foci formation and increase DNA damage in S phase, leading to the reduction of overall cell survival. Thus, our study reveals that acetylation of the ChAM 7K-patch acts as a molecular switch to enable dynamic PALB2 shuttling for HR repair while protecting active genes during DNA replication.
An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice
Authors: Singh Sudhuman , Wilson Torri D , Valdivia Spring , Benowitz Barbara , Chaudhry Sarah , Ma Jun , Adke Anisha P , Soler-Cedeño Omar , Velasquez Daniela , Penzo Mario A , Carrasquillo Yarimar
Published: October 2022

Central amygdala neurons expressing protein kinase C-delta (CeA-PKCδ) are sensitized following nerve injury and promote pain-related responses in mice. The neural circuits underlying modulation of pain-related behaviors by CeA-PKCδ neurons, however, remain unknown. In this study, we identified a neural circuit that originates in CeA-PKCδ neurons and terminates in the ventral region of the zona incerta (ZI), a subthalamic structure previously linked to pain processing. Behavioral experiments show that chemogenetic inhibition of GABAergic ZI neurons induced bilateral hypersensitivity in uninjured mice and contralateral hypersensitivity after nerve injury. In contrast, chemogenetic activation of GABAergic ZI neurons reversed nerve injury-induced hypersensitivity. Optogenetic manipulations of CeA-PKCδ axonal terminals in the ZI further showed that inhibition of this pathway reduces nerve injury-induced hypersensitivity whereas activation of the pathway produces hypersensitivity in the uninjured paws. Altogether, our results identify a novel nociceptive inhibitory efferent pathway from CeA-PKCδ neurons to the ZI that bidirectionally modulates pain-related behaviors in mice.
Who is in the sample? An analysis of real and surrogate users as participants in user study research in the information technology fields
Authors: Salminen Joni , Jung Soon-gyo , Kamel Ahmed , Froneman Willemien , Jansen Bernard J.
Published: October 2022

Background

Constructing a sample of real users as participants in user studies is considered by most researchers to be vital for the validity, usefulness, and applicability of research findings. However, how often user studies reported in information technology academic literature sample real users or surrogate users is unknown. Therefore, it is uncertain whether or not the use of surrogate users in place of real users is a widespread problem within user study practice.

Objective

To determine how often user studies reported in peer-reviewed information technology literature sample real users or surrogate users as participants.

Method

We analyzed 725 user studies reported in 628 peer-reviewed articles published from 2013 through 2021 in 233 unique conference and journal outlets, retrieved from the ACM Digital Library, IEEE Xplore, and Web of Science archives. To study the sample selection choices, we categorized each study as generic (i.e., users are from the general population) or targeted (i.e., users are from a specific subpopulation), and the sampled study participants as real users (i.e., from the study population) or surrogate users (i.e., other than real users).

Results

Our analysis of all 725 user studies shows that roughly two-thirds (75.4%) sampled real users. However, of the targeted studies, only around half (58.4%) sampled real users. Of the targeted studies sampling surrogate users, the majority (69.7%) used students, around one-in-four (23.6%) sampled through crowdsourcing, and the remaining 6.7% of studies used researchers or did not specify who the participants were.

Conclusions

Key findings are as follows: (a) the state of sampling real users in information technology research has substantial room for improvement for targeted studies; (b) researchers often do not explicitly characterize their study participants in adequate detail, which is probably the most disconcerting finding; and (c) suggestions are provided for recruiting real users, which may be challenging for researchers.

Implications

The results imply a need for standard guidelines for reporting the types of users sampled for a user study. We provide a template for reporting user study sampling with examples.
Computational study of potential inhibitors for fat mass and obesity-associated protein from seaweed and plant compounds
Authors: Prabhakar Lavanya , Davis G Dicky John
Published: October 2022

Background

Over the past three decades, with substantial changes in lifestyle, the tendency to gain weight has increased, which is resulting in significant consequences affecting an individual’s well-being. The fat mass and obesity-associated (FTO) gene is involved in food intake and energy expenditure and plays a crucial role in regulating homeostasis and controlling energy expenditure by hindering signals that generate from the brain. Edible seaweeds have been shown to enhance satiety owing to their health benefits.

Methods

Extensive screening of plant-derived anti-obesity compounds and seaweed compounds was conducted and validated for ADME properties and toxicity prediction. Further, the top ranked compounds were docked against the FTO protein to identify potential inhibitors and were subjected to molecular dynamic simulation studies to understand the binding stability of ligand protein complex. Finally, MM/PBSA studies were performed to calculate the binding free energy of the protein-ligand complexes.

Results

Through the virtual screening of 1,210 compounds, 443 compounds showed good docking scores less than −7.00 kcal/mol. Drug likeness screenings of 443 compounds showed that only 369 compounds were in accordance with these properties. Further toxicity prediction resulted in 30 non-toxic compounds. Molecular docking studies revealed four top ranked marine compounds. Finally, RL074 (2-hydroxyluzofuranone B) and RL442 (10-acetoxyangasiol) from marine red alga Laurencia sp showed good stability from molecular dynamic simulation studies. MM/PBSA results revealed that BT012 (24ε-hydroperoxy-6β-hydroxy-24-ethylcholesta-4,-28(29)-dien-3-one), an oxygenated fucosterol from brown alga Turbinaria conoides, possessed higher binding energy. Hence, with all the data obtained it could be concluded that three seaweed compounds, BT012, RL074 and RL442, may act as a potential anti-obesity lead compound in targeting FTO.
Ultrasound Guided versus Peripheral Nerve Stimulator Guided Transversus Abdominis Plane Block for Postoperative Analgesia in Patients Undergoing Laparoscopic Cholecystectomy: A Randomised Clinical Study
Authors: Prajapati Kapil , Patel Kuldeep Kumar , Baghel Hansraj , Prakash Ravi , Singh Alok Pratap
Published: October 2022

Introduction: The Transversus Abdominis Plane (TAP) block is a relatively simple technique that provides analgesia that, as part of a multimodal analgesic treatment, may be useful in the prevention of postoperative pain. Ultrasound (USG) versus Peripheral Nerve Stimulator (PNS) guided TAP blocks are being frequently given postoperatively for pain these days in laparoscopic cholecystectomy. Aim: To assess the analgesic efficacy of USG guided and PNS guided transversus abdominis plane block in patients undergoing laparoscopic cholecystectomy. Materials and Methods: The randomised clinical study was conducted in the Department of Anaesthesiology, Shyam Shah Medical College, Rewa, Madhya Pradesh, India, from March 2020 to June 2021. Ninety adult patients were enrolled and randomly allocated into three groups. Group 1 (n=30) received bilateral USG-guided TAP block with 20 mL of 0.375% ropivacaine along with standard postoperative analgesia regimen. Group 2 (n=30) received bilateral PNS-guided TAP block with 20 mL 0.375% ropivacaine along with standard postoperative analgesia regimen. Group 3 (Control) (n=30) received standard postoperative analgesia regimen consisting of inj. paracetamol iv 1 gm (6 hourly) and inj. diclofenac 75 mg i.v. (12 hourly). Each patient was assessed for VAS score, duration of analgesia, total analgesic consumption and patient satisfaction for 24 hours postoperatively. Results: The average mean VAS score in first 24 hrs was 2.04±0.80 in group 1, 2.10±0.70 in group 2 and 3.18±0.63 in group 3. The duration of analgesia was least in group 3 (5.8±2.31 hrs) followed by group 2 (9.67±2.47 hrs) and maximum in group 1 (11.87±2.97 hrs). The total tramadol requirement in first 24 hrs postoperatively was 126.67±44.98 mg in group 1, 140±62.15 mg in group 2 and 226.67±63.97 mg in group 3. Conclusion: Postoperative analgesia with USG and PNS guided TAP block enables better pain control and less analgesic consumption. PNS guided TAP block is good alternative when compared with control for postoperative analgesia when USG machine is not available.
Effect of a Novel Brief Motivational Intervention for Alcohol-Intoxicated Young Adults in the Emergency Department
Authors: Gaume Jacques , Bertholet Nicolas , McCambridge Jim , Magill Molly , Adam Angéline , Hugli Olivier , Daeppen Jean-Bernard
Published: October 2022

Importance

Heavy drinking among young adults is a major public health concern. Brief motivational interventions in the emergency department have shown promising but inconsistent results.

Objective

To test whether young adults receiving a newly developed brief motivational intervention reduce their number of heavy drinking days and alcohol-related problems over 1 year compared with participants receiving brief advice.

Design, Setting, and Participants

This randomized clinical trial was conducted at an emergency department of a tertiary care university hospital in Lausanne, Switzerland. Recruitment ran from December 2016 to August 2019. Follow-up was conducted after 1, 3, 6, and 12 months. All adults aged 18 to 35 years presenting for any cause and presenting with alcohol intoxication were eligible (N = 2108); 1764 were excluded or refused participation. Follow-up rate was 79% at 12 months and 89% of participants provided follow-up data at least once and were included in the primary analyses. Statistical analysis was performed from September 2020 to January 2021.

Interventions

The novel intervention was based on motivational interviewing and comprised in-person discussion in the emergency department and up to 3 booster telephone calls. The control group received brief advice.

Main Outcomes and Measures

Primary outcomes were the number of heavy drinking days (at least 60 g of ethanol) over the previous month and the total score on the Short Inventory of Problems (0-45, higher scores indicating more problems) over the previous 3 months. Hypotheses tested were formulated before data collection.

Results

There were 344 young adults included (median [IQR] age: 23 [20-28] years; 84 women [24.4%]). Among the 306 participants providing at least 1 follow-up point, a statistically significant time × group interaction was observed (β = −0.03; 95% CI, −0.05 to 0.00;P = .02), and simple slopes indicated an increase of heavy drinking days over time in the control (β = 0.04; 95% CI, 0.02 to 0.05;P < .001) but not in the intervention group (β = 0.01; 95% CI, −0.01 to 0.03;P = .24). There was no effect on the Short Inventory of Problems score (β = −0.01; 95% CI, −0.03 to 0.02;P = .71).

Conclusions and Relevance

This randomized clinical trial found that a brief motivational intervention implemented in the emergency department provided beneficial effects on heavy drinking, which accounts for a substantial portion of mortality and disease burden among young adults.

Trial Registration

ISRCTN registry:13832949
Analysis of US County Characteristics and Clinicians With Waivers to Prescribe Buprenorphine After Changes in Federal Education Requirements
Authors: Nguyen Thuy , Andraka-Christou Barbara , Arnaudo Camila , Bradford W. David , Simon Kosali , Spetz Joanne
Published: October 2022

This cross-sectional study investigates the growth in the number of clinicians in the US who obtained waivers for prescribing buprenorphine after the elimination of federal educational requirements.
Perspectives of Historically Black College and University Advisors to Premedical Students During the COVID-19 Pandemic
Authors: Weiss Jasmine , Holaday Louisa , Keene Danya , Akingbesote Ngozi D. , Balasuriya Lilanthi , Sharifi Mona , Latimore Darin , Genao Inginia
Published: October 2022

Importance

Black students remain underrepresented in medicine despite national efforts to increase diversity in the physician workforce. Historically Black College and University (HBCU) students play a vital role in increasing representation in the workforce. Currently, there is a paucity of literature understanding the impact of COVID-19 on premedical students from HBCUs. Understanding the adverse impact of the pandemic on HBCU students is essential to inform strategies that promote holistic medical school admissions and increased diversity, equity, and inclusion in the medical workforce.

Objective

To explore premedical advisors' perspectives on the impact of the COVID-19 pandemic on HBCU premedical students pursuing admission to medical school.

Design, Setting, and Participants

In this qualitative study, semistructured interviews of HBCU premedical advisors were performed from March 2020 to March 2021. One-on-one interviews were conducted with 21 advisors with a depth of experience as advisors, varied educational backgrounds, and diverse geographic representation. Data analysis was performed from March 2021 to December 2021.

Main Outcomes and Measures

The experiences of HBCU premedical students during the COVID-19 pandemic from the perspective of the premedical advisor.

Results

Among the 21 participants, 13 (62%) were female, 15 (71%) were Black or African American, 11 (52%) had a doctorate degree, and 7 (33%) had more than 10 years of experience as advisors. Participants described 3 major themes: (1) balancing academic responsibilities with family demands; (2) distraction, disruption, and isolation in the virtual learning environment; and (3) harmful impact of new stressors for HBCU applicants in the medical school admissions process.

Conclusions and Relevance

In this qualitative study of HBCU advisors to premedical students, advisors described how the COVID-19 pandemic adversely affected undergraduate HBCU premedical students; students faced family hardships, challenges with virtual learning, and uncertainty in the medical school admissions process. These findings suggest that medical schools should continue to create direct interventions to address the challenges that HBCU students faced during the height of the pandemic and as longitudinal consequences of the pandemic. Addressing these issues may improve physician workforce representation and promote more equitable patient care for underserved communities disproportionately affected by COVID-19 and other health disparities.
Cancer Stem Cells
Authors: Bushnell Grace G. , Brooks Michael D. , Wicha Max S.
Published: October 2022

Overview

There is substantial evidence that many, if not most, tumors contain a subpopulation of cells that display stem cell properties. These “cancer stem cells” (CSC) play an important role in tumor initiation and propagation. Furthermore, these cells may mediate metastasis and resistance to cancer therapeutic agents and therefore play a fundamental role in cancer relapse. This highlights the importance of developing therapeutic approaches to target this cell population. In this article, we will review current thoughts on the role of tissue stem cells in carcinogenesis and the pathways that regulate the plasticity and heterogeneity of these cells. We will then review clinical implications of CSC in dormancy and metastasis and current efforts to therapeutically target these cells.
Cancer and Cell Death
Authors: Reed John C.
Published: October 2022

Overview

Cell death is a normal facet of human physiology, ensuring tissue homeostasis by offsetting cell production with cell demise. Neoplasms arise in part because of defects in physiological cell death mechanisms, contributing to pathological cell expansion when genetic or epigenetic alternations impart a selective survival advantage to premalignant or malignant cells. Defects in normal cell death pathways also contribute to cancer progression by permitting progressively aberrant cell behaviors, while also desensitizing tumor cells to immune‐mediated attack, radiation, and chemotherapy. Multiple mechanisms have been identified that account for dysregulation of cell death mechanisms in human malignancies, providing insights into cancer pathogenesis and providing targets for therapeutic intervention based on the concept of restoring sensitivity to natural pathways for triggering cell suicide. Moreover, the extensive overlap of components of the cell death machinery with responses to pathogens has been implicated in tumor immunity mechanisms.
Systems Biology and Genomics
Authors: Hassan Saima , Gray Joe W. , Heiser Laura M.
Published: October 2022

Overview

Cancers are complex, adaptive systems comprised of cancer cells that are influenced by supporting cells, immune cells, as well as soluble and insoluble proteins that make up the local physical environment. Features associated with cancer cells are referred to as intrinsic to the cancer and those comprising the proximal and distal microenvironments are referred to as extrinsic to the cancer. Genomics studies seek to develop comprehensive cellular and molecular profiles of cancers while cancer systems biology studies seek to develop the experimental and theoretical methods needed to understand how these diverse components work together to determine cancer function. The overall goal of these efforts is to develop analytical approaches to predict cancer behavior—including progression and response to therapy—from measurements of the intrinsic and extrinsic molecular and cellular components of tumors. Here, we review recent progress in international efforts to measure the genomic, epigenomic, and proteomic features of major tumor types. We summarize work to establish associations between these omic features and cancer behavior including risk of progression and response to therapy. Finally, we summarize the computational and experimental models employed to understand and manipulate the behavior of complex cancer systems.
Ultraviolet Radiation Carcinogenesis
Authors: Cleaver James E. , Ortiz‐Urda Susana , Arron Sarah
Published: October 2022

Overview

Skin carcinogenesis from solar UV exposure is initiated by UV photoproducts formed in the DNA of precursor cells that give rise to squamous cell carcinomas (SCC), basal cell carcinomas (BCC), and cutaneous malignant melanomas (CMM). SCC and BCC are caused by UVB but CMM by reactive oxygen generated through UVA absorption in melanin. The UVB photoproducts consist of dimers between adjacent pyrimidines that are repaired by nucleotide excision repair (NER). Two branches of NER differ in mechanisms of damage recognition: in global genome repair (GGR) damage is recognized in nontranscribed DNA by the DDB2 and XPC proteins; in transcription‐coupled repair (TCR) damage is recognized by arrest of the transcribing RNA polymerase at damaged sites. The T = C photoproduct is the predominant mutagenic product which, if unrepaired, gives rise to C to T or CC to TT mutations through replication by the low fidelity polymerase Pol H. TCR reduces the mutation frequency in regions of transcription. Deficiencies in GGR in the human disease xeroderma pigmentosum cause earlier onset and increased rates of skin cancer. Deficiencies in TCR in the human disease Cockayne syndrome are associated with photosensitivity, developmental and neurological disorders, but no cancer has been reported.
Folate Antagonists
Authors: Gennarini Lisa , Cole Peter D. , Bertino Joseph R.
Published: October 2022

Overview

Folic acid antagonists (antifols) are cytotoxic drugs used as antineoplastic, antimicrobial, anti‐inflammatory, and immune‐suppressive agents. While several folate antagonists have been developed, methotrexate (4‐amino‐4‐deoxy‐10‐
N
‐methyl‐pteroylglutamic acid, MTX) is the antifol with the most extensive history and widest spectrum of use. MTX remains an essential drug in curative chemotherapy regimens used to treat patients with acute lymphoblastic leukemia, osteosarcoma, and choriocarcinoma, and is an important agent in the therapy of patients with lymphoma, breast cancer, bladder cancer, and head and neck cancer. In addition, it is used for patients with nonmalignant diseases such as rheumatoid arthritis, psoriasis, autoimmune diseases, and graft‐versus‐host disease. This article will review the clinical use of and metabolism of MTX and discuss structurally related folate antagonists that have been developed to overcome resistance or have alternate intracellular targets.
Alkylating Agents and Platinum Antitumor Compounds
Authors: Siddik Zahid H.
Published: October 2022

Overview

Alkylating agents and platinum‐based compounds constitute two important classes of antitumor drugs in the war against cancer. These drugs transform spontaneously or metabolically to induce DNA monofunctional adducts and interstrand and intrastrand crosslinks. As a result, the DNA unwinds and/or bends, which are then recognized by specialized DNA damage recognition proteins to induce cell cycle arrest that allows cells time to repair the DNA and survive. If DNA damage is extensive and repair cannot be completed, then cells undergo programmed cell death to result in a positive antitumor response. Since active species in the two drug classes are not tumor‐selective, they will also interact with DNA in normal cells to induce several side effects, some of which can be irreversible and cumulative and, thereby, become life threatening. Another limitation is that tumor cells can become resistance to alkylating and platinating drugs through mechanisms that are either intrinsic or acquired. Such resistance mechanisms are manifested as reduced drug accumulation, increased drug inactivation, increased DNA repair, failure of DNA damage recognition system to recognize the damage, and aberrant apoptotic signal transduction pathways. Therefore, identifications of rational personalized combination therapeutic strategies involving these two potent classes of DNA‐reactive drugs are desperately needed to combat resistance mechanisms and enhance curative responses.
Monoclonal Antibody and Targeted Toxin Therapy
Authors: Bast Robert C. , Zalutsky Michael R.
Published: October 2022

Overview

Monoclonal antibodies have impacted significantly on the care of patients with cancer. Overall, the US FDA has approved 100 different monoclonal antibodies for the treatment of human diseases. More than 40 monoclonal antibodies, cytotoxic drug conjugates, radionuclide conjugates, and targeted toxins have been approved for the treatment of more than two dozen different malignancies. Useful monoclonal antibodies have most frequently targeted structural proteins and receptors on the cancer cell surface (CD20 by rituximab, HER2 by trastuzumab, and pertuzumab), inhibiting growth, inducing apoptosis, and enhancing chemotherapy, but some have targeted cytokines (IL‐6 by siltuximab), growth factors (vascular endothelial growth factor (VEGF) by bevacizumab), and growth factor receptors (VEGFR2 by ramucirumab) that affect both cancer cells and normal stromal cells including endothelial cells and lymphocytes. Monoclonal antibodies have disrupted checkpoint inhibition of effector T lymphocytes by blocking CTLA4 (ipilimumab), PD1 (pembrolizumab, nivolumab, and cemiplimab), and PD‐L1 (atezolizumab, durvalumab, and avelumab). In the case of trastuzumab and pertuzumab, binding of the two antibodies to different sites on the HER2 cell surface receptor has produced greater antitumor activity than either alone. Enhanced cancer cell killing has also been achieved by conjugation of antibodies with cytotoxic drugs (emtansine to anti‐HER2 trastuzumab and vedotin to anti‐CD30 brentuximab) or radionuclide conjugates (
90
Y to anti‐CD20 ibritumomab tiuxetan) permitting effective treatment of patients who had failed therapy with unconjugated antibodies. There are several barriers to effective therapy with monoclonal antibodies including antigen specificity, antigenic modulation, heterogeneity of antigen expression, effective delivery of antibodies to cancer cells, potency of effector mechanisms, and response to immunologically foreign globulin. The latter problem has been circumvented with the use of chimeric constructs, humanization of murine antibodies, and developing genetically engineered mice with the ability to develop fully human antibodies. Use of unconjugated antibodies is likely to improve as our knowledge of tumor biology and immunology grows, identifying targets such as OX‐40 ligand. Use of smaller molecularly engineered binding constructs may improve pharmacokinetics and pharmacodynamics of monoclonal antibody and conjugate therapy. Combinations of antibodies may be required to compensate for antigenic heterogeneity. Development of more effective antibody–drug conjugates will require the identification of monoclonal reagents that target tumor‐initiating stem cells. Use of antibody fragments, pretargeting, and the use of alpha‐emitters are promising approaches to improving antibody–radionuclide conjugates. Development of targeted toxins must be further explored.
Neoplasms of the Thyroid
Authors: Ringel Matthew D.
Published: October 2022

Overview

Thyroid cancer is the most common malignancy of a classical endocrine organ. The most common forms of thyroid cancer derive from follicular thyroid cells, are characterized by cellular and histological patterns (e.g., papillary and follicular thyroid cancer), and are associated with outstanding overall survivorship but a high frequency of disease persistence. Less commonly, thyroid cancers can derive from thyroid neuroendocrine C‐cells (medullary thyroid cancer) that can occur as part of defined genetic syndromes (e.g., multiple endocrine neoplasia type 2). Thyroid cancers can present as or develop into poorly differentiated or dedifferentiated (anaplastic thyroid cancer) that are associated with highly aggressive courses and poor outcomes. Over the past decade, a more individualized approach has been taken for patients with early‐stage thyroid cancer, with reduced emphasis on aggressive surgical approaches, expansion of active surveillance approaches, and reduced use and/or dosing strategies for radioiodine therapy (RAI) using I‐131. RAI, TSH suppression therapy, and for selected local recurrence, reoperation, and external beam radiation therapy remain cornerstones of therapy for patients with progressive or nonremitting forms of thyroid cancer. For those who do not respond to those treatments, or those with specific gene mutations, there has been expansion of options including the use of targeted inhibitors of mutated driver oncogenes in all forms of thyroid cancer, anti‐angiogenic multikinase inhibitors in patients with progressive differentiated thyroid cancers, and immune checkpoint inhibitors.
Cancer of the Lung
Authors: Morgensztern Daniel , Boffa Daniel , Chen Alexander , Dhanasopon Andrew , Goldberg Sarah B. , Decker Roy H. , Devarakonda Siddhartha , Ko Jane P. , Solis Soto Luisa M. , Waqar Saiama N. , Wistuba Ignacio I. , Herbst Roy S.
Published: October 2022

Overview

Lung cancer is the most common cause of death from cancer both worldwide and in the United States. There has been a remarkable progress in the treatment of lung cancer with an increasing number of highly effective targeted therapies and the incorporation of immune checkpoint inhibitors into the standard therapy of non‐small‐cell lung cancer, initially in patients with metastatic disease and more recently in earlier stages. These therapeutic advances in combination with reduced incidence of lung cancer associated with the decreased tobacco smoking have led to a sharp decrease in lung cancer mortality over the past few years.
Thymomas and Thymic Tumors
Authors: Mody Mayur D. , Sica Gabriel L. , Ramalingam Suresh S. , Shin Dong M.
Published: October 2022

Overview

Malignancies of the thymus gland comprise a group of uncommon but heterogeneous diseases with variable clinical behavior. Recent collaborative efforts have helped to create consensus histopathological and staging criteria. Furthermore, developments in molecular and gene signature technology have helped us to better understand the pathogenesis of thymic tumors. Diagnosis and treatment frequently require a multidisciplinary approach, with surgery, radiation, and systemic therapy all having a synergistically important role. While there are several chemotherapy regimens available for first‐line treatment for advanced‐stage or recurrent disease, numerous novel chemotherapeutics, immunotherapeutics, and targeted therapies are being evaluated. In this article, we provide a comprehensive overview of the histopathology, diagnosis, and management of most intriguing tumors.
Neoplasms of the Exocrine Pancreas
Authors: Wolff Robert A. , Li Donghui , Maitra Anirban , Tsai Susan , Koay Eugene , Evans Douglas B.
Published: October 2022

Overview

Pancreatic cancer is largely preventable with healthier lifestyle choices perhaps to include a predominantly plant‐based diet. Currently, about 10% of patients have germline mutations putting them at increased risk for pancreatic cancer. Population‐wide reductions in smoking, obesity, and diabetes will probably increase the proportion of patients with genetically driven disease, expanding the options for precision medicine. Pancreatic cancer is notorious for local invasion and metastatic dissemination and treatment paradigms must account for both. Surgical resection of localized disease provides the only meaningful chance for cure, with improvements in survival seen using both adjuvant and neoadjuvant approaches. Cytotoxic therapy is the mainstay of treatment for locally advanced and metastatic disease. The role of radiation is in evolution. Small subsets of patients are benefiting from precision medicine using targeted treatments and immunotherapy.