bluuebunny/crossref_metadata_2025 huggingface dataset:
A review of pregnancy and lactation postmarketing studies required by the FDA
Authors: Krastein Jason , Sahin Leyla , Yao Lynne
Published: November 2022

Since pregnant and lactating women have historically been excluded from drug development trials, safety studies need to be conducted postapproval. This study evaluated FDA's Post Marketing Requirements for pregnancy and lactation studies from 2007 to 2020, and identified trends and potential future opportunities. The number of studies required to be conducted in the postmarketing setting was compared with the number of new drugs approved during the same time period. We excluded drugs that were approved for use in men, children, or postmenopausal women. Since 2007, there has been an increase in pregnancy and lactation studies required to be conducted postapproval. However, only 16% of drugs that may be used in females of reproductive potential were issued a postmarketing requirement for a pregnancy and/or lactation study. The most common type of required pregnancy safety study was a pregnancy registry (37%), followed by a descriptive pregnancy safety study (27%), and a retrospective cohort study (26%). In conclusion, there is a need for more comprehensive data collection in pregnant and lactating individuals to better inform prescribers and patients about the safety of medication use during pregnancy and lactation so that they can make a fully informed decision about medication use.
Investigating drug safety in pregnancy based on the German Pharmacoepidemiological Research Database (GePaRD): A proof‐of‐concept analysis on the association between valproate and spina bifida
Authors: Haug Ulrike , Kollhorst Bianca , Schink Tania , Thöne Kathrin , Dathe Katarina , Schaefer Christof , Onken Marlies
Published: November 2022

Purpose

Large health‐care databases are increasingly used for research on drug utilization and safety in pregnancy. For the German Pharmacoepidemiological Research Database (GePaRD), covering ~20% of the German population, algorithms have been developed to identify pregnancies, to estimate their date of onset and to link mothers to their babies. Using this methodology, we aimed to conduct a proof‐of‐concept analysis on the known association between valproate (VPA) exposure in early pregnancy and spina bifida in the exposed child.

Methods

We identified all pregnancies in GePaRD between 2006 and 2016 in women aged 12 to 50 years. To each VPA dispensation of these women, an exposure period was assigned, based on the dispensation date and the number of defined daily doses in the dispensed package. A pregnancy was classified as exposed to VPA in the critical time window if this exposure period overlapped with the first 55 days of pregnancy. Risk ratios were calculated for spina bifida in live births and induced abortions comparing VPA‐exposed ones to all pregnancies.

Results

Overall, we identified 1 271 384 pregnancies fulfilling the inclusion criteria. Of these, 668 pregnancies (0.053%) were classified as exposed to VPA in the critical time window regarding spina bifida. An induced abortion accompanied by a diagnosis of spina bifida was observed in one of the VPA‐exposed pregnancies (0.15%) and in 154 of all pregnancies (0.012%), yielding a risk ratio of 12.4 (95% confidence interval [CI]: 1.7–88.2). Out of 775 875 pregnancies ending in a live birth, 366 (0.047%) were classified as VPA exposed. A diagnosis of spina bifida was coded in 3 of 366 VPA‐exposed live births (0.82%) and in 260 of all live births (0.03%), yielding a relative risk of 24.5 (95% CI: 7.9–76.0).

Conclusions

Our proof‐of‐concept analysis based on GePaRD showed a strong association between intrauterine exposure to VPA and occurrence of spina bifida. The results are plausible and consistent with the literature, supporting the suitability of GePaRD and the developed algorithms to conduct studies on drug safety in pregnancy.
Treatment of persistent methicillin‐susceptible Staphylococcus aureus bacteremia and presumed osteomyelitis with oxacillin and ertapenem in a premature neonate
Authors: Hitchins Margaret , O'Mara Keliana , Edwards Laura , Bouchard Jeannette
Published: November 2022

Neonatal sepsis remains a high cause of morbidity and mortality in preterm neonates. Methicillin‐susceptible Staphylococcus aureus (MSSA) can cause persistent bloodstream infections and invasive disease in neonates. We report the first published case of persistent MSSA bacteremia in a preterm neonate successfully treated with oxacillin and ertapenem combination therapy.
Characteristics of High‐Crystallinity ZrO2Thin Films Deposited Using Remote Plasma Atomic Layer Deposition
Authors: Song Seokhwi , Jung Chanwon , Kim Jisoo , Kim Younsoo , Lim Hanjin , Jeon Hyeongtag
Published: November 2022

ZrO2deposition using the plasma‐enhanced atomic layer deposition (PEALD) process with a cyclopentadienyl tris(dimethylamino) zirconium (CpZr(NMe2)3) precursor is investigated. The effect of deposition temperature and plasma power on ZrO2thin films’ bonding and electrical properties is studied. CpZr(NMe2)3is used for the deposition at 100 W and 200–400 °C and at 50–1000 W at 300 °C. When generating O2plasma, Ar gas and O2gas are used together to generate more radicals. It is found that CpZr(NMe2)3's PEALD process window is 200–300 °C and the film's crystallinity is strongly influenced by deposition temperature and plasma power. In both process conditions, only the tetragonal phase changes. As a result, the ZrO2film deposited at 50 W and 300 °C has the highest dielectric constant. This is due to the higher O radical ratio that corresponds to lower plasma power. A high O radical ratio causes a chemical reaction rather than an ion bombardment.
Efficient Carrier Confinement in AlGaN‐Based Deep‐Ultraviolet Light‐Emitting Diodes with a Composition‐Graded Electron‐Blocking Layer
Authors: Ye Wei-Te , Cheng Zai-Jun , Ren Zhi-Yu , Li Chen , Zheng Jin-Jian , Gao Mo-Ran , Cai Li-E , Yang Yu-Lin
Published: November 2022

The serious electron leakage and poor transport of hole injection layers in deep‐ultraviolet (DUV) light‐emitting diodes (LEDs) lead to an imbalance between the hole and electron currents, which reduces the device's performance. Herein, a new DUV LED structure is designed. The aluminum composition of the p‐type electron‐blocking layer (p‐EBL) gradually decreases from 0.95 to 0.75 along the growth direction, replacing the traditional bulk p‐EBL. When the injection current is 100 mA, the optical power of this structure is about 32% higher than that of the traditional structure. In addition, when the p‐EBL adopts the opposite gradient (the Al composition gradually increases from 0.75 to 0.95), the device performance suddenly drops dramatically. The related devices are simulated by Silvaco TCAD software. The results show that the performance outputs of the two opposite aluminum gradient growth modes are completely opposite. The proposed p‐EBL with a gradual step‐down Al composition along the growth direction helps to improve the efficiency of hole injection into multiple quantum wells (MQWs) and reduce the level of electron leakage. This work provides an effective solution for increasing the light output power of high‐performance DUV LEDs.
Effects of Lycium barbarum Polysaccharide on Pasting, Rheology, and In Vitro Digestibility of Starch
Authors: Jia Shuyu , Tao Haiteng , Zhao Haibo , Yu Bin , Wu Zhengzong , Liu Pengfei , Cui Bo
Published: November 2022

Lycium barbarum polysaccharide (LBP) is widely used in functional foods, but it is rarely used in starchy foods. This study aims to evaluate the effects of LBP on the pasting, rheological, textural properties, and digestibility of different types of starch (wheat starch (WS), sweet potato starch (SPS), and pea starch (PS)). Results show that LBP increases the pasting characteristics of PS but shows decreasing and no influence on these characteristics in WS and SPS, respectively. The apparent viscosity of SPS paste decreases with the increase in the LBP content. LBP reduces the hardness, adhesion, and chewiness of PS gels, as also evidenced by the alterations in the microstructure. The results of FT‐IR and X‐ray diffraction indicate that LBP promotes the formation of ordered structures within retrograded starch. LBP increases the slowly digested starch and resistant starch content, implying that LBP decreases the digestibility of starches. The changes in the physicochemical properties of starches depend on the interactions between starch and LBP.
A tale of two saddles
Authors: Chandrasekaran Venkatesa , Engelhardt Netta , Fischetti Sebastian , Hernández-Cuenca Sergio
Published: November 2022

Abstract

We find a new on-shell replica wormhole in a computation of the generating functional of JT gravity coupled to matter. We show that this saddle has lower action than the disconnected one, and that it is stable under restriction to real Lorentzian sections, but can be unstable otherwise. The behavior of the classical generating functional thus may be strongly dependent on the signature of allowed perturbations. As part of our analysis, we give an LM-style construction for computing the on-shell action of replicated manifolds even as the number of boundaries approaches zero, including a type of one-step replica symmetry breaking that is necessary to capture the contribution of the new saddle. Our results are robust against quantum corrections; in fact, we find evidence that such corrections may sometimes stabilize this new saddle.
Monopole deformations of 3d Seiberg-like dualities with adjoint matters
Authors: Hwang Chiung , Kim Sungjoon , Park Jaemo
Published: November 2022

Abstract

We propose new 3d $$ \mathcal{N} $$
N
= 2 Seiberg-like dualities by considering various monopole superpotential deformations on 3d $$ \mathcal{N} $$
N
= 2 U(Nc) SQCDs with fundamental and adjoint matter fields. We provide nontrivial evidence of these new dualities by comparing the superconformal indices, from which we analyze the change of the moduli space due to the monopole deformation. In addition, we perform the F-maximization to check the relevance of the monopole deformation for some examples, one of which is found to exhibit nontrivial symmetry enhancement in the IR. We prove such enhancement of the global symmetry using the superconformal index.
Causality constraints on nonlinear supersymmetry
Authors: Bonnefoy Quentin , Casagrande Gabriele , Dudas Emilian
Published: November 2022

Abstract

It is well-known that gravitino propagation in standard supergravities is free of any causality problems. However, two issues related to gravitino propagation were recently uncovered in specific supergravities with nonlinear supersymmetry. One of them concerns potential acausality/superluminality, whereas the second one arises from the vanishing of the sound speed at specific points during inflation. The former is famously related to positivity constraints on specific EFT operators, derived from dispersion relations on the energy-growing part of scattering amplitudes, and indeed we show that subluminality constraints for the gravitino are related via the equivalence theorem to positivity bounds in low-energy goldstino actions. However, the former are stronger, in the sense that they apply to functions of the scalar fields not only in the ground state, but for any field values such as those scanned by time-dependent solutions, unlike bounds derived from 2 → 2 scattering amplitudes in the vacuum. We also argue that nontrivial causality constraints arise only in the case where nonlinear supersymmetry in the matter sector is encoded into superfield constraints which do not seem to arise from microscopic two-derivative lagrangians, in particular for the orthogonal constraint used to build minimal models of inflation in supergravity. This allows us to propose simple alternatives which maintain the minimality of the spectra and are causal in all points of the theory parameter space. We also discuss minimal supergravity models of inflation along these lines.
Monopole-fermion scattering and varying Fock space
Authors: Hamada Yuta , Kitahara Teppei , Sato Yoshiki
Published: November 2022

Abstract

We propose a four-dimensional interpretation of the outgoing state of the scattering of a massless fermion off a Dirac monopole. It has been known that such a state has fractional fermion numbers and is necessarily outside the Fock space on top of ordinary perturbative vacuum, when more than two flavours of charged Dirac fermions are considered. In this paper, we point out that the Fock space of the fermions depends on the rotor degree of freedom of the monopole and changes by a monopole-fermion s-wave scattering. By uplifting the fermion-rotor system introduced by Polchinski, from two to four dimensions, we argue that the outgoing state can be understood as a state in a different Fock space.
Power sum polynomials and the ghosts behind them
Authors: Della Vedova Marco L. , Pagani Silvia M. C. , Pianta Silvia
Published: November 2022

The power sum polynomial associated to a multi-subset of the projective plane$$\text {PG}(2,q)$$PG(2,q)is the sum of the$$(q-1)$$(q-1)-th powers of the Rédei factors of the points in the multi-subset. The classification of multi-subsets having the same power sum polynomial passes through the determination of those multi-subsets associated to the zero polynomial, called ghosts. In this paper we provide new classes of ghosts and compute the dimension of the ghost subspace by exploiting the linear code generated by the lines of$$\text {PG}(2,q)$$PG(2,q)and its dual. Moreover, we explicitly enumerate and classify ghosts for planes of order 2, 3, 4.
Comparative study of v-ring indenter configurations in fineblanking in order to derive tool design guidelines
Authors: Nürnberger Anian , Müller Daniel , Martinitz Lukas , Hartmann Christoph , Tobie Thomas , Stahl Karsten , Volk Wolfram
Published: November 2022

The v-ring indenters and their configurations play a major role in the fineblanking process, directly influencing component quality and characteristics. While past studies regarding residual stresses of blanked components focused mainly on the use of a pair of v-rings, so far no efforts were undertaken to compare different v-ring setups, deducing tool design guidelines and enabling possible cost savings. Therefore, a comparative study of different v-ring indenter setups and their influence on cut surface parameters, surface hardness and induced residual stresses of the produced components was performed. The obtained results indicate a minor influence of blank holder-sided v-rings on the observed component characteristics in comparison to indenters situated on the die leading to recommendations with regard to cost-efficient tool design.
Projector matrix product operators, anyons and higher relative commutants of subfactors
Authors: Kawahigashi Yasuyuki
Published: November 2022

A bi-unitary connection in subfactor theory of Jones producing a subfactor of finite depth gives a 4-tensor appearing in a recent work of Bultinck–Mariën–Williamson–Şahinoğlu-Haegeman–Verstraete on two-dimensional topological order and anyons. In their work, they have a special projection called a projector matrix product operator. We prove that the range of this projection of lengthkis naturally identified with thekth higher relative commutant of the subfactor arising from the bi-unitary connection. This gives a further connection between two-dimensional topological order and subfactor theory.
A theoretical study of dynamic processes observed in trimethylsilyl-1H-pyrazoles: prototropy and silylotropy
Authors: Claramunt Rosa M. , Elguero José , Alkorta Ibon
Published: November 2022

The 1H, 13C, 15N and 29Si chemical shifts of three trimethylsilyl-1H-pyrazoles were calculated and compared with literature results; the calculations were carried out at the GIAO/B3LYP/6–311 +  + G(d,p) level resulting in a very good agreement that allows to predict with confidence the missing experimental values. The prototropic barrier of 4-trimethylsilyl-1H-pyrazole (1) as well as the silylotropic barriers of 1-trimethylsilyl-1H-pyrazole (2) and 1-trimethylsilyl-4-methyl-1H-pyrazole (3) were also calculated and the mechanism was established, the accordance with the experimental values being satisfactory.
Global Well-Posedness for $$H^{-1}(\mathbb {R})$$ Perturbations of KdV with Exotic Spatial Asymptotics
Authors: Laurens Thierry
Published: November 2022

Given a suitable solution V(t, x) to the Korteweg–de Vries equation on the real line, we prove global well-posedness for initial data $$u(0,x) \in V(0,x) + H^{-1}(\mathbb {R})$$

u

(
0
,
x
)

∈
V

(
0
,
x
)

+

H

-
1

(
R
)

. Our conditions on V do include regularity but do not impose any assumptions on spatial asymptotics. We show that periodic profiles $$V(0,x)\in H^5(\mathbb {R}/\mathbb {Z})$$

V

(
0
,
x
)

∈

H
5

(
R
/
Z
)

satisfy our hypotheses. In particular, we can treat localized perturbations of the much-studied periodic traveling wave solutions (cnoidal waves) of KdV. In the companion paper Laurens (Nonlinearity. 35(1):343–387, 2022. https://doi.org/10.1088/1361-6544/ac37f5) we show that smooth step-like initial data also satisfy our hypotheses. We employ the method of commuting flows introduced in Killip and Vişan (Ann. Math. (2) 190(1):249–305, 2019. https://doi.org/10.4007/annals.2019.190.1.4) where $$V\equiv 0$$

V
≡
0

. In that setting, it is known that $$H^{-1}(\mathbb {R})$$

H

-
1

(
R
)

is sharp in the class of $$H^s(\mathbb {R})$$

H
s

(
R
)

spaces.
Nomogram based on MRI for preoperative prediction of Ki-67 expression in patients with intrahepatic mass cholangiocarcinoma
Authors: Chen Xiang , Zhu Jingfen , Zou Zigui , Du Mingzhan , Xie Junjian , Ye Yujie , Zhang Ling , Li Yonggang
Published: November 2022

Objectives

To validate a new nomogram based on magnetic resonance imaging (MRI) for pre-operative prediction of Ki-67 expression in patients with intrahepatic mass cholangiocarcinoma (IMCC).

Methods

A total of 78 patients with clinicopathologically confirmed IMCC who underwent pre-operative gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced MRI between 2016 and 2022 were enrolled in the training and validation group (53 patients and 25 patients, respectively). Images including qualitative, quantitative MRI features and clinical data were evaluated. Univariate analysis and multivariate logistic regression were used to select the independent predictors and establish different predictive models. The predictive performance was validated by operating characteristic curve (ROC) analysis, calibration curve, and decision curve analysis (DCA). The validation cohort was used to test the predictive performance of the optimal model. The nomogram was constructed with the optimal model.

Results

In the training cohort, independent predictors obtained from the combined model were DWI (OR 1822.741; 95% CI 6.189, 536,781.805; P = 0.01) and HBP enhancement pattern (OR 14.270; 95% CI 1.044, 195.039; P = 0.046). The combined model showed the good performance (AUC 0.981; 95% CI 0.952, 1.000) for predicting Ki-67 expression. In the validation cohort, The combined model (AUC 0.909; 95% CI 0.787, 1.000)showed the best performance compared to the clinical model (AUC 0.448; 95% CI 0.196, 0.700) and MRI model (AUC 0.770; 95% CI 0.570, 0.970).

Conclusion

This new nomogram has a good performance in predicting Ki-67 expression in patients with IMCC, which could help the decision-making of the patients’ therapy strategies.

Graphical abstract
Outcome of patients with idiopathic ventricular fibrillation and correlation with ECG markers of early repolarization
Authors: Rath Benjamin , Willy Kevin , Ellermann Christian , Leitz Patrick , Köbe Julia , Reinke Florian , Lange Philipp Sebastian , Frommeyer Gerrit , Eckardt Lars
Published: November 2022

Background

Early repolarization pattern (ERP) has been associated with idiopathic ventricular fibrillation (IVF) and with cardiovascular mortality in the general population. As there is limited data about long- term outcome of IVF, the aim of our study was to observe ventricular arrhythmia (VA) recurrences in these patients and to identify a possible correlation of VA with ECG markers of early repolarization.

Methods and results

We investigated 56 consecutive IVF patients who received an implantable cardioverter-defibrillator for secondary prevention. ERP was defined as a J-point elevation ≥ 0.1 mV in two or more contiguous inferior or lateral leads. Markers of early repolarization were present in 32.1% of cases with a preponderance of QRS slurring (77.8%). During a mean follow-up of 41.2 months, 11 patients (19.6%) received in total 18 adequate ICD-therapies. VF was most the common cause for ICDtherapy (61.1%) but monomorphic VT also occurred in four patients. Presence of ERP was associated with a significant trend towards arrhythmia recurrences. 38.9% patients with ERP received appropriate ICD-therapies whereas only 10.5% of patients without ERP had arrhythmia recurrence (p = 0.05). Inappropriate ICD-therapies occurred in seven patients (12.5%) with a non-significant trend towards a higher incidence in patients with a transvenous ICD (p = 0.15).

Conclusion

A significant correlation between ERP and VA recurrences in patients with IVF could be observed. Though monomorphic VA also play a role in the studied IVF-population, our data support the use of the S-ICD in this collective.

Graphical abstract
Proteomics uncover EPHA2 as a potential novel therapeutic target in colorectal cancer cell lines with acquired cetuximab resistance
Authors: Torlot Lucien , Jarzab Anna , Albert Johanna , Pók-Udvari Ágnes , Stahler Arndt , Holch Julian Walter , Gerlinger Marco , Heinemann Volker , Klauschen Frederick , Kirchner Thomas , Kumbrink Jörg , Küster Bernhard , Jung Andreas
Published: November 2022

Background

In metastatic colorectal cancer (mCRC), acquired resistance against anti-EGFR targeted monoclonal antibodies, such as cetuximab (CET), was shown to be frequently caused by activating alterations in the RAS genes KRAS or NRAS. To this day, no efficient follow-up treatment option has emerged to treat mCRC in such a setting of resistance.

Methods

To uncover potential targets for second-line targeted therapies, we used mass-spectrometric proteomics to shed light on kinome reprogramming in an established cellular model of acquired, KRAS-associated CET resistance.

Results

This CET resistance was reflected by significant changes in the kinome, most of them individual to each cell line. Interestingly, all investigated resistant cell lines displayed upregulation of the Ephrin type-A receptor 2 (EPHA2), a well-known driver of traits of progression. Expectedly resistant cell lines displayed increased migration (p < 0.01) that was significantly reduced by targeting the EPHA2 signalling axis using RNA interference (RNAi) (p < 0.001), ephrin-A1 stimulation (p < 0.001), dasatinib (p < 0.01), or anti-EPHA2 antibody treatment (p < 0.001), identifying it as an actionable target in mCRC with acquired CET resistance.

Conclusion

These results highlight EPHA2 and its role in mCRC with KRAS-gene mutated acquired CET resistance and support its use as a potential actionable target for the development of future precision medicine therapies.
Combined anterior and posterior approach in treatment of ankylosing spondylitis-associated cervical fractures: a systematic review and meta-analysis
Authors: Chen Hua-Jian , Chen De-Yuan , Zhou Shao-zhen , Sang Li-li , Wu Jun-zhe , Huang Fu-li
Published: November 2022

Objective

Cervical fractures with ankylosing spondylitis (CAS) are a specific type of spinal fracture with poor stability, low healing rate, and high disability rate. Its treatment is mainly surgical, predominantly through the anterior approach, posterior approach, and the anterior–posterior approach. Although many clinical studies have been conducted on various surgical approaches, controversy still exists concerning the choice of these surgical approaches by surgeons. The authors present here a systematic evaluation and meta-analysis exploring the utility of the anterior–posterior approach versus the anterior approach and the posterior approach.

Methods

After a comprehensive literature search of PubMed, Cochrane, Web of Science, and Embase databases, 12 clinical studies were included in the final qualitative analysis and 8 in the final quantitative analysis. Of these studies, 11 conducted a comparison between the anterior–posterior approach and the anterior approach and posterior approaches, while one examined only the anterior–posterior approach. Where appropriate, statistical advantage ratios and 95% confidence intervals were calculated.

Results

The present meta-analysis of postoperative neurological improvement showed no statistical difference in the overall neurological improvement rate between the anterior–posterior approach and anterior approach (OR 1.70, 95% CI 0.61 to 4.75; p = 0.31). However, the mean change in postoperative neurological function was lower in patients who received the anterior approach than in those who received the anterior–posterior approach (MD 0.17, 95% CI -0.02 to 0.36; p = 0.08). There was an identical trend between the anterior–posterior approach and posterior approach, with no statistically significant difference in the overall rate of neurological improvement (OR 1.37, 95% CI 0.70 to 2.56; p = 0.38). Nevertheless, the mean change in neurological function was smaller in patients receiving the anterior–posterior approach compared with the posterior approach, but there was no statistically significant difference between the two (MD 0.17, 95% CI -0.02 to 0.36; p = 0.08).

Conclusions

The results of this review and meta-analysis suggest that the benefits of the anterior–posterior approach are different from those of the anterior and posterior approaches in the treatment of ankylosing spondylitis-related cervical fractures. In a word, there is no significant difference between the cervical surgical approach and the neurological functional improvement. Therefore, surgeons should pay more attention to the type of cervical fracture, the displacement degree of cervical fracture, the spinal cord injury, the balance of cervical spine and other aspects to comprehensively consider the selection of appropriate surgical methods.
Variation in attitudes toward diagnosis and medication of ADHD: a survey among clinicians in the Norwegian child and adolescent mental health services
Authors: Lyhmann Ingvild , Widding-Havneraas Tarjei , Zachrisson Henrik Daae , Bjelland Ingvar , Chaulagain Ashmita , Mykletun Arnstein , Halmøy Anne
Published: November 2022

Prevalence and medication rates of ADHD vary geographically, both between and within countries. No absolute cutoff exists between ADHD and normal behavior, making clinician attitudes (leading to local practice cultures) a potential explanation for the observed variation in diagnosis and medication rates. The objective of this study was to describe variation in attitudes toward diagnosis and medication of ADHD among clinicians working in child and adolescent mental health services (CAMHS). We hypothesized that attitudes would vary along a spectrum from “restrictive” to “liberal”. We also explored whether differences in attitudes between clinicians were related to professional background and workplace (clinic). A survey in the form of a web-based questionnaire was developed. All CAMHS outpatient clinics in Norway were invited. Potential respondents were all clinicians involved in diagnosing and treating children and adolescents with ADHD. To investigate the existence of attitudes toward diagnosis and medication as latent constructs, we applied confirmatory factor analysis (CFA). We further examined how much of variance in attitudes could be ascribed to profession and clinics by estimating intraclass correlation coefficients. In total, 674 respondents representing 77 (88%) of the clinics participated. We confirmed variation in attitudes with average responses leaning toward the “restrictive” end of the spectrum. CFA supported “attitude toward diagnosis” and “attitude toward medication” as separate, and moderately correlated (r = 0.4) latent variables, representing a scale from restrictive to liberal. Professional background and workplace explained only a small part of variance in these attitudes.
Design and evaluation of a collaborative UML modeling environment in virtual reality
Authors: Yigitbas Enes , Gorissen Simon , Weidmann Nils , Engels Gregor
Published: November 2022

Modeling is a key activity in conceptual design and system design. Through collaborative modeling, end-users, stakeholders, experts, and entrepreneurs are able to create a shared understanding of a system representation. While the Unified Modeling Language (UML) is one of the major conceptual modeling languages in object-oriented software engineering, more and more concerns arise from the modeling quality of UML and its tool-support. Among them, the limitation of the two-dimensional presentation of its notations and lack of natural collaborative modeling tools are reported to be significant. In this paper, we explore the potential of using virtual reality (VR) technology for collaborative UML software design by comparing it with classical collaborative software design using conventional devices (desktop PC/laptop). For this purpose, we have developed a VR modeling environment that offers a natural collaborative modeling experience for UML Class Diagrams. Based on a user study with 24 participants, we have compared collaborative VR modeling with conventional modeling with regard to efficiency, effectiveness, and user satisfaction. Results show that the use of VR has some disadvantages concerning efficiency and effectiveness, but the user’s fun, the feeling of being in the same room with a remote collaborator, and the naturalness of collaboration were increased.
Bone-related behaviours of captive chimpanzees (Pan troglodytes) during two excavating experiments
Authors: Motes-Rodrigo Alba , Tennie Claudio , Hernandez-Aguilar R. Adriana
Published: November 2022

After stone tools, bone tools are the most abundant artefact type in the Early Pleistocene archaeological record. That said, they are still relatively scarce, which limits our understanding of the behaviours that led to their production and use. Observations of extant primates constitute a unique source of behavioural data with which to construct hypotheses about the technological forms and repertoires exhibited by our hominin ancestors. We conducted two different experiments to investigate the behavioural responses of two groups of captive chimpanzees (Pan troglodytes; n = 33 and n = 9) to disarticulated, defleshed, ungulate bones while participating in a foraging task aimed at eliciting excavating behaviour. Each chimpanzee group was provided with bone specimens with different characteristics, and the two groups differed in their respective experience levels with excavating plant tools. We found that several individuals from the inexperienced group used the provided bones as tools during the task. In contrast, none of the individuals from the experienced group used bones as excavating tools, but instead continued using plant tools. These chimpanzees also performed non-excavating bone behaviours such as percussion and tool-assisted extraction of organic material from the medullary cavity. Our findings serve as a proof-of-concept that chimpanzees can be used to investigate spontaneous bone tool behaviours such as bone-assisted excavation. Furthermore, our results raise interesting questions regarding the role that bone characteristics, as well as previous tool-assisted excavating experience with other raw materials, might have in the expression of bone tool-assisted excavation.
Low prevalence of haemosporidian and trypanosome infections in the Eurasian Nightjar (Caprimulgus europaeus)
Authors: Dubiec Anna , Da Silva Arnaud , Celej Marta
Published: November 2022

Research on the occurrence and community composition of vector-transmitted protozoan haemoparasites in birds is heavily skewed toward passerines with many other orders underrepresented. In caprimulgids, a family of primarily ground-nesting, crepuscular/nocturnal birds occupying a wide range of dry habitats, research on protozoan haemoparasites is limited and in most cases based on only a few individuals. Here, using the molecular approach, the occurrence and diversity of parasites from four genera (Haemosporida:Haemoproteus,Plasmodium,Leucocytozoon; Trypanosomatida:Trypanosoma) were investigated in a representative of the family—the Eurasian Nightjar (Caprimulgus europaeus). Birds were sampled at a breeding location in south-eastern Poland at the beginning of the breeding season. Overall, 20 individuals, including 17 males and 3 females, were screened. Only 10% of birds were infected and in total, two parasite lineages—both representingPlasmodiumgenus—were identified. Detected parasite lineages were previously registered in a wide range of avian hosts. Known transmission areas of these lineages indicate that breeding populations of Eurasian Nightjars from south-eastern Poland contract infections on non-breeding grounds. This study reinforces earlier observations of the low prevalence of haemosporidians and trypanosomes in caprimulgids.
Sexual reproduction in two mixed stands of coastal and interior Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) in Germany
Authors: Pakull Birte , Wojacki Janine , Eusemann Pascal , Fussi Barbara , Ahnert Diana , Liesebach Heike
Published: November 2022

Adult individuals and seeds of two mixed stands of coastal and interior Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) were analysed for genetic differentiation between the two varieties and evidence of intervarietal pollination. Clear genetic discrimination between the two varieties was observed based on multilocus evaluation of nine microsatellite markers using other Douglas-fir stands of known variety composition for comparison. Analysis of pollination distances showed that 80% of pollinations took place within a distance of about 44–55 m. Analysis of stand structure showed clearly separated areas of mainly coastal or interior Douglas-fir within both stands. Together with short pollination distances this led to an apparent dominance of intravarietal pollinations. However, analysis of pollination partners of trees growing near the border of the variety specific areas, does not indicate the existence of reproductive barriers between trees of the two varieties growing in mixed stands. Therefore, commercial seed harvesting in mixed stands should be avoided if the production of seed lots of pure coastal or interior Douglas-fir is intended.
First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone in advanced esophageal squamous cell carcinoma: a Japanese subgroup analysis of open-label, phase 3 trial (CheckMate 648/ONO-4538-50)
Authors: Kato Ken , Doki Yuichiro , Ogata Takashi , Motoyama Satoru , Kawakami Hisato , Ueno Masaki , Kojima Takashi , Shirakawa Yasuhiro , Okada Morihito , Ishihara Ryu , Kubota Yutaro , Amaya-Chanaga Carlos , Chen Tian , Matsumura Yasuhiro , Kitagawa Yuko
Published: November 2022

Background

Programmed cell death 1 (PD-1)-based treatments are approved for several cancers. CheckMate 648, a global, phase 3 trial, showed that first-line nivolumab (anti-PD-1 antibody) plus ipilimumab (NIVO + IPI) or nivolumab plus chemotherapy (NIVO + Chemo) significantly increased survival in advanced esophageal squamous cell carcinoma (ESCC) without new safety signals versus chemotherapy alone (Chemo).

Methods

We evaluated the Japanese subpopulation of CheckMate 648 (n = 394/970), randomized to receive first-line NIVO + IPI, NIVO + Chemo, or Chemo. Efficacy endpoints included overall survival (OS) and progression-free survival assessed by blinded independent central review in Japanese patients with tumor-cell programmed death-ligand 1 (PD-L1) expression ≥ 1% and in all randomized Japanese patients.

Results

In the Japanese population, 131, 126, and 137 patients were treated with NIVO + IPI, NIVO + Chemo, and Chemo, and 66, 62, and 65 patients had tumor-cell PD-L1 ≥ 1%, respectively. In patients with tumor-cell PD-L1 ≥ 1%, median OS was numerically longer with NIVO + IPI (20.2 months; hazard ratio [95% CI], 0.46 [0.30–0.71]) and NIVO + Chemo (17.3 months; 0.53 [0.35–0.82]) versus Chemo (9.0 months). In all randomized patients, median OS was numerically longer with NIVO + IPI (17.6 months; 0.68 [0.51–0.92]) and NIVO + Chemo (15.5 months; 0.73 [0.54–0.99]) versus Chemo (11.0 months). Grade 3–4 treatment-related adverse events were reported in 37%, 49%, and 36% of all patients in the NIVO + IPI, NIVO + Chemo, and Chemo arms, respectively.

Conclusion

Survival benefits with acceptable tolerability observed for NIVO + IPI and NIVO + Chemo treatments strongly support their use as a new standard first-line treatment in Japanese patients with advanced ESCC.

ClinicalTrials.gov ID

NCT03143153.
Climate change implications for olive flowering in Crete, Greece: projections based on historical data
Authors: Grillakis Manolis G. , Kapetanakis Evangelos G. , Goumenaki Eleni
Published: November 2022

Climate change is expected to pose major challenges for olive cultivation in many Mediterranean countries. Predicting the development phases of olive trees is important for agronomic management purposes to foresee future climate impact and proactively act toward adaptation and mitigation strategies. In this study, a statistical model was developed based on winter chill accumulation and, in sequence, on heat accumulation to assess the changes in flowering occurrence for Olea europaea cv. Koroneiki, in the island of Crete, Greece. The model was based on and calibrated with long-term phenological observations and temperature data from four different sites in the island, spanning an elevation gradient between 45 and 624 m a.s.l. This model was used to assess the changes in flowering emergence under two Representative Concentration Pathway scenarios, RCP4.5 and RCP8.5, as projected by seven high-resolution Euro-CORDEX Regional Climate Models. Changes in chill accumulation were determined using the Dynamic Model. Reduction rates in chill accumulation for the whole chilling season ranged between 12.0 and 28.3% for the near future (2021–2060) and 22.7 and 70.9% for the far future (2061–2100), in comparison to the reference period of 1979–2019. Flowering was estimated to occur between 6 and 10 days earlier in the near future and between 12 and 26 days earlier in the far future, depending on the elevation and the climate change scenario.
Workflow analysis of data science code in public GitHub repositories
Authors: Ramasamy Dhivyabharathi , Sarasua Cristina , Bacchelli Alberto , Bernstein Abraham
Published: November 2022

Despite the ubiquity of data science, we are far from rigorously understanding how coding in data science is performed. Even though the scientific literature has hinted at the iterative and explorative nature of data science coding, we need further empirical evidence to understand this practice and its workflows in detail. Such understanding is critical to recognise the needs of data scientists and, for instance, inform tooling support. To obtain a deeper understanding of the iterative and explorative nature of data science coding, we analysed 470 Jupyter notebooks publicly available in GitHub repositories. We focused on the extent to which data scientists transition between different types of data science activities, or steps (such as data preprocessing and modelling), as well as the frequency and co-occurrence of such transitions. For our analysis, we developed a dataset with the help of five data science experts, who manually annotated the data science steps for each code cell within the aforementioned 470 notebooks. Using the first-order Markov chain model, we extracted the transitions and analysed the transition probabilities between the different steps. In addition to providing deeper insights into the implementation practices of data science coding, our results provide evidence that the steps in a data science workflow are indeed iterative and reveal specific patterns. We also evaluated the use of the annotated dataset to train machine-learning classifiers to predict the data science step(s) of a given code cell. We investigate the representativeness of the classification by comparing the workflow analysis applied to (a) the predicted data set and (b) the data set labelled by experts, finding an F1-score of about 71% for the 10-class data science step prediction problem.
Device-based percutaneous treatments to decompress the left atrium in heart failure with preserved ejection fraction
Authors: Riccardi Mauro , Tomasoni Daniela , Vizzardi Enrico , Metra Marco , Adamo Marianna
Published: November 2022

Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of heart failure hospital admissions in the last years and is burdened by high mortality and poor quality of life. Providing effective management for HFpEF patients is a major unmet clinical need. Increase in left atrial pressure is the key determinant of pulmonary congestion, with consequent dyspnoea and exercise limitation. Evidence on benefits of medical treatment in HFpEF patients is limited. Thus, alternative strategies, including devices able to reduce left atrial pressure, through an interatrial communication determining a left–right shunt, were developed. This review aims to summarize evidence regarding the use of percutaneous interatrial shunting devices. These devices are safe and effective in improving hemodynamic and clinical parameters, including pulmonary capillary wedge pressure, 6-min walking distance, and New York Heart Association functional class. Data on cardiovascular mortality and re-hospitalization for heart failure are still scarce.
Taxonomic and functional structure of macrobenthic invertebrate communities and their response to environmental variables along the subbranches of the Nile River (rayahs), Egypt
Authors: Bendary Reda E. , Ibrahim Shaimaa M. , Goher Mohamed E. , Elsaied Hosam E. , El Shabrawy Gamal M. , El Mordy Mohamed Abd , Khalil Magdy T.
Published: November 2022

Macrobenthic invertebrate communities serve as markers of anthropogenic stress in freshwater ecosystems. In this study, 17 sampling sites were selected from two Nile river subbranches (El-Rayah El-Behery and El-Rayah El-Nassery) and subjected to different anthropogenic influences to explore the ecological environment and characteristics of macrobenthos communities. Macrobenthos were studied using taxonomic diversity and biological trait analysis to investigate how human activity and variation in water quality affect their structure and function. A total of 37 taxa represented by 43,389 individuals were recognized. The communities are composed chiefly of Oligochaeta and aquatic insects. Multivariate statistical analyses found that the most influential environmental variables in the structural and functional community were sodium, dissolved oxygen, silicate, pH, calcium, and cadmium. At high levels of pollution, notably sewage and industrial pollution in the northern part of El-Rayah El-Behery, characteristics such as larger body size, detritus feeders, burrowers, and high tolerance to pollution predominated, whereas at low levels of pollution, features such as small body sizes, scraper and predator feeders, intolerant and fairly tolerant of pollution, and climber and swimmer mobility are predominant. The results confirm our prediction that the distribution of macroinvertebrate traits varies spatially in response to environmental changes. The diversity-based method distinguished impacted sewage and industrial sites from thermal effluent sites, while the trait-based approach illustrated an apparent variance between the ecological status of contaminated regions. Therefore, the biological features should be employed in addition to structural aspects for assessing the biodiversity of macroinvertebrate communities under environmental stressors.
Attitudes Towards Rape and Their Determinants Among Men, Women and Non-Binary People in Poland
Authors: Olszewska Klaudia , Piotrowski Przemysław , Wojciechowski Bartosz W.
Published: November 2022

The aim of this paper is to present the results of research on attitudes towards rape conducted in a group of 850 adult Poles, including 505 women, 310 men and 35 non-binary people, and to analyze their selected correlates: rape myth acceptance, right-wing authoritarianism and rape empathy. Non-binary people have only recently been included in research as a distinct group and little information can be found in the literature on the characteristics of their attitudes towards social problems. Therefore particular attention was paid to comparing the attitudes towards rape of non-binary people with those of women and men. In analyzing the results, the authors took into account the current socio-political situation in Poland. The results indicate that attitudes toward sexual aggression are related to the type of gender identification. The most positive attitudes towards rape victims among the groups participating in the research are held by non-binary people. Furthermore, attitudes towards rape are determined by rape myths, right-wing authoritarianism and empathy for victims of rape.
Mastectomy with one-stage or two-stage reconstruction in breast cancer: analysis of early outcomes and patient’s satisfaction
Authors: Gurrado Angela , Pasculli Alessandro , Toma Alessia , Maruccia Michele , Elia Rossella , Moschetta Marco , Telegrafo Michele , De Luca Giuseppe Massimiliano , Lavermicocca Walter , Poli Elisabetta , Prete Francesco Paolo , Sgaramella Lucia Ilaria , Giudice Giuseppe , Testini Mario
Published: November 2022

Aim of this study is to compare early post-operative outcomes and patient’s satisfaction after skin-sparing and/or nipple-sparing mastectomy (SSM/SNSM) followed either by breast reconstruction with one-stage prepectoral implantation or two-stage technique for breast cancer (BC) or BRCA1/2 mutation.

From January 2018 to December 2021, 96 patients (mean age of 51.12 ± 10.9) underwent SSM/SNSM and were divided into two groups: in group A (65 patients, 67.7%), mastectomy was followed by one-stage reconstruction; in group B (31 patients, 32.3%) by two-stage. Operative time was significantly longer in A vs. B (307.6 ± 95.7 vs. 254.4 ± 90.91; P < 0.05). Previous breast surgery was more common in B vs. A (29.0% vs. 7.7%; P < 0.05), while bilateral surgery was performed more frequently in A vs. B (40% vs. 6.5%; P = 0.001). All SSM/SNSM for BRCA1/2 mutation were followed by immediate prepectoral implantation. No significant differences were found between groups in terms of post-operative complications. At pathology, DCIS and invasive ST forms, such as multicentric/multifocal forms, were detected more frequently in B, while NST type in A (all P < 0.05). A multivariate analysis showed improved post-operative satisfaction at BREAST-Q survey in Group A (P = 0.001). Encouraging oncologic outcomes after SSM/SNSM for BC enabled the improvement of breast reconstructive techniques. One-stage reconstruction is characterized by better aesthetic outcomes and by greater patient’s satisfaction. When SSM/SNSM is technically difficult to perform, as in multicentric/multifocal forms or previous breast surgery, mastectomy followed by two-stage reconstruction should be considered to achieve a radical surgery.
Finite convergence of extragradient-type methods for solving variational inequalities under weak sharp condition
Authors: Trinh Thanh Quoc , Vinh Le Van , Vuong Phan Tu
Published: November 2022

We prove the finite convergence of the sequences generated by some extragradient-type methods solving variational inequalities under the weakly sharp condition of the solution set. In addition, we provide estimations for the number of iterations to guarantee the sequence converges to a point in the solution set and prove that these estimations are optimal. Numerical examples are presented to illustrate the theoretical results.
Serre duality for tame Deligne–Mumford stacks
Authors: Levchenko Denis
Published: November 2022

Using the exceptional inverse image functor for quasi-finite proper morphisms of separated tame Deligne–Mumford stacks of finite type over a fieldk, Serre duality is obtained in varying degrees of generality for tame Deligne–Mumford stacks. The approach follows that for schemes.