bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies
Authors: Liao Minru , Qin Rui , Huang Wei , Zhu Hong-Ping , Peng Fu , Han Bo , Liu Bo
Published: April 2022

Triple-negative breast cancer (TNBC) is a subtype of human breast cancer with one of the worst prognoses, with no targeted therapeutic strategies currently available. Regulated cell death (RCD), also known as programmed cell death (PCD), has been widely reported to have numerous links to the progression and therapy of many types of human cancer. Of note, RCD can be divided into numerous different subroutines, including autophagy-dependent cell death, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis and anoikis. More recently, targeting the subroutines of RCD with small-molecule compounds has been emerging as a promising therapeutic strategy, which has rapidly progressed in the treatment of TNBC. Therefore, in this review, we focus on summarizing the molecular mechanisms of the above-mentioned seven major RCD subroutines related to TNBC and the latest progress of small-molecule compounds targeting different RCD subroutines. Moreover, we further discuss the combined strategies of one drug (e.g., narciclasine) or more drugs (e.g., torin-1 combined with chloroquine) to achieve the therapeutic potential on TNBC by regulating RCD subroutines. More importantly, we demonstrate several small-molecule compounds (e.g., ONC201 and NCT03733119) by targeting the subroutines of RCD in TNBC clinical trials. Taken together, these findings will provide a clue on illuminating more actionable low-hanging-fruit druggable targets and candidate small-molecule drugs for potential RCD-related TNBC therapies.

Graphical abstract
Effects of double vs triple injection on block dynamics for ultrasound-guided intertruncal approach to the supraclavicular brachial plexus block in patients undergoing upper limb arteriovenous access surgery: study protocol for a double-blinded, randomized controlled trial
Authors: Luo Quehua , Liu Huiying , Deng Longjiao , Nong Lidan , Li Haifeng , Cai Yujing , Zheng Junyi , Shu Haihua , Yao Weifeng , Zhang Jianxing
Published: April 2022

Background

Ultrasound-guided intertruncal approach (IA) has been proposed to be an alternative and promising approach to the supraclavicular block (SCB), in which double injection (DI) of local anesthetics (LA) is sequentially administered between intertruncal planes. We would like to apply a refined injection technique, named triple injection (TI) technique, based on the 3 separate compartments visualized by ultrasound. The aim of this study is to compare the percentage of patients with complete sensory blockade at 20 min of DI vs TI technique, when they are applied in patients undergoing upper limb arteriovenous access surgery.

Methods

This study is a prospective parallel-group randomized controlled trial. A total of 86 end-stage renal disease patients will be randomly allocated to receive IA-SCB using either DI or TI technique with identical LA (0.5% ropivacaine 24 mL). The primary outcome is the percentage of patients with complete sensory blockade of all 4 terminal nerves (median, ulnar, radial, and musculocutaneous nerves) of the brachial plexus measured at 20 min after injection. The secondary outcomes will consist of the sensory or motor blockade of all individual nerves, onset times, performance time, diaphragmatic paralysis, surgical anesthesia, and adverse events.

Discussion

It is expected that ultrasound-guided IA-SCB with the TI technique results in better block dynamic in patients undergoing upper limb arteriovenous access surgery.

Trial registration

Chinese Clinical Trial Registry ChiCTR2100045075.
Patient and clinician characteristics and preferences for increasing participation in placebo surgery trials: a scoping review of attributes to inform a discrete choice experiment
Authors: Hinwood Madeleine , Wall Laura , Lang Danielle , Balogh Zsolt J. , Smith Angela , Dowsey Michelle , Clarke Phillip , Choong Peter , Bunzli Samantha , Paolucci Francesco
Published: April 2022

Background

Orthopaedic surgeries include some of the highest volume surgical interventions globally; however, studies have shown that a significant proportion of patients report no clinically meaningful improvement in pain or function after certain procedures. As a result, there is increasing interest in conducting randomised placebo-controlled trials in orthopaedic surgery. However, these frequently fail to reach recruitment targets suggesting a need to improve trial design to encourage participation. The objective of this study was to systematically scope the available evidence on patient and clinician values and preferences which may influence the decision to participate in placebo surgery trial.

Methods

A systematic review was conducted via a literature search in the MEDLINE, Embase, PsycInfo, CINAHL, and EconLit databases as of 19 July 2021, for studies of any design (except commentaries or opinion pieces) based on two key concepts: patient and clinician characteristics, values and preferences, and placebo surgery trials.

Results

Of 3424 initial articles, we retained 18 eligible studies. Characteristics, preferences, values, and attitudes of patients (including levels of pain/function, risk/benefit perception, and altruism) and of clinicians (including concerns regarding patient deception associated with placebo, and experience/training in research) influenced their decisions to participate in placebo-controlled trials. Furthermore, some aspects of trial design, including randomisation procedures, availability of the procedure outside of the trial, and the information and consent procedures used, also influenced decisions to participate.

Conclusion

Participant recruitment is a significant challenge in placebo surgery trials, and individual decisions to participate appear to be sensitive to preferences around treatment. Understanding and quantifying the role patient and clinician preferences may play in surgical trials may contribute to the optimisation of the design and implementation of clinical trials in surgery.
Cross-tissue and generation predictability of relative Wolbachia densities in the mosquito Aedes aegypti
Authors: Mejia Austin J. , Dutra H. L. C. , Jones M. J. , Perera R. , McGraw E. A.
Published: April 2022

Background

The insect endosymbiotic bacterium Wolbachia is being deployed in field populations of the mosquito Aedes aegypti for biological control. This microbe prevents the replication of human disease-causing viruses inside the vector, including dengue, Zika and chikungunya. Relative Wolbachia densities may in part predict the strength of this ‘viral blocking’ effect. Additionally, Wolbachia densities may affect the strength of the reproductive manipulations it induces, including cytoplasmic incompatibility (CI), maternal inheritance rates or induced fitness effects in the insect host. High rates of CI and maternal inheritance and low rates of fitness effects are also key to the successful spreading of Wolbachia through vector populations and its successful use in biocontrol. The factors that control Wolbachia densities are not completely understood.

Methods

We used quantitative PCR-based methods to estimate relative density of the Wolbachia wAlbB strain in both the somatic and reproductive tissues of adult male and female mosquitoes, as well as in eggs. Using correlation analyses, we assessed whether densities in one tissue predict those in others within the same individual, but also across generations.

Results

We found little relationship among the relative Wolbachia densities of different tissues in the same host. The results also show that there was very little relationship between Wolbachia densities in parents and those in offspring, both in the same and different tissues. The one exception was with ovary–egg relationships, where there was a strong positive association. Relative Wolbachia densities in reproductive tissues were always greater than those in the somatic tissues. Additionally, the densities were consistent in females over their lifetime regardless of tissue, whereas they were generally higher and more variable in males, particularly in the testes.

Conclusions

Our results indicate that either stochastic processes or local tissue-based physiologies are more likely factors dictating Wolbachia densities in Ae. aegypti individuals, rather than shared embryonic environments or heritable genetic effects of the mosquito genome. These findings have implications for understanding how relative Wolbachia densities may evolve and/or be maintained over the long term in Ae. aegypti.

Graphical Abstract
Giant parathyroid adenoma: a case report
Authors: Mahmodlou Rahim , Sedokani Amin , Pezeshk Apameh , Najafinejad Bita
Published: April 2022

Background

Giant parathyroid adenoma is a type of parathyroid adenoma weighing > 3.5 g and having a size of more than 2 cm.

Case presentation

This report describes giant primary parathyroid adenoma with reference to the literature. We report the case of a 48-year-old Persian man referred to the clinic with knee and lower back pain. He had a history of mitral valve replacement and several episodes of bilateral nephrolithiasis. After a thorough assessment, a neck mass with a possible thyroid origin was detected, but further assessment showed it was of parathyroid origin. The resected mass was 9 × 6× 4 cm and weighed 122 g, and histopathology showed a giant parathyroid adenoma.

Conclusion

Giant parathyroid adenomas that weigh more than 110 g and are larger than 8 cm can lead to significant hypercalcemia. Despite giant parathyroid adenomas and high parathyroid hormone levels, a calcium crisis may not always occur in these patients, and the masses may be initially misdiagnosed as a thyroid mass.
Treatment of male and female spontaneously hypertensive rats with TNF-α inhibitor etanercept increases markers of renal injury independent of an effect on blood pressure
Authors: Snyder Elizabeth C. , Abdelbary Mahmoud , El-Marakby Ahmed , Sullivan Jennifer C.
Published: April 2022

Hypertension remains the leading risk factor for cardiovascular disease. Young females tend to be protected from hypertension compared with age-matched males. Although it has become increasingly clear that the immune system plays a key role in the development of hypertension in both sexes, few studies have examined how cytokines mediate hypertension in males versus females. We previously published that there are sex differences in the levels of the cytokine tumor necrosis factor (TNF)-α in spontaneously hypertensive rats (SHR). The goal of this study was to test the hypothesis that TNF-α inhibition with etanercept will lower BP in male and female SHR. However, as male SHR have a more pro-inflammatory status than female SHR, we further hypothesize that males will have a greater decrease in BP with TNF-α inhibition than females. Young adult male and female SHR were administered increasing doses of the TNF-α inhibitor etanercept or vehicle twice weekly for 31 days and BP was continuously measured via telemetry. Following treatment, kidneys and urine were collected and analyzed for markers of inflammation and injury. Despite significantly decreasing renal TNF-α levels, renal phospho-NFκB and urinary MCP-1 excretion, etanercept did not alter BP in either male or female SHR. Interestingly, treatment with etanercept increased urinary excretion of protein, creatinine and KIM-1 in both sexes. These results indicate that TNF-α does not contribute to sex differences in BP in SHR but may be vital in the maintenance of renal health.
Endurance exercise attenuates juvenile irradiation-induced skeletal muscle functional decline and mitochondrial stress
Authors: O’Connor Thomas N. , Kallenbach Jacob G. , Orciuoli Haley M. , Paris Nicole D. , Bachman John F. , Johnston Carl J. , Hernady Eric , Williams Jacqueline P. , Dirksen Robert T. , Chakkalakal Joe V.
Published: April 2022

Background

Radiotherapy is commonly used to treat childhood cancers and can have adverse effects on muscle function, but the underlying mechanisms have yet to be fully elucidated. We hypothesized that endurance exercise following radiation treatment would improve skeletal muscle function.

Methods

We utilized the Small Animal Radiation Research Platform (SARRP) to irradiate juvenile male mice with a clinically relevant fractionated dose of 3× (every other day over 5 days) 8.2 Gy X-ray irradiation locally from the knee to footpad region of the right hindlimb. Mice were then singly housed for 1 month in cages equipped with either locked or free-spinning voluntary running wheels. Ex vivo muscle contractile function, RT-qPCR analyses, resting cytosolic and sarcoplasmic reticulum (SR) store Ca2+ levels, mitochondrial reactive oxygen species levels (MitoSOX), and immunohistochemical and biochemical analyses of muscle samples were conducted to assess the muscle pathology and the relative therapeutic impact of voluntary wheel running (VWR).

Results

Irradiation reduced fast-twitch extensor digitorum longus (EDL) muscle-specific force by 27% compared to that of non-irradiated mice, while VWR post-irradiation improved muscle-specific force by 37%. Radiation treatment similarly reduced slow-twitch soleus muscle-specific force by 14% compared to that of non-irradiated mice, while VWR post-irradiation improved specific force by 18%. We assessed intracellular Ca2+ regulation, oxidative stress, and mitochondrial homeostasis as potential mechanisms of radiation-induced pathology and exercise-mediated rescue. We found a significant reduction in resting cytosolic Ca2+ concentration following irradiation in sedentary mice. Intriguingly, however, SR Ca2+ store content was increased in myofibers from irradiated mice post-VWR compared to mice that remained sedentary. We observed a 73% elevation in the overall protein oxidization in muscle post-irradiation, while VWR reduced protein nitrosylation by 35% and mitochondrial reactive oxygen species (ROS) production by 50%. Finally, we found that VWR significantly increased the expression of PGC1α at both the transcript and protein levels, consistent with an exercise-dependent increase in mitochondrial biogenesis.

Conclusions

Juvenile irradiation stunted muscle development, disrupted proper Ca2+ handling, damaged mitochondria, and increased oxidative and nitrosative stress, paralleling significant deficits in muscle force production. Exercise mitigated aberrant Ca2+ handling, mitochondrial homeostasis, and increased oxidative and nitrosative stress in a manner that correlated with improved skeletal muscle function after radiation.
Mapping groundwater nitrate contaminant risk using the modified DRASTIC model: a case study in Ethiopia
Authors: Alamne Samuel B. , Assefa Tewodros T. , Belay Sisay A. , Hussein Misbah A.
Published: April 2022

Background

Nitrate contamination of groundwater often occurs in urban and industrial areas due to point and non-point sources of anthropological activities. Groundwater constitutes a a significant portion of the water supply system for Bahir Dar City in Ethiopia, though the level of groundwater pollution is not known. This study was conducted to assess the the extent of the aquifer and groundwater pollution (nitrate) based on contaminant vulnerability risk mapping using the GIS integrated modified DRASTIC model. A field survey was conducted to collect samples from boreholes for nitrate analysis and to modify the DRASTIC model.

Results

Compared to the original intrinsic vulnerability assessment, land use as external factors changed from moderate-high to high vulnerability class from 18 to 88%. The FR-APH modified model showed a good correlation (0.53) compared to the other methods. Based on the FR-APH modified model, about 31% of the area was under moderate to high and high vulnerability range, 39% was under moderate vulnerability range while 30% was under low and moderate to low vulnerability range.

Conclusions

The integrated vulnerability map showed high risk in the central part of the City due to the flat slope and shallow depth to groundwater. Besides, the sensitivity analysis indicated that the contribution of aquifer media and vadose zone to contaminant risk was found trivial. In general, groundwater at Bahir Darwas found vulnerable to nitrate contamination and needs proper management.
Dynamics of the infant gut microbiota in the first 18 months of life: the impact of maternal HIV infection and breastfeeding
Authors: Grant-Beurmann Silvia , Jumare Jibreel , Ndembi Nicaise , Matthew Olayemi , Shutt Ashley , Omoigberale Augustine , Martin Olivia A. , Fraser Claire M. , Charurat Man
Published: April 2022

Background

Access to antiretroviral therapy (ART) during pregnancy and breastfeeding for mothers with HIV has resulted in fewer children acquiring HIV peri- and postnatally, resulting in an increase in the number of children who are exposed to the virus but are not infected (HEU). HEU infants have an increased likelihood of childhood infections and adverse growth outcomes, as well as increased mortality compared to their HIV-unexposed (HUU) peers. We explored potential differences in the gut microbiota in a cohort of 272 Nigerian infants born to HIV-positive and negative mothers in this study during the first 18 months of life.

Results

The taxonomic composition of the maternal vaginal and gut microbiota showed no significant differences based on HIV status, and the composition of the infant gut microbiota at birth was similar between HUU and HEU. Longitudinal taxonomic composition of the infant gut microbiota and weight-for-age z-scores (WAZ) differed depending on access to breast milk. HEU infants displayed overall lower WAZ than HUU infants at all time points. We observed a significantly lower relative abundance of Bifidobacterium in HEU infants at 6 months postpartum. Breast milk composition also differed by time point and HIV infection status. The antiretroviral therapy drugs, lamivudine and nevirapine, as well as kynurenine, were significantly more abundant in the breast milk of mothers with HIV. Levels of tiglyl carnitine (C5) were significantly lower in the breast milk of mothers without HIV. ART drugs in the breast milk of mothers with HIV were associated with a lower relative abundance of Bifidobacterium longum.

Conclusions

Maternal HIV infection was associated with adverse growth outcomes of HEU infants in this study, and these differences persist from birth through at least 18 months, which is a critical window for the development of the immune and central nervous systems. We observed that the relative abundance of Bifidobacterium spp. was significantly lower in the gut microbiota of all HEU infants over the first 6 months postpartum, even if HEU infants were receiving breast milk. Breastfeeding was of benefit in our HEU infant cohort in the first weeks postpartum; however, ART drug metabolites in breast milk were associated with a lower abundance of Bifidobacterium.
Lungworms (Metastrongylus spp.) demonstrated in domestic pigs with respiratory disease: was there a clinical relevance?
Authors: Wallgren Per , Pettersson Emelie
Published: April 2022

Background

An outdoor pig herd was affected by severe respiratory disease in one out of three pastures. At necropsy, Mycoplasma hyopneumoniae and Pasteurella multocida were detected in the lungs, as well as the lung worm Metastrongylus apri. The life cycle of Metastrongylus spp. includes earthworms as intermediate hosts, and since domestic pigs mainly are reared indoors, lungworm infections have not been diagnosed in domestic pigs in Sweden for decades, not even in pigs reared outdoors. Therefore, this disease outbreak was scrutinised from the view of validating the impact of Metastrongylus spp.

Results

At the time of the disease outbreak, neither eggs of Metastrongylus spp., Trichuris suis nor Ascaris suum were detected in faeces of pigs aged ten weeks. In contrast, five-months-old pigs at the pasture with respiratory disease shed up to 3800 eggs per gram (Epg) of Ascaris suum and up to 1100 Epg of Trichuris suis, whereas eggs of these parasites were not demonstrated in healthy pigs aged six months at another pasture. Low numbers of eggs from Metastrongylus spp. (< 150 Epg) were seen in faecal samples from both these age categories. At slaughter, seven weeks later, ten normal weighted pigs in the preceding healthy batch were compared with ten normal weighted and five small pigs from the affected batch. Healing Mycoplasma-like pneumonic lesions were seen in all groups. All small pigs shed eggs of Ascaris suum in the faeces, compared to around 50% of the larger pigs. Metastrongylus spp. were demonstrated in 13 of the 25 pigs (52%), representing all groups included.

Conclusion

As Metastrongylus spp. were demonstrated regardless of health status, and also in another healthy outdoor herd, the impact of Metastrongylus spp. on the outbreak of respiratory disease was depreciated. Instead, a possible association with a high burden of Ascaris suum was suggested to have preceded the severe outbreak with respiratory disease in the affected herd. Further, it was concluded that Metastrongylus spp. will escape detection at routine meat inspections made at slaughterhouses, and as they appeared to generally not induce clinical signs of respiratory disease Metastrongylus spp. may be more common in outdoor production than previously believed.
Unilateral radiculopathy away from the puncture site due to adhesive arachnoiditis after spinal anesthesia for an emergent cesarean delivery: a case report
Authors: Shimizu Satoshi
Published: April 2022

Background

Adhesive arachnoiditis has been described as a deteriorating neurological complication after neuraxial blockade; however, few pieces of literatures have reported minor cases that resemble peripheral neuropathy.

Case presentation

A 29-year-old nulliparous woman underwent an emergent cesarean delivery under spinal anesthesia at the second and third lumbar interspace (L2/3) without any specific concerns. Subsequently, she developed left L5 and sacral first (S1) radiculopathy that persisted for 2 months. Although the neurological findings more likely indicated peripheral neuropathy, magnetic resonance imaging revealed localized adhesive arachnoiditis at the left L5/S1 level. Her symptoms gradually improved and entirely disappeared within 2 months without any particular treatment.

Conclusion

The neurological symptoms that show a clear tendency to improve spontaneously do not always undergo a detailed workup. Therefore, such minor adhesive arachnoiditis might have occurred more than expected. Imaging such cases might cumulatively further the understanding of its etiology.
Venous cannula occlusion during cardiopulmonary bypass recognized by ultrasonography of the internal jugular vein
Authors: Narasaki Soshi , Miyoshi Hirotsugu , Nakamura Ryuji , Sumii Ayako , Watanabe Tomoyuki , Otsuki Sachiko , Tsutsumi Yasuo M.
Published: April 2022

Background

Occlusion or malposition of the venous cannula during cardiopulmonary bypass (CPB) increases central venous pressure (CVP). When high CVP is measured, we need to determine if it is actually high or if it is measured due to catheter occlusion or technical problems with the measurement.

Case presentation

We experienced a case of excessively high CVP due to malposition of the venous cannula during CPB. A 78-year-old woman underwent an aortic arch replacement for acute aortic dissection. During CPB, CVP increased up to 78 mmHg, and the time above 50 mmHg was 48 min. In this case, ultrasonography of the internal jugular vein (IJV) was useful to confirm high CVP.

Conclusions

Ultrasonography is now a familiar diagnostic tool and can be used at any time. We should consider ultrasonography as the first choice for diagnosing the cause of high CVP during CPB.
A dataset of ecological sensitivity evaluation of Sanya City in 2020
Authors:   Hainan Aerospace Information Research Institute, Key Laboratory of Earth Observation of Hainan Province, SONG Peilin ,   Aerospace Information Research Institute, Chinese Academy of Sciences,   Shandong University of Science and Technology, YANG Tengfei ,   Hainan Aerospace Information Research Institute, Key Laboratory of Earth Observation of Hainan Province,   Aerospace Information Research Institute, Chinese Academy of Sciences, XIE Jibo ,   Hainan Aerospace Information Research Institute, Key Laboratory of Earth Observation of Hainan Province,   Aerospace Information Research Institute, Chinese Academy of Sciences, GAO Xinyue ,   Hainan Aerospace Information Research Institute, Key Laboratory of Earth Observation of Hainan Province,   Aerospace Information Research Institute, Chinese Academy of Sciences,   Shandong University of Science and Technology, MOU Naixia ,   Shandong University of Science and Technology
Published: April 2022

Ecological sensitivity refers to the sensitivity of the ecological environment to the natural phenomena and human activities in a region. As one of the main methods to analyze the stability of the regional ecological environment, it can reflect the possibility of the occurrence of ecological imbalance and ecological environmental problems. It is important for regional ecological protection and decision-making. For Sanya City, the central city in the southern part of Hainan Province, improving and protecting the ecological environment plays an important role in the sustainable development of the region. In this paper, we chose Sanya City as the study area to compile a dataset of ecological sensitivity evaluation of Sanya City in 2020. We used 9 factors (i.e. elevation, slope, aspect, vegetation coverage, water body, land use type, soil erosion intensity, population density distribution, and road accessibility distance) as the ecological sensitivity evaluation indicators. And we adopted the analytic hierarchy process (AHP) to calculate the weight of each evaluation index, and divided the study area into five levels: non-sensitive, low-sensitive, medium-sensitive, high-sensitive, and extremely high-sensitive through GIS spatial analysis and calculation. In terms of the data quality control, we carried out various data verifications by screening cloud-free images in the Sanya City area, the kappa coefficient of the land use supervision and classification consistency test (about 0.85), and combined the NDWI results with the remote sensing images to obtain the water body range, so as to improve the reliability of data quality. This dataset can reflect the ecological sensitivity of Sanya City, and provide a reference data source for ecological environmental protection, resource development and land planning in Sanya City.
Overcoming KRAS-Mutant Lung Cancer
Authors: Luo Jia , Ostrem Jonathan , Pellini Bruna , Imbody Denis , Stern Yaakov , Solanki Hitendra S. , Haura Eric B. , Villaruz Liza C.
Published: April 2022

More than 50 years after the discovery of RAS family proteins, which harbor the most common activating mutations in cancer, the U.S. Food and Drug Administration approved the first direct allele-specific inhibitor of mutant KRAS in lung cancer. We highlight the history of discovering RAS and decades of studies targeting KRAS-driven lung cancer. A landmark article by Shokat and colleagues in 2013 elucidated allosteric inhibition of this undruggable target and paved the way for the first-in-class direct KRASG12C inhibitor. Although these drugs have impressive 36%–45% objective response rates with a median duration of response of 10 months, many tumors do not respond, and diverse mechanisms of resistance have already been observed; this includes new KRAS alterations, activation of alternate RTK pathway proteins, bypass pathways, and transcriptional remodeling. These resistance mechanisms can be profiled using tissue-based and plasma-based testing and help to inform clinical trial options for patients. We conclude with a discussion of research informing ongoing clinical trials to rationally test promising treatments to thwart or overcome resistance to KRASG12C inhibitors and target other KRAS-altered lung cancers.
Ion-scale solitary waves in magnetoplasma with non-thermal electrons
Authors: Khalid Muhammad , Kabir Abdul , Irshad Muhammad
Published: April 2022

The propagation of ion acoustic (IA) solitary waves (SWs) is investigated in a magnetized electron-ion (EI) plasma with Cairns-Tsallis distributed electrons. A Zakharov-Kuznetsov (ZK) type equation is derived for the electrostatic potential via a reductive perturbation method (RPM). It is found that increasing values of non-extensive parameter q leads to reduction (enhancement) in amplitude of compressive (rarefactive) solitary structures. The amplitude of compressive (rarefactive) solitary wave (SW) decreases (increases) with increasing values of non-thermality parameter α. Furthermore, it is found that magnetic field strength Ω only affects the width of solitary structures.
Essentially Dispossessed
Authors: Dubal Veena
Published: April 2022

As the COVID-19 pandemic ravaged human bodies and economies across the world, millions of app-deployed drivers in the United States—primarily immigrants and subordinated racial minorities—faced a dangerous and perplexing paradox created by law. Simultaneously treated as independent contractors, excluded from economic security, and anointed as “essential workers,” these workers were both celebrated and disproportionately exposed to poverty, disease, and death. This essay makes sense of the legal and lived condition of being essentially dispossessed during this moment. The author argues that this cruel contradiction became possible through a mystification generated by the fragmented nature of work law. Together with obscuring narratives of techno-modernism, seven years of arbitrary legal outcomes made the central legal question (are they employees or independent contractors?) appear unresolvable. Activist-drivers confronted their relegation to being essentially dispossessed by using their situated knowledges about their jobs, work law, and bureaucratic processes to demand economic security through direct actions.
New Aristocracy
Authors: Jackson Jack
Published: April 2022

We are in a period when US legal thought is again opening up to renewed and sustained critiques of capitalism. This article situates this renaissance within both a longer history of political thought and the current political context in the United States. Drawing upon the observations of Alexis de Tocqueville, who argued that the rise of industry could lay the groundwork for a return to aristocracy, the article also considers how US jurisprudence since the early 1970s has proved Tocqueville somewhat prophetic. Today, we confront the accelerating rise of political wealth alongside the fall of the working classes into neofeudal labor practices—trajectories embedded in and abetted by decisions of the US Supreme Court.
Provocation as Strategy
Authors: Kennedy Duncan , Blalock Corinne
Published: April 2022

In the fall of 2021, Corinne Blalock conducted a series of interviews with Duncan Kennedy, one of the founders of Critical Legal Studies (CLS). During these wide-ranging and at times unruly conversations, which have been edited for length and clarity, the themes that repeatedly emerged were questions of strategy and tactics in building the legal left, as well as the very different political moments in which CLS and the emerging Law and Political Economy movement are situated.
Effect of stimulation frequency on force, power and fatigue of isolated mouse extensor digitorum longus muscle
Authors: Shelley Sharn P. , James Rob S. , Eustace Steven J. , Eyre Emma , Tallis Jason
Published: April 2022

This study examined the effect of stimulation frequency (140, 200, 230 and 260 Hz) on isometric force, work loop (WL) power and the fatigue resistance of extensor digitorum longus (EDL) muscle (n=32), isolated from 8- to 10-week-old CD-1 female mice. Stimulation frequency had significant effects on isometric properties of isolated mouse EDL, whereby increasing stimulation frequency evoked increased isometric force, quicker activation and prolonged relaxation (P<0.047) up to 230 Hz and above; thereafter, force and activation did not differ (P>0.137). Increasing stimulation frequency increased maximal WL power output (P<0.001; 140 Hz, 71.3±3.5; 200 Hz, 105.4±4.1; 230 Hz, 115.5±4.1; 260 Hz, 121.1±4.1 W kg−1), but resulted in significantly quicker rates of fatigue during consecutive WLs (P<0.004). WL shapes indicate impaired muscle relaxation at the end of shortening and subsequent increased negative work appeared to contribute to fatigue at 230 and 260 Hz, but not at lower stimulation frequencies. Cumulative work was unaffected by stimulation frequency, except at the start of the fatigue protocol, where 230 and 260 Hz produced more work than 140 Hz (P<0.039). We demonstrate that stimulation frequency affects force, power and fatigue, but these effects are not uniform between different assessments of contractile performance. Therefore, future work examining the contractile properties of isolated skeletal muscle should consider increasing the stimulation frequency beyond that needed for maximal force when examining maximal power but should utilise a sub-maximal stimulation frequency for fatigue assessments to avoid a high degree of negative work atypical of in vivo function.
Palladium-catalyzed Dehydrogenative [3+3] Aromatization of Propyl Ketones and Allyl Carbonates
Authors: Koike Kenta , Ueno Satoshi
Published: April 2022

A Pd-catalyzed dehydrogenative [3+3] aromatization of 3-phenylpropyl ketones and allyl carbonates has been developed. The reaction gives various di- or tri-substituted aromatic ketones. The reaction consisting of five steps efficiently proceeded in a one-batch, one-manipulation setup. The postulated active species, η3-allyl palladium complex, works as a catalyst for triple dehydrogenations and mono allylation with high substrate controls.
4’-fluorouridine and its derivatives as potential COVID-19 oral drugs: a review
Authors: Abas Abdul Hawil , Tallei Trina Ekawati , Fatimawali Fatimawali , Celik Ismail , Alhumaydhi Fahad A. , Emran Talha Bin , Dhama Kuldeep , Rabaan Ali A. , Garout Mohammed A. , Halwani Muhammad A. , Al Mutair Abbas , Alhumaid Saad , Harapan Harapan
Published: April 2022

Background: Although vaccination is underway, antiviral drugs against coronavirus disease 2019 (COVID-19) are lacking. Remdesivir, a nucleoside analog that works by inhibiting the viral RNA-dependent RNA polymerase (RdRp), is the only fully approved antiviral for the treatment of COVID-19. However, it is limited to intravenous use and is usually recommended only for hospitalized patients with severe COVID-19; therefore, oral drugs that can be prescribed even to non-hospitalized patients are required. According to a recent study, 4′-fluoruridine, a nucleoside analog similar to remdesivir, is a promising candidate for COVID-19 oral therapy due to its ability to stall viral RdRp.

Methods: We examined the antiviral activity of 4′-fluorouridine and compared it to other drugs currently in development. The current literature on 4′-fluorouridine's antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been compiled and discussed in this review.

Results: The 4'-fluorouridine has antiviral activity against the respiratory syncytial virus, hepatitis C virus, lymphocytic choriomeningitis virus, and other RNA viruses, including SARS-CoV-2. In vitro studies have shown that SARS-CoV-2 is susceptible to 4'-fluorouridine, with the half-maximal effective concentration (EC50) of 0.2 to 0.6 M, and that the 4′-fluorouridine derivative, 4′-fluorouridine-5′-triphosphate, inhibited RdRp via a mechanism distinct from that of the already approved COVID-19 oral drug, molnupiravir. In addition, an in vivo study revealed that SARS-CoV-2 is highly susceptible to 4'-fluorouridine and was effective with a single daily dose versus molnupiravir administered twice daily.

Conclusions: Concerns about the genetic effects of molnupiravir may be resolved by the use of 4′-fluorouridine and its derivative, which, unlike molnupiravir, do not alter genetics, but inhibit RdRp instead. Although they are currently considered as strong candidates, further studies are required to determine the antiviral activity of 4′-fluorouridine and its derivative against SARS-CoV-2 and their genetic effects on humans.
Does the impact of medical publications vary by disease indication and publication type? An exploration using a novel, value-based, publication metric framework: the EMPIRE Index
Authors: Rees Tomas , Pal Avishek
Published: April 2022

Background: The EMPIRE (EMpirical Publication Impact and Reach Evaluation) Index is a value-based, multi-component metric framework to assess the impact of medical publications in terms of relevance to different stakeholders. It comprises three component scores (social, scholarly and societal impact), each incorporating related altmetrics that indicate a different aspect of engagement with the publication. Here, we present an exploratory investigation of whether publication types or disease indications influence EMPIRE Index scores.

Methods: Article-level metrics were extracted and EMPIRE Index scores were calculated for 5825 journal articles published from 1 May 2017 to 1 May 2018, representing 12 disease indications (chosen to reflect a wide variety of common and rare diseases with a variety of aetiologies) and five publication types.

Results: There were significant differences in scores between article types and disease indications. Median (95% CI) social and scholarly impact scores ranged from 1.2 (0.3–1.6) to 4.8 (3.1–6.6), respectively, for phase 3 clinical trials, and from 0.3 (0.3–0.4) to 2.3 (1.9–2.6), respectively, for observational studies. Social and scholarly impact scores were highest for multiple sclerosis publications and lowest for non-small cell lung cancer publications. Systematic reviews achieved greater impact than regular reviews. Median trends in the social impact of different disease areas matched the level of public interest as assessed through Google search interest. Although most articles did not register societal impact, mean societal impact scores were highest for migraine publications.

Conclusions: The EMPIRE Index successfully identified differences in impact by disease area and publication type, which supports the notion that the impact of each publication needs to be evaluated in the context of these factors, and potentially others. These findings should be considered when using the EMPIRE Index to assess publication impact.
Complete proofs of the main theorems on summability factors
Authors: Baron Simson , Peyerimhoff Alexander
Published: April 2022

In this article the shortest proofs up to the present of the main theorems on summability factors for Cesàro methods are given. The necessity part of these theorems is proved for more general methods. Especially short is the proof of the sufficiency part of the theorem for summability factors of types (C0α,|Cβ|) and (Cα,|Cβ|).
Two new multivariate tests, in particular for a high dimension
Authors: Läuter Jürgen
Published: April 2022

Two new test statistics for the multivariate one-sample problem are introduced that are applicable to normally distributed data in all cases with a sample size n≥2 and a dimension p≥1. The dimension may also be greater than the sample size. The tests are based on the theory of spherical distributions. They utilize the principal components of the total sums of product matrices of the given data. Under the null hypothesis, the statistics are exactly beta distributed. The performance of the tests is investigated by simulations. Finally, the methods are applied to high-dimensional data from gene expression analysis (dimension p=12625).
Using copulas for modeling the dependence between tree height and diameter at breast height
Authors: Adermann Veiko , Pihlak Margus
Published: April 2022

In the paper the relation between height and diameter at breast height of a tree is modeled by means of copulas. For this modeling the marginal distributions of tree height and diameter at breast height are estimated and thereafter the multivariate joint distribution function is approximated with copulas. Several Archimedean copulas and the Gaussian copula are used in modeling of the bivariate distribution of the interest. Different obtained models are compared.
Inference in normal models with commutative orthogonal block structure
Authors: Fonseca Miguel , Mexia João Tiago , Zmyślony Roman
Published: April 2022

Linear mixed normal models are studied in this paper. Using commutative Jordan algebras, the algebraic properties of these models are studied, as well as optimal estimators, hypothesis tests and confidence regions for fixed and random effects. Model crossing andnesting is then presented and analyzed.
The method of three-parameter Weibull distribution estimation
Authors: Bartkutė Vaida , Sakalauskas Leonidas
Published: April 2022

In this paper we develop Maximum Likelihood (ML) and Improved Analytical (IA) numerical algorithms to estimate parameters of the Weibull distribution, namely, location, scale and shape parameters, using order statistics of a noncensored sample. Since ML methodleads to multiextremal numerical problem we establish conditions to localize extremes of the ML function, which enables us to avoid problems related with ML estimation failure and to create a simple estimation procedure by solving one-dimensional equation. IA estimation also has been developed by solving the equation in one variable. The estimates proposed are studied by computer modeling and compared with the theoretical ones with respect to sample size and number of order statistics used for estimation. Recommendations for implementation of the estimates are also discussed.
Infinite Viterbi alignments in the two state hidden Markov models
Authors: Koloydenko Alexey , Lember Jüri
Published: April 2022

Since the early days of digital communication, hidden Markov models (HMMs) have now been routinely used in speech recognition, processing of natural languages, images, and in bioinformatics. An HMM (Xi, Yi)i≥1 assumes observations X1, X2, . . . to be  conditionally independent given an “explanatary” Markov process Y1, Y2, . . ., which itself is not observed; moreover, the conditional distribution of Xi depends solely on Yi. Central to the theory and applications of HMM is the Viterbi algorithm to find a maximum a posteriori estimate q1:n = (q1, q2, . . . , qn) of Y1:n given the observed data x1:n. Maximum a posteriori paths are also called Viterbi paths or alignments. Recently, attempts have been made to study the behavior of Viterbi alignments of HMMs with two hidden states when n tends to infinity. It has indeed been shown that in some special cases a well-defined limiting Viterbi alignment exists. While innovative, these attempts have relied on rather strong assumptions. This work proves the existence of infinite Viterbi alignments for virtually any HMM with two hidden states.
Beyond Mixed Logics
Authors: Toranzo Calderón Joaquín , Pailos Federico
Published: April 2022

In order to define some interesting consequence relations, certain generalizations have been proposed in a many-valued semantic setting that have been useful for defining what have been called pure, mixed and ordertheoretic consequence relations. But these generalizations are insufficient to capture some other interesting relations, like other intersective mixed relations (a relation that cannot be defined as a mixed relation, but only as the intersection of two mixed relations) or relations with a conjunctive (or, better, “universal”) interpretation for multiple conclusions. We propose a broader framework to define these cases, and many others, and to set a common background that allows for a direct compared analysis. At the end of the work, we illustrate some of these comparisons
The impact of increasing returns on knowledge and big data: from Adam Smith and Allyn Young to the age of machine learning and digital platforms
Authors: Hu Yao-Su
Published: April 2022

Allyn Young's concept of increasing returns (not to be confused with static, equilibrium constructs of economies of scale and increasing returns to scale) is applied to analyse how and why increasing returns arise in the production (generation) and use (application) of knowledge and big data, thereby driving economic growth and progress. Knowledge is chosen as our focus because it is said to be our most powerful engine of production, and big data are included to make the analysis more complete and recent. We analyse four mechanisms or sources of increasing returns in the production of knowledge, and four in the use of knowledge. Turning to big data, we analyse increasing returns in the functioning of digital platforms and increasing returns in machine learning from gigantic amounts of training data. Concluding remarks concern some key differences between big data and knowledge, some policy implications, and some of the social negative impacts from the ways in which big data are being used.
The impact of the European patent system on SMEs and national states
Authors: Xenos Dimitris
Published: April 2022

A centralized and federal patent system in the EU changes economic and constitutional law structures by creating a ‘nationalized’ international patent. As the underlying economic policy has concentrated on the development needs of small and medium-sized enterprises (SMEs), accounting for 99% of all businesses in Europe, statistical analysis and data of their patenting activity and patent ownership are used to assess whether the new regime can help or hinder SMEs and the states in which they are based. Due consideration is given to the monopoly effect of patents and the adversarial nature of the judicial, federal system that is introduced in the absence of a federation of states. Although there are always costs and benefits in such a system, new legal/institutional developments amplify existing imbalances in technological and economic capacities between and within member states, and between them and non-EU states.
The importance of drug target selection capability for new drug innovation: definition, fostering process, and interaction with organizational management
Authors: Okuyama Ryo , Tsujimoto Masaharu
Published: April 2022

The productivity of new drug discovery has not changed for decades, although the information on physiological functions and molecules, which are the sources for new drug discovery, has markedly increased. Furthermore, technologies for lead compound acquisition and compound optimization for creating drug candidates have greatly progressed. One possible reason for this low productivity is that it is still difficult for drug discovery researchers to correctly evaluate and select physiological mechanisms that could be drug targets. Nevertheless, there are very few studies on drug target selection capability, specifically on researchers' capability to determine whether modulating the function of a newly discovered physiological mechanism would be a suitable therapeutic option for a certain disease. How is this capability developed? In this study, we propose that the long-term experience of researchers in investigating disease causes and existing drug action mechanisms contributes to enhancing their insights into druggable physiological mechanisms, based on the comparative analysis of cases that were focused on the same physiological mechanism, where one was successfully developed as an innovative new drug while the other failed. We also discuss managerial practices to strengthen capability.