bluuebunny/crossref_metadata_2025 huggingface dataset:
XdfA, a novel membrane-associated DedA family protein of
Xanthomonas campestris
, is required for optimum virulence, maintenance of magnesium, and membrane homeostasis
Authors: Padhi Yasobanta , Chatterjee Subhadeep
Published: July 2023

Xanthomonas campestris
is an important member of the
Xanthomonas
group of phytopathogens that causes diseases in crucifers. In
X. campestris
, several virulence-associated functions, including some belonging to unknown predicted functions, have been implicated in the colonization and disease processes. However, the role of many of these unknown predicted proteins in
Xanthomonas
-host interaction and their exact physiological function is not clearly known. In this study, we identified a novel membrane-associated protein belonging to the DedA super family, XdfA, which is required for virulence in
X. campestris
. The DedA family of proteins are generally ubiquitous in bacteria; however, their function and actual physiological role are largely elusive. Characterization of ∆
xdfA
by homology modeling, membrane localization, and physiological studies indicated that XdfA is a membrane-associated protein that plays a role in the maintenance of membrane integrity. Furthermore, functional homology modeling analysis revealed that the XdfA exhibits structural similarity to a CorA-like magnesium transporter and is required for optimum growth under low magnesium ion concentration. We report for the first time that a putative DedA family of protein in
Xanthomonas
is required for optimum virulence and plays a role in the maintenance of membrane-associated functions and magnesium homeostasis.

IMPORTANCE

Bacterial DedA family proteins are involved in a range of cellular processes such as ion transport, signal transduction, and cell division. Here, we have discussed about a novel DedA family protein XdfA in
Xanthomonas campestris
pv.
campestris
that has a role in membrane homeostasis, magnesium transport, and virulence. Understanding membrane and magnesium homeostasis will aid in our comprehension of bacterial physiology and eventually will help us devise effective antimicrobial strategies to safeguard horticulturally and agriculturally important crop plants.
180° view on general practitioners’ leadership skills: practice-level comparisons of leader and staff assessments using data from the cluster-randomised controlled IMPROVEjobstudy
Authors: Schmidt Manuela , Seifried-Dübon Tanja , Göbel Julian , Degen Lukas , Werners Brigitte , Grot Matthias , Rind Esther , Pieper Claudia , Jöckel Karl-Heinz , Minder Karen , Rieger Monika A , Weltermann Birgitta
Published: July 2023

Objectives

Strong primary care leaders are needed to assure high quality services for patient populations. This study analysed general practitioners’ (GP) leadership skills comparing practice-level self and staff assessments based on the full range of leadership model and the leader-member exchange (LMX).

Setting

The questionnaire survey was conducted among German general practice leaders and their staff participating in the IMPROVEjobtrial.

Participants

The study population comprised 60 German general practices with 366 participants: 84 GP practice leaders and 282 employees (28 physicians and 254 practice assistants).

Primary and secondary outcome measures

Leadership skills of the practice leaders were measured using the Integrative Leadership Questionnaire (German Fragebogen für integrative Führung) and the LMX-7 questionnaire. Leaders rated themselves and practice staff rated their leaders. The data was analysed by paired mean comparisons on the practice level.

Results

For most leadership dimensions, practice leaders rated themselves higher than their employees rated them. Differences were found for transformational leadership (p<0.001, d=0.41), especially for the dimensions ‘innovation’ (p<0.001, d=0.69) and ‘individuality focus’ (p<0.001, d=0.50). For transactional leadership, the dimension ‘goal setting’ differed significantly (p<0.01, d=0.30) but not the other dimensions. Scores for negative leadership were low and showed no differences between leaders and employees. Interestingly, employed physicians’ rated their practice leaders higher on the two transformational (‘performance development’, ‘providing a vision’) and all transactional dimensions. The LMX-7 scale showed high quality relationships between leaders and employees.

Conclusions

This 180° analysis of GPs’ leadership skills with self and employee ratings indicated good relationships. There is a potential to improve leadership regarding goal-setting, innovation and focusing on individual team members. These results allow for the development of targeted interventions.

Trial registration number

German Clinical Trials Register, DRKS00012677. Registered 16 October 2019.
Level of education and sustainable return to work among long-term sick-listed workers with depression: a register-based cohort study (The Norwegian GP-DEP Study)
Authors: Meling Heidi Marie , Ruths Sabine , Baste Valborg , Hensing Gunnel , Haukenes Inger
Published: July 2023

Objectives

Sick-listed workers with depression are at higher risk of long-term, recurrent sickness absence and work disability, suggesting reduced likelihood of sustainable return to work (SRTW). Though likelihood of RTW has been associated with education level, less is known about the association over time, post-RTW. We aimed to investigate associations between educational level and SRTW among long-term sick-listed workers with depression.

Methods

Nationwide cohort study, based on linked data from Norwegian health and population registries, including all inhabitants of Norway aged 20–64 years on long-term sick leave with a depression diagnosis given in general practice between 1 January 2009 and 10 April 2011 (n=13.624, 63.7% women). Exposure was the highest attained education level (five groups). Three outcome measures for SRTW were used, with 0 days, ≤30 days and ≤90 days of accumulated sickness absence post-RTW during a 2-year follow-up. Associations between exposure and outcomes were estimated in gender-stratified generalised linear models, adjusting for sociodemographic factors and duration of sick leave.

Results

Higher-educated workers had a higher likelihood of SRTW 0, SRTW ≤30 and SRTW ≤90 than the lowest-educated groups in the crude models. Among men, this association was mainly explained when adjusting for occupation. Among women, the highest educated group had a higher likelihood of SRTW 0 (RR=1.45, 95% CI 1.23 to 1.71) and SRTW ≤30 and SRTW ≤90 in the fully adjusted models.

Conclusions

An educational gradient in SRTW was mainly explained by occupation among men but not among women. These findings suggest gendered differences in associations between education level and SRTW, which could inform interventions aiming to promote equal opportunities for SRTW.
Agata: in-beam spectroscopy with relativistic beams
Authors: Bentley M. A. , Benzoni G. , Wimmer K.
Published: July 2023

An analysis of the capabilities of AGATA for in-beam $$\gamma $$
γ
-ray spectroscopy at relativistic energies is presented. AGATA’s ability to determine the position of $$\gamma $$
γ
-ray interaction points in the Germanium crystal provides the crucial ingredient for attaining high $$\gamma $$
γ
-ray energy resolution when the emitting nucleus is traveling at more than half the speed of light. This is the typical velocity of exotic nuclei exiting the SuperFRS spectrometer at the future FAIR facility, where AGATA will be deployed as part of the high-resolution in-beam spectroscopy project, HISPEC. A discussion of different experimental techniques using AGATA under these conditions is presented, including analysis of the different Doppler-based methods for lifetime determination. The properties of the key reaction mechanisms expected to be applied for in-beam $$\gamma $$
γ
-ray spectroscopy at FAIR are discussed, along with the aspects of those reactions that can be exploited by the advanced capabilities of the AGATA array.
Canonical momenta in digitized Su(2) lattice gauge theory: definition and free theory
Authors: Jakobs Timo , Garofalo Marco , Hartung Tobias , Jansen Karl , Ostmeyer Johann , Rolfes Dominik , Romiti Simone , Urbach Carsten
Published: July 2023

Hamiltonian simulations of quantum systems require a finite-dimensional representation of the operators acting on the Hilbert space$$\mathcal {H}$$H. Here we give a prescription for gauge links and canonical momenta of an SU(2) gauge theory, such that the matrix representation of the former is diagonal in$$\mathcal {H}$$H. This is achieved by discretising the sphere$$S_3$$S3isomorphic to SU(2) and the corresponding directional derivatives. We show that the fundamental commutation relations are fulfilled up to discretisation artefacts. Moreover, we directly construct the Casimir operator corresponding to the Laplace–Beltrami operator on$$S_3$$S3and show that the spectrum of the free theory is reproduced again up to discretisation effects. Qualitatively, these results do not depend on the specific discretisation of SU(2), but the actual convergence rates do.
Breaking Down the Performance Losses in O2-Evolution Stability Tests of IrO2-based Electrocatalysts
Authors: Diklić Nataša , Beard Alexandra , Herranz Juan , Heinritz Adrian , Cen Tianyu , Garbe Steffen , Abbott Daniel F. , Povia Mauro , Schmidt Thomas J.
Published: July 2023

Understanding the deactivation mechanisms affecting the state-of-the-art, Ir oxide catalysts employed in polymer electrolyte water electrolyser (PEWE-) anodes is of utmost importance to guide catalyst design and improve PEWE-durability. With this motivation, we have tried to decouple the contributions of various degradation mechanisms to the overall performance losses observed in rotating disk electrode (RDE) tests on three different, commercial Ir oxide catalysts (pure or supported on Nb2O5). Specifically, we investigated whether these performance decays stem from an intrinsic deactivation of the catalysts caused by alterations in their oxidation state, crystalline structure, morphology and/or Ir-dissolution, and also assessed possible decreases in the catalyst loading caused by the delamination of the materials over the course of these OER-stability tests. Additionally, we also examined recently reported artifacts related to the use of RDE voltammetry for such measurements and found that neither these nor the above mechanisms (or combinations thereof) can cause the totality of the observed performance losses. Beyond these uncertainties, complementary PEWE-tests showed that this apparent RDE-instability is not reproduced in this application-relevant environment.
Thermal Stress Analysis of a Solid Oxide Fuel Cell Considering Interconnect Deformation
Authors: Xu Qi , Wang Chengtian , Miao Fuxing , Guan Wanbing , Singhal Subhash C.
Published: July 2023

Deformation of the interconnect in a solid oxide fuel cell (SOFC) stack affects the internal thermal stresses of the cell at high temperatures. In this study, the effect of the interconnect deformation on the cell temperature and thermal stress at different operating voltages was simulated based on the thermal-chemical-electrical-mechanical multiphysics coupling theory. The results show that when the operating voltage of the cell is above 0.85 V, the interconnect mainly generates a compressive strain. When the operating voltage is below 0.85 V, the interconnect produces tensile strain, which increases with decreasing voltage. Interconnect deformation significantly increases the thermal stress of the cells within the stack, but effectively improves the uniform distribution of thermal stress. The coupling effect of interconnect deformation on cell thermal stress within the stack varies at different operating voltages.
Recent Advances in Prelithiation of Silicon Anode: Enhanced Strategy for Boosting Practicability of Li-Ion Battery
Authors: Bhujbal Akshay V. , Ng Kok Long , Khazraei Sepehr , Bekou Jack , Riahi A. Reza
Published: July 2023

The anode material used in batteries plays a major role in determining their performance. Given its high theoretical capacity, which is ten times more than that of graphite, the anode material routinely used in commercial Lithium-ion batteries (LIB), Si has been recognized as a viable alternative for LIB. With a focus on practical application, prelithiation approaches that are inherently scalable are discussed, characterized, and compared based on their ease of operation, cost, atmospheric stability, compatibility with existing manufacturing processes, homogeneity, and safety. Herein, this review aims to provide (i) a critical investigation of cutting-edge modeling progress for prelithiation strategies and (ii) a summary of the underlying causes of low initial coulombic efficiency (ICE). Mutual learning from these prelithiation processes is anticipated to create more sustainable strategies for manufacturing LIBs.
Physiology education and teaching in Chinese mainland medical schools: the status quo and the changes over the past two decades
Authors: Feng Haixiao , Wang Yuechun
Published: July 2023

This study conducted a nationwide survey of the top 100 medical schools in the Chinese mainland in 2022 to provide first-hand data on the current situation and changes in physiology education and teaching in the Chinese mainland with focuses on the faculty composition, curriculum integration, teaching methods, and assessment modes, which is a microcosm of the reform and development of the medical education in the Chinese mainland, hoping to improve the quality of preclinical medical education.
Dietary anions control potassium excretion: it is more than a poorly absorbable anion effect
Authors: Al-Qusairi Lama , Ferdaus Mohammed Z. , Pham Truyen D. , Li Dimin , Grimm P. Richard , Zapf Ava M. , Abood Delaney C. , Tahaei Ebrahim , Delpire Eric , Wall Susan M. , Welling Paul A.
Published: July 2023

Dietary anions profoundly impact K+ homeostasis. Here, we found that a K+-rich diet, containing [Formula: see text] as the counteranion, enhances the electrogenic K+ excretory machinery, epithelial Na+ channels, and renal outer medullary K+ channels, much more than a high-KCl diet. It also uniquely induces KCC3a and pendrin, in B-intercalated cells, providing an electroneutral KHCO3 secretion pathway. These findings reveal new K+ balance mechanisms that drive adaption to alkaline and K+-rich foods, which should guide new treatment strategies for K+ disorders.
Distribution of upper limit of the prescriptive zone values for acclimatized and unacclimatized individuals
Authors: Bernard Thomas E. , Ashley Candi D. , Wolf S. Tony , Odera Ayub M. , Lopez Rebecca M. , Kenney W. Larry
Published: July 2023

Occupational exposure limit guidelines using wet bulb globe temperature (WBGT) distinguish between acclimatized and unacclimatized workers with about a 3°C difference between them. For the first time, empirical data from two laboratories provide support for acclimatization state adjustments. Using a constant difference rather than increasing differences with metabolic rate better describes the limit for unacclimatized participants. Furthermore, the lower upper limit of the prescriptive zone (ULPZ) values set forth for women do not relate to fitness level but are partly explained by their smaller body surface area (BSA). An examination of individual ULPZ values suggests that many unacclimatized individuals should be able to sustain safe work at the exposure limit for acclimatized workers.
Numerical Study of Thermal Performance Influence on Design Parameter and Fe3O4 Nanofluid of Flat Plate Direct Absorption Solar Collector
Authors: Tong Yijie , Ham Jeonggyun , Cho Honghyun
Published: July 2023

In this study, the influence of design factors (concentration of Fe3O4 nanofluid (NF), mass flow rate, FPDASC height, and emissivity of the receiver) of flat plate direct absorption solar collector (FPDASC) using Fe3O4 NF was investigated using the CFD (computational fluid dynamics) method. As a result, when the concentration of Fe3O4 NF increases up to 0.1 wt%, the thermal and exergy efficiencies increase by 0.773 and 0.0293, respectively, due to the increased optical absorbance. Increasing the mass flow rate of Fe3O4, NF decreases the outlet temperature; however, thermal efficiency increases due to reduced heat loss and improved heat transfer. Moreover, there is little effect on the irreversibility of the FPDASC due to the Bejan number with almost one, although the mass flow rate increases the pressure loss. The increasing height of the FPDASC and the emissivity of the receiver improve the thermal and exergy efficiencies in the case of water with low optical absorbance. In contrast, the increasing height of the FPDASC and the emissivity of the receiver decrease the thermal and exergy efficiencies when the optical absorbance is high (0.1 wt% Fe3O4 NF).
Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: July 2023

Purpose:

Ring sideroblasts (RS) define the low-risk myelodysplastic neoplasm (MDS) subgroup with RS but may also reflect erythroid dysplasia in higher risk myeloid neoplasm. The benign behavior of MDS with RS (MDSRS+) is limited to SF3B1-mutated cases without additional high-risk genetic events, but one third of MDSRS+ carry no SF3B1 mutation, suggesting that different molecular mechanisms may underlie RS formation. We integrated genomic and transcriptomic analyses to evaluate whether transcriptome profiles may improve current risk stratification.

Experimental Design:

We studied a prospective cohort of MDSRS+ patients irrespective of World Health Organization (WHO) class with regard to somatic mutations, copy-number alterations, and bone marrow CD34+ cell transcriptomes to assess whether transcriptome profiles add to prognostication and provide input on disease classification.

Results:

SF3B1, SRSF2, or TP53 multihit mutations were found in 89% of MDSRS+ cases, and each mutation category was associated with distinct clinical outcome, gene expression, and alternative splicing profiles. Unsupervised clustering analysis identified three clusters with distinct hemopoietic stem and progenitor (HSPC) composition, which only partially overlapped with mutation groups. IPSS-M and the transcriptome-defined proportion of megakaryocyte/erythroid progenitors (MEP) independently predicted survival in multivariable analysis.

Conclusions:

These results provide essential input on the molecular basis of SF3B1-unmutated MDSRS+ and propose HSPC quantification as a prognostic marker in myeloid neoplasms with RS.
Supplementary Figures S1-S18 from FH Variant Pathogenicity Promotes Purine Salvage Pathway Dependence in Kidney Cancer
Authors: Wilde Blake R. , Chakraborty Nishma , Matulionis Nedas , Hernandez Stephanie , Ueno Daiki , Gee Michayla E. , Esplin Edward D. , Ouyang Karen , Nykamp Keith , Shuch Brian , Christofk Heather R.
Published: July 2023

Supplementary Fig. S1: Analysis of FH variants and their associated interpretations of pathogenicity. Supplementary Fig. S2: Kinetic parameters for active/partially-active VUS/CI. Supplementary Fig. S3: Recombinant FH produced for 74 VUS/CI. Supplementary Fig. S4: Michaelis-Menten graphs for VUS/CI incubated with fumarate. Supplementary Fig. S5: Michaelis-Menten graphs for VUS/CI incubated with malate. Supplementary Fig. S6: Broad analysis of recombinant FH. Supplementary Fig. S7: Multimerization status of 74 VUS/CI. Supplementary Fig. S8: Tetramerization correlates with catalytic activity. Supplementary Fig. S9: Expression of FH variants in HLRCC cells. Supplementary Fig. S10: Fumarate accumulation decreases TCA intermediates. Supplementary Fig. S11: FH loss enhances de novo glutathione biosynthesis. Supplementary Fig. S12: Coessentiality of FH and nucleotide biosynthesis genes. Supplementary Fig.S13: Loss of FH activity disrupts de novo purine biosynthesis. Supplementary Fig. S14: Dysregulated purine metabolism is independent of HLRCC cell proliferation rate. Supplementary Fig. S15: FH-deficient cells use the purine salvage pathway to maintain purine nucleotide levels. Supplementary Fig. S16: Pyrimidine metabolism in FH-deficient and FH-expressing cells. Supplementary Fig. S17: Disrupting expression of purine salvage enzymes impairs tumor growth. Supplementary Fig. S18: Purine salvage inhibitor 6-mercaptopurine (6-MP) impairs tumor growth.
Supplementary Figure 3 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer
Authors: Yaeger Rona , Mezzadra Riccardo , Sinopoli Jenna , Bian Yu , Marasco Michelangelo , Kaplun Esther , Gao Yijun , Zhao HuiYong , Paula Arnaud Da Cruz , Zhu Yingjie , Perez Almudena Chaves , Chadalavada Kalyani , Tse Edison , Chowdhry Sudhir , Bowker Sydney , Chang Qing , Qeriqi Besnik , Weigelt Britta , Nanjangud Gouri J. , Berger Michael F. , Der-Torossian Hirak , Anderes Kenna , Socci Nicholas D. , Shia Jinru , Riely Gregory J. , Murciano-Goroff Yonina R. , Li Bob T. , Christensen James G. , Reis-Filho Jorge S. , Solit David B. , de Stanchina Elisa , Lowe Scott W. , Rosen Neal , Misale Sandra
Published: July 2023

RW7213 cell lines sequencing analysis
Supplementary Figure 2 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer
Authors: Yaeger Rona , Mezzadra Riccardo , Sinopoli Jenna , Bian Yu , Marasco Michelangelo , Kaplun Esther , Gao Yijun , Zhao HuiYong , Paula Arnaud Da Cruz , Zhu Yingjie , Perez Almudena Chaves , Chadalavada Kalyani , Tse Edison , Chowdhry Sudhir , Bowker Sydney , Chang Qing , Qeriqi Besnik , Weigelt Britta , Nanjangud Gouri J. , Berger Michael F. , Der-Torossian Hirak , Anderes Kenna , Socci Nicholas D. , Shia Jinru , Riely Gregory J. , Murciano-Goroff Yonina R. , Li Bob T. , Christensen James G. , Reis-Filho Jorge S. , Solit David B. , de Stanchina Elisa , Lowe Scott W. , Rosen Neal , Misale Sandra
Published: July 2023

C106 cell lines single cell sequencing analysis
Supplementary File 1 from Next-Generation JAK2 Inhibitors for the Treatment of Myeloproliferative Neoplasms: Lessons from Structure-Based Drug Discovery Approaches
Authors: Nair Pramod C. , Piehler Jacob , Tvorogov Denis , Ross David M. , Lopez Angel F. , Gotlib Jason , Thomas Daniel
Published: July 2023

JAK2-monomer-0ns.pdb. (Model of human JAK2 monomer used for molecular dynamics simulation).
Figure S5 from HTLV-1 bZIP Factor-Induced Reprogramming of Lactate Metabolism and Epigenetic Status Promote Leukemic Cell Expansion
Authors: Toyoda Kosuke , Yasunaga Jun-ichirou , Shichijo Takafumi , Arima Yuichiro , Tsujita Kenichi , Tanaka Azusa , Salah Tarig , Zhang Wenyi , Hussein Osama , Sonoda Miyu , Watanabe Miho , Kurita Daisuke , Nakashima Kazutaka , Yamada Kyohei , Miyoshi Hiroaki , Ohshima Koichi , Matsuoka Masao
Published: July 2023

Transcriptional regulation of SLC16A1 and SLC16A3 by TAp73, and mRNA expression levels of MCT-coding genes among various cancers.
Figure S3 from HTLV-1 bZIP Factor-Induced Reprogramming of Lactate Metabolism and Epigenetic Status Promote Leukemic Cell Expansion
Authors: Toyoda Kosuke , Yasunaga Jun-ichirou , Shichijo Takafumi , Arima Yuichiro , Tsujita Kenichi , Tanaka Azusa , Salah Tarig , Zhang Wenyi , Hussein Osama , Sonoda Miyu , Watanabe Miho , Kurita Daisuke , Nakashima Kazutaka , Yamada Kyohei , Miyoshi Hiroaki , Ohshima Koichi , Matsuoka Masao
Published: July 2023

Regulation of TP73 by BATF3 and IRF4.
Figure S1 from HTLV-1 bZIP Factor-Induced Reprogramming of Lactate Metabolism and Epigenetic Status Promote Leukemic Cell Expansion
Authors: Toyoda Kosuke , Yasunaga Jun-ichirou , Shichijo Takafumi , Arima Yuichiro , Tsujita Kenichi , Tanaka Azusa , Salah Tarig , Zhang Wenyi , Hussein Osama , Sonoda Miyu , Watanabe Miho , Kurita Daisuke , Nakashima Kazutaka , Yamada Kyohei , Miyoshi Hiroaki , Ohshima Koichi , Matsuoka Masao
Published: July 2023

Transcriptional regulation by HBZ protein and RNA and the status of TP73 expression.
Supplementary Figure S3 from A pilot study of neoadjuvant nivolumab, ipilimumab and intralesional oncolytic virotherapy for HER2-negative breast cancer
Authors: Nguyen Vina P , Campbell Katie M. , Nowicki Theodore S , Elumalai Nila , Medina Egmidio , Baselga-Carretero Ignacio , DiNome Maggie L , Chang Helena R. , Oseguera Denise K , Ribas Antoni , Glaspy John A.
Published: July 2023

Detection of talimogene laherparepvec (T-VEC) vector reads in case #2. This screenshot from the integrated genomics viewer shows reads aligning to CSF2 (GM-CSF) from the peripheral blood, baseline, and end-of-treatment (EOT) whole exome sequencing (WES) data from the surgical specimen of case #2. The short-clipped ends of the reads at the 5’ end of CSF2 contained the T-VEC cytomegalovirus (CMV) promoter sequence, and reads spanned the exon-exon junctions of the CSF2 transcript. This pattern was not observed in the surgical (EOT) specimens from the other patients or in baseline samples.
Supplementary Figure S1 from A pilot study of neoadjuvant nivolumab, ipilimumab and intralesional oncolytic virotherapy for HER2-negative breast cancer
Authors: Nguyen Vina P , Campbell Katie M. , Nowicki Theodore S , Elumalai Nila , Medina Egmidio , Baselga-Carretero Ignacio , DiNome Maggie L , Chang Helena R. , Oseguera Denise K , Ribas Antoni , Glaspy John A.
Published: July 2023

Surgical specimens after neoadjuvant therapy from patients who did not respond to treatment. Color scheme: Yellow: CD8, Red: IgG4, White: CK7, Green: PD-L1, Magenta: PD-1, Blue: DAPI. Staining demonstrates minor CD8 T-cell infiltration within viable tumor tissue, with no detectable PD-1, PD-L1, or IgG4 signal present.
Figure S5 from Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Gräßle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina A. , Fuhr Olaf , Munuganti Ravi S. N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C. B.
Published: July 2023

X15695-mediated regulation of expression and cellular localization of p53 in prostate cancer cells.
FIGURE 8 from Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Gräßle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina A. , Fuhr Olaf , Munuganti Ravi S. N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C. B.
Published: July 2023

X15695 induces cell-cycle arrest and inhibits proliferation of AR+ and ER+ prostate and breast cancer cells. Cell-cycle profile measured by flow cytometry of LNCaP (A) and LAPC-4 cells (B) treated with vehicle or 1 μmol/L X15695 for 48 hours. Cells for flow cytometry were stained with DRAQ5. The quantified results are the mean ± SEM (n = 3; *, P ≤ 0.05; **, P ≤ 0.01). C, Representative examples of LAPC-4 xenograft mouse tumors after daily treatment with vehicle, X15695 (10 and 30 mg/kg), and enzalutamide (10 mg/kg) for 43 days. D, Tumor weights at the end of treatment were recorded and presented as a bar chart. The values are the means ± SEM expressed (**, P ≤ 0.01; ****, P ≤ 0.0001; n = 14; ns, not significant). E, Mouse body weights were measured twice weekly over the 43 days. Presented are the mouse body weight changes, in percentages, for each group. F, Quantification of the effect of the indicated concentrations of X15695 on clonal expansion of the indicated tumor cells (n = 3).
FIGURE 7 from Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Gräßle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina A. , Fuhr Olaf , Munuganti Ravi S. N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C. B.
Published: July 2023

X15695-mediated regulation of AR action in prostate cancer cells. A, Western blot analysis of BAG1 in LNCaP cells transduced with BAG-1 shRNA and control shRNA. Antibodies to vinculin, AR, tubulin, and GAPDH were used as controls. B, Quantification of the effect of X15695 on clonal expansion of control and BAG1 shRNA knockdown LNCaP cells. Each point represents the mean ± SEM. n = 3. C, Western blot analysis of AR and BAG1 in extracts of LNCaP and 22Rv.1 cells treated with the indicated concentrations of X15695 for 24 hours. β-actin was used as a loading control. D–F, GSEA plots of the topmost signaling pathways and heat maps of log2 fold-change in gene expression in the comparison of DHT + X15695 versus DHT and X15695 versus vehicle in LNCaP cells. G, Quantitative RT-PCR was carried to detect the effect of X15695 on DHT- mediated expression of the indicated target genes in LNCaP cells. Cells were treated with vehicle or 10 nmol/L DHT and X15695 (5 μmol/L) for 16 hours. The results are the means ± SEM (n = 4; *, P ≤ 0.05; ***, P ≤ 0.001; ****, P ≤ 0.0001; ns, not significant). H, 22Rv.1, LAPC-4, and LNCaP cells were transfected with control and p53 siRNA for 16 hours and treated with vehicle or X15695 (5 μmol/L) for 24 hours. Western blot analysis was performed with anti-p53 and anti-β-actin antibodies. I, MTT cell viability assay carried out with 22Rv.1, LAPC-4, and LNCaP cells previously transfected with control and p53 siRNA and treated with vehicle and X15695 for 72 hours. The results are the mean ± SEM (n = 3; *, P ≤ 0.05).
Civic Purpose among Higher Education Students – A Study of Four Dutch and Finnish Institutions
Authors: Kuusisto Elina , de Groot Isolde , Schutte Ingrid , Rissanen Inkeri
Published: July 2023

Given the increasing interest in academic citizenship in higher education, this study examines the civic purposes of higher education students in two European countries, namely the Netherlands and Finland, and relations between students’ worldviews and their civic purposes. The majority of students was categorized as so-called disengaged or dreamers, respectively either not civically interested or active or then visioning but not actualizing civic interests. Students with a purposeful profile referring to high civic interest, action, and identity, were most prevalent among Dutch students with a humanistic worldview and Finnish students reporting religions other than Christianity. Students from both countries not identifying with any organized worldviews were more likely to be allocated to the disengaged profile. Possible explanations for differences in student profiles are discussed.
New troglobitic species of Benthana Budde-Lund, 1908 and Benthanoides Lemos de Castro, 1958 from iron-ore caves and their important record in the Amazon biome (Crustacea: Isopoda: Philosciidae)
Authors: CARDOSO GIOVANNA MONTICELLI , FERREIRA RODRIGO LOPES
Published: July 2023

A new cave-restricted species of Benthana and two cave-restricted species of Benthanoides are described from iron-ore caves located in the Serra dos Carajás complex, Pará state, in the Amazon biome. Benthana alba n. sp. occurs only in one cave in the south of Serra Norte, in the plateau N5 (cave N5SM2_0077); Benthanoides amazonicus n. sp. occurs in several caves in the north of Serra Norte, in the plateau N1; and Benthanoides tarzan n. sp. occurs in several caves in the Serra do Tarzan. This record represents an important distribution data for Benthana that typically occurs in the Brazilian Atlantic Forest, indicating that such species may represent a relict lineage of this genus. Additionally, efforts must be directed towards the conservation of these species, all of which are associated with caves occurring in areas of intense mining activity.
Fusing Numerical Weather Prediction Ensembles with Refractivity Inversions during Surface Ducting Conditions
Authors: Greenway Daniel P. , Haack Tracy , Hackett Erin E.
Published: July 2023

This study investigates the use of numerical weather prediction (NWP) ensembles to aid refractivity inversion problems during surface ducting conditions. Thirteen sets of measured thermodynamic atmospheric data from an instrumented helicopter during the Wallops Island field experiment are fit to a two-layer parametric surface duct model to characterize the duct. This modeled refractivity is considered “ground truth” for the environment and is used to generate the synthetic radar propagation loss field that then drives the inversion process. The inverse solution (refractivity derived from the synthetic radar data) is compared with this ground truth refractivity. For the inversion process, parameters of the two-layer model are iteratively estimated using genetic algorithms to determine which parameters likely produced the synthetic radar propagation field. Three numerical inversion experiments are conducted. The first experiment utilizes a randomized set of two-layer model parameters to initialize the inversion process, while the second experiment initializes the inversion using NWP ensembles, and the third experiment uses NWP ensembles to both initialize and restrict the parameter search intervals used in the inversion process. The results show that incorporation of NWP data benefits the accuracy and speed of the inversion result. However, in a few cases, an extended NWP ensemble forecast period was needed to encompass the ground truth parameters in the restricted search space. Furthermore, it is found that NWP ensemble populations with smaller spreads are more likely to hinder the inverse process than to aid it.
Validation of the Atmospheric Dispersion Model NAME against Long-Range Tracer Release Experiments
Authors: Selvaratnam Vibha , Thomson David J. , Webster Helen N.
Published: July 2023

The Met Office’s atmospheric dispersion model Numerical Atmospheric-Dispersion Modeling Environment (NAME) is validated against controlled tracer release experiments, considering the impact of the driving meteorological data and choices in the parameterization of unresolved motions. The Cross-Appalachian Tracer Experiment (CAPTEX) and Across North America Tracer Experiment (ANATEX) were long-range dispersion experiments in which inert tracers were released and the air concentrations measured across North America in the 1980s. NAME simulations of the experiments have been driven by both reanalysis meteorological data from European Centre for Medium-Range Weather Forecasts (ECMWF) and data from the Advanced Research version of the Weather Research and Forecasting (WRF) Model. NAME predictions of air concentrations are assessed against the experimental measurements, using a ranking method composed of four statistical parameters. Differences in the performance of NAME according to this ranking method are compared when driven by different meteorological sources. The effect of changing parameter values in NAME for the unresolved mesoscale motions parameterization is also considered, in particular, whether the parameter values giving the best performance rank are consistent with values typically used. The performance ranks are compared with analyses in the literature for other particle dispersion models, namely, Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT), Stochastic Time-Inverted Lagrangian Transport (STILT), and Flexible Particle (FLEXPART). It is found that NAME performance is comparable to the other dispersion models considered, with the different models responding similarly to differences in driving meteorological data.
Mesh Fixation Versus Nonfixation in Laparoscopic Inguinal Hernia Repair: A Systematic Review and Meta-Analysis
Authors: Lv Yuxing , Yang Bo , Hao Gaopeng , Wang Yinquan
Published: July 2023

Background

It remains controversial whether mesh should be fixed during laparoscopic inguinal hernia repair. A systematic review and meta-analysis of randomized-controlled trials (RCTs) was conducted to compare fixation and nonfixation in laparoscopic groin hernia repair.

Methods

A registration was listed with PROSPERO (International Prospective Register of Systematic Reviews; registration no. CRD42022350469). Databases including PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched to identify RCTs comparing fixation with nonfixation in laparoscopic groin hernia repair. The primary outcomes were postoperative pain at 24 hours and recurrence. Secondary outcomes were mean operative time, urinary retention, and postoperative pain at 6 months.

Results

A total of 18 trials, including 2617 patients with 2878 hernias, were included in this meta-analysis. In contrast to the fixation group, the nonfixation group was associated with lower postoperative pain scores at 24 hours and 6 months, a shorter mean operative time, and a lower incidence of urinary retention. There were no significant differences between the 2 types of procedures in terms of the rate of recurrence for patients with an inguinal hernia orifice smaller than 4 cm in size.

Conclusions

The nonfixation technique is an effective method to reduce urinary retention, mean operative time, and postoperative pain at 24 hours and at 6 months; however, the rate of recurrence was comparable to that of the fixation method.
Management of Pediatric Aortic Pseudoaneurysm Due to Penetrating Trauma
Authors: Mehl Steven C. , Moturu Anoosha , Miranda Jorge , Mills Joseph , Rosenfeld Eric , Stapleton Gary , Naik-Mathuria Bindi
Published: July 2023

Due to the increasing frequency of pediatric penetrating trauma, pediatric surgeons need to be prepared to evaluate and manage complex penetrating injuries. In this report, we discuss the endovascular management of a traumatic aortic pseudoaneurym and subsequent bullet retrieval following penetrating chest trauma in a child. The key to successful management included multidisciplinary decision making and use of an expandable covered stent generally used for management of aortic coarctation.
Let the cracking open continue: Believing in kenosis, practicing solidarity for the common good
Authors: García Francisco
Published: July 2023

Stephanie Spellers’ The Church Cracked Open should be required reading for every Episcopalian and Christian who seeks to follow the liberative, loving, compassionate, pastoral, and prophetic way of Jesus. The “cracking open” of the church and of our lives, however painful and traumatic, can be leveraged for the good, as it allows for the structural injustices and spiritual wounds aided and abetted by dominant forms of church to be uncovered, examined, and possibly healed and transformed in the liberating way of Jesus. In this reflection, I focus on two of the core spiritual and ethical practices that Spellers proposes in the culmination of her book—kenosis and solidarity—asking questions and offering examples of how these practices might show up in our church polity, our places of worship, and in the broader communities in which we minister.
Audiologic Consequences of Gunshot Wounds to the Temporal Bone Show No Relation to Concomitant Neurologic or Vascular Injuries
Authors: Maxwell Anne K. , Kahane Jacob B. , Murphy Terrence P.
Published: July 2023

Objectives:

To evaluate audiologic consequences of gunshot wounds (GSWs) to the temporal bone (TB), and to correlate hearing outcomes with neurologic and vascular injuries adjacent to the temporal bone.

Study design:

Retrospective case series.

Setting:

University-based level-one trauma center.

Methods:

Retrospective review of 35 patients surviving TB ballistic injury, 2012 to 2021. Main outcomes were audiologic results. Demographics, concomitant injuries, CT, and interventions were reviewed.

Results:

Mean age was 30.7 years; 80% male. Seventeen patients (48.6%) underwent audiologic testing. Mean pure tone average (PTA) was 75 ± 35 dB, bone line average 41 ± 26 dB, and speech discrimination score (SDS) 60 ± 43%. Nineteen (54.3%) demonstrated facial nerve injury (FNI), who were more likely to show SNHL especially anacusis, though their mean PTA and SDS were not statistically different from those without ( P = .30 and .47, respectively). Radiographic review of those with sensorineural loss (SNHL, 6/17) revealed otic capsule-disrupting fracture (n = 2), pneumolabyrinth (n = 2), intracranial hemorrhage (n = 3). Those with mixed loss (6/17) showed otic capsule-sparing fracture (n = 6), EAC injury (n = 5), ossicular discontinuity (n = 2), and intracranial hemorrhage (n = 4). Two with mastoid tip fractures alone had normal audiograms. Audiometric outcomes were not predicted by concomitant CSF leak, spinal injuries, vascular injuries, cranial neuropathies, or traumatic brain injury.

Conclusions:

All patterns of hearing loss—conductive, sensorineural, mixed and normal—may be seen following TB ballistic injuries. Trauma severe enough to disrupt the facial nerve is more likely to cause anacusis. However, all should be formally evaluated, since ballistic injuries complicated by neurologic or vascular damage do not necessarily correlate with worse audiologic outcomes, while patients with minimal fractures may demonstrate losses.
Toward Humanistic Business Ethics
Authors: de Colle Simone , Freeman R. Edward , Wicks Andrew C.
Published: July 2023

We theorize that, in the current development of business ethics, there is a fruitful evolution that dissolves the dichotomy between the normative and behavioral research approaches developed, respectively, by philosophers and social scientists; this approach avoids many of the limitations originated by such distinction by reconnecting their two separate narratives. We call this emerging research model Humanistic Business Ethics (HBE) as it emphasizes the centrality of the human dimension of business and the importance of adopting a richer concept of humanity in business ethics research. We argue that this specific research model in business ethics emerges when scholars combine a pragmatist philosophical approach with some key ideas coming from stakeholder theory, which we summarize and connect. By leveraging collaboration across ethics, economics, psychology, and entrepreneurship, HBE can help business and society scholars undertake fruitful inquiries into the way business works (and should work) at its best.
Vigilance Decrement During On-Road Partially Automated Driving Across Four Systems
Authors: Biondi Francesco N. , McDonnell Amy S. , Mahmoodzadeh Mobina , Jajo Noor , Balakumar Balasingam  , Strayer David L.
Published: July 2023

Objective

This study uses a detection task to measure changes in driver vigilance when operating four different partially automated systems.

Background

Research show temporal declines in detection task performance during manual and fully automated driving, but the accuracy of using this approach for measuring changes in driver vigilance during on-road partially automated driving is yet unproven.

Method

Participants drove four different vehicles (Tesla Model 3, Cadillac CT6, Volvo XC90, and Nissan Rogue) equipped with level-2 systems in manual and partially automated modes. Response times to a detection task were recorded over eight consecutive time periods.

Results

Bayesian analysis revealed a main effect of time period and an interaction between mode and time period. A main effect of vehicle and a time period x vehicle interaction were also found.

Conclusion

Results indicated that the reduction in detection task performance over time was worse during partially automated driving. Vehicle-specific analysis also revealed that detection task performance changed across vehicles, with slowest response time found for the Volvo.

Application

The greater decline in detection performance found in automated mode suggests that operating level-2 systems incurred in a greater vigilance decrement, a phenomenon that is of interest for Human Factors practitioners and regulators. We also argue that the observed vehicle-related differences are attributable to the unique design of their in-vehicle interfaces.
Employment interventions to assist people who experience borderline personality disorder: A scoping review
Authors: Kernot Jocelyn , Baker Amy , Oster Candice , Petrakis Melissa , Dawson Suzanne
Published: July 2023

Background:

Employment is an important social determinant of health and is associated with positive health outcomes. However, individuals who have been diagnosed with borderline personality disorder (BPD) are significantly underrepresented in the workforce. Whilst there is an array of evidence based therapeutic interventions, there remains a gap in knowledge regarding the most effective ways to enhance employment outcomes for people with a diagnosis of BPD.

Aim:

To explore employment interventions for people with BPD, map the available evidence and identify key concepts and knowledge gaps.

Methods:

A scoping review was conducted to identify and map the relevant literature. Findings were summarised using a narrative approach. Consultation was provided by a reference group including peer support workers with lived experience of BPD and mental health clinicians.

Results:

Seven articles met the inclusion criteria, including non-randomised and case study/series designs and a randomised controlled trial protocol, with participant numbers generally low. All programmes combined a psychotherapeutic component with work related goals; however, there were notable differences in relation to the conceptual/theoretical approach of the psychotherapeutic component and delivery of the work-related components. Barriers and enablers to programme participation and success are explored.

Conclusions:

This review provides important insights into the characteristics of vocational rehabilitation interventions for people diagnosed with BPD. The findings will inform the co-production of approaches to support people with BPD to engage in employment.
Turning the Tables: Military Intervention and the Onset of Negotiations in Civil War
Authors: Dudley Rebecca
Published: July 2023

When do negotiations occur in civil war? How does military intervention alter this process? While the existing literature presents models of the onset of negotiations – both mediated and unassisted – they are incomplete if they do not consider third-party states involved in the conflict prior to negotiations. I argue that military intervention impacts negotiation onset by adjusting barriers to negotiation through three pathways: the likelihood of military victory, the risk of signaling weakness, and the presence of additional veto players. I examine these mechanisms using logistic random effects models on a dataset of African civil wars. An extension of the argument addresses how expectations of intervention shape conflict behavior. Rebel-supporting interventions, interventions with independent interests, and asymmetric interventions lead to an increase in the likelihood of negotiations occurring. Models controlling for expectations of intervention also suggest that third parties can impact belligerents’ behavior through both expectations and follow-through.