bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Neuroscientists Test a New Physicalist Mind/Body View: DiCoToP (Diachronic Conjunctive Token Physicalism)?
Authors: Brakel Linda A. W.
Published: December 2021

Given that disparate mind/body views have interfered with interdisciplinary research in psychoanalysis and neuroscience, the mind/body problem itself is explored here. Adding a philosophy of mind framework, problems for both dualists and physicalists are presented, along with essential concepts including: independent mental causation, emergence, and multiple realization. To address some of these issues in a new light, this article advances an original mind/body account—Diachronic Conjunctive Token Physicalism (DiCoToP). Next, puzzles DiCoTop reveals, psychoanalytic problems it solves, and some empirical evidence accrued for views consistent with DiCoToP are presented. In closing, this piece challenges/appeals for neuroscience research to gain evidence for (or against) the DiCoToP view.
Aberrant Interhemispheric Functional Connectivity in Diabetic Retinopathy Patients
Authors: Wan Song , Xia Wen Qing , Zhong Yu Lin
Published: December 2021

Background: Accumulating lines of evidence demonstrated that diabetic retinopathy (DR) patients trigger abnormalities in brain’s functional connectivity (FC), whereas the alterations of interhemispheric coordination pattern occurring in DR are not well understood. Our study was to investigate alterations of interhemispheric coordination in DR patients.

Methods: Thirty-four DR individuals (19 males and 15 females: mean age: 52.97 ± 8.35 years) and 37 healthy controls (HCs) (16 males and 21 females; mean age: 53.78 ± 7.24 years) were enrolled in the study. The voxel-mirrored homotopic connectivity (VMHC) method was conducted to investigate the different interhemispheric FC between two groups. Then, the seed-based FC method was applied to assess the different FCs with region of interest (ROI) in the brain regions of decreased VMHC between two groups.

Results: Compared with HC groups, DR groups showed decreased VMHC values in the bilateral middle temporal gyrus (MTG), lingual/calcarine/middle occipital gyrus (LING/CAL/MOG), superior temporal gyrus (STG), angular (ANG), postcentral gyrus (PosCG), inferior parietal lobule (IPL), and precentral gyrus (PreCG). Meanwhile, altered FC includes the regions of auditory network, visual network, default mode network, salience network, and sensorimotor network. Moreover, a significant positive correlation was observed between the visual acuity-oculus dexter (OD) and zVMHC values in the bilateral LING/CAL/MOG (r = 0.551, p = 0.001), STG (r = 0.426, p = 0.012), PosCG (r = 0.494, p = 0.003), and IPL (r = 0.459, p = 0.006) in DR patients.

Conclusion: Our results highlighted that DR patients were associated with substantial impairment of interhemispheric coordination in auditory network, visual network, default mode network, and sensorimotor network. The VMHC might be a promising therapeutic target in the intervention of brain functional dysfunction in DR patients.
MN1 Neurodevelopmental Disease-Atypical Phenotype Due to a Novel Frameshift Variant in the MN1 Gene
Authors: Tian Qi , Shu Li , Zhang Pu , Zeng Ting , Cao Yang , Xi Hui , Peng Ying , Wang Yaqin , Mao Xiao , Wang Hua
Published: December 2021

Background:MN1 C-terminal truncation (MCTT) syndrome is caused by variants in the C-terminal region of MN1, which were first described in 2020. The clinical features of MCTT syndrome includes severe neurodevelopmental and brain abnormalities. We reported on a patient who carried the MN1 variant in the C-terminal region with mild developmental delay and normal brain magnetic resonance image (MRI).

Methods: Detailed clinical information was collected in the pedigree. Whole-exome sequencing (WES) accompanied with Sanger sequencing validation were performed. A functional study based on HEK239T cells was performed.

Results: A de novo heterozygous c.3734delT: p.L1245fs variant was detected. HEK239T cells transinfected with the de novo variant showed decreased proliferation, enhanced apoptotic rate, and MN1 nuclear aggregation.

Conclusion: Our study expended the clinical and genetic spectrum of MCTT which contributes to the genetic counseling of the MN1 gene.
Loculations and Associated Risk Factors of Childhood Pleural Tuberculosis
Authors: Wang Jun-Li , Zhou Ming , Zhang Yan-An , Wang Mao-Shui
Published: December 2021

Background: Pleural loculation in childhood pleural tuberculosis (TB) remains a problem in practice, it is usually associated with failure drainage. Therefore, to improve the management of childhood pleural TB, a retrospective study was conducted to identify the risk factors associated with loculated effusion in childhood pleural TB.

Methods: Between January 2006 and December 2019, consecutive children (≤15 years old) with tuberculous pleural effusion (definite and possible) were included for further analysis. The demographic, clinical, laboratory, and radiographic features were collected from the medical records. Univariate and multivariate logistic regressions were used to explore the factors associated with the presence of pleural loculation in children with pleural TB.

Results: A total of 154 children with pleural TB (definite, 123 cases; possible, 31 cases) were included in our study and then were classified as loculated effusion (n = 27) and non-loculated effusion (n = 127) groups by chest X-ray or ultrasonography. Multivariate analysis revealed that male gender (age-adjusted OR = 3.903, 95% CI: 1.201, 12.683), empyema (age-adjusted OR = 4.499, 95% CI: 1.597, 12.673), peripheral monocytes ≤0.46 × 109/L (age-adjusted OR = 4.122, 95% CI: 1.518, 11.193) were associated with the presence of loculated effusion in children with pleural TB.

Conclusion: In conclusion, several characteristics, such as male gender, empyema, and peripheral monocyte count have been identified as risk factors for pleural loculation in children with pleural TB. Our findings may be helpful to improve the management of pleural loculation in childhood pleural TB.
Mechanisms Underlying Gastrodin Alleviating Vincristine-Induced Peripheral Neuropathic Pain
Authors: Wang Xiangyu , Zhang Boxuan , Li Xuedong , Liu Xingang , Wang Songsong , Xie Yuan , Pi Jialing , Yang Zhiyuan , Li Jincan , Jia Qingzhong , Zhang Yang
Published: December 2021

Gastrodin (GAS) is the main bioactive ingredient of Gastrodia, a famous Chinese herbal medicine widely used as an analgesic, but the underlying analgesic mechanism is still unclear. In this study, we first observed the effects of GAS on the vincristine-induced peripheral neuropathic pain by alleviating the mechanical and thermal hyperalgesia. Further studies showed that GAS could inhibit the current density of NaV1.7 and NaV1.8 channels and accelerate the inactivation process of NaV1.7 and NaV1.8 channel, thereby inhibiting the hyperexcitability of neurons. Additionally, GAS could significantly reduce the over-expression of NaV1.7 and NaV1.8 on DRG neurons from vincristine-treated rats according to the analysis of Western blot and immunofluorescence results. Moreover, based on the molecular docking and molecular dynamic simulation, the binding free energies of the constructed systems were calculated, and the binding sites of GAS on the sodium channels (NaV1.7 and NaV1.8) were preliminarily determined. This study has shown that modulation of NaV1.7 and NaV1.8 sodium channels by GAS contributing to the alleviation of vincristine-induced peripheral neuropathic pain, thus expanding the understanding of complex action of GAS as a neuromodulator.
Phenotypic Variability in iPSC-Induced Cardiomyocytes and Cardiac Fibroblasts Carrying Diverse LMNA Mutations
Authors: Yang Jiajia , Argenziano Mariana A. , Burgos Angulo Mariana , Bertalovitz Alexander , Beidokhti Maliheh Najari , McDonald Thomas V.
Published: December 2021

Mutations in the LMNA gene (encoding lamin A/C) are a significant cause of familial arrhythmogenic cardiomyopathy. Although the penetrance is high, there is considerable phenotypic variability in disease onset, rate of progression, arrhythmias, and severity of myopathy. To begin to address whether this variability stems from specific LMNA mutation sites and types, we generated seven patient-specific induced pluripotent stem cell (iPSC) lines with various LMNA mutations. IPSC-derived cardiomyocytes (iCMs) and cardiac fibroblasts (iCFs) were differentiated from each line for phenotypic analyses. LMNA expression and extracellular signal-regulated kinase pathway activation were perturbed to differing degrees in both iCMs and iCFs from the different lines. Enhanced apoptosis was observed in iCMs but not in iCFs. Markedly diverse irregularities of nuclear membrane morphology were present in iCFs but not iCMs, while iCMs demonstrated variable sarcomere disarray. Heterogenous electrophysiological aberrations assayed by calcium indicator imaging and multi-electrode array suggest differing substrates for arrhythmia that were accompanied by variable ion channel gene expression in the iCMs. Coculture studies suggest enhancement of the LMNA mutation effects on electrophysiological function exerted by iCFs. This study supports the utility of patient-specific iPSC experimental platform in the exploration of mechanistic and phenotypic heterogeneity of different mutations within a cardiac disease-associated gene. The addition of genetically defined coculture of cardiac-constituent non-myocytes further expands the capabilities of this approach.
How to Put It Plainly? Findings From Two Randomized Controlled Studies on Writing Plain Language Summaries for Psychological Meta-Analyses
Authors: Kerwer Martin , Stoll Marlene , Jonas Mark , Benz Gesa , Chasiotis Anita
Published: December 2021

Plain language summaries (PLS) aim to communicate research findings to laypersons in an easily understandable manner. Despite the societal relevance of making psychological research findings available to the public, our empirical knowledge on how to write PLS of psychology studies is still scarce. In this article, we present two experimental studies investigating six characteristics of PLS for psychological meta-analyses. We specifically focused on approaches for (1) handling technical terms, (2) communicating the quality of evidence by explaining the methodological approach of meta-analyses, (3) explaining how synthesized studies operationalized their research questions, (4) handling statistical terms, (5) structuring PLS, and (6) explaining complex meta-analytic designs. To develop empirically validated guidelines on writing PLS, two randomized controlled studies including large samples stratified for education status, age, and gender (NStudy1=2,288 and NStudy2=2,211) were conducted. Eight PLS of meta-analyses from different areas of psychology were investigated as study materials. Main outcome variables were user experience (i.e., perceived accessibility, perceived understanding, and perceived empowerment) and knowledge acquisition, as well as understanding and knowledge of the quality of evidence. Overall, our hypotheses were partially confirmed, with our results underlining, among other things, the importance of explaining or replacing content-related technical terms (i.e., theoretical concepts) and indicating the detrimental effects of providing too many details on statistical concepts on user experience. Drawing on these and further findings, we derive five empirically well-founded rules on the lay-friendly communication of meta-analytic research findings in psychology. Implications for PLS authors and future research on PLS are discussed.
Body Image in BRCA-Positive Young Women Following Bilateral Risk-Reducing Mastectomy: A Review of the Literature
Authors: Torrisi Christa
Published: December 2021

Background/Significance: The presence of a breast cancer (BRCA) gene mutation increases a woman’s lifetime risk of developing breast cancer. Bilateral risk-reducing mastectomy is a proactive treatment option which lowers that risk. However, breast removal can create a change in physical appearance. It is unclear if BRCA-positive women undergoing this surgery in young adulthood, a life stage where intimate relationships, families, and careers are being established, have the same experience with body image as women in later stages of life.

Purpose: The aim of this literature review is to assess how bilateral risk-reducing mastectomy impacts body image in young BRCA-positive women less than 40 years of age, with no history of breast cancer.

Methods: Database searches were performed, yielding 402 results. Studies were considered if participants had an increased lifetime breast cancer risk/BRCA-positive diagnosis and history of bilateral risk-reducing mastectomy, body image was evaluated, and mean age was less than 40 years. A total of three qualitative studies and three quantitative studies were identified as relevant for this review.

Results: A dearth of information exists on body image in young women following bilateral risk-reducing mastectomy. It was found in this review that some women experienced a decline in body image following surgery, while in others body image was maintained or improved.

Conclusion: Understanding factors that impact body image following this risk-reducing surgery will allow clinicians to support this unique population. Open and informative discussion should be encouraged with young women considering, or who have undergone, bilateral risk-reducing mastectomy.
Partial Agonists and Dual Disorders: Focus on Dual Schizophrenia
Authors: Peris Lola , Szerman Nestor
Published: December 2021

Dual disorder is a term applied to patients with an addictive disorder and other mental disorder. Epidemiological studies have established that dual disorders are an expectation rather than an exception. They are difficult to diagnose and treat and constitute a huge burden for both patients and their relatives and society. Current treatments are a combination of those needed to treat the addictive disorder with those focused on the co-occurring psychiatric disorder. Focusing specifically on schizophrenia, growing scientific evidence supports the existence of a shared vulnerability for substance use in these patients and those at risk. Various antipsychotics have been found to be useful in the treatment of psychotic symptoms and disorders; however, few effective treatments have been identified until now for substance use disorders in patients with dual schizophrenia. Partial agonism stands as a new pharmacological option available in recent years. Molecules with this kind of action may act as functional agonists or as antagonists, depending on the surrounding levels of the neurotransmitter. Studies have found their efficacy in schizophrenia, addiction, anxiety and depression. Certain partial agonist antipsychotics seem to have a role in the treatment of dual schizophrenia. That could be the case with cariprazine. Because of its higher affinity for dopaminergic D3 receptors compared to D2, a potential to prevent relapse to addiction, added to its antipsychotic efficacy, has been suggested. Here we briefly review current advances and future directions and introduce some personal insights into the role of partial agonists in co-occurring schizophrenia and substance use.
Psychiatric Comorbidity and Stress in Medical Students Using Neuroenhancers
Authors: Jebrini Tarek , Manz Kirsi , Koller Gabriele , Krause Daniela , Soyka Michael , Franke Andreas G.
Published: December 2021

Background: Pharmacological neuroenhancement (PN) is a common healthcare problem at least among students. PN seems to be associated with stressful situations. There is a lack of data about personal characteristics, comorbidities, and coping strategies regarding stress and factors of resilience in students and medical staff.

Methods: A web-based survey about the non-medical use of PN drugs with a focus on neuroenhancement was developed and distributed among medical students throughout Germany; the questionnaire was open in April and May of 2020. The survey contained questions about the use of well-known PN drugs, frequency, special purposes, reasons for the use, psychiatric disorders, use of psychotropic drugs apart from PN purposes, and factors of resilience using the brief resilience scale.

Results: Data of 1,159 students of medicine were analyzed. The most frequently used substances for PN were coffee (78.8% lifetime prevalence rate), energy drinks (45.7%), caffeine tablets (24.3%), methylphenidate (5.2%), illicit amphetamines (2.0%), and cocaine (1.7%). 98.4% suspected that PN drug use could lead to addiction. PN drug use specifically for PN was significantly associated with the use of (a) any psychotropic drug (other than neuroenhancers), (b) any psychiatric disorder, and (c) higher values of feeling pressure to perform in professional/students' life and in private life as well as (d) the subjective feeling of pressure to perform to be burdening and (e) harmful to one's own health. PN drug use in general was significantly associated with being less resilient. The use of illicit PN drugs, over the counter drugs and prescription drugs was associated with being less resilient.

Conclusion: This study indicates that PN with legal and illegal drugs is a widespread phenomenon among German medical students. Users seem to be more often burdened by psychiatric disorders, especially addictive disorders, the perception of stress, pressure to perform and low levels of resilience. These aspects should be considered in further investigation of PN drug use.
Wound Botulism Among Persons Who Inject Black Tar Heroin in New Mexico, 2016
Authors: Middaugh Nicole , Edwards Leslie , Chatham-Stephens Kevin , Arguello D. Fermin
Published: December 2021

Outbreaks of wound botulism are rare, but clinicians and health departments should maintain suspicion for signs, symptoms, and risk factors of wound botulism among persons who inject drugs in order to initiate treatment quickly. This report describes an outbreak of three wound botulism cases among persons in two adjacent counties who injected drugs. Provisional information about these cases was previously published in the CDC National Botulism Surveillance Summary. All three cases in this outbreak were laboratory-confirmed, including one case with detection of botulinum toxin type A in a wound culture sample taken 43 days after last possible heroin exposure. Findings highlight the delay in diagnosis which led to prolonged hospitalization and the persistence of botulinum toxin in one patient.
Patho-Physiology of Aging and Immune-Senescence: Possible Correlates With Comorbidity and Mortality in Middle-Aged and Old COVID-19 Patients
Authors: Farheen Saba , Agrawal Sudhanshu , Zubair Swaleha , Agrawal Anshu , Jamal Fauzia , Altaf Ishrat , Kashif Anwar Abu , Umair Syed Mohammad , Owais Mohammad
Published: December 2021

During the last 2 years, the entire world has been severely devastated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) as it resulted in several million deaths across the globe. While the virus infects people indiscriminately, the casualty risk is higher mainly in old, and middle-aged COVID-19 patients. The incidences of COVID-19 associated co-morbidity and mortality have a great deal of correlation with the weakened and malfunctioning immune systems of elderly people. Presumably, due to the physiological changes associated with aging and because of possible comorbidities such as diabetes, hypertension, obesity, cardiovascular, and lung diseases, which are more common in elderly people, may be considered as the reason making the elderly vulnerable to the infection on one hand, and COVID-19 associated complications on the other. The accretion of senescent immune cells not only contributes to the deterioration of host defense, but also results in elevated inflammatory phenotype persuaded immune dysfunction. In the present review, we envisage to correlate functioning of the immune defense of older COVID-19 patients with secondary/super infection, increased susceptibility or aggravation against already existing cancer, infectious, autoimmune, and other chronic inflammatory diseases. Moreover, we have discussed how age-linked modulations in the immune system affect therapeutic response against administered drugs as well as immunological response to various prophylactic measures including vaccination in the elderly host. The present review also provides an insight into the intricate pathophysiology of the aging and the overall immune response of the host to SARS-CoV-2 infection. A better understanding of age-related immune dysfunction is likely to help us in the development of targeted preemptive strategies for deadly COVID-19 in elderly patients.
Microplastics: Small Particles, Big Threat
Authors: Arossa Silvia , Martin Cecilia , Rossbach Susann , Duarte Carlos M.
Published: December 2021

You have probably heard that plastic pollution is becoming a big problem for the environment, and especially for the oceans. When a piece of plastic reaches the sea, the seawater and sunlight make it slowly fall apart into tiny plastic particles. These small particles are called microplastics and are even smaller than a ladybug—and sometimes not even visible. Scientists have found that many marine animals mistake these microplastics for food and eat them! But what about the animals in coral reefs? Many animals in reefs, including corals and giant clams, are fixed to the bottom of the sea and cannot move. So, they cannot escape from the microplastics that are literally “raining down” on them. Recently, we discovered that many of these coral reef animals are not only eating the microplastics, but the plastics can also stick on their bodies like flies on flypaper!
Comparison of Ceramic-on-Ceramic vs. Ceramic-on-Polyethylene for Primary Total Hip Arthroplasty: A Meta-Analysis of 15 Randomized Trials
Authors: Fang Yan , Shang Xiaobin
Published: December 2021

Objective: This meta-analysis aimed to compare ceramic-on-ceramic (COC) components and ceramic-on-polyethylene (COP) components during total hip arthroplasty (THA).

Settings: A meta-analysis of randomized controlled trials (RCTs) comparing COC and COP during primary THA was conducted. Electronic searches were current to March 2021.

Participants: Trials were included for meta-analysis if they compared at least the bearing surfaces of COC and COP for patients undergoing primary THA and if they reported the outcomes of THA after a certain period of follow-up and only RCTs in English were included.

Primary and Secondary Outcome Measures: The primary endpoints consist of audible noise, prosthesis fracture, and revision. Secondary endpoints include dislocation, deep infection, osteolysis, and prosthesis loosening. Extracted data were statistically analyzed with the Stata11.0.

Results: A total of 15 RCTs containing 2,702 patients (2,813 hips) were included in this study. The audible noise [odds ratio (OR) = 5.919; 95% CI: 2.043, 17.146; p ≤ 0.001] and prosthesis fracture (OR = 35.768; 95% CI: 8.957, 142.836; p = 0.001) were significantly higher in the COC group. Hip function, revision rate, dislocation rate, deep infection rate, osteolysis rate, and prosthesis loosening rate were comparable between these two groups, while the wear rate was higher in the COP group.

Conclusion: This study indicated comparable outcomes of COC and COP bearing surfaces in primary THA; high-quality RCTs with a long-term follow-up are still urgently needed to provide more evidence on the optimal bearing surfaces in primary THA.
Liver- and Spleen-Specific Immune Responses in Experimental Leishmania martiniquensis Infection in BALB/c Mice
Authors: Sukhumavasi Woraporn , Kaewamatawong Theerayuth , Somboonpoonpol Nawaphat , Jiratanh Montakan , Wattanamethanont Juntra , Kaewthamasorn Morakot , Leelayoova Saovanee , Tiwananthagorn Saruda
Published: December 2021

Leishmania martiniquensisis a neglected cause of an emerging leishmaniasis in many countries, including France, Germany, Switzerland, the United States of America, Myanmar, and Thailand, with different clinical manifestations ranging from asymptomatic, cutaneous (CL), visceral (VL), and atypically disseminated CL and VL. The persistence of parasites and the recurrence of the disease after treatment are challenges in controlling the disease. To explore efficient prophylaxis and therapy, this study aimed to investigate infection outcome and organ-specific immune responses after inoculation withL. martiniquensis(MHOM/TH/2011/PG; 5 x 106promastigotes) in BALB/c miceviaintravenous and intraperitoneal routes. A quantitative PCR technique, targetingL. martiniquensisITS1, was primarily established to estimate the parasite burden. We found that the infection in the liver resolved; however, persistent infection was observed in the spleen. Histopathology withLeishmania-specific immunostaining revealed efficient hepatic granuloma formation, while splenic disorganization with parasitized macrophages at different locations was demonstrated. The mRNA expression of Th1 cytokines (IFN-γ, TNF-α, IL-12p40) andiNOSin the liver and spleen was upregulated. In addition, high expression ofIL-10was observed in the spleen in the chronic phase, revealing a significant moderate correlation with the parasite persistence [r(12)= 0.72,P= 0.009]. Further clarification of the mechanisms of persistent infection and experimental infection in immunosuppressed murine models are warranted.
Is Cork Growth a Reliable Proxy for Stem Diameter Growth in Cork Oak (Quercus suber L.)? Implications for Forest Management under Climate Change in Mediterranean Regions
Authors: Costa Augusta , Cherubini Paolo
Published: December 2021

Cork-ring widths have been extensively used in dendroecological studies assessing the relationship between cork growth patterns and climate (precipitation and temperature). Generally, cork growth is assumed as a proxy for stem diameter growth to address cork oak (Quercus suber L.) growth sensitivity to climate and cork yield modeling. Cork growth represents a large part of stem radial increment in this species due to the enhanced activity of phellogen when compared to the cambium activity; thus, similar inter-annual variations of cork-ring widths and tree diameter growth might be expected. However, so far, the influence of rainfall and temperature on stem diameter growth has scarcely been addressed; moreover, it is still not clear whether tree size relates, and in what way, to the variations in radial growth of cork and stem diameter and whether these reflect (proportional) quantitative variations in stem basal area growth. In this study, we computed the annual growth of cork and of stem diameter at breast-height in data series of 47 trees, from 2000 to 2012, corresponding to a full cork production cycle. Results showed a tight link between cork-ring width and stem diameter growth indices. However, while cork growth strongly correlated with climate conditions in autumn–winter prior to the growing season, stem diameter growth correlated with climate conditions of the current growing season, and, more importantly, it was tree size-related. The extrapolation from cork-ring increments to stem basal area growth is likely to progressively underestimate tree growth and biomass increment in larger cork oaks and to further bias it due to climate change effects in the Mediterranean region.
Chemokines in the Landscape of Cancer Immunotherapy: How They and Their Receptors Can Be Used to Turn Cold Tumors into Hot Ones?
Authors: Karin Nathan
Published: December 2021

Over the last decade, monoclonal antibodies to immune checkpoint inhibitors (ICI), also known as immune checkpoint blockers (ICB), have been the most successful approach for cancer therapy. Starting with mAb to cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors in metastatic melanoma and continuing with blockers of the interactions between program cell death 1 (PD-1) and its ligand program cell death ligand 1 (PDL-1) or program cell death ligand 2 (PDL-2), that have been approved for about 20 different indications. Yet for many cancers, ICI shows limited success. Several lines of evidence imply that the limited success in cancer immunotherapy is associated with attempts to treat patients with “cold tumors” that either lack effector T cells, or in which these cells are markedly suppressed by regulatory T cells (Tregs). Chemokines are a well-defined group of proteins that were so named due to their chemotactic properties. The current review focuses on key chemokines that not only attract leukocytes but also shape their biological properties. CXCR3 is a chemokine receptor with 3 ligands. We suggest using Ig-based fusion proteins of two of them: CXL9 and CXCL10, to enhance anti-tumor immunity and perhaps transform cold tumors into hot tumors. Potential differences between CXCL9 and CXCL10 regarding ICI are discussed. We also discuss the possibility of targeting the function or deleting a key subset of Tregs that are CCR8+ by monoclonal antibodies to CCR8. These cells are preferentially abundant in several tumors and are likely to be the key drivers in suppressing anti-cancer immune reactivity.
Recent Developments and Current Status of Commercial Production of Fuel Ethanol
Authors: Hoang Tuan-Dung , Nghiem Nhuan
Published: December 2021

Ethanol produced from various biobased sources (bioethanol) has been gaining high attention lately due to its potential to cut down net emissions of carbon dioxide while reducing burgeoning world dependence on fossil fuels. Global ethanol production has increased more than six-fold from 18 billion liters at the turn of the century to 110 billion liters in 2019, only to fall to 98.6 billion liters in 2020 due to the pandemic. Sugar cane and corn have been used as the major feedstocks for ethanol production. Lignocellulosic biomass has recently been considered as another potential feedstock due to its non-food competing status and its availability in very large quantities. This paper reviews recent developments and current status of commercial production of ethanol across the world with a focus on the technological aspects. The review includes the ethanol production processes used for each type of feedstock, both currently practiced at commercial scale and still under developments, and current production trends in various regions and countries in the world.
Distributed Architectures and Constellations for γ-ray Burst Science
Authors: Fiore Fabrizio , Werner Norbert , Behar Ehud
Published: December 2021

The gravitational wave/γ-ray burst GW/GRB170817 event marked the beginning of the era of multi-messenger astrophysics, in which new observations of Gravitational Waves (GW) are combined with traditional electromagnetic observations from the very same astrophysical source. In the next few years, Advanced LIGO/VIRGO and KAGRA in Japan and LIGO-India will reach their nominal/ultimate sensitivity. In the electromagnetic domain, the Vera C. Rubin Observatory and the Cherenkov Telescope Array (CTA) will come online in the next few years, and they will revolutionize the investigation of transient and variable cosmic sources in the optical and TeV bands. The operation of an efficient X-ray/γ-ray all-sky monitor with good localisation capabilities will play a pivotal role in providing the high-energy counterparts of the GW interferometers and Rubin Observatory, bringing multi-messenger astrophysics to maturity. To reach the required precision in localisation and timeliness for an unpredictable physical event in time and space requires a sensor distribution covering the whole sky. We discuss the potential of large-scale, small-platform-distributed architectures and constellations to build a sensitive X-ray/γ-ray all-sky monitor and the programmatic implications of this, including the set-up of an efficient assembly line for both hardware development and data analysis. We also discuss the potential of a constellation of small platforms operating at other wavelengths (UV/IR) that are capable of repointing quickly to follow-up high-energy transients.
Stiffness Variation of 3D Collagen Networks by Surface Functionalization of Network Fibrils with Sulfonated Polymers
Authors: Riedl Philipp , Schricker Maria , Pompe Tilo
Published: December 2021

Fibrillar collagen is the most prominent protein in the mammalian extracellular matrix. Therefore, it is also widely used for cell culture research and clinical therapy as a biomimetic 3D scaffold. Charged biopolymers, such as sulfated glycosaminoglycans, occur in vivo in close contact with collagen fibrils, affecting many functional properties such as mechanics and binding of growth factors. For in vitro application, the functions of sulfated biopolymer decorations of fibrillar collagen materials are hardly understood. Herein, we report new results on the stiffness dependence of 3D collagen I networks by surface functionalization of the network fibrils with synthetic sulfonated polymers, namely, poly(styrene sulfonate) (PSS) and poly(vinyl sulfonate) (PVS). A non-monotonic stiffness dependence on the amount of adsorbed polymer was found for both polymers. The stiffness dependence correlated to a transition from mono- to multilayer adsorption of sulfonated polymers on the fibrils, which was most prominent for PVS. PVS mono- and multilayers caused a network stiffness change by a factor of 0.3 and 2, respectively. A charge-dependent weakening of intrafibrillar salt bridges by the adsorbed sulfonated polymers leading to fibrillar softening is discussed as the mechanism for the stiffness decrease in the monolayer regime. In contrast, multilayer adsorption can be assumed to induce interfibrillar bridging and an increase in network stiffness. Our in vitro results have a strong implication on in vivo characteristics of fibrillar collagen I, as sulfated glycosaminoglycans frequently attach to collagen fibrils in various tissues, calling for an up to now overlooked impact on matrix and tendon mechanics.
In Situ Pinpoint Photopolymerization of Phos-Tag Polyacrylamide Gel in Poly(dimethylsiloxane)/Glass Microchip for Specific Entrapment, Derivatization, and Separation of Phosphorylated Compounds
Authors: Yamamoto Sachio , Yano Shoko , Kinoshita Mitsuhiro , Suzuki Shigeo
Published: December 2021

An improved method for the online preconcentration, derivatization, and separation of phosphorylated compounds was developed based on the affinity of a Phos-tag acrylamide gel formed at the intersection of a polydimethylsiloxane/glass multichannel microfluidic chip toward these compounds. The acrylamide solution comprised Phos-tag acrylamide, acrylamide, and N,N-methylene-bis-acrylamide, while 2,2′-azobis[2-methyl-N-(2-hydroxyethyl)propionamide] was used as a photocatalytic initiator. The Phos-tag acrylamide gel was formed around the channel crossing point via irradiation with a 365 nm LED laser. The phosphorylated peptides were specifically concentrated in the Phos-tag acrylamide gel by applying a voltage across the gel plug. After entrapment of the phosphorylated compounds in the Phos-tag acrylamide gel, 5-(4,6-dichlorotriazinyl)aminofluorescein (DTAF) was introduced to the gel for online derivatization of the concentrated phosphorylated compounds. The online derivatized DTAF-labeled phosphorylated compounds were eluted by delivering a complex of phosphate ions and ethylenediamine tetraacetic acid as the separation buffer. This method enabled sensitive analysis of the phosphorylated peptides.
Method and Test Bench for Hydro-Mechanical Continuously Variable Transmission Based on Multi-Level Test and Verification
Authors: Dai Hanzheng , Wan Lirong , Zeng Qingliang , Lu Zhenguo , Sun Zhiyuan , Liu Wenting
Published: December 2021

According to the structural characteristics of Hydro-mechanical continuously variable transmission (HMCVT), a multi-functional test bench was developed, and the basic structure, working principle, and test functions of the test bench were introduced. The test bench has the following characteristics: To analyze the impact of mechanical transmission and hydraulic transmission on the HMCVT transmission system, the performance can be tested separately by using a test bench; the coupling characteristics of the hydraulic transmission and mechanical transmission can also be tested; it can also test and verify the performance of the HMCVT transmission system and the control system; the test bench has a simple structure, diverse functions, and convenient operation. Using the multi-functional test bench, this paper proposes a method of multi-level test and verification. Through this method, the simulation models are revised and improved many times, and the accuracy of the models is improved, which are consistent with the physical model, and eventually, the accuracy of the simulation result is improved. This method is used to test and verify the hydraulic transmission system, analyze the characteristics of the hydraulic transmission system, and verify the feasibility and practicability of the multi-level verification method.
Deep Learning Models for Predicting Monthly TAIEX to Support Making Decisions in Index Futures Trading
Authors: Ha Duy-An , Liao Chia-Hung , Tan Kai-Shien , Yuan Shyan-Ming
Published: December 2021

Futures markets offer investors many attractive advantages, including high leverage, high liquidity, fair, and fast returns. Highly leveraged positions and big contract sizes, on the other hand, expose investors to the risk of massive losses from even minor market changes. Among the numerous stock market forecasting tools, deep learning has recently emerged as a favorite tool in the research community. This study presents an approach for applying deep learning models to predict the monthly average of the Taiwan Capitalization Weighted Stock Index (TAIEX) to support decision-making in trading Mini-TAIEX futures (MTX). We inspected many global financial and economic factors to find the most valuable predictor variables for the TAIEX, and we examined three different deep learning architectures for building prediction models. A simulation on trading MTX was then performed with a simple trading strategy and two different stop-loss strategies to show the effectiveness of the models. We found that the Temporal Convolutional Network (TCN) performed better than other models, including the two baselines, i.e., linear regression and extreme gradient boosting. Moreover, stop-loss strategies are necessary, and a simple one could be sufficient to reduce a severe loss effectively.
Steffensen Type Inequalites for Convex Functions on Borel σ-Algebra
Authors: Smoljak Kalamir Ksenija
Published: December 2021

In the paper, we prove Steffensen type inequalities for positive finite measures by using functions which are convex in point. Further, we prove Steffensen type inequalities on Borel σ-algebra for the function of the form f/h which is convex in point. We conclude the paper by showing that these results also hold for convex functions.
Simplified Point-of-Care Full SARS-CoV-2 Genome Sequencing Using Nanopore Technology
Authors: Pembaur Anton , Sallard Erwan , Weil Patrick Philipp , Ortelt Jennifer , Ahmad-Nejad Parviz , Postberg Jan
Published: December 2021

The scale of the ongoing SARS-CoV-2 pandemic warrants the urgent establishment of a global decentralized surveillance system to recognize local outbreaks and the emergence of novel variants of concern. Among available deep-sequencing technologies, nanopore-sequencing could be an important cornerstone, as it is mobile, scalable, and cost-effective. Therefore, streamlined nanopore-sequencing protocols need to be developed and optimized for SARS-CoV-2 variants identification. We adapted and simplified existing workflows using the ‘midnight’ 1200 bp amplicon split primer sets for PCR, which produce tiled overlapping amplicons covering almost the entire SARS-CoV-2 genome. Subsequently, we applied Oxford Nanopore Rapid Barcoding and the portable MinION Mk1C sequencer combined with the interARTIC bioinformatics pipeline. We tested a simplified and less time-consuming workflow using SARS-CoV-2-positive specimens from clinical routine and identified the CT value as a useful pre-analytical parameter, which may help to decrease sequencing failures rates. Complete pipeline duration was approx. 7 h for one specimen and approx. 11 h for 12 multiplexed barcoded specimens. The adapted protocol contains fewer processing steps and can be completely conducted within one working day. Diagnostic CT values deduced from qPCR standardization experiments can act as principal criteria for specimen selection. As a guideline, SARS-CoV-2 genome copy numbers lower than 4 × 106 were associated with a coverage threshold below 20-fold and incompletely assembled SARS-CoV-2 genomes. Thus, based on the described thermocycler/chemistry combination, we recommend CT values of ~26 or lower to achieve full and high-quality SARS-CoV-2 (+)RNA genome coverage.
Diverse Single-Stranded DNA Viruses Identified in Chicken Buccal Swabs
Authors: Chrzastek Klaudia , Kraberger Simona , Schmidlin Kara , Fontenele Rafaela S. , Kulkarni Arun , Chappell Len , Dufour-Zavala Louise , Kapczynski Darrell R. , Varsani Arvind
Published: December 2021

High-throughput sequencing approaches offer the possibility to better understand the complex microbial communities associated with animals. Viral metagenomics has facilitated the discovery and identification of many known and unknown viruses that inhabit mucosal surfaces of the body and has extended our knowledge related to virus diversity. We used metagenomics sequencing of chicken buccal swab samples and identified various small DNA viruses with circular genome organization. Out of 134 putative circular viral-like circular genome sequences, 70 are cressdnaviruses and 26 are microviruses, whilst the remaining 38 most probably represent sub-genomic molecules. The cressdnaviruses found in this study belong to the Circoviridae, Genomoviridae and Smacoviridae families as well as previously described CRESS1 and naryavirus groups. Among these, genomoviruses and smacoviruses were the most prevalent across the samples. Interestingly, we also identified 26 bacteriophages that belong to the Microviridae family, whose members are known to infect enterobacteria.
TES Nanoemulsions: A Review of Thermophysical Properties and Their Impact on System Design
Authors: Iacob-Tudose Eugenia Teodora , Mamaliga Ioan , Iosub Alexandru Vasilica
Published: December 2021

Thermal energy storage materials (TES) are considered promising for a large number of applications, including solar energy storage, waste heat recovery, and enhanced building thermal performance. Among these, nanoemulsions have received a huge amount of attention. Despite the many reviews published on nanoemulsions, an insufficient number concentrate on the particularities and requirements of the energy field. Therefore, we aim to provide a review of the measurement, theoretical computation and impact of the physical properties of nanoemulsions, with an integrated perspective on the design of thermal energy storage equipment. Properties such as density, which is integral to the calculation of the volume required for storage; viscosity, which is a decisive factor in pressure loss and for transport equipment power requirements; and thermal conductivity, which determines the heating/cooling rate of the system or the specific heat directly influencing the storage capacity, are thoroughly discussed. A comparative, critical approach to all these interconnected properties in pertinent characteristic groups, in close association with the practical use of TES systems, is included. This work aims to highlight unresolved issues from previous investigations as well as to provide a summary of the numerical simulation and/or application of advanced algorithms for the modeling, optimization, and streamlining of TES systems.
Pharmacists as Personalized Medicine Experts (PRIME): Experiences Implementing Pharmacist-Led Pharmacogenomic Testing in Primary Care Practices
Authors: Luke Miles J. , Krupetsky Nina , Liu Helen , Korenvain Clara , Crown Natalie , Toenjes Sameera , Sproule Beth A. , Piquette-Miller Micheline , Guirguis Lisa M. , McCarthy Lisa M.
Published: December 2021

Research exploring the integration of pharmacogenomics (PGx) testing by pharmacists into their primary care practices (including community pharmacies) has focused on the “external” factors that impact practice implementation. In this study, additional “internal” factors, related to the capabilities, opportunities, and motivations of pharmacists that influence their ability to implement PGx testing, were analyzed. Semi-structured interview data from the Pharmacists as Personalized Medicine Experts (PRIME) study, which examined the barriers and facilitators to implementing PGx testing by pharmacists into primary care practice, were analyzed. Through thematic analysis, using the theoretical domains framework (TDF) domains as deductive codes, the authors identified the most relevant TDF domains and applied the behavioural change wheel (BCW) to generate intervention types to aid in the implementation of PGx testing. Pharmacists described how their professional identities, practice environments, self-confidence, and beliefs in the benefits of PGx impacted their ability to provide a PGx-testing service. Potential interventions to improve the implementation of the PGx service included preparing pharmacists for managing an increased patient load, helping pharmacists navigate the software and technology requirements associated with the PGx service, and streamlining workflows and documentation requirements. As interest in the wide-scale implementation of PGx testing through community pharmacies grows, additional strategies need to address the “internal” factors that influence the ability of pharmacists to integrate testing into their practices.
Correction: Tantlevskij et al. Network Analysis of the Interaction between Different Religious and Philosophical Movements in Early Judaism. Philosophies 2021, 6, 2
Authors: Tantlevskij Igor R. , Gromova Ekaterina V. , Gromov Dmitry
Published: December 2021

The authors would like to make the following corrections to the published paper [...]
Bodily Contraction Arises with Dukkha: Embodied Learning to Foster Racial Healing
Authors: Nichols Brian J.
Published: December 2021

Black somatic therapist Resmaa Menakem has persuasively argued that racism exist in our bodies more than our heads and that racial healing requires learning to become mindful of our embodied states. The reason that racism remains prevalent despite decades of anti-racist education and the work of diversity and inclusion programs, according to Menakem, is that racist reactions that shun, harm, and kill black bodies are programmed into white, black, and police bodies. The first step in racial healing, from this point of view, is to shift the focus from cognitive solutions to an embodied solution, namely, embodied composure in the face of stressful situations that enables everyone to act more skillfully. Similar to how racial healing has been hampered by a misguided overemphasis on cognitive interventions, might our teaching be analogously encumbered by lack of attention to the bodies of teacher and students? In this article, I emphasize the value of cultivating body awareness in the classroom. I introduce an embodied exercise that teaches students to recognize embodied clues of the experience of dukkha, the first āryasatya. Through such exercises, students take a step towards acting more skillfully and intentionally in stressful situations.
Drivers of the Cash Paradox
Authors: Pietrucha Jacek
Published: December 2021

An upward trend in the share of cash in GDP has been observed since the beginning of the 21st century and has not yet been fully explained in the literature. In fact, the interest rate is the only variable that has been well researched and well confirmed as a determinant of the cash/GDP ratio. The novelty of this study is primarily considering new determinants of the share of cash in GDP (including in particular monetization and financial development), as well as testing the significance of uncertainty and institutions. The data cover the period 2001–2020 for 82 countries. The most important conclusions include: the share of cash in GDP is primarily dependent on its lagged values (payment habits) and the ultra-loose monetary policy of central banks. However, some other variables also contribute to this process—such as monetization and crises in the real economy.