bluuebunny/crossref_metadata_2025 huggingface dataset:
Brigatinib in Japanese patients with tyrosine kinase inhibitor-naive ALK-positive non-small cell lung cancer: first results from the phase 2 J-ALTA study
Authors: Sugawara Shunichi , Kondo Masashi , Yokoyama Toshihide , Kumagai Toru , Nishio Makoto , Goto Koichi , Nakagawa Kazuhiko , Seto Takashi , Yamamoto Nobuyuki , Kudou Kentarou , Asato Takayuki , Zhang Pingkuan , Ohe Yuichiro
Published: August 2022

Background

We evaluated the safety and efficacy of the anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) brigatinib in Japanese patients with TKI-naive ALK-positive non-small cell lung cancer (NSCLC) from the phase 2, open-label, single-arm, multicenter J-ALTA study.

Methods

In the TKI-naive cohort of J-ALTA, the primary end point was independent review committee (IRC)-assessed 12-month progression-free survival (PFS). Secondary end points included objective response rate (ORR), intracranial response, overall survival (OS), and safety.

Results

The data were cut approximately 12 months after last patient enrollment. Thirty-two patients with ALK TKI-naive ALK-positive NSCLC were enrolled (median age [range], 60.5 [29–85] years; median duration of follow-up, 14.2 [3.2–19.3] months; median treatment duration, 13.8 [0.4–19.3] months). IRC-assessed 12-month PFS was 93.0% (90% confidence interval (CI) 79.2–97.8%); ORR, 96.9% (95% CI 83.8–99.9%), 12-month OS, 96.9% (95% CI 79.8–99.6%), and median OS was not reached. Of five patients with measurable baseline CNS metastases, two had partial intracranial response. The most common treatment-emergent adverse events were increased blood creatine phosphokinase (81%), hypertension (59%), and diarrhea (47%). Grade ≥ 3 adverse events occurred in 91% of patients; pneumonitis was reported in 3 (9%) patients.

Conclusions

In the J-ALTA TKI-naive cohort, brigatinib demonstrated clinically meaningful efficacy consistent with the international phase 3 study. The safety profile in Japanese patients was consistent with previous studies. Brigatinib is an important first-line option for Japanese patients with ALK-positive NSCLC.

Clinical registration

NCT03410108
Required distal mesorectal resection margin in partial mesorectal excision: a systematic review on distal mesorectal spread
Authors: Grüter A. A. J. , van Lieshout A. S. , van Oostendorp S. E. , Ket J. C. F. , Tenhagen M. , den Boer F. C. , Hompes R. , Tanis P. J. , Tuynman J. B.
Published: August 2022

Background

The required distal margin in partial mesorectal excision (PME) is controversial. The aim of this systematic review was to determine incidence and distance of distal mesorectal spread (DMS).

Methods

A systematic search was performed using PubMed, Embase and Google Scholar databases. Articles eligible for inclusion were studies reporting on the presence of distal mesorectal spread in patients with rectal cancer who underwent radical resection.

Results

Out of 2493 articles, 22 studies with a total of 1921 patients were included, of whom 340 underwent long-course neoadjuvant chemoradiotherapy (CRT). DMS was reported in 207 of 1921 (10.8%) specimens (1.2% in CRT group and 12.8% in non-CRT group), with specified distance of DMS relative to the tumor in 84 (40.6%) of the cases. Mean and median DMS were 20.2 and 20.0 mm, respectively. Distal margins of 40 mm and 30 mm would result in 10% and 32% residual tumor, respectively, which translates into 1% and 4% overall residual cancer risk given 11% incidence of DMS. The maximum reported DMS was 50 mm in 1 of 84 cases. In subgroup analysis, for T3, the mean DMS was 18.8 mm (range 8–40 mm) and 27.2 mm (range 10–40 mm) for T4 rectal cancer.

Conclusions

DMS occurred in 11% of cases, with a maximum of 50 mm in less than 1% of the DMS cases. For PME, substantial overtreatment is present if a distal margin of 5 cm is routinely utilized. Prospective studies evaluating more limited margins based on high-quality preoperative magnetic resonance imaging and pathological assessment are required.
Genetic variability of indigenous (Quercus robur L.) and late flushing oak (Quercus robur L. subsp. slavonica (Gáyer) Mátyás) in adult stands compared with their natural regeneration
Authors: Burger Katrin , Gailing Oliver
Published: August 2022

Slavonian oak (Quercus robur subsp. slavonica (Gáyer) Mátyás) is currently gaining interest in forestry due to forest restructuring in Germany caused by climate change. Slavonian oaks originating from Croatia have been introduced into Germany mainly in the Münsterland region of North Rhine-Westphalia since the second half of the nineteenth century. They are characterized by their late bud burst, long clear bole, stem straightness and faster height and diameter growth compared to indigenous oaks in Germany. In this study, the genetic differentiation of adult trees and their respective progeny of two Slavonian and two indigenous stands in Hamm-Westtünnen, was evaluated. Genetic diversity and structure were estimated using 23 nuclear simple sequence repeat (SSRs) and 5 maternally inherited chloroplast microsatellite markers (cpSSRs). The mean expected heterozygosity of 0.545 and allelic richness of 6.23 indicate high genetic diversity in the studied populations. The group of progenies (AR = 8.40, Ho = 0.524, He = 0.559, FIS = 0.064) shows similar levels of genetic variation as the adult stands (AR = 8.37, Ho = 0.513, He = 0.554, FIS = 0.075). The genetic differentiation between adult stands and progeny was low (FST = 0.013). Genetic assignment of individuals using STRUCTURE revealed that the studied populations were divided into two clusters. There was no evidence of extensive hybridization or gene flow between Slavonian and native populations, possibly due to the different timing of bud burst of the two taxa.
Eighteen Months of COVID-19 Pandemic Through the Lenses of Self or Others: A Meta-Analysis on Children and Adolescents’ Mental Health
Authors: Raccanello Daniela , Rocca Emmanuela , Vicentini Giada , Brondino Margherita
Published: August 2022

Background

The COVID-19 pandemic can have a serious impact on children and adolescents’ mental health. We focused on studies exploring its traumatic effects on young people in the first 18 months after that the pandemic was declared, distinguishing them also according to the type of informants (self-report and other-report instruments).

Objective

We applied a meta-analytic approach to examine the prevalence of depression, anxiety, posttraumatic stress disorder, and psychological distress among children and adolescents during the COVID-19 pandemic, considering the moderating role of kind of disorder and/or symptom, type of instrument, and continent.

Method

We used PsycINFO, PubMed, and Scopus databases to identify articles on the COVID-19 pandemic, applying the following filters: participants until 20 years of age, peer-review, English as publication language. Inclusion required investigating the occurrence of disorders and/or symptoms during the first 18 months of the pandemic. The search identified 26 publications.

Results

The meta-analysis revealed that the pooled prevalence of psychological disorders and/or symptoms for children and adolescents, who were not affected by mental health disturbances before the outbreak of the COVID-19 pandemic, was .20, 95% CI [.16, .23]. Moreover, we found a moderating role of type of instrument: occurrence was higher for self-report compared to other-report instruments.

Conclusions

The study presented an analysis of the psychological consequences for children and adolescents of the exposure to the COVID-19 pandemic, soliciting further research to identify factors underlying resilience. Notwithstanding limitations such as the small number of eligible articles and the fact that we did not examine the role of further characteristics of the studies (such as participants’ age or design), this meta-analysis is a first step for future research documenting the impact of such an unexpected and devastating disaster like the COVID-19 pandemic.
ACOT7 protects epidermal stem cells against lipid peroxidation
Authors: Zhang Guang , Ma Jiaxu , Wu Zhenjie , Cao Guoqi , Liu Chunyan , Song Ru , Sun Rui , Chen Aoyu , Wang Yibing , Yin Siyuan
Published: August 2022

Epidermal stem cells (ESCs) are critical for skin regeneration and repair. Previous studies have shown that ESCs are susceptible to oxidative stress, which in turn leads to lipid peroxidation and affects skin repair. Our study aims to explore how ESCs resist lipid peroxidation. By performing proteomics analysis, we found that the expression of Acyl-CoA thioesterase 7 (ACOT7) was positively correlated with the concentration of transferrin. Overexpression adenovirus vectors of ACOT7 were constructed and transfected into ESCs. Levels of lipid peroxidation by flow cytometry, cell viabilities, and MDA levels were measured. The results revealed that ACOT7 could inhibit lipid peroxidation, reduce the level of malondialdehyde (MDA), and improve the survival rate of ESCs induced by H2O2, Erastin, and RSL3. Our data suggest that ACOT7 has an effect on protecting ESCs against iron-dependent lipid peroxidation.
Changes in biomarkers of exposure and biomarkers of potential harm after 360 days in smokers who either continue to smoke, switch to a tobacco heating product or quit smoking
Authors: Gale Nathan , McEwan Michael , Hardie George , Proctor Christopher J. , Murphy James
Published: August 2022

The aim of this study was to investigate whether biomarkers of exposure (BoE) and potential harm (BoPH) are modified when smokers either continue to smoke or switch from smoking cigarettes to exclusive use of a tobacco heating product (THP) in an ambulatory setting over the period of a year, and to compare any changes with smokers who quit tobacco use completely and with never smokers’ biomarker levels. Participants in this year-long ambulatory study were healthy smokers with a self-reported low intent to quit assigned either to continue smoking or switch to a THP; a group of smokers with a self-reported high intent to quit who abstained from tobacco use; and a group of never smokers. Various BoE and BoPH related to oxidative stress, cardiovascular and respiratory diseases and cancer were assessed at baseline and up to 360 days. Substantial and sustained reductions in BoE levels were found at 360 days for both participants who switched from smoking to THP use and participants who quit smoking, in many cases the reductions being of a similar order for both groups. The never smoker group typically had lower levels of the measured BoEs than either of these groups, and much lower levels than participants who continued to smoke. Several BoPHs were found to change in a favourable direction (towards never smoker levels) over the year study for participants who completely switched to THP or quit, while BoPHs such as soluble intercellular adhesion molecule-1 were found to change in an unfavourable direction (away from never smoker levels) in participants who continued to smoke. Our findings, alongside chemical and toxicological studies undertaken on the THP used in this study, lead to the conclusion that smokers who would have otherwise continued to smoke and instead switch entirely to the use of this THP, will reduce their exposure to tobacco smoke toxicants and as a consequence are reasonably likely to reduce disease risks compared to those continuing to smoke.
Environmental disruptors and testicular cancer
Authors: Faja Fabiana , Esteves Sandro , Pallotti Francesco , Cicolani Gaia , Di Chiano Silvia , Delli Paoli Enrico , Lenzi Andrea , Lombardo Francesco , Paoli Donatella
Published: August 2022

Purpose

Testicular cancer (TC) is the most common malignancy among young adult males. The etiology is multifactorial, and both environmental and genetic factors play an essential role in the origin and development of this tumor. In particular, exposure to environmental endocrine disruptors (EEDs), resulting from industrialization and urbanization, seems crucial both in pre-and postnatal life. However, the lack of long-term studies on a wide caseload and the difficulty in evaluating their toxic effects in vivo make it challenging to establish a causal link. This review aims to discuss the main human epidemiological studies currently available in the literature to define a possible association between these chemicals and TC.

Methods

A comprehensive Medline/PubMed and Embase search was performed, selecting all relevant, peer-reviewed papers in English published from 2002 to January 2022. Other relevant papers were selected from the reference lists.

Results

To date, literature evidence is limited due to the scarcity and heterogeneity of human studies and shows controversial data, highlighting the complexity of the topic. However, most human epidemiological studies seem to point toward a correlation between EEDs exposure and TC.

Conclusion

Although the molecular mechanisms are not yet fully understood, the role of EEDs in TC onset is plausible, but several factors, such as the individual genetic background, the exposure time, and the complex mechanism of action of these chemicals, do not allow defining the causal link with certainty and make further studies necessary to investigate this complex topic.
Hepatitis E Virus in Water Environments: A Systematic Review and Meta-analysis
Authors: Takuissu G. R. , Kenmoe S. , Ndip L. , Ebogo-Belobo J. T. , Kengne-Ndé C. , Mbaga D. S. , Bowo-Ngandji A. , Oyono M. G. , Kenfack-Momo R. , Tchatchouang S. , Kenfack-Zanguim J. , Lontuo Fogang R. , Zeuko’o Menkem E. , Kame-Ngasse G. I. , Magoudjou-Pekam J. N. , Nkie Esemu S. , Veneri C. , Mancini P. , Bonanno Ferraro G. , Iaconelli M. , Suffredini E. , La Rosa G.
Published: August 2022

Hepatitis E virus (HEV) is responsible for acute hepatitis in humans, through foodborne, zoonotic, and waterborne transmission routes. This study aimed to assess the prevalence of HEV in water matrices. Six categories were defined: untreated and treated wastewater, surface water (river, lake, and seawater), drinking water, groundwater, and other water environments (irrigation water, grey water, reservoir water, flood water, and effluent of pig slaughterhouse). We searched PubMed, Web of Science, Global Index Medicus, and Excerpta Medica Database. Study selection and data extraction were performed by at least two independent investigators. Heterogeneity (I2) was assessed using the χ2 test on the Cochran Q statistic and H parameter. Sources of heterogeneity were explored by subgroup analysis. This study is registered with PROSPERO, number CRD42021289116. We included 87 prevalence studies from 58 papers, 66.4% of which performed in Europe. The overall prevalence of HEV in water was 9.8% (95% CI 6.4–13.7). The prevalence was higher in untreated wastewater (15.1%) and lower in treated wastewater (3.8%) and in drinking water (4.7%). In surface water, prevalence was 7.4%, and in groundwater, the percentage of positive samples, from only one study available, was 8.3%. Overall, only 36.8% of the studies reported the genotype of HEV, with genotype 3 (HEV-3) prevalent (168 samples), followed by HEV-1 (148 sample), and HEV-4 (2 samples). High-income countries were the most represented with 59/87 studies (67.8%), while only 3/87 (3.5%) of the studies were performed in low-income countries. The overall prevalence obtained of this study was generally higher in industrialized countries. Risk of bias was low in 14.9% of the studies and moderate in 85.1%. The results of this review showed the occurrence of HEV in different waters environments also in industrialized countries with sanitation and safe water supplies. While HEV transmission to humans through water has been widely demonstrated in developing countries, it is an issue still pending in industrialized countries. Better knowledge on the source of pollution, occurrence, survival in water, and removal by water treatment is needed to unravel this transmission path.

Graphical Abstract
Commissioning NIS 1 kN·m Primary Torque Standard Machine
Authors: Khaled K. M. , Aggag Gamal A.
Published: August 2022

The presented work shows the design and evaluation of the NIS 1 kN·m primary torque standard machine. The machine covers the range up to 1000 N·m with a very wide range of torque steps thanking different 4 mass stacks. The machine has a double-side lever arm with half-moon ends to provide calibration in the clockwise and anticlockwise directions. An air bearing was used as a fulcrum to provide a low friction coefficient. FEA was used in the design and optimization process of the lever arm. The relative expanded uncertainty of the machine is 0.03% which is proved by recalibration of two reference torque transducers of 200 N·m and 1000 N·m capacity. All En values are less than unity, which reveals the competence of the developed machine.
Calibration of pneumatic multi-hole probes for transonic turbomachinery flows
Authors: Bachner Johannes R. , Pahs Andreas , Weggler Philipp , Kocian Frank , Rößling Marcel
Published: August 2022

The calibration data of a five-hole probe and a six-hole probe designed for measurements in transonic turbomachinery flows are presented. The probes feature a special base pressure hole on the back side to avoid the Mach number insensitivity of pressure probes near Mach number unity. There is only little literature available on the performance of such probes, especially in flows with large radial flow angles. To close this gap, the probes are calibrated for radial flow angles up to 32$$^\circ$$

∘

. A significant influence of this flow angle on the coefficients used for Mach number determination is shown. At large positive flow angles, the relationship between the pressure coefficient using the base pressure and the Mach number is not biunique for the six-hole probe. Therefore, an experimental study of Mach number measurement deviations is performed at the calibration wind tunnel. Different evaluation methods are examined. The sample standard deviation over 210 randomly distributed points is reduced by 66% compared to the same probe design without the base pressure hole. This is achieved using two calibration coefficients for the Mach number simultaneously in a multidimensional interpolation.
Feynman–Kac formula for perturbations of order $$\le 1$$, and noncommutative geometry
Authors: Boldt Sebastian , Güneysu Batu
Published: August 2022

Let Q be a differential operator of order $$\le 1$$

≤
1

on a complex metric vector bundle $$\mathscr {E}\rightarrow \mathscr {M}$$

E
→
M

with metric connection $$\nabla $$
∇
over a possibly noncompact Riemannian manifold $$\mathscr {M}$$
M
. Under very mild regularity assumptions on Q that guarantee that $$\nabla ^{\dagger }\nabla /2+Q$$

∇
†

∇
/
2
+
Q

canonically induces a holomorphic semigroup $$\mathrm {e}^{-zH^{\nabla }_{Q}}$$

e

-
z

H
Q
∇

in $$\Gamma _{L^2}(\mathscr {M},\mathscr {E})$$

Γ

L
2

(
M
,
E
)

(where z runs through a complex sector which contains $$[0,\infty )$$

[
0
,
∞
)

), we prove an explicit Feynman–Kac type formula for $$\mathrm {e}^{-tH^{\nabla }_{Q}}$$

e

-
t

H
Q
∇

, $$t>0$$

t
>
0

, generalizing the standard self-adjoint theory where Q is a self-adjoint zeroth order operator. For compact $$\mathscr {M}$$
M
’s we combine this formula with Berezin integration to derive a Feynman–Kac type formula for an operator trace of the form $$\begin{aligned} \mathrm {Tr}\left( \widetilde{V}\int ^t_0\mathrm {e}^{-sH^{\nabla }_{V}}P\mathrm {e}^{-(t-s)H^{\nabla }_{V}}\mathrm {d}s\right) , \end{aligned}$$

Tr

V
~

∫
0
t

e

-
s

H
V
∇

P

e

-

(
t
-
s
)

H
V
∇

d
s

,

where $$V,\widetilde{V}$$

V
,

V
~

are of zeroth order and P is of order $$\le 1$$

≤
1

. These formulae are then used to obtain a probabilistic representations of the lower order terms of the equivariant Chern character (a differential graded extension of the JLO-cocycle) of a compact even-dimensional Riemannian spin manifold, which in combination with cyclic homology play a crucial role in the context of the Duistermaat–Heckmann localization formula on the loop space of such a manifold.
From non-unitary wheeled PROPs to smooth amplitudes and generalised convolutions
Authors: Clavier Pierre J. , Foissy Loïc , Paycha Sylvie
Published: August 2022

We introduce the concept of TRAP (Traces and Permutations), which can roughly be viewed as a wheeled PROP (Products and Permutations) without unit. TRAPs are equipped with a horizontal concatenation and partial trace maps. Continuous morphisms on an infinite-dimensional topological space and smooth kernels (respectively, smoothing operators) on a closed manifold form a TRAP but not a wheeled PROP. We build the free objects in the category of TRAPs as TRAPs of graphs and show that a TRAP can be completed to a unitary TRAP (or wheeled PROP). We further show that it can be equipped with a vertical concatenation, which on the TRAP of linear homomorphisms of a vector space, amounts to the usual composition. The vertical concatenation in the TRAP of smooth kernels gives rise to generalised convolutions. Graphs whose vertices are decorated by smooth kernels (respectively, smoothing operators) on a closed manifold form a TRAP. From their universal properties we build smooth amplitudes associated with the graph.
Development of non-fullerene electron acceptors for efficient organic photovoltaics
Authors: He Qiao , Kafourou Panagiota , Hu Xiantao , Heeney Martin
Published: August 2022

Compared to fullerene based electron acceptors, n-type organic semiconductors, so-called non-fullerene acceptors (NFAs), possess some distinct advantages, such as readily tuning of optical absorption and electronic energy levels, strong absorption in the visible region and good morphological stability for flexible electronic devices. The design and synthesis of new NFAs have enabled the power conversion efficiencies (PCEs) of organic photovoltaic (OPV) devices to increase to around 19%. This review summarises the important breakthroughs that have contributed to this progress, focusing on three classes of NFAs, i.e. perylene diimide (PDI), diketopyrrolopyrrole (DPP) and acceptor–donor–acceptor (A-D-A) based NFAs. Specifically, the PCEs of PDI, DPP, and A-D-A series based non-fullerene OPVs have been reported up to 11%, 13% and 19%, respectively. Structure–property relationships of representative NFAs and their impact on OPV performances are discussed. Finally, we consider the remaining challenges and promising directions for achieving high-performing NFAs.
The radical ambiguity at the heart of Pierre Bourdieu’s critique of journalism
Authors: Harrison Steve
Published: August 2022

The influence of media theorist and sociologist of the journalistic field Pierre Bourdieu has been widespread since his death in 2002 yet his relationship with journalism was at best an ambivalent one. On the one hand, he acknowledged journalism’s primary role in shaping public discourse, and his ideas have spurred on journalism researchers and writers. On the other, he authored a best-selling polemic which offered a withering analysis of what he saw as television’s malign influence over not only journalism but cultural production as a whole. Through a close reading of key texts, this paper identifies an underlying ambiguity within Bourdieu’s writings regarding the status and legitimacy of journalism. It argues that this ambiguity produces theoretical effects which work against—or at least outside—the self-declared aims of field theory to provide the tools for an objective critique of journalism by smuggling into the theory terms which are value-laden. Finally, some of the epistemological and ontological grounds on which Bourdieu’s thought has been labelled as reductionist are considered. This fresh perspective helps to re-contextualise Bourdieu’s important contribution to journalism studies.
Speciesist bias in AI: how AI applications perpetuate discrimination and unfair outcomes against animals
Authors: Hagendorff Thilo , Bossert Leonie N. , Tse Yip Fai , Singer Peter
Published: August 2022

Massive efforts are made to reduce biases in both data and algorithms to render AI applications fair. These efforts are propelled by various high-profile cases where biased algorithmic decision-making caused harm to women, people of color, minorities, etc. However, the AI fairness field still succumbs to a blind spot, namely its insensitivity to discrimination against animals. This paper is a critical comment on current fairness research in AI. It is the first to describe the ‘speciesist bias’ and investigate it in several different AI systems by reflecting on the problem via a normative analysis and by probing, in several case studies, image recognition, word embedding, and language models with established methods for bias detection. We claim that animals matter morally and that discriminating against them is unethical. Furthermore, we provide evidence for speciesist biases in all the mentioned areas of AI. We find that speciesist biases are solidified by many mainstream AI applications, especially in the fields of computer vision as well as natural language processing. In both cases, this occurs because the models are trained on datasets in which speciesist patterns prevail. Therefore, AI technologies currently play a significant role in perpetuating and normalizing violence against animals. To change this, AI fairness frameworks must widen their scope and include mitigation measures for speciesist biases. This paper addresses the AI community in this regard and stresses the influence AI systems can have on either increasing or reducing the violence that is inflicted on animals, especially on farmed animals.
Deep House - datasets, estrangement, and the problem of the new
Authors: del Campo Matias
Published: August 2022

The purpose of this article is to discuss the application of artificial intelligence (AI) in the design of the Deep House project (Fig. 1), an attempt to use estrangement as a method to emancipate a house from a canonical approach to the progressive design of a one-family house project. The main argument in this text is that the results created by Artificial Neural Networks (ANNs), whether in the form of GANs, CNNs, or other networks, generate results that fall into the category of Estranged objects. In this article, I would like to offer a possible definition of what architecture in this plateau of thinking represents and how it differentiates from previous attempts to use estrangement to explain the phenomena observed when working with NNs in architecture design. A potpourri of thoughts that demonstrate the intellectual tradition of exploring estrangement, especially in theater and literature, that ultimately circles back to its implications for architecture, particularly in light of the application of AI.
Identity
Authors: Shumener Erica
Published: August 2022

Identity criteria are powerful tools for the metaphysician. They tell us when items are identical or distinct. Some varieties of identity criteria also try to explain in virtue of what items are identical or distinct. This Element has two objectives: to discuss formulations of identity criteria and to take a closer look at one notorious criterion of object identity, Leibniz's Law. The first section concerns the form of identity criteria. The second section concerns the better-regarded half of Leibniz's Law, the indiscernibility of identicals. The third section turns to the more controversial half of Leibniz's Law, the identity of indiscernibles. The author considers alternatives to Leibniz's Law as well as the possibility that there are no adequate identity criteria to be found.
Ocean Surface Wind Estimation From Waves Based on Small GPS Buoy Observations in a Bay and the Open Ocean
Authors: Shimura Tomoya , Mori Nobuhito , Baba Yasuyuki , Miyashita Takuya
Published: August 2022

Ocean surface wind and wave information is important in a wide variety of areas, such as coastal disaster reduction, offshore structure design, and atmosphere‐ocean flux estimation. This study proposed a new method for ocean surface wind estimation from surface wave spectrum information measured by small global positioning system buoys. The concept of this method relies on the assumption that the high‐frequency part of the ocean‐wave spectrum is proportional to where is the friction velocity and is the frequency. The determination algorithm for the coefficient of was optimized in this study. The wind direction was determined by the wave cross‐spectrum, assuming that the wind direction aligns the propagation direction of the high‐frequency part of the wave. The proposed wind estimation method was applied to bay and open ocean observations, and the performance of the proposed wind estimation method was similar between the bay and the open ocean. The proposed method improves the wind estimation especially in coastal areas and at high wind speeds in the open ocean compared with the previous method. The performance of the method of the previous study differs between the bay and open ocean due to their spectral shape differences. High‐quality wind and wave information can be obtained using the proposed method. If the mass deployment of small drifting buoys covered the global ocean, the information based on the proposed method could be considerably powerful, and could compensate for the weakness of satellite‐based wind and wave estimations.
Snowband Characteristics Associated With Lake‐Effect Misovortices During the OWLeS Project
Authors: Steiger Scott M. , Lynne Matthew , Mulholland Jake P. , Kosiba Karen A. , Wurman Joshua
Published: August 2022

Vortices of diameters 100 m to 10 km have been observed during lake‐effect snowstorms. Lines of misovortices (diameters = 40–4,000 m) have recently been documented forming over Lake Ontario during long lake‐axis‐parallel (LLAP)‐type lake‐effect storms. Using National Weather Service Weather Surveillance Radar—1988 Doppler (WSR‐88D) and Doppler on Wheels radar data from the Ontario Winter Lake‐effect Systems (OWLeS) project, lines of misovortices (also referred to as “misovortex lines” in this study) were investigated for intensive observation period (IOP)7 (7 January 2014) and IOP9 (9 January 2014). Results revealed that the misovortex lines formed on the southern or northern side of the west‐to‐east‐oriented LLAP band, whichever was closest to a low‐level boundary nearest the corresponding south or north shoreline (northern part in IOP7, southern part in IOP9). Examination of these two IOPs in the context of a total of 23 OWLeS IOPs, 11 of which had predominantly LLAP band morphology, showed that, in 4 of the 11 LLAP IOPs, horizontal shear zones/reflectivity bands formed in preferred regions over Lake Ontario and nearby land areas where low‐level boundaries (e.g., land breeze fronts) have been noted to develop near shoreline irregularities. Horizontal shear zones were predominant in approximately half of the OWLeS LLAP IOPs and were associated with storms having a well‐organized, solid banded reflectivity structure. Misovortices occurred when horizontal shear zones were prevalent, supporting the idea that horizontal shearing instability was important to their formation.
Fabrication and in vivo 2-photon microscopy validation of transparent PEDOT:PSS microelectrode arrays
Authors: Dijk Gerwin , Kaszas Attila , Pas Jolien , O’Connor Rodney Philip
Published: August 2022

Transparent microelectrode arrays enable simultaneous electrical recording and optical imaging of neuronal networks in the brain. Electrodes made of the conducting polymer poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) are transparent; however, device fabrication necessitates specific processes to avoid deterioration of the organic material. Here, we present an innovative fabrication scheme for a neural probe that consists of transparent PEDOT:PSS electrodes and demonstrate its compatibility with 2-photon microscopy. The electrodes show suitable impedance to record local field potentials from the cortex of mice and sufficient transparency to visualize GCaMP6f-expressing neurons underneath the PEDOT:PSS features. The results validate the performance of the neural probe, which paves the way to study the complex dynamics of in vivo neuronal activity with both a high spatial and temporal resolution to better understand the brain.
Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder
Authors: Campbell Iain H. , Campbell Harry , Smith Daniel J.
Published: August 2022

In this paper, we propose that lithium may exert its therapeutic effect in bipolar disorder by acting on insulin signaling pathways. Specifically, we assess the importance of the phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) insulin signaling pathway and we assess how the action of lithium on both glycogen synthase kinase-3 (GSK3) and the phosphatidylinositol cycle may lead to mood stabilization mediated by PI3K/Akt insulin signaling. We also highlight evidence that several other actions of lithium (including effects on Akt, Protein kinase C (PKC), and sodium myo-inositol transporters) are putative mediators of insulin signaling. This novel mode of action of lithium is consistent with an emerging consensus that energy dysregulation represents a core deficit in bipolar disorder. It may also provide context for the significant co-morbidity between bipolar disorder, type 2 diabetes, and other forms of metabolic illness characterized by impaired glucose metabolism. It is suggested that developments in assessing neuronal insulin signaling using extracellular vesicles would allow for this hypothesis to be tested in bipolar disorder patients.
Microbiome-derived antimicrobial peptides offer therapeutic solutions for the treatment of Pseudomonas aeruginosa infections
Authors: Mulkern Adam J. , Oyama Linda B. , Cookson Alan R. , Creevey Christopher J. , Wilkinson Toby J. , Olleik Hamza , Maresca Marc , da Silva Giarla C. , Fontes Patricia P. , Bazzolli Denise M. S. , Mantovani Hilario C. , Damaris Bamu F. , Mur Luis A. J. , Huws Sharon A.
Published: August 2022

Microbiomes are rife for biotechnological exploitation, particularly the rumen microbiome, due to their complexicity and diversity. In this study, antimicrobial peptides (AMPs) from the rumen microbiome (Lynronne 1, 2, 3 and P15s) were assessed for their therapeutic potential against seven clinical strains of Pseudomonas aeruginosa. All AMPs exhibited antimicrobial activity against all strains, with minimum inhibitory concentrations (MICs) ranging from 4–512 µg/mL. Time-kill kinetics of all AMPs at 3× MIC values against strains PAO1 and LES431 showed complete kill within 10 min to 4 h, although P15s was not bactericidal against PAO1. All AMPs significantly inhibited biofilm formation by strains PAO1 and LES431, and induction of resistance assays showed no decrease in activity against these strains. AMP cytotoxicity against human lung cells was also minimal. In terms of mechanism of action, the AMPs showed affinity towards PAO1 and LES431 bacterial membrane lipids, efficiently permeabilising the P. aeruginosa membrane. Transcriptome and metabolome analysis revealed increased catalytic activity at the cell membrane and promotion of β-oxidation of fatty acids. Finally, tests performed with the Galleria mellonella infection model showed that Lynronne 1 and 2 were efficacious in vivo, with a 100% survival rate following treatment at 32 mg/kg and 128 mg/kg, respectively. This study illustrates the therapeutic potential of microbiome-derived AMPs against P. aeruginosa infections.
Biomarker characterization of clinical subtypes of Parkinson Disease
Authors: Deng Xiao , Saffari Seyed Ehsan , Liu Nan , Xiao Bin , Allen John Carson , Ng Samuel Yong Ern , Chia Nicole , Tan Yi Jayne , Choi Xinyi , Heng Dede Liana , Lo Yew-long , Xu Zheyu , Tay Kay-Yaw , Au Wing-Lok , Ng Adeline , Tan Eng-King , Tan Louis C. S.
Published: August 2022

The biological underpinnings of the PD clusters remain unknown as the existing PD clusters lacks biomarker characterization. We try to identify clinical subtypes of Parkinson Disease (PD) in an Asian cohort and characterize them by comparing clinical assessments, genetic status and blood biochemical markers. A total of 206 PD patients were included from a multi-centre Asian cohort. Hierarchical clustering was performed to generate PD subtypes. Clinical and biological characterization of the subtypes were performed by comparing clinical assessments, allelic distributions of Asian related PD gene (SNCA, LRRK2, Park16, ITPKB, SV2C) and blood biochemical markers. Hierarchical clustering method identified three clusters: cluster A (severe subtype in motor, non-motor and cognitive domains), cluster B (intermediate subtype with cognitive impairment and mild non-motor symptoms) and cluster C (mild subtype and young age of onset). The three clusters had significantly different allele frequencies in two SNPs (Park16 rs6679073 A allele carriers in cluster A B C: 67%, 74%, 89%, p = 0.015; SV2C rs246814 T allele distribution: 7%, 12%, 25%, p = 0.026). Serum homocysteine (Hcy) and C-reactive protein (CRP) levels were also significantly different among three clusters (Mean levels of Hcy and CRP among cluster A B C were: 19.4 ± 4.2, 18.4 ± 5.7, 15.6 ± 5.6, adjusted p = 0.005; 2.5 ± 5.0, 1.5 ± 2.4, 0.9 ± 2.1, adjusted p < 0.0001, respectively). Of the 3 subtypes identified amongst early PD patients, the severe subtype was associated with significantly lower frequency of Park16 and SV2C alleles and higher levels of Hcy and CRP. These biomarkers may be useful to stratify PD subtypes and identify more severe subtypes.
Airway-resident T cells from unexposed individuals cross-recognize SARS-CoV-2
Authors: Diniz Mariana O. , Mitsi Elena , Swadling Leo , Rylance Jamie , Johnson Marina , Goldblatt David , Ferreira Daniela , Maini Mala K.
Published: August 2022

T cells can contribute to clearance of respiratory viruses that cause acute-resolving infections such as SARS-CoV-2, helping to provide long-lived protection against disease. Recent studies have suggested an additional role for T cells in resisting overt infection: pre-existing cross-reactive responses were preferentially enriched in healthcare workers who had abortive infections1, and in household contacts protected from infection2. We hypothesize that such early viral control would require pre-existing cross-reactive memory T cells already resident at the site of infection; such airway-resident responses have been shown to be critical for mediating protection after intranasal vaccination in a murine model of SARS-CoV3. Bronchoalveolar lavage samples from the lower respiratory tract of healthy donors obtained before the COVID-19 pandemic revealed airway-resident, SARS-CoV-2-cross-reactive T cells, which correlated with the strength of human seasonal coronavirus immunity. We therefore demonstrate the potential to harness functional airway-resident SARS-CoV-2-reactive T cells in next-generation mucosal vaccines.
Le Petit Prince multilingual naturalistic fMRI corpus
Authors: Li Jixing , Bhattasali Shohini , Zhang Shulin , Franzluebbers Berta , Luh Wen-Ming , Spreng R. Nathan , Brennan Jonathan R. , Yang Yiming , Pallier Christophe , Hale John
Published: August 2022

Neuroimaging using more ecologically valid stimuli such as audiobooks has advanced our understanding of natural language comprehension in the brain. However, prior naturalistic stimuli have typically been restricted to a single language, which limited generalizability beyond small typological domains. Here we present the Le Petit Prince fMRI Corpus (LPPC–fMRI), a multilingual resource for research in the cognitive neuroscience of speech and language during naturalistic listening (OpenNeuro: ds003643). 49 English speakers, 35 Chinese speakers and 28 French speakers listened to the same audiobook The Little Prince in their native language while multi-echo functional magnetic resonance imaging was acquired. We also provide time-aligned speech annotation and word-by-word predictors obtained using natural language processing tools. The resulting timeseries data are shown to be of high quality with good temporal signal-to-noise ratio and high inter-subject correlation. Data-driven functional analyses provide further evidence of data quality. This annotated, multilingual fMRI dataset facilitates future re-analysis that addresses cross-linguistic commonalities and differences in the neural substrate of language processing on multiple perceptual and linguistic levels.
Probabilistic atlas for the language network based on precision fMRI data from >800 individuals
Authors: Lipkin Benjamin , Tuckute Greta , Affourtit Josef , Small Hannah , Mineroff Zachary , Kean Hope , Jouravlev Olessia , Rakocevic Lara , Pritchett Brianna , Siegelman Matthew , Hoeflin Caitlyn , Pongos Alvincé , Blank Idan A. , Struhl Melissa Kline , Ivanova Anna , Shannon Steven , Sathe Aalok , Hoffmann Malte , Nieto-Castañón Alfonso , Fedorenko Evelina
Published: August 2022

Two analytic traditions characterize fMRI language research. One relies on averaging activations across individuals. This approach has limitations: because of inter-individual variability in the locations of language areas, any given voxel/vertex in a common brain space is part of the language network in some individuals but in others, may belong to a distinct network. An alternative approach relies on identifying language areas in each individual using a functional ‘localizer’. Because of its greater sensitivity, functional resolution, and interpretability, functional localization is gaining popularity, but it is not always feasible, and cannot be applied retroactively to past studies. To bridge these disjoint approaches, we created aprobabilistic functional atlasusing fMRI data for an extensively validated language localizer in 806 individuals. This atlas enables estimating the probability that any given location in a common space belongs to the language network, and thus can help interpret group-level activation peaks and lesion locations, or select voxels/electrodes for analysis. More meaningful comparisons of findings across studies should increase robustness and replicability in language research.
The geometry of evolved community matrix spectra
Authors: Låstad Silja Borring , Haerter Jan O.
Published: August 2022

Random matrix theory has been applied to food web stability for decades, implying elliptical eigenvalue spectra and that large food webs should be unstable. Here we allow feasible food webs to self-assemble within an evolutionary process, using simple Lotka–Volterra equations and several elementary interaction types. We show that, as complex food webs evolve under$${10^5}$$105invasion attempts, the community matrix spectra become bi-modal, rather than falling onto elliptical geometries. Our results raise questions as to the applicability of random matrix theory to the analysis of food web steady states.
Effects of complex spa therapy in patients with osteoarthritis of the spine receiving treatments in health resorts in south-eastern Poland
Authors: Zwolińska Jolanta , Gąsior Monika
Published: August 2022

Management of patients with degenerative diseases commonly comprises health-resort based treatment programs, including spa therapies, balneotherapy as well as terrain therapy making use of microclimate factors. The study was designed to assess short- and long-term effects of spa therapy administered to patients with osteoarthritis of the spine who received treatment in health resorts located in Poland. The study involved 102 patients receiving treatment in health resorts, a group of subjects receiving outpatient treatment (100 patients) and a group receiving no therapy (100 patients). The assessment survey included: Pain VAS and Laitinen, LISAT-9 and HAQ-20 questionnaires. The assessments were carried out three times: at the start of the therapy program, as well as one month and six months after the end of the program. Short-term effects showed statistically significant improvement in all the outcome measures in spa group and outpatient treatment group. The long-term effects showed statistically significant improvement in all the outcome measures in spa group only. In conclusion spa therapy reduces pain, improves functional efficiency and increases the level of life satisfaction in patients with osteoarthritis of the spine. Its effects are sustained for at least six months. Spa therapy is more effective long-term, than outpatient treatment.

Trial registration: The study was registered at Clinical Trials: NCT03974308. First registration: 04/06/2019.
Differential persistence of neutralizing antibody against SARS-CoV-2 in post immunized Bangladeshi population
Authors: Roy Dipa , Rahman Md. Mosfequr , Chaity Arnaba Saha , Reza Md. Abu , Haque Ariful
Published: August 2022

Development of effective vaccines have been immensely welcomed by the world to prevent the transmission of SARS-CoV-2. However, the duration and clinical implications of antibody-mediated natural immunity in SARS-CoV-2 have not been adequately elucidated alongside some other immune system transforming factors. In a cohort study, we measured NAb titer following the 2nd immunization dosage of the CoviShield (AZD1222) vaccine. The enzyme-linked immunoassay was used to look for SARS-CoV-2—specific NAb. We measured NAb at 30 days after the 2nd dosage of immunization and > 96% titer was detected in 42.9% of subjects, but only 5.1% of subjects retained the same level after 180 days. The median NAb titer dropped significantly, from 92% at 30 days to 58% at 180 days (p < 0.001). Besides, there were significant differences observed in NAb titer after 180 days by age, sex, COVID-19 infection, tobacco use, and asthma patients. However, SARS-CoV-2 infection along with two dosages of immunization upheld NAb titer (p < 0.001) even at the end of the study period.
Clinical factors affecting depression in patients with painful temporomandibular disorders during the COVID-19 pandemic
Authors: Lee Yeon-Hee , Auh Q-Schick
Published: August 2022

Temporomandibular disorders (TMD) are a multifactorial condition associated with both physical and psychological factors. Stress has been known to trigger or worsens TMD. We aimed to investigate whether the novel coronavirus disease-2019 (COVID-19) pandemic aggravates depression in patients with painful TMD, and the factors that affect their level of depression. We included 112 patients with painful TMD (74 females, 38 males; mean age: 35.90 ± 17.60 years; myalgia [n = 38], arthralgia [n = 43], mixed joint–muscle TMD pain [n = 31]). TMD was diagnosed based on the Diagnostic Criteria for TMD Axis I. Physical pain intensity was recorded using the visual analog scale (VAS); psycho-emotional status (depression: Beck Depression Inventory [BDI], anxiety: Beck Anxiety Inventory [BAI], and generalized stress related to COVID19: Global Assessment of Recent Stress [GARS]) was investigated twice (before [BC] and after COVID-19 [AC]). Additionally, factors affecting BDI-AC were investigated. BDI (p < 0.001), BAI (p < 0.001), GARS (p < 0.001), and VAS (p < 0.01) scores were significantly increased at AC than BC. The depression, anxiety, and stress levels were significantly positively correlated, and the AC and BC values of each factor showed a high correlation. In the mixed TMD group, BDI-AC was positively correlated with VAS-AC (p < 0.001). In the multiple regression analysis, clenching habit was the strongest predictor of an increase in the BDI scores from moderate to severe, followed by psychological distress, muscle stiffness, female sex, BAI-AC, and TMJ sounds. COVID-19 has negatively affected the psycho-emotional state of patients with painful TMD, and several clinical factors, including female sex and clenching habits, have influenced depression.