bluuebunny/crossref_metadata_2025 huggingface dataset:
18‐Crown‐6 Additive to Enhance Performance and Durability in Solution‐Processed Halide Perovskite Electronics
Authors: Sim Kihyung , Nakao Takuya , Sasase Masato , Iimura Soshi , Kim Junghwan , Hosono Hideo
Published: July 2022

Recently, an “interlayer” has been often adopted in organic–inorganic hybrid perovskite light‐emitting diodes (PeLEDs). The term “interlayer” infers that the layer function is not clear, but it improves electroluminescence (EL) performance. In this respect, it is of interest to determine the exact role of the interlayer and how it works in PeLEDs. In this study, the interlayer is determined to play a crucial role in suppressing the chemical reaction between the metal oxide and hybrid perovskite layers. Nevertheless, the use of an interlayer, a wide gap insulator, does not guarantee the best PeLED performance because it hinders charge injection into the emission layer. Here, a method is proposed that does not apply an “interlayer” but enables simultaneous attainment of high EL performance and outstanding device stability. 18‐crown 6‐ether (18C6) additive (2.5 mg mL−1) is found to fully suppress the chemical reaction between the metal oxide and hybrid perovskite layers. With the 18C6 additive, an 82‐fold longer device lifetime and very low operating voltage (3.2 V at 10 000 cd m−2) are demonstrated in a PeLED.
Rationally Designed Heptamethine Cyanine Photosensitizers that Amplify Tumor‐Specific Endoplasmic Reticulum Stress and Boost Antitumor Immunity
Authors: Huang Xie , Gao Mingquan , Xing Haiyan , Du Zaizhi , Wu Zifei , Liu Jing , Li Tao , Cao Jiang , Yang Xiaochao , Li Rong , Wang Weidong , Wang Junping , Luo Shenglin
Published: July 2022

Cancer phototherapy activates immunogenic cell death (ICD) and elicits a systemic antitumor immune response, which is an emerging approach for tumor treatment. Most available photosensitizers require a combination of immune adjuvants or checkpoint inhibitors to trigger antitumor immunity because of the immunosuppressive tumor microenvironment and the limited phototherapeutic effect. A class of tumor‐targeting heptamethine cyanine photosensitizers modified with an endoplasmic reticulum (ER)‐targeting group (benzenesulfonamide) are synthesized. Phototherapy of tumor cells markedly amplifies ER stress and promotes tumor antigen release, as the ER is required for protein synthesis, secretion, and transport. More importantly, different electron‐donating or ‐withdrawing substitutions are introduced into benzenesulfonamide to modulate the nonradiative decay pathways through intramolecular charge transfer, including singlet–triplet intersystem crossing (photodynamic effect) and internal thermal conversion (photothermal effect). Thus, a heptamethine cyanine photosensitizer containing a binitro‐substituted benzenesulfonamide (ER‐Cy‐poNO2) is identified that preferentially accumulates in the ER of tumor cells. It significantly enhances the phototherapeutic effect by inducing excessive ER stress and robust ICD. Consequently, this small molecular photosensitizer triggers a sufficient antitumor immune response and effectively suppresses the growth of both primary and distant metastatic tumors, whereas no apparent toxicity is observed. This heptamethine cyanine photosensitizer has the potential to enhance cancer‐targeted immunotherapy.
Robust Heterostructures in Two‐Dimensional Perovskites by Threshold‐Dominating Anion Exchange
Authors: He Chengyu , Li Jing , Bao Yanan , Li Jianliang , Wang Hengshan , Zhang Mingqun , Li HuaFeng , Tang Huayi , Sun Zhiguang , Zhang Qi , Fang Yurui , Xu Jiao , Yang Yiming
Published: July 2022

Heterostructures play an irreplaceable role in high‐performance optoelectronic devices. However, the preparation of robust perovskite heterostructures is challenging due to spontaneous interdiffusion of halogen anions. Herein, a vapor‐phase anion exchange method universally suitable for the preparation of robust 2D Ruddlesden–Popper perovskite (RPP) heterostructures is developed. A variety of heterostructures are fabricated based on exfoliated RPP microplates (MPs). Depending on the specific organic cations, the heterostructures can be either sharp and uniform, or broad and gradient, suggesting a new anion diffusion behavior different from that in 3D perovskites. Further experimental studies reveal that the lateral transport of anions follows a threshold‐dominating mechanism, while the vertical transport can be partially or completely suppressed by organic cations. Subsequently, quantitative investigation of anion diffusion in 2D perovskites is conducted. The lateral diffusion coefficient of halogen anions is calculated to be 6 to 7 orders of magnitude larger than the vertical coefficient, consistent with the observed highly anisotropic anion diffusion. In addition, it is shown that the anion exchange threshold can also enhance the thermodynamic stability of the heterostructures at elevated temperature. These results provide a general method to fabricate robust lateral RPP heterostructures, and offer important insights into anion behavior in low‐dimensional perovskites.
Effect of different exposure conditions on the self‐healing capacity of engineered cementitious composites with crystalline admixture
Authors: Mahmoodi Sina , Sadeghian Pedram
Published: July 2022

In this study, the effect of different exposure conditions of ambient air, tap water, and seawater on two levels of crack widths in engineered cementitious composites (ECC) were investigated. Crystalline admixture (CA) was implemented in the ECC mix to promote self‐healing capacity. Flexural testing on prism specimens (100 × 100 × 350 mm) was conducted to evaluate self‐healing by recovering the stiffness in the specimens with crack widths below 200 μm. Water permeability test was also carried out to assess the crack‐filling capability of ECC disk specimens (100‐mm diameter × 50‐mm thickness) with single crack widths over 1 mm. Digital image correlation technique was used to monitor crack propagation patterns and crack widths. To analyze the microstructure of the healing products, X‐ray diffraction test was conducted on groups of tap water and seawater exposures. Concluding results proved seawater to be a promising environmental condition for the self‐healing process in ECC specimens incorporating CA, in terms of recovery of mechanical and transport properties. Brucite was found to be formed as the additional healing agent that promoted self‐healing in this condition. These results can be applied for coastal concrete structures.
In Vitro Selection of Deoxyribozymes for the Detection of RNA Modifications
Authors: Liaqat Anam , Sednev Maksim V. , Höbartner Claudia
Published: July 2022

Deoxyribozymes are artificially evolved DNA molecules with catalytic abilities. RNA-cleaving deoxyribozymes have been recognized as an efficient tool for detection of modifications in target RNAs and provide an alternative to traditional and modern methods for detection of ribose or nucleobase methylation. However, there are only few examples of DNA enzymes that specifically reveal the presence of a certain type of modification, including N6-methyladenosine, and the knowledge about how DNA enzymes recognize modified RNAs is still extremely limited. Therefore, DNA enzymes cannot be easily engineered for the analysis of desired RNA modifications, but are instead identified by in vitro selection from random DNA libraries using synthetic modified RNA substrates. This protocol describes a general in vitro selection stagtegy to evolve new RNA-cleaving DNA enzymes that can efficiently differentiate modified RNA substrates from their unmodified counterpart.
Non-radioactive In Vivo Labeling of RNA with 4-Thiouracil
Authors: Braun Christina , Knüppel Robert , Perez-Fernandez Jorge , Ferreira-Cerca Sébastien
Published: July 2022

RNA molecules and their expression dynamics play essential roles in the establishment of complex cellular phenotypes and/or in the rapid cellular adaption to environmental changes. Accordingly, analyzing RNA expression remains an important step to understand the molecular basis controlling the formation of cellular phenotypes, cellular homeostasis or disease progression. Steady-state RNA levels in the cells are controlled by the sum of highly dynamic molecular processes contributing to RNA expression and can be classified in transcription, maturation and degradation. The main goal of analyzing RNA dynamics is to disentangle the individual contribution of these molecular processes to the life cycle of a given RNA under different physiological conditions. In the recent years, the use of nonradioactive nucleotide/nucleoside analogs and improved chemistry, in combination with time-dependent and high-throughput analysis, have greatly expanded our understanding of RNA metabolism across various cell types, organisms, and growth conditions.

In this chapter, we describe a step-by-step protocol allowing pulse labeling of RNA with the nonradioactive nucleotide analog, 4-thiouracil, in the eukaryotic model organism Saccharomyces cerevisiae and the model archaeon Haloferax volcanii.
Translation Phases in Eukaryotes
Authors: Blanchet Sandra , Ranjan Namit
Published: July 2022

Protein synthesis in eukaryotes is carried out by 80S ribosomes with the help of many specific translation factors. Translation comprises four major steps: initiation, elongation, termination, and ribosome recycling. In this review, we provide a comprehensive list of translation factors required for protein synthesis in yeast and higher eukaryotes and summarize the mechanisms of each individual phase of eukaryotic translation.
Thermofluor-Based Analysis of Protein Integrity and Ligand Interactions
Authors: Pinz Sophia , Doskocil Eva , Seufert Wolfgang
Published: July 2022

Thermofluor is a fluorescence-based thermal shift assay, which measures temperature-induced protein unfolding and thereby yields valuable information about the integrity of a purified recombinant protein. Analysis of ligand binding to a protein is another popular application of this assay. Thermofluor requires neither protein labeling nor highly specialized equipment, and can be performed in a regular real-time PCR instrument. Thus, for a typical molecular biology laboratory, Thermofluor is a convenient method for the routine assessment of protein quality. Here, we provide Thermofluor protocols using the example of Cdc123. This ATP-grasp protein is an essential assembly chaperone of the eukaryotic translation initiation factor eIF2. We also report on a destabilized mutant protein version and on the ATP-mediated thermal stabilization of wild-type Cdc123 illustrating protein integrity assessment and ligand binding analysis as two major applications of the Thermofluor assay.
Establishment and Maintenance of Open Ribosomal RNA Gene Chromatin States in Eukaryotes
Authors: Schächner Christopher , Merkl Philipp E. , Pilsl Michael , Schwank Katrin , Hergert Kristin , Kruse Sebastian , Milkereit Philipp , Tschochner Herbert , Griesenbeck Joachim
Published: July 2022

In growing eukaryotic cells, nuclear ribosomal (r)RNA synthesis by RNA polymerase (RNAP) I accounts for the vast majority of cellular transcription. This high output is achieved by the presence of multiple copies of rRNA genes in eukaryotic genomes transcribed at a high rate. In contrast to most of the other transcribed genomic loci, actively transcribed rRNA genes are largely devoid of nucleosomes adapting a characteristic “open” chromatin state, whereas a significant fraction of rRNA genes resides in a transcriptionally inactive nucleosomal “closed” chromatin state. Here, we review our current knowledge about the nature of open rRNA gene chromatin and discuss how this state may be established.
Eukaryotic Ribosome assembly and Nucleocytoplasmic Transport
Authors: Oborská-Oplová Michaela , Fischer Ute , Altvater Martin , Panse Vikram Govind
Published: July 2022

The process of eukaryotic ribosome assembly stretches across the nucleolus, the nucleoplasm and the cytoplasm, and therefore relies on efficient nucleocytoplasmic transport. In yeast, the import machinery delivers ~140,000 ribosomal proteins every minute to the nucleus for ribosome assembly. At the same time, the export machinery facilitates translocation of ~2000 pre-ribosomal particles every minute through ~200 nuclear pore complexes (NPC) into the cytoplasm. Eukaryotic ribosome assembly also requires >200 conserved assembly factors, which transiently associate with pre-ribosomal particles. Their site(s) of action on maturing pre-ribosomes are beginning to be elucidated. In this chapter, we outline protocols that enable rapid biochemical isolation of pre-ribosomal particles for single particle cryo-electron microscopy (cryo-EM) and in vitro reconstitution of nuclear transport processes. We discuss cell-biological and genetic approaches to investigate how the ribosome assembly and the nucleocytoplasmic transport machineries collaborate to produce functional ribosomes.
Medicine, the Holocaust, and Human Dignity: Lessons from Human Rights
Authors: Wasserman Jason Adam , Navin Mark Christopher
Published: July 2022

The development of bioethics in the late Twentieth Century parallels the development of human rights discourses. Both intellectual movements have ideological roots in a reckoning with the tragedy of the Holocaust and both invoke conceptions of human dignity that have sometimes been accused of being vague or empty and therefore useless. However, despite its ambiguity, human dignity plays an important role in both discourses. In particular, we argue that bioethics scholars can learn from how advocates of human rights have balanced their idealized and abstract conceptions of dignity (and other values) with a focus on how real-world personal and institutional moral failures can inform efforts to promote human rights. We argue that a reengagement with the horrors of the Holocaust can supplement and motivate a critical, real-world bioethics, one that is responsive to the personal and institutional failures of our time and which provides practical guidance undernon-idealconditions.
The Physician’s Role: Patient v. Population
Authors: Urion David K.
Published: July 2022

There is always a tension between Public health and individual medical care. The former seeks, by one ethical optic, a fundamentally consequentialist goal: the greatest good for the greatest number of individuals. The latter has, at its moral base, an encounter between a medical provider and a patient, and its ethical goal is to optimize the outcome that the patient desires. While this dichotomy of intent and effort must be nuanced, setting it out in these terms helps us understand the tensions that we see between Public health initiatives and individual medical care. This chapter will suggest that by examining two movements that attempted to insert larger community concerns into the individual patient encounter, we might gain insight into what happens in the moral space of the patient encounter when the provider is compelled to consider these larger concerns. The Eugenics movement of the late nineteenth and early twentieth centuries, and the population health movement of the late twentieth and early twenty-first centuries will be considered as two examples of attempts to alter the individual patient encounter through the lens of larger societal concerns.
Ultralight millicharged dark matter via misalignment
Authors: Bogorad Zachary , Toro Natalia
Published: July 2022

Abstract

We explore the cosmology and phenomenology of millicharged and millicharge-like dark matter with masses from 1 eV to 10 keV and charges of 10−18 to 10−14. Dark matter in this mass range cannot be thermally produced, but can arise from non-thermal mechanisms. We propose a concrete model employing a spontaneously broken approximate global symmetry, in which millicharged dark matter is produced via the misalignment mechanism. We show that this production mechanism is cosmologically consistent and compatible with the observed dark matter abundance. This model can be implemented using either fundamental scalars or hidden-sector quarks, and coupled either to the Standard Model photon or to a hidden photon. We then consider the phenomenology of light millicharged dark matter, regardless of its cosmological origin, and determine the parameter space consistent with existing experiments and observations. A significant part of the new parameter space we consider may be accessible in the near future through direct deflection experiments, measurements of the cosmic microwave background blackbody spectrum, and future constraints on plasma instabilities due to dark matter self-interaction.
Complementary signals of lepton flavor violation at a high-energy muon collider
Authors: Homiller Samuel , Lu Qianshu , Reece Matthew
Published: July 2022

Abstract

A muon collider would be a powerful probe of flavor violation in new physics. There is a strong complementary case for collider measurements and precision low-energy probes of lepton flavor violation (as well as CP violation). We illustrate this by studying the collider reach in a supersymmetric scenario with flavor-violating slepton mixing. We find that the collider could discover sleptons and measure the slepton and neutralino masses with high precision, enabling event reconstruction that could cleanly separate flavor-violating new physics signals from Standard Model backgrounds. The discovery reach of a high-energy muon collider would cover a comparably large, and overlapping, range of parameter space to futureμ → econversion and electron EDM experiments, and unlike precision experiments could immediately shed light on the nature of new physics responsible for flavor violation. This complementarity strengthens the case that a muon collider could be an ideal energy-frontier laboratory in the search for physics beyond the Standard Model.
Primitive ideals in affinoid enveloping algebras of semisimple Lie algebras
Authors: Stanciu Ioan
Published: July 2022

For a semisimple Lie algebra defined over a discrete valuation ring with field of fractions K, we prove that any primitive ideal with rational central character in the affinoid enveloping algebra, $$\widehat{U({\mathfrak {g}})_{K}}$$

U

(
g
)

K

^

, is the annihilator of an affinoid highest weight module. In the case $$n>0$$

n
>
0

, we characterise all the primitive ideals in the affinoid algebra $$\widehat{U(\mathfrak {{g}})_{n,K}}$$

U

(
g
)

n
,
K

^

.
Kosten-Erlös-Defizit der ambulanten Versorgung von Bagatellverletzungen in der Notaufnahme
Authors: Mühlenfeld Nils , Vollrath Jan Tilmann , Hörauf Jason-Alexander , Schöffski Oliver , Sterz Jasmina , Riemenschneider Julia , Störmann Philipp , Marzi Ingo , Verboket René D.
Published: July 2022

Hintergrund

Viele Patienten mit Bagatellverletzungen gehen heutzutage häufig vorschnell in die Notaufnahmen und binden dort Ressourcen und Personal.

Ziel der Arbeit

Das Erstellen des Kosten-Erlös-Verhältnis der ambulanten Versorgung von Bagatellverletzungen in der unfallchirurgischen Notaufnahme.

Material und Methoden

Die Kalkulation erfolgte anhand der einheitlich abgerechneten Notfallpauschalen des Einheitlichen Bemessungsmaßstabes (EBM). Mittels der gängigen Tarifverträge für Ärzte und Pflegepersonal wurden Minutenkosten berechnet. Der zeitliche Behandlungsaufwand wurde anhand von 100 Referenzpatienten mit einer Bagatellverletzung ermittelt. Die Fallkostenkalkulation mit den jeweilig anfallenden Ressourcen erfolgte mit dem operativen Controlling des Universitätsklinikums Frankfurt.

Ergebnisse

Eingeschlossen wurden 4088 Patienten mit Bagatellverletzungen, welche sich 2019 eigenständig fußläufig vorstellten. Die häufigsten Gründe für die Vorstellung waren Prellungen der unteren (31,9 %; n = 1303) und oberen Extremität (16,6 %; n = 677). Kalkuliert wurden Zeitaufwände von 166,7 min/Tag für das ärztliche und 213,8 min/Tag für das Pflegepersonal. Es wurde ein Gesamterlös von 29.384,31 € und Gesamtlosten von 69.591,22 € berechnet. Somit lässt sich ein Erlösdefizit von 40.206,91 € für das Jahr 2019 berechnen. Das entspricht einem monetären Defizit von 9,84 €/Patienten.

Diskussion

Es herrscht Knappheit an der medizinischen Ressource „Personal“, um das heutzutage hohe Aufkommen an sich selbst vorstellenden fußläufigen Patienten mit Bagatellverletzungen zufriedenstellend und ökonomisch zu bewältigen. Die bisherige Vergütung der Behandlung von Bagatellverletzungen durch den EBM ist für den Krankenhaussektor unzureichend.
Long‐Term Health‐Related Quality of Life Outcomes Following Thyroid Surgery for Malignant or Benign Disease: Deficits Persist in Cancer Survivors Beyond Five Years
Authors: Blefari Nicholas D. A. , Rowe Christopher W. , Wiadji Elvina , Lambkin David , Carroll Rosemary , Fradgley Elizabeth A. , O'Neill Christine J.
Published: July 2022

Background

Thyroid cancer diagnoses are increasing and treatment can lead to significant morbidity. Long‐term health‐related quality of life (HRQoL) in thyroid cancer is understudied and lacks reference populations. This study compares long‐term HRQoL between patients with thyroid cancer or benign disease, following thyroid surgery.

Methods

Patients undergoing thyroidectomy between 2000 and 2017 were identified from a pathology database. 696 participants (278 malignant, 418 benign) were invited to complete a validated disease‐specific HRQoL tool, City of Hope—Thyroid Version. Propensity scores were used to adjust for demographic and clinical differences between cohorts.

Results

206 patients (102 malignant, 104 benign), 71% female, returned surveys a median of 6.5 (range 1–19) years after thyroidectomy. Of the cancer cohort, 95% had differentiated thyroid cancer and 83% remained disease‐free. There were no significant differences in overall HRQoL scores between groups. In comparison to the benign cohort, cancer patients showed a significant detriment in the social subdomain score (OR 0.10–0.96, p = 0.017) but not in other subdomains (physical, psychological, spiritual). Female gender, increasing BMI and cancer recurrence were significantly associated with decreased overall HRQoL. Compared to the benign cohort, cancer patients reported more personal and family distress associated with diagnosis and treatment, increased future uncertainty, poorer concentration and greater financial burden.

Conclusion

Although no difference in overall HRQoL was found between patients undergoing thyroidectomy for benign or malignant disease, detriments in social well‐being may persist many years after surgery. Thyroid cancer patients and their families may benefit from increased supports around the time of diagnosis and treatment.
Do E2 and P4 contribute to the explained variance in core temperature response for trained women during exertional heat stress when metabolic rates are very high?
Authors: Zheng Huixin , Badenhorst Claire E. , Lei Tze-Huan , Che Muhamed Ahmad Munir , Liao Yi-Hung , Fujii Naoto , Kondo Narihiko , Mündel Toby
Published: July 2022

Purpose

Women remain underrepresented in the exercise thermoregulation literature despite their participation in leisure-time and occupational physical activity in heat-stressful environments continuing to increase. Here, we determined the relative contribution of the primary ovarian hormones (estrogen [E2] and progesterone [P4]) alongside other morphological (e.g., body mass), physiological (e.g., sweat rates), functional (e.g., aerobic fitness) and environmental (e.g., vapor pressure) factors in explaining the individual variation in core temperature responses for trained women working at very high metabolic rates, specifically peak core temperature (Tpeak) and work output (mean power output).

Methods

Thirty-six trained women (32 ± 9 year, 53 ± 9 ml·kg−1·min−1), distinguished by intra-participant (early follicular and mid-luteal phases) or inter-participant (ovulatory vs. anovulatory vs. oral contraceptive pill user) differences in their endogenous E2and P4concentrations, completed a self-paced 30-min cycling work trial in warm–dry (2.2 ± 0.2 kPa, 34.1 ± 0.2 °C, 41.4 ± 3.4% RH) and/or warm–humid (3.4 ± 0.1 kPa, 30.2 ± 1.2 °C, 79.8 ± 3.7% RH) conditions that yielded 115 separate trials. Stepwise linear regression was used to explain the variance of the dependent variables.

Results

Models were able to account for 60% of the variance inTpeak($$\overline{R }$$R¯2: 41% core temperature at the start of work trial,$$\overline{R }$$R¯2: 15% power output,$$\overline{R }$$R¯2: 4% [E2]) and 44% of the variance in mean power output ($$\overline{R }$$R¯2: 35% peak aerobic power,$$\overline{R }$$R¯2: 9% perceived exertion).

Conclusion

E2contributes a small amount toward the core temperature response in trained women, whereby starting core temperature and peak aerobic power explain the greatest variance inTpeakand work output, respectively.
A 2-tier subdivision of papillary proliferations of the endometrium (PPE) only emphasizing the complexity of papillae precisely predicts the neoplastic risk and reflects the neoplasia-related molecular characteristics—a single-centered analysis of 207 cases
Authors: Liu Danyang , Chen Tingting , Yu Kexuan , Li Jing , Wang Shunni , Ma Xiaoxi , Zhu Qin , Ning Yan , Wang Yiqin
Published: July 2022

Papillary proliferation of the endometrium (PPE) is subdivided based on the complexity of the papillae and the proliferation of lesions, and the complex group is considered to have an increased risk of concurrent/subsequent endometrial neoplasia. However, the current subdivision criteria fail to prove the equivalence of the quantity of simple papillae and structural complexity. In this study, we divided PPE of 207 cases from 2014 to 2022 into 3 groups according to structural complexity and proliferation degrees: Group 1 equaled to the simple PPE with a simple papillary structure and typical localized proliferation; group 2 had the simple structure similar to group 1 but occupy over 50% of the endometrial polyp or > 2 lesions in the surface of nonpolypoid endometrium; group 3 had the truly complex branching papillae despite of its proportion. Group 3 was implicated with significantly more concurrent endometrial neoplasia (EAH and carcinoma) compared with groups 1 and 2 (P < 0.01), while no difference was found between groups 1 and 2. In 128 cases with no concurrent endometrial abnormalities in the initial biopsy or curettage specimens, 4 cases presented endometrial neoplasia (3 carcinoma and 1 atypical hyperplasia) in the subsequent specimens, all of which presented PPE of group 3 but not group 1 or 2 in the prior tissues (P < 0.01). The immunochemistry of 83 cases showed similar expressions of ER, PTEN, ARID1A, PTEN, p16, β-catenin, and p53 between PPE and the surrounding normal endometrium. Nearly 100% of PPE cases lost expressions of PR. A total of 2/83 cases showing PAX2 expression were all in the group 3 and correlated with endometrial neoplasia (2/17, 11.76%, P < 0.05). 76/83 (91.57%) of PPE lesions had KRAS mutations, and the distributions of which were similar among 3 groups. The frequency of mucinous metaplasia was significantly higher in the PPE lesions with KRAS mutations (72/74, 97.30%, P < 0.01). Group 3 showed higher frequency of single KRAS mutations compared with the combination of groups 1 and 2 (P < 0.01). Finally, the concordance of KRAS mutation profiles between PPE and endometrial neoplasia was significantly higher in group 3 than either group 1 or 2 (P < 0.01), while no difference was found between group 1 and 2. Thus, a new 2-tier subdivision system only emphasizing the complexity of papillae is recommended, which might precisely predict the risk of endometrial neoplasia and neoplasia-related molecular characteristics.
Immuno-histochemical correlation of fibrosis-related markers with the desmoplastic reaction of the mesentery in small intestine neuroendocrine neoplasms
Authors: Bösch Florian , Altendorf-Hofmann Annelore , Koliogiannis Vanessa , Ilhan Harun , Jacob Sven , Pretzsch Elise , Nölting Svenja , Werner Jens , Klauschen Frederick , Auernhammer Christoph J. , Angele Martin K. , Knösel Thomas
Published: July 2022

Introduction

Small intestine neuroendocrine neoplasms (siNENs) will attain more importance due to their increasing incidence. Moreover, siNENs might lead to a desmoplastic reaction (DR) of the mesentery causing severe complications and deteriorating prognosis. The expression of fibrosis-related proteins appears to be the key mechanisms for the development of this desmoplastic reaction. Therefore, this study aimed to investigate the association of the desmoplastic mesentery with specific fibrosis-related protein expression levels.

Materials and methods

By immunohistochemistry, the protein expression levels of four fibrosis-related markers (APLP2, BNIP3L, CD59, DKK3) were investigated in primary tumors of 128 siNENs. The expression levels were correlated with the presence of a desmoplastic reaction and clinico-pathological parameters.

Results

In the primary tumor, APLP2, BNIP3L, CD59 and DKK3 were highly expressed in 29.7% (n = 38), 64.9% (n = 83), 92.2% (n = 118) and 80.5% (n = 103), respectively. There was no significant correlation of a single marker or the complete marker panel to the manifestation of a desmoplastic mesentery. The desmoplastic mesentery was significantly associated with clinical symptoms, such as flushing and diarrhea. However, neither the fibrosis-related marker panel nor single marker expressions were associated with clinical symptoms.

Discussion

The expression rates of four fibrosis-related markers in the primary tumor display a distinct pattern. However, the expression patterns are not associated with desmoplastic altered mesenteric lymph node metastases and the expression patterns did not correlate with prognosis. These findings suggest alternative mechanisms being responsible for the desmoplastic reaction.
Affective Symptoms and Oropharyngeal Dysphagia in Head-and-Neck Cancer Patients: A Systematic Review
Authors: Krebbers Iris , Pilz Walmari , Vanbelle Sophie , Verdonschot Rob J. C. G. , Baijens Laura W. J.
Published: July 2022

Oropharyngeal dysphagia (OD) is a high impact morbidity in head-and-neck cancer (HNC) patients. A wide variety of instruments are developed to screen for affective symptoms and OD. The current paper aims to systematically review and appraise the literature to obtain insight into the prevalence, strength, and causal direction of the relationship between affective symptoms and OD in HNC patients. This review was conducted in accordance with the PRISMA statement. A systematic search of the literature was performed using PubMed, PsycINFO, Cochrane, and Embase. All available publications reporting on the relationship between affective conditions and swallowing function in HNC patients were included. Conference papers, tutorials, reviews, and studies with less than 5 patients were excluded. Fifteen studies met the inclusion criteria. The level of evidence and methodological quality were assessed using the ABC-rating scale and QualSyst critical appraisal tool. Eleven studies reported a positive relationship between affective symptoms and OD. The findings of this paper highlight the importance of affective symptom screening in dysphagic HNC patients as clinically relevant affective symptoms and OD seems to be prevalent and coincident in this population. Considering the impact of affective symptoms and OD on patients’ daily life, early detection and an integrated interdisciplinary approach are recommended. However, due to the heterogeneity of study designs, outcomes, and outcome measures, the generalization of study results is limited.
Selective intraoperative cholangiography should be considered over routine intraoperative cholangiography during cholecystectomy: a systematic review and meta-analysis
Authors: Kovács Norbert , Németh Dávid , Földi Mária , Nagy Bernadette , Bunduc Stefania , Hegyi Péter , Bajor Judit , Müller Katalin Eszter , Vincze Áron , Erőss Bálint , Ábrahám Szabolcs
Published: July 2022

Background

Decades of debate surround the use of intraoperative cholangiography (IOC) during cholecystectomy. To the present day, the role of IOC is controversial as regards decreasing the rate of bile duct injury (BDI). We aimed to review and analyse the available literature on the benefits of IOC during cholecystectomy.

Methods

A systematic literature search was performed until 19 October 2020 in five databases using the following search keys: cholangiogra* and cholecystectomy. The primary outcomes were BDI and retained stone rate. To investigate the differences between the groups (routine IOC vs selective IOC and IOC vs no IOC), we calculated weighted mean differences (WMD) for continuous outcomes and relative risks (RR) for dichotomous outcomes, with 95% confidence intervals (CI).

Results

Of the 19,863 articles, 38 were selected and 32 were included in the quantitative synthesis. Routine IOC showed no superiority compared to selective IOC in decreasing BDI (RR = 0.91, 95% CI 0.66; 1.24). Comparing IOC and no IOC, no statistically significant differences were found in the case of BDI, retained stone rate, readmission rate, and length of hospital stay. We found an increased risk of conversion rate to open surgery in the no IOC group (RR = 0.64, CI 0.51; 0.78). The operation time was significantly longer in the IOC group compared to the no IOC group (WMD = 11.25 min, 95% CI 6.57; 15.93).

Conclusion

Our findings suggest that IOC may not be indicated in every case, however, the evidence is very uncertain. Further good quality research is required to address this question.
Strong well-posedness, stability and optimal control theory for a mathematical model for magneto-viscoelastic fluids
Authors: Garcke Harald , Knopf Patrik , Mitra Sourav , Schlömerkemper Anja
Published: July 2022

In this article, we study the strong well-posedness, stability and optimal control of an incompressible magneto-viscoelastic fluid model in two dimensions. The model consists of an incompressible Navier–Stokes equation for the velocity field, an evolution equation for the deformation tensor, and a gradient flow equation for the magnetization vector. First, we prove that the model under consideration posseses a global strong solution in a suitable functional framework. Second, we derive stability estimates with respect to an external magnetic field. Based on the stability estimates we use the external magnetic field as the control to minimize a cost functional of tracking-type. We prove existence of an optimal control and derive first-order necessary optimality conditions. Finally, we consider a second optimal control problem, where the external magnetic field, which represents the control, is generated by a finite number of fixed magnetic field coils.
Cardiovascular biomarkers in pregnancy with diabetes and associations to glucose control
Authors: Jacobsen Daniel P. , Røysland Ragnhild , Strand Heidi , Moe Kjartan , Sugulle Meryam , Omland Torbjørn , Staff Anne Cathrine
Published: July 2022

Aim

Cardiovascular disease (CVD) is a leading cause of death in both men and women. Type 1 and 2 diabetes mellitus (DM1 and DM2) are well-known risk factors for CVD. In addition, gestational diabetes mellitus (GDM) is a female sex-specific risk factor for CVD. Here, we measure circulating concentrations of cardiac troponin T (cTNT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) during pregnancy—a window of time often referred to as a cardiovascular stress test for women.

Methods

This study utilized data from 384 pregnant women: 64 with DM1, 16 with DM2, 35 with GDM and 269 euglycemic controls. Blood was predominantly sampled within a week before delivery. Cardiovascular biomarker concentrations were measured in serum using electrochemiluminescence immunoassay.

Result

Circulating cTnT levels were higher in women with DM1, DM2 and GDM as compared to controls, whereas NT-proBNP and GDF-15 levels were only increased in women with DM1. Glucose dysregulation, assessed by third trimester HbA1c levels, positively correlated with all three CVD biomarker levels, whereas pregestational body mass index correlated negatively with GDF-15.

Conclusions

Our results support the presence of myocardial affection in women with diabetic disorders during pregnancy. Although pregestational DM1 in this study was associated with the most adverse CVD biomarker profile, women with GDM displayed an adverse cTnT profile similar to what we found in women with pregestational DM2. This supports that women with GDM should be offered long-term intensified cardiovascular follow-up and lifestyle advice following delivery, similarly to the well-established CV follow-up of women with pregestational DM.
Taking real steps in virtual nature: a randomized blinded trial
Authors: Litleskare Sigbjørn , Fröhlich Fred , Flaten Ole Einar , Haile Amelia , Kjøs Johnsen Svein Åge , Calogiuri Giovanna
Published: July 2022

Studies show that green exercise (i.e., physical activity in the presence of nature) can provide the synergistic psychophysiological benefits of both physical exercise and nature exposure. The present study aimed to investigate the extent to which virtual green exercise may extend these benefits to people that are unable to engage in active visits to natural environments, as well as to promote enhanced exercise behavior. After watching a video validated to elicit sadness, participants either performed a treadmill walk while exposed to one of two virtual conditions, which were created using different techniques (360° video or 3D model), or walked on a treadmill while facing a blank wall (control). Quantitative and qualitative data were collected in relation to three overarching themes: “Experience,” “Physical engagement” and “Psychophysiological recovery.” Compared to control, greater enjoyment was found in the 3D model, while lower walking speed was found in the 360° video. No significant differences among conditions were found with respect to heart rate, perceived exertion, or changes in blood pressure and affect. The analysis of qualitative data provided further understanding on the participants’ perceptions and experiences. These findings indicate that 3D model-based virtual green exercise can provide some additional benefits compared to indoor exercise, while 360° video-based virtual green exercise may result in lower physical engagement.
Unfreezing of molecular motions in protein-polymer conjugates: a calorimetric study
Authors: Pelosi C. , Tombari E. , Wurm F. R. , Tiné M. R.
Published: July 2022

Protein-polymer conjugates are a promising class of biohybrids. In this work, the dynamics of a set of biodegradable conjugates myoglobin-poly(ethyl ethylene phosphate) (My-PEEP) with variations in the number of attached polymers and their molar mass in the dry-state, have been investigated to understand the role of polymer on protein dynamics. We performed Differential Scanning Calorimetry measurements between 190 and 300 K, observing the large-scale dynamics arising from reorganization of conformational states, i.e. within the 100 s timescale. The application of an annealing time during the cooling scans was used to investigate the non-equilibrium glassy-state of the samples, observing the relaxation enthalpy at different annealing temperatures. This procedure permitted to extensively describe the transition broadness and the system relaxation kinetics in the glassy state. The samples show an experimental behaviour different from the theoretical predictions, suggesting the establishment of interactions among the protein and the polymer chains. The different behaviour of the conjugates and the physical mixture (composed of the protein and the polymer physically mixed) highlighted the importance of the covalent bond in defining the system dynamics.

Graphical abstract
Is artificial intelligence improving the audit process?
Authors: Fedyk Anastassia , Hodson James , Khimich Natalya , Fedyk Tatiana
Published: July 2022

How does artificial intelligence (AI) impact audit quality and efficiency? We explore this question by leveraging a unique dataset of more than 310,000 detailed individual resumes for the 36 largest audit firms to identify audit firms’ employment of AI workers. We provide a first look into the AI workforce within the auditing sector. AI workers tend to be male and relatively young and hold mostly but not exclusively technical degrees. Importantly, AI is a centralized function within the firm, with workers concentrating in a handful of teams and geographic locations. Our results show that investing in AI helps improve audit quality, reduces fees, and ultimately displaces human auditors, although the effect on labor takes several years to materialize. Specifically, a one-standard-deviation change in recent AI investments is associated with a 5.0% reduction in the likelihood of an audit restatement, a 0.9% drop in audit fees, and a reduction in the number of accounting employees that reaches 3.6% after three years and 7.1% after four years. Our empirical analyses are supported by in-depth interviews with 17 audit partners representing the eight largest U.S. public accounting firms, which show that (1) AI is developed centrally; (2) AI is widely used in audit; and (3) the primary goal for using AI in audit is improved quality, followed by efficiency.
Nutraceuticals and mitochondrial oxidative stress: bridging the gap in the management of bronchial asthma
Authors: Allam Venkata Sita Rama Raju , Paudel Keshav Raj , Gupta Gaurav , Singh Sachin Kumar , Vishwas Sukriti , Gulati Monica , Gupta Saurabh , Chaitanya M. V. N. L. , Jha Niraj Kumar , Gupta Piyush Kumar , Patel Vyoma K. , Liu Gang , Kamal Mohammad Amjad , Hansbro Philip M. , Oliver Brian Gregory George , Chellappan Dinesh Kumar , Dua Kamal
Published: July 2022

Asthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mortality in the world. Oxidative stress further complicates the pathology of the disease. The current treatment strategies for asthma mainly involve the use of anti-inflammatory agents and bronchodilators. However, long-term usage of such medications is associated with severe adverse effects and complications. Hence, there is an urgent need to develop newer, novel, and safe treatment modalities for the management of asthma. This has therefore prompted further investigations and detailed research to identify and develop novel therapeutic interventions from potent untapped resources. This review focuses on the significance of oxidative stressors that are primarily derived from both mitochondrial and non-mitochondrial sources in initiating the clinical features of asthma. The review also discusses the biological scavenging system of the body and factors that may lead to its malfunction which could result in altered states. Furthermore, the review provides a detailed insight into the therapeutic role of nutraceuticals as an effective strategy to attenuate the deleterious effects of oxidative stress and may be used in the mitigation of the cardinal features of bronchial asthma.
A Mathematical Model of Salivary Gland Duct Cells
Authors: Su Shan , Rugis John , Wahl Amanda , Doak Sam , Li Yating , Suresh Vinod , Yule David , Sneyd James
Published: July 2022

Saliva is produced in two stages in the salivary glands: the secretion of primary saliva by the acinus and the modification of saliva composition to final saliva by the intercalated and striated ducts. In order to understand the saliva modification process, we develop a mathematical model for the salivary gland duct. The model utilises the realistic 3D structure of the duct reconstructed from an image stack of gland tissue. Immunostaining results show that TMEM16A and aquaporin are expressed in the intercalated duct cells and that ENaC is not. Based on this, the model predicts that the intercalated duct does not absorb Na$$^+$$

+

and Cl$$^-$$

-

like the striated duct but secretes a small amount of water instead. The input to the duct model is the time-dependent primary saliva generated by an acinar cell model. Our duct model produces final saliva output that agrees with the experimental measurements at various stimulation levels. It also shows realistic biological features such as duct cell volume, cellular concentrations and membrane potentials. Simplification of the model by omission of all detailed 3D structures of the duct makes a negligible difference to the final saliva output. This shows that saliva production is not sensitive to structural variation of the duct.
Effect of Carbon Content on Variant Pairing in Bainitic Low Alloy Steel
Authors: Ståhlkrantz Adam , Hedström Peter , Sarius Niklas , Borgenstam Annika
Published: July 2022

Variant pairing in bainite was evaluated in four different commercial low alloy steels with medium to high carbon content. The steels investigated were austempered in the temperature range 275 °C to 450 °C to obtain a bainitic microstructure. It was found that the V1–V6 is the most frequent variant pairing at lower temperature, while it gradually decreases towards intermediate temperatures, and at the highest austempering temperatures the variant pairing with low misorientation boundaries such as V1–V4 and V1–V8 is the most frequent. The preferred variant pairing is the least pronounced after austempering of steels with higher carbon contents at intermediate temperature. Nonetheless, a continuous increase of variant pairing within the same Bain group was observed with increasing austempering temperature for all steels. Furthermore, it was observed that the deviation from the theoretical Kurdjumov–Sachs orientation relationship increases with increasing austempering temperature for all steels.
Comparison of 5-Year Follow-up Outcomes Between Primary and Revision Roux-en-Y Gastric Bypasses After Open Vertical Banded Gastroplasty: an Inverse Propensity Score-Weighted Analysis
Authors: Hany Mohamed , Torensma Bart , Ibrahim Mohamed , Zidan Ahmed , Gaballah Muhammad , Aly Ayman Farouk Mohammad Ahmed , Abu-Sheasha Ghada Ahmed
Published: July 2022

Introduction

Vertical banded gastroplasty (VBG) is associated with high weight regain; Roux-en-Y gastric bypass (RYGB) is used as a revision procedure in patients with VBG experiencing weight regain. This study compared the 5-year follow-up outcomes of primary (PRYGB) and revision RYGB after VBG (RRYGB).

Methods

Patients who underwent PRYGB or RRYGB after VBG from 2008 to 2016 were enrolled. Data on weight regain, weight loss (WL), food tolerance (FT), early and late complications, and resolution or improvement in associated medical conditions were analyzed.

Results

PRYGB and RRYGB groups had 558 and 156 patients, respectively, after exclusion of the lost to follow-up patients. PRYGB group showed significantly lower mean body mass index (over the entire follow-up period), early complications, reintervention rates for late complications, and overall reintervention rates than that of the RRYGB group. On the other hand, FT scores, odds of late complications, and improvements (in the fifth year) in associated medical conditions were comparable between the two groups.

Conclusion

RRYGB in patients with VBG who regained weight showed comparable safety and resolution of associated diseases to that of PRYGB over the 5-year follow-up period. The WL in the RRYGB group was acceptable despite being less than that of the PRYGB group. FT was better after RRYGB than that of PRYGB in the first year; however, both were comparable at the fifth year follow-up. Patients with VBG undergoing RYGB should receive attentive treatment and evaluation of associated factors.

Graphical abstract