bluuebunny/crossref_metadata_2025 huggingface dataset:
Model-informed approach for risk management of bleeding toxicities for bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1
Authors: Vugmeyster Yulia , Grisic Ana-Marija , Wilkins Justin J. , Loos Anja H. , Hallwachs Roland , Osada Motonobu , Venkatakrishnan Karthik , Khandelwal Akash
Published: September 2022

Purpose

Bintrafusp alfa (BA) is a bifunctional fusion protein composed of the extracellular domain of the transforming growth factor-β (TGF-β) receptor II fused to a human immunoglobulin G1 antibody blocking programmed death ligand 1 (PD-L1). The recommended phase 2 dose (RP2D) was selected based on phase 1 efficacy, safety, and pharmacokinetic (PK)–pharmacodynamic data, assuming continuous inhibition of PD-L1 and TGF-β is required. Here, we describe a model-informed dose modification approach for risk management of BA-associated bleeding adverse events (AEs).

Methods

The PK and AE data from studies NCT02517398, NCT02699515, NCT03840915, and NCT04246489 (n = 936) were used. Logistic regression analyses were conducted to evaluate potential relationships between bleeding AEs and BA time-averaged concentration (Cavg), derived using a population PK model. The percentage of patients with trough concentrations associated with PD-L1 or TGF-β inhibition across various dosing regimens was derived.

Results

The probability of bleeding AEs increased with increasing Cavg; 50% dose reduction was chosen based on the integration of modeling and clinical considerations. The resulting AE management guidance to investigators regarding temporary or permanent treatment discontinuation was further refined with recommendations on restarting at RP2D or at 50% dose, depending on the grade and type of bleeding (tumoral versus nontumoral) and investigator assessment of risk of additional bleeding.

Conclusion

A pragmatic model-informed approach for management of bleeding AEs was implemented in ongoing clinical trials of BA. This approach is expected to improve benefit-risk profile; however, its effectiveness will need to be evaluated based on safety data generated after implementation.
Assessing the effectiveness of indirect questioning techniques by detecting liars
Authors: Perri Pier Francesco , Manoli Eleni , Christofides Tasos C.
Published: September 2022

In many fields of applied research, mostly in sociological, economic, demographic and medical studies, misreporting due to untruthful responding represents a nonsampling error that frequently occurs especially when survey participants are presented with direct questions about sensitive, highly personal or embarrassing issues. Untruthful responses are likely to affect the overall quality of the collected data and flaw subsequent analyses, including the estimation of salient characteristics of the population under study such as the prevalence of people possessing a sensitive attribute. The problem may be mitigated by adopting indirect questioning techniques which guarantee privacy protection and enhance respondent cooperation. In this paper, making use of direct and indirect questions, we propose a procedure to detect the presence of liars in sensitive surveys which allows researchers to evaluate the impact of untruthful responses on the estimation of the prevalence of a sensitive attribute. We first introduce the theoretical framework, then apply the proposal to the Warner randomized response method, the unrelated question model, the item count technique, the crosswise model and the triangular model. To assess the effectiveness of the procedure, a simulation study is carried out. Finally, the presence and the amount of liars is discussed in two real studies concerning racism and workplace mobbing.
Accurate computation of partial volumes in 3D peridynamics
Authors: Scabbia Francesco , Zaccariotto Mirco , Galvanetto Ugo
Published: September 2022

The peridynamic theory is a nonlocal formulation of continuum mechanics based on integro-differential equations, devised to deal with fracture in solid bodies. In particular, the forces acting on each material point are evaluated as the integral of the nonlocal interactions with all the neighboring points within a spherical region, called “neighborhood”. Peridynamic bodies are commonly discretized by means of a meshfree method into a uniform grid of cubic cells. The numerical integration of the nonlocal interactions over the neighborhood strongly affects the accuracy and the convergence behavior of the results. However, near the boundary of the neighborhood, some cells are only partially within the sphere. Therefore, the quadrature weights related to those cells are computed as the fraction of cell volume which actually lies inside the neighborhood. This leads to the complex computation of the volume of several cube–sphere intersections for different positions of the cells. We developed an innovative algorithm able to accurately compute the quadrature weights in 3D peridynamics for any value of the grid spacing (when considering fixed the radius of the neighborhood). Several examples have been presented to show the capabilities of the proposed algorithm. With respect to the most common algorithm to date, the new algorithm provides an evident improvement in the accuracy of the results and a smoother convergence behavior as the grid spacing decreases.
10-year follow-up of interventional electrophysiology: updated German survey during the COVID-19 pandemic
Authors: Eckardt Lars , Doldi Florian , Busch Sonia , Duncker David , Estner H. , Kuniss M. , Metzner A. , Meyer C. , Neuberger H.-R. , Tilz R. , Voss F. , Steven D. , Sommer P.
Published: September 2022

Introduction

This study provides an update of survey-based data providing an overview of interventional electrophysiology over the last decade. Overall infrastructure, procedures, and training opportunities in Germany were assessed.

Methods

By analyzing mandatory quality reports, German cardiology centres performing electrophysiological studies were identified to repeat a questionnaire from 2010 and 2015.

Results

A complete questionnaire was returned by 192 centers performing about 75% of all ablations in Germany in 2020. In the presence of the COVID-19 pandemic, a total of 76.304 procedures including 68.407 ablations were reported representing a 38% increase compared to 2015. The median number of ablations increased from 180 in 2010 to 377 in 2020. AF was the most common arrhythmia ablated (51 vs. 35% in 2010). PVI with radiofrequency point-by-point ablation (64%) and cryo-balloon ablation (34%) were the preferred strategies. Less than 50 (75) PVI were performed by 31% (36%) of all centres. Only 25 and 24% of participating centres fulfilled EHRA and national requirements for training centre accreditation, respectively. There was a high number of EP centres with no fellows (38%). The proportion of female fellows in EP increased from 26% in 2010 to 33% in 2020.

Conclusion

Comparing 2020, 2010 and 2015, an increasing number of EP centres and procedures were registered. In 2020, more than every second ablation was for therapy of AF. In the presence of an increasing number of procedures, training opportunities were still limited, and most centres did not fulfill recommended EHRA or national requirements for accreditation.

Graphical abstract
Chronic cigarette smoking is associated with increased arterial stiffness in men and women: evidence from a large population-based cohort
Authors: Hahad Omar , Schmitt Volker H. , Arnold Natalie , Keller Karsten , Prochaska Jürgen H. , Wild Philipp S. , Schulz Andreas , Lackner Karl J. , Pfeiffer Norbert , Schmidtmann Irene , Michal Matthias , Schattenberg Jörn M. , Tüscher Oliver , Daiber Andreas , Münzel Thomas
Published: September 2022

Background

Cigarette smoking is a threat to global human health and a leading cause of the cardiovascular disease (CVD) morbidity and mortality. Importantly, sex-specific differences in smoking-induced arterial stiffness, an early key event in the development of atherosclerotic CVD, remain still elusive. Thus, this study sought out to investigate sex-specific associations between smoking and measures of arterial stiffness.

Methods and results

Overall, 15,010 participants (7584 men and 7426 women aged 35–74 years) of the Gutenberg Health Study were examined at baseline during 2007–2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a standardized computer-assisted interview. Arterial stiffness and wave reflection were determined by stiffness index (SI) and augmentation index (AI). In the total sample, 45.8% had never smoked, 34.7% were former smokers, and 19.4% were current smokers. Median cumulative smoking exposure was 22.0 pack-years in current male smokers and 16.0 in current female smokers. In general, multivariable linear regression models adjusted for a comprehensive set of confounders revealed that smoking status, pack-years of smoking, and years since quitting smoking were dose-dependently associated with markers of arterial stiffness. In sex-specific analyses, these associations were overall more pronounced in men and SI was stronger related to the male sex, whereas differences between men and women in the case of AI appeared to be less substantial.

Discussion

The present results indicate that chronic smoking is strongly and dose-dependently associated with increased arterial stiffness in a large population-based cohort regardless of sex but with a stronger association in men.
Post-mortem oxycodone blood concentrations of hospitalized cancer and surgery patients compared with fatal poisonings
Authors: Kriikku Pirkko , Kalso Eija , Ojanperä Ilkka
Published: September 2022

Oxycodone is a strong opioid drug commonly used to treat acute, cancer, and chronic non-malignant pain. In this study, all oxycodone-related medico-legal cases where death had occurred in a hospital or nursing home in Finland were investigated to determine the range of post-mortem (PM) oxycodone blood concentrations in a therapeutic setting. All toxicology cases in which oxycodone was detected in PM femoral blood during the 4-year period of 2016–2019 in Finland were retrieved from the national PM toxicology database. In this material, the 365 deceased hospital patient cases that met the study inclusion criteria were divided into four groups according to the cause and manner of death. The reference group of 121 fatal oxycodone poisoning cases comprised two groups: those with verified associated drug abuse and those without drug abuse. The median oxycodone concentration in PM blood was significantly higher in cancer patients (0.10 mg/L) than in patients with recent surgery (0.07 mg/L) or other disease (0.06 mg/L) (p < 0.05). In addition, the median oxycodone concentration was significantly lower in all hospital patient groups than in the poisoning groups, the latter displaying 0.38 mg/L (abuse) and 0.64 mg/L (no abuse) (p < 0.001). This study shows that half of the subjects in the cancer patient group had PM blood oxycodone concentrations above the typical clinical therapeutic plasma concentration range (0.005–0.10 mg/L). Appropriate medication of hospitalized surgery and cancer patients can result in concentrations of up to 0.2 and 0.6 mg/L, respectively, while higher concentrations are exceptional.
Muscle quantitative MRI as a novel biomarker in hereditary transthyretin amyloidosis with polyneuropathy: a cross-sectional study
Authors: Vegezzi Elisa , Cortese Andrea , Bergsland Niels , Mussinelli Roberta , Paoletti Matteo , Solazzo Francesca , Currò Riccardo , Ascagni Lucia , Callegari Ilaria , Quartesan Ilaria , Lozza Alessandro , Deligianni Xeni , Santini Francesco , Marchioni Enrico , Cosentino Giuseppe , Alfonsi Enrico , Tassorelli Cristina , Bastianello Stefano , Merlini Giampaolo , Palladini Giovanni , Obici Laura , Pichiecchio Anna
Published: September 2022

Background

The development of reproducible and sensitive outcome measures has been challenging in hereditary transthyretin (ATTRv) amyloidosis. Recently, quantification of intramuscular fat by magnetic resonance imaging (MRI) has proven as a sensitive marker in patients with other genetic neuropathies. The aim of this study was to investigate the role of muscle quantitative MRI (qMRI) as an outcome measure in ATTRv.

Methods

Calf- and thigh-centered multi-echo T2-weighted spin-echo and gradient-echo sequences were obtained in patients with ATTRv amyloidosis with polyneuropathy (n = 24) and healthy controls (n = 12). Water T2 (wT2) and fat fraction (FF) were calculated. Neurological assessment was performed in all ATTRv subjects. Quantitative MRI parameters were correlated with clinical and neurophysiological measures of disease severity.

Results

Quantitative imaging revealed significantly higher FF in lower limb muscles in patients with ATTRv amyloidosis compared to controls. In addition, wT2 was significantly higher in ATTRv patients. There was prominent involvement of the posterior compartment of the thighs. Noticeably, FF and wT2 did not exhibit a length-dependent pattern in ATTRv patients. MRI biomarkers correlated with previously validated clinical outcome measures, Polyneuropathy Disability scoring system, Neuropathy Impairment Score (NIS) and NIS-lower limb, and neurophysiological parameters of axonal damage regardless of age, sex, treatment and TTR mutation.

Conclusions

Muscle qMRI revealed significant difference between ATTRv and healthy controls. MRI biomarkers showed high correlation with clinical and neurophysiological measures of disease severity making qMRI as a promising tool to be further investigated in longitudinal studies to assess its role at monitoring onset, progression, and therapy efficacy for future clinical trials on this treatable condition.
Can workplace intervention prolong work life of older workers? A quasi-experimental study
Authors: Neupane Subas , Kyrönlahti Saila , Oakman Jodi , Siukola Anna , Riekhoff Aart-Jan , Kuivalainen Susan , Nygård Clas-Håkan
Published: September 2022

Background

We aimed to evaluate the impact of a workplace senior program intervention on early exit from labor market and on the disability retirement among older employees and work-related physical factors associated with it.

Methods

A total of 259 individuals aged 55 + years participated in the study (107 in intervention and 152 were controls). A questionnaire survey was conducted among Finnish food industry employees between 2003 and 2009 and the intervention “senior program” was provided between 2004 and 2009. The type of pension for the respondents who had retired by 2019 was obtained and dichotomized as statutory vs. early labor market exit. Disability pension was investigated as a separate outcome. Information on work-related factors was obtained from the survey. Cox regression analysis was used to estimate hazard ratios (HR) with their 95% confidence intervals.

Results

Fifty-one employees had early labor market exit. Of them, 70% (n = 36) were control participants. Employees in the senior program worked for longer years (mean years 7.4, 95% CI 6.4–8.1) compared to the control (6.6, 95% CI 6.3–7.5). Sixty percent lower risk of early labor market exit (HR 0.40, 95% CI 0.19–0.84) and disability pension was found among employees in the senior program compared to the control group. Good work ability had a 94% lower risk (0.06, 95% CI 0.01–0.29) of early labor market exit and 85% lower risk (0.15, 95% CI 0.03–0.73) of disability pension compared to poor work ability. Employees with musculoskeletal pain had 4 times higher risk of disability pension compared to those without musculoskeletal pain.

Conclusions

A workplace senior program intervention prolonged work life and had positive effect on reducing disability pension among older industrial workers.
Effects of inhaled nitric oxide (iNO) in pulmonary hypertension secondary to arteriovenous malformations: a retrospective cohort study from the European iNO registry
Authors: Chakkarapani Aravanan Anbu , Gupta Samir , Jamil Asma , Yadav Santosh Kumar , Subhedar Nim , Hummler Helmut D.
Published: September 2022

This study aims to assess the effects of inhaled nitric oxide (iNO) on oxygenation in the management of pulmonary hypertension (PH) secondary to arteriovenous malformations (AVMs) in neonates. This is a matched retrospective cohort study from January 1, 2013, to December 31, 2017. The European inhaled nitric oxide registry from 43 neonatal and pediatric ICUs in 13 countries across Europe was used to extract data. The target population was neonates treated with iNO for the management of PH. The cases (PH secondary to AVMs treated with iNO) were matched (1:4 ratio) to controls (PH without AVMs treated with iNO). The main outcome measure was the absolute change of oxygenation index (OI) from baseline to 60 min after starting iNO in cases and controls. The primary outcome of our study was that the mean absolute change in OI from baseline to after 60 min was higher among cases 10.7 (14), than in controls 6 (22.5), and was not statistically different between the groups. The secondary outcome variable — death before discharge — was found to be significantly higher in cases (55%) than in controls (8%). All the other variables for secondary outcome measures remained statistically insignificant.

   Conclusion: Infants with PH secondary to AVMs treated with iNO did not respond differently compared to those presented with PH without AVMs treated with iNO. Right ventricular dysfunction on echocardiography was higher in cases than controls (cases: 66.7% and controls: 28.6%) but was not statistically significant.

What is Known:• Arterioenous malformation (AVM) is a well-known cause of persistent pulmonary hypertension in newborns. Inhaled nitric oxide (iNO) is most commonly used as first-line therapy for pulmonary hypertension in newborns.• Around 40–50% of vein of Galen malformations (VOGMs) are found to have congestive heart failure in the neonatal period.

What is New:• Neonates may present with an isolated PH of the newborn as the main feature of the VOGMs. A large proportion of cases with AVMs have been associated with right ventricular cardiac dysfunction. • Results from one of the largest database registries in the world for iNO have been used to answer our research question.
A new homogenization scheme for beam and plate structures without a priori requirements on boundary conditions
Authors: Müller Maximilian , Klarmann Simon , Gruttmann Friedrich
Published: September 2022

This contribution picks up on a novel approach for a first order homogenization procedure based on the Irving-Kirkwood theory and provides a finite element implementation as well as applications to beam and plate structures. It does not have the fundamental problems of dependency from representative volume element (RVE) size in determining the shear and torsional stiffness for beams and plates, that is present in classic Hill-Mandel methods. Due to the possibility of using minimal boundary conditions whilst simultaneously reusing existing homogenization algorithms, creation of models and numerical implementation are much more straight forward. The presented theory and FE formulation are limited to materially and geometrically linear problems. The approach to determining shear stiffness is based on the assumption of a quadratic shear stress distribution over the height (and width in case of the beam), which causes warping of the cross-section under transverse shear loading. Results for the homogenization scheme are shown for various beam and plate configurations and compared to values from well known analytical solutions or computed full scale models.
Changes in coastal farming systems in a changing climate in Bangladesh
Authors: Hasan Md Kamrul , Kumar Lalit
Published: September 2022

Changes in farming systems are dominated by changes in global climate and local environment, apart from the non-climatic drivers. Given the challenges in partitioning the contribution of climatic and non-climatic factors to the changes in farming systems, this paper aims to assess the types and changes of coastal farming systems, the farmer perceptions of the causes of the changes in farming systems, and the relationship between the influencing factors and perceptions. A structured interview schedule was used to collect data from 381 randomly selected coastal households during September–October 2018. The random forest classification model was applied to estimate the relative importance of the farmers’ characteristics on their perception of causes of changes in farming systems. This study reveals that the coastal farmers had mostly semi-subsistence type of mixed farming systems, which were going through dynamic changes in terms of their sizes and number of farmers. In general, the participation in rice, vegetables, and livestock farming was decreasing but increasing in fisheries, forestry, and fruit farming. Most (95.5%) of the farmers had to change at least one of the farming enterprises over the past decade (2009–2018) compared with the previous decade (1999–2008). About two-thirds of the farmers perceived that climate change had caused changes in their farming systems. Compared with the eastern coasts, the farmers in the western coasts tended to blame climate change to a higher extent for the effect on their agricultural activities. The random forest model outputs imply that the farmers who are younger in age and with less formal education, larger family, and smaller farmland should be supported with scientific knowledge on causes of changes in farming systems. This could help them more aware of climate change issues related to agriculture and increase their enthusiasm to take part in adaptive changes in farming systems.
Examining the role of soft dimensions on the implementation of ISO 14000 environmental management systems: a graph-theoretic approach
Authors: Ali Syed Mithun , Belal H. M. , Roy Sanjeeb , Rahman Md. Tayabur , Raihan Ahmed Shoyeb
Published: September 2022

Organizations worldwide are now embracing different standards while approaching environmental management systems (EMS) to be environmentally and economically sustainable. The ISO 14001 EMS has captured much attention by offering efficient environmental practices organization-wide and throughout the supply chain. Human factors (HFs) are crucial behind implementing ISO 14001 EMS since research articles about ISO 14001 strongly emphasize different HFs. This study proposes a framework that solely focuses on those HFs. Influential HFs are extracted through content analysis of related literature and categorized into 5 main HFs. Opinions from experts in the relevant field about interrelationships and inheritances of the HFs are collected and converted into quantitative data. Incorporating the graph theoretic and matrix approach (GTMA), the data delivered permanent values corresponding to the main HFs and their best and worst possible values. Among the main HFs, EMS Training has been found to have the most scopes for improvement, followed by Employee Empowerment and EMS Teamwork. This study demonstrates a framework about how to assess the role of HFs behind internalizing ISO 14001 EMS and enables organizations to go for competitive benchmarking and to define and adjust goals for environmental management.
Twitter Activists’ Argumentation Through Subdiscussions: Theory, Method and Illustration of the Controversy Surrounding Sustainable Fashion
Authors: Greco Sara
Published: September 2022

“Why are millions of dollars worth of orders being left unpaid?”. With tweets like this questioning brands’ policies, activists advocating for sustainable fashion re-discuss material starting points that are assumed by fashion brands, who argue that they are sustainable because they care about their workers’ conditions. This paper argues that activists use tweets to open subdiscussions on material starting points to engage citizens and consumers, re-discussing factual data that brands take for granted, such as the fact that they provide fair conditions for their garment workers. Activists justify their opening of subdiscussions, often through an argumentative pattern that includes an argument based on the locus from effects to cause. They argue that if there are negative effects, the brand cannot claim to care about the conditions of its workers. In discussing how subdiscussions are used by fashion activists, this paper also introduces a conceptualization of Twitter argumentation as a discussion that is not isolated, but is part of a polylogical argumentation that takes place in different venues. For this reason, the argumentation used in tweets is reconstructed as a response to a fashion brand’s communication campaigns around sustainability, which extend beyond the confines of Twitter. As an empirical illustration, this paper is based on the campaign targeting fashion retailer Primark; the dataset includes the brand’s website as well as activists’ tweets.
Thermal stress and mutation accumulation increase heat shock protein expression in Daphnia
Authors: Scheffer Henry , Coate Jeremy E. , Ho Eddie K. H. , Schaack Sarah
Published: September 2022

Understanding the short- and long-term consequences of climate change is a major challenge in biology. For aquatic organisms, temperature changes and drought can lead to thermal stress and habitat loss, both of which can ultimately lead to higher mutation rates. Here, we examine the effect of high temperature and mutation accumulation on gene expression at two loci from the heat shock protein (HSP) gene family, HSP60 and HSP90. HSPs have been posited to serve as ‘mutational capacitors’ given their role as molecular chaperones involved in protein folding and degradation, thus buffering against a wide range of cellular stress and destabilization. We assayed changes in HSP expression across 5 genotypes of Daphnia magna, a sentinel species in ecology and environmental biology, with and without acute exposure to thermal stress and accumulated mutations. Across genotypes, HSP expression increased ~ 6× in response to heat and ~ 4× with mutation accumulation, individually. Both factors simultaneously (lineages with high mutation loads exposed to high heat) increased gene expression ~ 23×—much more than that predicted by an additive model. Our results corroborate suggestions that HSPs can buffer against not only the effects of heat, but also mutations—a combination of factors both likely to increase in a warming world.
Concise review of the macroalgal species Pelvetia canaliculata (Linnaeus) Decaisne & Thuret
Authors: Lalegerie Fanny , Stengel Dagmar B.
Published: September 2022

Pelvetia canaliculata (L.) Dcne. et Thur. is a marine brown macroalga within the Fucaceae (Fucales, Phaeophyceae, Ochrophyta) and the only species remaining in the monotypic genus Pelvetia. Abundant on sheltered rocky shores of the North-East Atlantic, Pelvetia forms a distinct horizontal band along the upper fringe in the intertidal, between maritime lichens and Fucus spp. Pelvetia canaliculata is a perennial species, characterized by dichotomously branching thalli 10–15 cm in length, forming narrow channels (“channelled wrack”). Distributed on the extreme upper shore, the species is exposed to atmospheric conditions for prolonged periods between spring high tides; photosynthesis recovers quickly, and fully, after water loss. Effective de-epoxidation of the xanthophyll cycle observed in P. canaliculata constitutes an important photoprotective mechanism in this species which receives high doses of solar radiation during tidal emersion. In comparison with other intertidal brown macroalgae, only few studies have investigated its chemical composition. Pelvetia typically presents high levels of sulphated polysaccharides, alginic acid, and polyphenols, associated with antioxidant and other biological activities. It accumulates high levels of mannitol and volemitol, two sugar alcohols considered to be involved in its tolerance to extended emersion. As a natural cation exchanger, Pelvetia biomass displays high biosorption capacities for toxic metals. Besides its slow growth rate and related small quantities of biomass, low protein content coupled with low degradability, have so far limited its potential for valorization.
Suppression of trinucleotide repeat expansion in spermatogenic cells in Huntington’s disease
Authors: Cho In K. , Easley Charles A. , Chan Anthony W. S.
Published: September 2022

Trinucleotide repeats (TNRs) are dispersed throughout the human genome. About 20 loci are related to human diseases, such as Huntington’s disease (HD). A larger TNR instability is predominantly observed in the paternal germ cells in some TNR disorders. Suppressing the expansion during spermatogenesis can provide a unique opportunity to end the vicious cycle of genetic anticipation. Here, using an in vitro differentiation method to derive advanced spermatogenic cells, we investigated the efficacy of two therapeutic agents, araC (cytarabine) and aspirin, on stabilizing TNRs in spermatogenic cells. Two WT patient-derived induced pluripotent stem cell (iPSC) lines and two HD hiPSC lines, with 44 Q and 180 Q, were differentiated into spermatogonial stem cell-like cells (SSCLCs). Both HD cell lines showed CAG tract expansion in SSCLC. When treated with araC and aspirin, HD1 showed moderate but not statistically significant stabilization of TNR. In HD2, 10 nM of aspirin and araC showed significant stabilization of TNR. All cell lines showed increased DNA damage response (DDR) gene expression in SSCLCs while more genes were significantly induced in HD SSCLC. In HD1, araC and aspirin treatment showed general suppression of DNA damage response genes. In HD2, onlyFAN1,OGG1, andPCNAshowed significant suppression. When the methylation profile of HD cells was analyzed,FAN1andOGG1showed significant hypermethylation after the aspirin and araC treatment in SSCLC compared to the control. This study underscores the utility of our in vitro spermatogenesis model to study and develop therapies for TNR disorders such as HD.
Mechanical response during bending of Ni–Mn–Ga-based melt-spun ribbons
Authors: Czaja P. , Kowalska M. , Brzoza-Kos A. , Szczerba M. J.
Published: September 2022

In this paper, we report on mechanical properties observed during bending experiments conducted on quinary Ni–Mn–Ga–Co–Cu melt-spun ribbons. Depending on the ribbon’s side to which force is applied, different mechanical response is noted. Substantially larger mechanical instabilities are observed when force is applied to the “free side” than to the “wheel side” of ribbons. When force is applied to the latter, much lower force fluctuations are recorded and the amplitude of the force–displacement response remains within the experimental resolution limit. It is also shown that the character of the force–displacement curve changes upon cycling; mainly by decreasing the maximum force and mechanical hysteresis. These results are important for materials design and optimization of the magnetic field-induced bending effect recently shown in Ni–Mn–Ga-based melt-spun ribbons.
A lack of a definite correlation between male sub-fertility and single nucleotide polymorphisms in sperm mitochondrial genes MT-CO3, MT-ATP6 and MT-ATP8
Authors: Saleh Jaweesh Mayyas , Hammadeh Mohamad Eid , Dahadhah Fatina W. , Al Smadi Mohammad A. , Al Zoubi Mazhar Salim , Alarjah Manal Issam Abu , Amor Houda
Published: September 2022

Background

An inability of a man to conceive a potentially fertile woman after a year of unprotected intercourse is defined as male infertility. It is reported that 30–40% of males in their reproductive years have abnormalities in sperm production, either qualitatively or quantitatively, or both. However, genetic factors result in up to 15% of male infertility cases. The present study aimed to analyze the possible correlations between sub-fertility and polymorphisms in sperm mitochondrial CO3, ATP6 and ATP8 genes in sub-fertile men.

Methods and results

For 67 sub-fertile and 44 fertile male samples, Sanger sequencing of selected mitochondrial DNA genes was done. A total of twelve SNPs in the MT-CO3 gene: rs2248727, rs7520428, rs3134801, rs9743, rs28358272, rs2853824, rs2856985, rs2854139, rs41347846, rs28380140, rs3902407, and 28,411,821, fourteen SNPs in the MT-ATP6: rs2001031, rs2000975, rs2298011, rs7520428, rs9645429, rs112660509, rs6650105, rs6594033, rs6594034, rs6594035, rs3020563, rs28358887, rs2096044, and rs9283154, and ten SNPs in the MT-ATP8: rs9285835, rs9285836, rs9283154, rs8179289, rs121434446, rs1116906, rs2153588, rs1116905, rs1116907, and rs3020563 were detected in the case and control groups at different nucleotide positions. Only the rs7520428 in the MT-CO3 and MT-ATP6 showed a statistically significant difference between sub-fertile and fertile groups in the genotype’s and allele’s frequency test (P < 0.0001 for both).

Conclusion

The results of our study suggest that male sub-fertility is linked with rs7520428 SNP in MT-CO3 and MT-ATP6. The studied polymorphic variations in the MT-ATP8 gene, on the contrary, did not reveal any significant association with male sub-fertility.
Neuroblastoma SH-SY5Y Cell Differentiation to Mature Neuron by AM580 Treatment
Authors: Cai Aojie , Lin Zehong , Liu Nana , Li Xiao , Wang Jingmin , Wu Ye , Gao Kai , Jiang Yuwu
Published: September 2022

Neuroblastoma is a type of developmental childhood cancer that arises from the neural crest. It is the most common pediatric solid tumor in the world. AM580 is a powerful cyto-differentiating molecule on acute promyelocytic leukemia cells and induced pluripotent stem cells, but its effect on neuroblastoma is still unknown. In this study, the neuronal differentiation impact of AM580 was investigated using the human neuroblastoma cell line SH-SY5Y as a model. AM580 successfully stimulated the SH-SY5Y cells to develop into neuron-like cells. Functional enrichment analysis of RNAseq data revealed that differentially expressed genes (DEGs) were substantially enriched for GO keywords and KEGG pathways linked to neuron development. Some potassium ion channel genes associated with neuronal excitation, such as KCNT1, were shown to be upregulated. Through the MEA tests, we found the AM580-induced neurons possessed electrical spikes as mature neurons. AM580 also induced the neuronal marker β-tubulin III and mature neurons marker Neurofilament H. Our study proved that AM580 can promote the differentiation of neurons and has the potential to treat neuroblastoma, neurodevelopmental and neurodegenerative diseases.
The Dependence of Chance-Corrected Weighted Agreement Coefficients on the Power Parameter of the Weighting Scheme: Analysis and Measurement
Authors: van Oest Rutger
Published: September 2022

We consider the dependence of a broad class of chance-corrected weighted agreement coefficients on the weighting scheme that penalizes rater disagreements. The considered class encompasses many existing coefficients with any number of raters, and one real-valued power parameter defines the weighting scheme that includes linear, quadratic, identity, and radical weights. We obtain the first-order and second-order derivatives of the coefficients with respect to the power parameter and decompose them into components corresponding to all pairs of different category distances. Each component compares its two distances in terms of the ratio of observed to expected-by-chance frequency. A larger ratio for the smaller distance than the larger distance contributes to a positive relationship between the power parameter and the coefficient value; the opposite contributes to a negative relationship. We provide necessary and sufficient conditions for the coefficient value to increase or decrease and the relationship to intensify or weaken as the power parameter increases. We use the first-order and second-order derivatives for corresponding measurement. Furthermore, we show how these two derivatives allow other researchers to obtain quite accurate estimates of the coefficient value for unreported values of the power parameter, even without access to the original data.
Attitudes and Beliefs Associated with Cyberbullying and Non-Consensual Sexting in Cisgender and Transgender Adults
Authors: Mussap Alexander J. , Clancy Elizabeth M. , Klettke Bianca
Published: September 2022

Cyberbullying and non-consensual sexting are prevalent and potentially harmful online behaviours. However, little is known about the attitudes and beliefs that underpin these behaviours in ciswomen and cismen and the extent to which they explain the online experiences of trans and gender diverse (TGD) people. A sample of 638 ciswomen, 722 cismen, and 146 TGD adults 18 to 66 years of age (M = 23.27, SD = 3.66), completed a survey of online perpetration behaviours, victimization experiences, and positive attitudes/beliefs about cyberbullying and sexting. MANCOVAs revealed significant gender differences in terms of both cyber and sexting perpetration and victimization. On average, ciswomen reported 8% less cyberbullying perpetration and 17% less non-consensual sexting perpetration than cismen, and experienced 77% more victimization from non-consensual sexting. TGD adults similarly reported 8% less cyberbullying perpetration than cismen, but also 65% less non-consensual sexting perpetration than cismen, as well as experiencing 77% more victimization from non-consensual sexts. MANCOVAs also revealed that cismen held more positive attitudes and beliefs about cyberbullying and sexting than ciswomen and TGD adults. Multigroup path analyses further revealed that positive attitudes and beliefs were related to perpetration behaviours but differently for different genders, with pro-cyberbullying attitudes/beliefs associated with perpetration behaviours in TGD adults, and pro-sexting attitudes/beliefs associated with perpetration behaviours in cisgender adults. These results highlight gender differences in online perpetration and victimization, extend this observation to TGD populations, and demonstrate the importance of underlying attitudes and beliefs.
A Versatile Micromanipulation Apparatus for Biophysical Assays of the Cell Nucleus
Authors: Currey Marilena L. , Kandula Viswajit , Biggs Ronald , Marko John F. , Stephens Andrew D.
Published: September 2022

Intro

Force measurements of the nucleus, the strongest organelle, have propelled the field of mechanobiology to understand the basic mechanical components of the nucleus and how these components properly support nuclear morphology and function. Micromanipulation force measurement provides separation of the relative roles of nuclear mechanical components chromatin and lamin A.

Methods

To provide access to this technique, we have developed a universal micromanipulation apparatus for inverted microscopes. We outline how to engineer and utilize this apparatus through dual micromanipulators, fashion and calibrate micropipettes, and flow systems to isolate a nucleus and provide force vs. extensions measurements. This force measurement approach provides the unique ability to measure the separate contributions of chromatin at short extensions and lamin A strain stiffening at long extensions. We then investigated the apparatus’ controllable and programmable micromanipulators through compression, isolation, and extension in conjunction with fluorescence to develop new assays for nuclear mechanobiology.

Results

Using this methodology, we provide the first rebuilding of the micromanipulation setup outside of its lab of origin and recapitulate many key findings including spring constant of the nucleus and strain stiffening across many cell types. Furthermore, we have developed new micromanipulation-based techniques to compress nuclei inducing nuclear deformation and/or rupture, track nuclear shape post-isolation, and fluorescence imaging during micromanipulation force measurements.

Conclusion

We provide the workflow to build and use a micromanipulation apparatus with any inverted microscope to perform nucleus isolation, force measurements, and various other biophysical techniques.
Case Series Analysis of Male Breast Cancer
Authors: Li Chao , Li Xujun
Published: September 2022

Male breast cancer is a rare disease, accounting for less than 1% of all cases of breast cancer. However, the incidence of male breast cancer is increasing. In this study, we systematically analyzed the cases of male breast cancer and evaluated the management of operable male breast cancer in daily clinical practice according to the international clinical guidelines. Data of male breast cancer characteristics and management were recorded from our electronic database. We present a case series of male breast cancer patients treated at our institution between 2013 and 2021 and summarize the recommendations on management of male patients with breast cancer. Twenty-six patients met the search criteria. The majority of tumors were hormone-receptor positive and human epidermal growth factor receptor 2 negative. Two tumors were derived from axillary accessory breast. All patients underwent mastectomy. Fifteen patients received adjuvant chemotherapy containing anthracycline or taxane. Ten patients received adjuvant radiotherapy for lymph node metastasis. Twenty-five patients received adjuvant endocrine therapy. None of patients received anti-human epidermal growth factor receptor 2 therapy. During the median follow-up period of 37 months, one patient died of previous lung cancer recurrence and one patient developed lung metastases 2 years after breast surgery. No recurrence or distant metastasis occurred in the other twenty-four patients. The incidence of male breast cancer is low. In this study, we present twenty-six cases of male patients with operable breast cancer in our department. All of them received surgery and adjuvant treatment. Early diagnosis and combined therapy benefit male patients with breast cancer. Surgery together with adjuvant treatment can bring a good prognosis.
Automatic event detection in football using tracking data
Authors: Vidal-Codina Ferran , Evans Nicolas , El Fakir Bahaeddine , Billingham Johsan
Published: September 2022

One of the main shortcomings of event data in football, which has been extensively used for analytics in the recent years, is that it still requires manual collection, thus limiting its availability to a reduced number of tournaments. In this work, we propose a deterministic decision tree-based algorithm to automatically extract football events using tracking data, which consists of two steps: (1) a possession step that evaluates which player was in possession of the ball at each frame in the tracking data, as well as the distinct player configurations during the time intervals where the ball is not in play to inform set piece detection; (2) an event detection step that combines the changes in ball possession computed in the first step with the laws of football to determine in-game events and set pieces. The automatically generated events are benchmarked against manually annotated events and we show that in most event categories the proposed methodology achieves $$+90\%$$

+
90
%

detection rate across different tournaments and tracking data providers. Finally, we demonstrate how the contextual information offered by tracking data can be leveraged to increase the granularity of auto-detected events, and exhibit how the proposed framework may be used to conduct a myriad of data analyses in football.
Identification of Q value and angular frequency of smart gear antenna using the resonant return loss of the receiving antenna
Authors: Mac Thanh-Tung , Iba Daisuke , Matsushita Yusuke , Inoue Takeru , Miura Nanako , Masuda Arata , Moriwaki Ichiro
Published: September 2022

A wireless smart gear system has been being developed as a gear health monitoring system. This system works based on the magnetic coupling between its two major elements consisting of a monitoring antenna and a smart gear. In operation, the smart gear works as a working gear in the power transmission system while the monitoring antenna monitors this gear continuously. Specifically, since the monitoring antenna is fixed and kept connecting to a network analyzer during the gear operation, it allows the magnetic coupling to occur and remain thoroughly. As a result, the return loss signal of the monitoring antenna becomes a resonant return loss data of the smart gear system. In this paper, the authors propose a method to use this resonant return loss signal for identifying two parameters called the $$Q$$
Q
value and the angular frequency of the smart gear side antenna. There are three cases of magnetic coupling that have been considered. These cases are called Open, Short, and Loaded by a 50 [Ω] resistor where the characteristics of the antenna on the smart gear side are changed via its connector by leaving Open or connecting to a Short and a 50 [Ω] resistor modules, respectively. The results indicate that the method is effective for parameter identification of the $$Q$$
Q
value and the angular frequency of the smart gear side antenna for all three cases. Moreover, the analysis of the validated $$Q$$
Q
value and the angular frequency also indicates the relation between these two characteristic values and the practical conditions of the smart gear. This finding consolidates the effectiveness of our developing wireless smart gear system.

Article Highlights

This article proposes a parameter identification method for a developing smart gear health monitoring system. By only using the resonant return loss data obtained from the monitoring antenna, there are two characteristic values of the smart gear have been achieved.

This article also introduces a completed return loss equation of a magnetically coupled system. This return loss equation is helpful for the computation of characteristic parameters of the magnetically coupled system such as a wireless power transfer system or a coupled antenna system.

The results figure out that the identified characteristic parameters and the physical condition of the smart gear side’s antenna circuit are related to each other. This finding affirms the effectiveness of not only the proposed parameter identification method but also the developing smart gear system.
Recycling Interdisciplinary Evidence: Abandoned Hypotheses and African Historiologies in the Settlement History of Littoral East Africa
Authors: Ray Daren E.
Published: September 2022

Scholars can elevate African voices as they recycle evidence from abandoned lines of research. This article discusses how to apply the confirmation and recycling methods of interdisciplinary research to engage with African historiologies. After reviewing contentious debates about Shungwaya from ca. 1955–2000, it draws on Mijikenda elder Thomas Govi’s descriptions of uganga and clanship (in a published collection of oral traditions) as a historiological theory for reimagining cross-linguistic collaborations, the formation of “stone towns,” and Islamic conversion in the settlement history of littoral East Africa.
Critical Junctures and Ontological Security in Unrecognized States: The Response of Northern Cyprus to the COVID-19 Pandemic
Authors: Gülseven Enver
Published: September 2022

This article will examine the response of the self-declared Turkish Republic of Northern Cyprus (TRNC) to the COVID-19 pandemic from an ontological security approach to illustrate how critical junctures may help de facto states in their quest for status and internal legitimacy. Stressing the pandemic’s role in the reconstruction of political narratives and self-legitimating practices among Turkish Cypriot elites, it sheds light on the effects of this global crisis on domestic power struggles in Northern Cyprus as well as its quasi-foreign relations with its patron state (Turkey), parent state (Republic of Cyprus), and the European Union. The study shows that both nationalist and federalist elites of the de facto entity instrumentalized the pandemic in their legitimation strategies and engaged in opportunistic behavior amid the outbreak. It also reveals how the pandemic enhanced the ontological security of Northern Cyprus while advancing its nationalist leadership’s claims for legitimate authority by enabling state-specific forms of agency and unilateral acts concerning the Cyprus dispute that may jeopardize the resumption of peace talks with Greek Cypriots. Thus, it can be assumed that advanced ontological security of the TRNC is highly volatile given the prospects of further isolation and de-engagement in the post-pandemic era.