bluuebunny/crossref_metadata_2025 huggingface dataset:
Anxiety and depression in lung cancer: effect of psychological interventions – network meta-analysis
Authors: Yuan Dongling , Huang Yuda , Wu Jialing , Guo Zhenli , Li Shansi , Zhang Yi
Published: November 2022

Background

The prevalence of depression and anxiety is high in patients with lung cancer, while multiple psychological interventions have revealed a positive impact on patients’ negative emotions. However, it remains scarce which psychological intervention is the best choice for patients.This study was conducted to compare and rank the efficacy of psychological interventions on anxiety and depression in patients with lung cancer using a network meta-analysis.

Methods

The Chinese academic database (CNKI, Wan Fang and Vip) and English academic database (The Cochrane Library, PubMed, PsycINFO and Web of Science) were searched from their inception to March 2022. Randomised controlled studies of psychological interventions on depression and anxiety in patients with lung cancer were included. Study selection and evaluation were conducted independently by two researchers. Included studies were performed a network meta-analysis to compare and rank the psychological interventions for negative emotions of patients with lung cancer. The clustered ranking of psychotherapies in the network was based on surface under the cumulative probability ranking curve values.

Results

23 studies (2221 participants) with 13 psychological interventions were retrieved. The random-effects model showed a significantly large effect size of supportive therapy for anxiety (mean difference, MD 14.38, 95% CI 2.42 to 26.21) and depression (MD 14.29, 95% CI 2.74 to 25.70). The supportive therapy, sandplay therapy and music therapy were top three rankings of interventions for anxiety, while supportive therapy, dignity therapy and sandplay therapy were the top three interventions for depression.

Conclusions

Supportive therapy would be a more appropriate option for alleviating negative emotions in patients with lung cancer. Other psychological intervention techniques may be used as alternatives, such as sandplay therapy and music therapy for anxiety, dignity therapy and sandplay therapy for depression.

PROSPERO registration number

CRD42022320188.
Online e-cigarette promotion in Indonesia
Authors: Bigwanto Mouhamad , Ramadhan Farandi Agesti , Wijayanto Xenia Angelica
Published: November 2022

Background

The decline in the global prevalence of cigarette smoking has prompted tobacco companies to expand their business by producing and marketing new nicotine-based products in various countries, including Indonesia. The study aims to assess e-cigarette promotional frequency and content on social media in Indonesia.

Methods

Monitoring was conducted on Instagram in October 2021. A total of 45 Instagram influencer accounts were monitored to assess the frequency of posting and interactions from 4 to 20 October for InstaStories and from 4 to 31 October for Instagram Feeds. Content analysis was carried out on 310 posts collected from 10 randomly selected accounts from 1 to 31 October (one post per account per day) to evaluate the form, type and characteristics of the promotions.

Results

There were a total of 2 897 327 followers across the 45 Instagram accounts. On average, the 45 accounts posted about 185 stories and 43 feed posts per day. Of the 310 feed posts analysed from 10 randomly selected accounts, 64% featured images of women; 50% highlighted or displayed the product; and 32% showed enjoyment of the product flavours.

Conclusions

The tobacco industry has successfully taken advantage of the e-cigarette promotion regulatory void. The Indonesian government needs to ban the promotion of these products, including those on online platforms.
Echoes of charged black-bounce spacetimes
Authors: Wu S. R. , Wang B. Q. , Liu Dong , Long Z. W.
Published: November 2022

In present work, the evolution of scalar field and electromagnetic field under the background of the charged black-bounce spacetimes are investigated, and we obtain an obvious echoes signal which appropriately reports the properties of the charged black-bounce spacetimes and disclose the physical reasons behind such phenomena. Furthermore, by studying the quasinormal ringdown, we analyze the three states of the charged black-bounce spacetimes in detail, our results show that the echoes signal only appears when $$(|{Q}|\le m)$$

(
|
Q
|
≤
m
)

and $$(|{l}|> m+ \sqrt{m ^{2}-Q^{2} })$$

(
|
l
|
>
m
+

m
2

-

Q
2

)

in this spacetime, while when the parameters demand $$(|{Q}|>m)$$

(
|
Q
|
>
m
)

, the echoes signal will be transformed into a quasinormal ringdown of the two-way traversable wormhole, and the charged black-bounce is a regular black hole with normal horizons by requiring $$(|{Q}|\le m)$$

(
|
Q
|
≤
m
)

and $$(|{l}|< m-\sqrt{m ^{2}-Q^{2} })$$

(
|
l
|
<
m
-

m
2

-

Q
2

)

.
Rudolph (Silas) Glossop: some fragments and family memories
Authors: Slack Emma
Published: November 2022

Not long after my father died at the age of 91 in 1993 my mother told me that a lecture and award were proposed in his name. She was very pleased and in 1997 when she was asked to attend and to present the prizes we were all very gratified, and the family have enjoyed the connection to the event ever since. It has not happened every year and it has varied in its grandeur but many images remain in our minds: the enormous rock that had crashed through the roof of a fisherman's hut on the harbour at St Helena; the climbers drilling screws into the Irish cliff to stabilize it to preserve the library that had been built at the top; the rocks bouncing across the floor of a quarry; the lovely old library of the Geological Society in the early years; the Geographical Society with the photographs of famous explorers on the walls of the staircase; the meals in the Polish Club; and now the Royal Institution. Such a splendid geotechnical affair would have delighted my father. We have learnt a good deal and enjoyed visiting the world of geologists and engineers. If only once a year, it does bring back memories of my father.
Ecological and evolutionary responses of terrestrial arthropods to Middle–Late Pennsylvanian environmental change
Authors: Donovan Michael P. , Schachat Sandra R. , Monarrez Pedro M.
Published: November 2022

The Middle–Late Pennsylvanian Subperiod was marked by recurrent glacial–interglacial cycles superimposed on a longer-term trend of increasing aridity. Wetland and drought-tolerant floras responded with repeated migrations in the tropics, and a major plant turnover occurred in swamp ecosystems in parts of Euramerica near the Middle–Late Pennsylvanian boundary. However, the corresponding ecological and evolutionary responses of insects and other terrestrial arthropods are poorly understood. Here, we review the record of plant–arthropod interactions and analyse origination and extinction rates of insects during the Middle–Late Pennsylvanian. Although preliminary, plant–arthropod associations broadly persist through the Middle–Late Pennsylvanian boundary, and new damage types and host-plant associations first appear in the Late Pennsylvanian, possibly related to increased availability of accessible vascular and foliar tissues associated with the shift from arborescent lycopsid to tree and seed fern dominance in Euramerican wetlands. Likewise, our analysis of the insect body fossil record does not suggest especially high rates of origination or extinction during this interval. Together, these results suggest that insects did not suffer major extinctions during the Middle–Late Pennsylvanian, despite short- and long-term changes in climate and environmental conditions.
An Efficient Data Protection Scheme Based on Hierarchical ID-Based Encryption for MQTT
Authors: Fan Chun-I , Shie Cheng-Han , Tseng Yi-Fan , Huang Hui-Chun
Published: November 2022

As
Internet of Things (IoT)
thrives over the whole world, more and more IoT devices and IoT-based protocols have been designed and proposed in order to meet people’s needs. Among those protocols,
message queueing telemetry transport (MQTT)
is one of the most emerging and promising protocols, which provides many-to-many message transmissions based on the “publish/subscribe” mechanism. It has been widely used in industries such as the energy industry, chemical engineering, self-driving, and so on. While transporting important messages, MQTT specification recommends the use of TLS protocol. However, the computation cost of TLS is too heavy. Since topics in a broker are stored with a hierarchical structure, in this manuscript, we propose a novel data protection protocol for MQTT from hierarchical ID-based encryption. Our protocol adopts the intrinsic hierarchical structures of MQTT, and achieves constant-size keys, i.e., independent of the depth in hierarchical structures. Besides, the formal security model for the proposed protocol have been defined in the manuscript. The proposed protocol have been formally proven chosen-plaintext secure under the ℓ-wBDHI assumption.
Conceptualizing the Researcher-Theory Relation
Authors: Tenenberg Josh
Published: November 2022

In this article, I interrogate the relation between a researcher and the theories that the researcher gets involved with. I use my own trajectory as a computing education researcher as a way to make visible how different conceptions of this relation are shaped through prior encounters with different theories in the human sciences, particularly theories of mind, language, and knowledge. While modernist theories stemming from the Enlightenment that presuppose a disengaged researcher have predominated in CS and CER, theories of mind, language, and knowledge associated with pragmatist and phenomenological philosophical perspectives from the 20th Century challenge these modernist views. Under these newer theoretical perspectives, the researcher is always already involved with theory, even if such theory has withdrawn into the unnoticed background, a background that gives every research study its intelligibility. Recognizing that all researchers are caught in the grip of theory may help in both abandoning theories that no longer serve and staying open to adopt new and emergent theories.
Linear Logic Properly Displayed
Authors: Greco Giuseppe , Palmigiano Alessandra
Published: November 2022

We introduce proper display calculi for intuitionistic, bi-intuitionistic and classical linear logics with exponentials, which are sound, complete, conservative, and enjoy cut elimination and subformula property. Based on the same design, we introduce a variant of Lambek calculus with exponentials, aimed at capturing the controlled application of exchange and associativity.
Properness
(i.e., closure under uniform substitution of all parametric parts in rules) is the main technical novelty of the present proposal, allowing both for the smoothest proof of cut elimination and for the development of an overarching and modular treatment for a vast class of axiomatic extensions and expansions of intuitionistic, bi-intuitionistic, and classical linear logics with exponentials. Our proposal builds on an algebraic and order-theoretic analysis of linear logic and applies the guidelines of the multi-type methodology in the design of display calculi.
Is Justice Colorblind? A Review of Workplace Racioethnic Differences Through the Lens of Organizational Justice
Authors: Avery Derek R. , Hall Alison V. , Preston McKenzie , Ruggs Enrica N. , Washington Ella
Published: November 2022

It is difficult to draw definitive conclusions about the workplace impact of race from the organizational psychology and organizational behavior literature. Topical coverage is spotty and the findings are fragmented, with little existing theory to orient, integrate, and reconcile them. Consequently, it is unsurprising that public opinion is highly divergent about the influence of race at work, and practitioners are left largely unassisted in determining evidence-based approaches to leveraging this form of difference among their personnel. To fill this void, we review the relevant findings through the lens of organizational justice to help clarify the impact of race on organizational experiences. Our findings suggest that justice indeed varies as a function of race, the magnitude of differences depends on the type of justice, and there are several potentially fruitful areas for additional inquiry.
Neural Mechanisms That Make Perceptual Decisions Flexible
Authors: Okazawa Gouki , Kiani Roozbeh
Published: November 2022

Neural mechanisms of perceptual decision making have been extensively studied in experimental settings that mimic stable environments with repeating stimuli, fixed rules, and payoffs. In contrast, we live in an ever-changing environment and have varying goals and behavioral demands. To accommodate variability, our brain flexibly adjusts decision-making processes depending on context. Here, we review a growing body of research that explores the neural mechanisms underlying this flexibility. We highlight diverse forms of context dependency in decision making implemented through a variety of neural computations. Context-dependent neural activity is observed in a distributed network of brain structures, including posterior parietal, sensory, motor, and subcortical regions, as well as the prefrontal areas classically implicated in cognitive control. We propose that investigating the distributed network underlying flexible decisions is key to advancing our understanding and discuss a path forward for experimental and theoretical investigations.
Fabrication of Disposable Electrodes Based on Green Synthesized Iron Oxide Nanoparticles for Enumeration of Bacteria in Water
Authors: Ijaz Ramsha , Hassan Syeda Sara , Panhwar Sallahuddin , Talpur Muhammad Younis , Uddin Salah , Ahmed Zubair
Published: November 2022

Poor drinking water quality is a leading cause of preventable deaths in young children. Identifying contaminated water is a major challenge, especially where water resources are very limited. There is an urgent need to fabricate smart disposable electrodes to detect specific Escherichia coli ATCC-25922 in water to protect against diseases such as gastroenteritis and acute diarrhea. In this article, we presented a simple method to fabricate disposable electrodes using single-pot green iron oxide nanoparticles. The nanostructure and detailed morphology of the green synthesized iron oxide nanoparticles (Ne-Ne-Fe3O4-NPs) were analyzed using analytical techniques. Modified Ne-Fe3O4-NPs developed the disposable electrode and cyclic voltammetry (CV) was used to detect the target bacteria. Under optimized experimental conditions, the signals increased linearly while the concentration range increased from 101−107 CFU ml−1, having a short response of time 35 min. In addition, the fabricated disposable electrode showed dynamic detection range, stability of the electrode, and selectivity and provides a new strategy by using green nanoparticles to detect selected bacteria from water.
Prolonged, physiologically relevant nicotine concentrations in the airways of smokers
Authors: Esther Charles R. , O’Neal Wanda K. , Alexis Neil E. , Koch Abigail L. , Cooper Christopher B. , Barjaktarevic Igor , Raffield Laura M. , Bowler Russel P. , Comellas Alejandro P. , Peters Stephen P. , Hastie Annette T. , Curtis Jeffrey L. , Ronish Bonnie , Ortega Victor E. , Wells J. Michael , Halper-Stromberg Eitan , Rennard Stephen I. , Boucher Richard C. ,   on behalf of SPIROMICS
Published: November 2022

Nicotine from cigarette smoke is a biologically active molecule that has pleiotropic effects in the airway, which could play a role in smoking-induced lung disease. However, whether nicotine and its metabolites reach sustained, physiologically relevant concentrations on airway surfaces of smokers is not well defined. To address these issues, concentrations of nicotine, cotinine, and hydroxycotinine were measured by mass spectrometry (MS) in supernatants of induced sputum obtained from participants in the subpopulations and intermediate outcome measures in COPD study (SPIROMICS), an ongoing observational study that included never smokers, former smokers, and current smokers with and without chronic obstructive pulmonary disease (COPD). A total of 980 sputum supernatants were analyzed from 77 healthy never smokers, 494 former smokers (233 with COPD), and 396 active smokers (151 with COPD). Sputum nicotine, cotinine, and hydroxycotinine concentrations corresponded to self-reported smoking status and were strongly correlated to urine measures. A cutoff of ∼8–10 ng/mL of sputum cotinine distinguished never smokers from active smokers. Accounting for sample dilution during processing, active smokers had airway nicotine concentrations in the 70–850 ng/mL (∼0.5–5 µM) range, and concentrations remained elevated even in current smokers who had not smoked within 24 h. This study demonstrates that airway nicotine and its metabolites are readily measured in sputum supernatants and can serve as biological markers of smoke exposure. In current smokers, nicotine is present at physiologically relevant concentrations for prolonged periods, supporting a contribution to cigarette-induced airway disease.
Dynamic alterations in yak (Bos grunniens) rumen microbiome in response to seasonal variations in diet
Authors: Jiang Hui , Cao Han-Wen , Chai Zhi-Xin , Chen Xiao-Ying , Zhang Cheng-Fu , Zhu Yong , Xin Jin-Wei
Published: November 2022

Rumen microorganisms play important roles in the healthy growth of yaks. This study investigated changes in yak rumen microbiome during natural grazing at the warm seasons and supplementary feeding at cold seasons. High-throughput sequencing of 16S rRNA and metagenome analysis were conducted to investigate the structures and functions of yak rumen microbial communities. The results indicated that Bacteroidetes and Firmicutes were the most abundant phyla. In addition, Bacteroidetes might play a more important role than Firmicutes during the supplementary feeding stage (spring and winter), but less during natural grazing stage (summer and autumn). KEGG analysis showed that the amino sugar and nucleotide sugar metabolism, glycolysis/gluconeogenesis, pyruvate metabolism, starch and sucrose metabolism, and fructose and mannose metabolism were the main pathways in the microbial community, which were significantly different between seasons. The carbohydrate-active enzymes (CAZyme) annotation revealed that cellulose was an important carbon source for microorganisms in yak rumen. Glycoside hydrolases (GHs) were the most abundant class of CAZymes, followed by glycosyl transferases (GTs), which were important to digestion of oil, cellulose, and hemicellulose in food. These results contribute to the understanding of microbial components and functions in yak rumen.
Low-Frequency Analytical Model of Superconducting Magnet Impedance
Authors: Martino Michele
Published: November 2022

A superconducting magnet for particle accelerators is often modeled as an ideal inductor, as it indeed exhibits a completely negligible resistance; this is fully satisfactory, as an example, for control purposes, as the time constant formed by the magnet inductance and the resistance of normal conducting cables connecting it to the power converter accurately describe the essentially dominant dynamics of the circuit. Such a model would however fail to correctly represent the noise attenuation mechanism at play in practical superconducting magnets, which also include a vacuum pipe or a beam screen in the inner part of the aperture, an iron yoke on the outer part, and, potentially, a stainless steel or aluminum collar in between. Even at relatively low frequencies, a more accurate model is therefore needed. A sufficiently general one is proposed and illustrated.
Curcumin Prevents Diabetic Osteoporosis through Promoting Osteogenesis and Angiogenesis Coupling via NF-κB Signaling
Authors: Fan Desheng , Lu Jiuqing , Yu Nijia , Xie Yajia , Zhen Lei
Published: November 2022

Diabetic osteoporosis (DOP) is a metabolic disease which is characterized by impaired bone microarchitecture and reduced bone mineral density resulting from hyperglycemia. Curcumin, an effective component extracted from Curcuma longa, exhibits antioxidation, regulation of bone metabolism and hypoglycemic effects. The BMSC-mediated osteogenesis and angiogenesis coupling seems to be important in bone formation and regeneration. We aimed to explore the effect of curcumin on BMSC-mediated osteogenesis-angiogenesis coupling in high glucose conditions and underlying mechanisms. Our results showed that high glucose impaired the osteogenic and proangiogenic ability of BMSCs and that curcumin pretreatment rescued the BMSC dysfunction induced by high-concentration glucose. Inhibition of the high glucose-activated NF-κB signaling pathway has been found to contribute to the protective effects of curcumin on high glucose-inhibited coupling of osteogenesis and angiogenesis in BMSCs. Furthermore, accelerated bone loss and decreased type H vessels were observed in diabetic osteoporosis mice models. However, curcumin treatment prevented bone loss and promoted vessel formation in diabetic osteoporosis mice. Based on these results, we concluded that curcumin ameliorated diabetic osteoporosis by recovering the osteogenesis and angiogenesis coupling of BMSCs in hyperglycemia, partly through inhibiting the high glucose-activated NF-κB signaling pathway.
An Investigation on the Influences of Construction Schemes on Backfilling the River-Crossing Section of a Utility Tunnel
Authors: Huang Jin-Kun , Lu Zhao-Xiang , Yin Wan-Yun , Jin Ren-Cai , Qian Yuan-Di , Shen Si-Dong , Wang Lei
Published: November 2022

The backfill construction of a utility tunnel is as important as its main structure construction. While the existing research on utility tunnels focuses on the construction of the main structure, rare attention has been paid to the backfill construction. In this paper, with a practical comprehensive utility tunnel project as the background, a variety of different backfill construction schemes were designed, and the corresponding numerical simulations were performed with the finite element analysis software Midas. The influence of different backfill construction schemes on the side wall, roof, and floor of the utility tunnel was systematically studied and analyzed, and the displacement and stress variation curves in the process of utility tunnel backfill were obtained. Based on the simulation results and the actual engineering situation, the optimal schemes for utility tunnel backfill construction were determined. The results show that the displacement of the side wall of the utility tunnel increased first and then decreased with increasing backfill soil in the unilateral backfill mode, and there was little displacement in the bilateral backfill mode. The shear stress of the side wall of the utility tunnel in both the unilateral and bilateral backfill modes gradually increased with the backfill process. Within the region 1 m above the roof of the utility tunnel, backfill modes had no effect on the final stress and displacement values, but the layering method made a difference. Accordingly, bilateral backfill mode is suggested for the region below the roof of the utility tunnel, while in the case of region 1 m above the roof, backfilling is recommended to be layered according to height rather than position.
Garlic Powder Supplementation Improves Growth, Nonspecific Immunity, Antioxidant Capacity, and Intestinal Flora of Chinese Mitten Crabs (Eriocheir sinensis)
Authors: Zhou Ruoyu , Liu Jinsong , Shi Xueyan , Fu Chunsheng , Jiang Ying , Zhang Ruiqiang , Wu Yanping , Yang Caimei
Published: November 2022

This study was conducted to survey the effects of garlic powder on growth performance, nonspecific immunity, antioxidant capacity, and intestinal flora structure of Chinese mitten crabs. Altogether, 216 crabs which originally weigh

20.71
±
0.13
 
g

were randomly allocated into three treatment groups with 6 replicates of 12 crabs per replicate. The control group (CN) was fed a basal diet, while the other two groups were fed the basal diet supplemented with 1000 mg/kg (GP1000) and 2000 mg/kg (GP2000) garlic powder, respectively. This trial lasted 8 weeks. The results showed that the supplementation of garlic powder improved the final body weight, weight gain rate, and specific growth rate of the crabs (

P
<
0.05

). Meanwhile, in serum, better nonspecific immune was confirmed by the enhancement of phenoloxidase and lysozyme levels, with the improvement of phosphatase activities in GP1000 and GP2000 (

P
<
0.05

). On the other hand, the levels of total antioxidant capacity, glutathione peroxidases, and total superoxide dismutase in serum and hepatopancreas were increased (

P
<
0.05

) while malondialdehyde content declined (

P
<
0.05

) as the garlic powder was added to the basal diet. And, catalase in serum also shows an increase (

P
<
0.05

). In both GP1000 and GP2000, genes related to antioxidant and immunity, for instance, Toll-like receptor 1, glutathione peroxidase, catalase, myeloid differentiation factor 88, TuBe, Dif, relish, crustins, antilipopolysaccharide factor, lysozyme, and prophenoloxidase mRNA expression levels, were increased (

P
<
0.05

). The abundance of Rhizobium and Rhodobacter was reduced by adding garlic powder (

P
<
0.05

). This study indicated that dietary addition of garlic powder promoted growth, enhanced nonspecific immunity and antioxidant capacity, activated Toll pathway, IMD pathway, and proPO system, increased antimicrobial peptide expression, while simultaneously improving the intestinal flora of Chinese mitten crabs.
Prophylactic Impella CP versus VA-ECMO in Patients Undergoing Complex High-Risk Indicated PCI
Authors: van den Buijs Deborah M.F. , Wilgenhof Adriaan , Knaapen Paul , Zivelonghi Carlo , Meijers Tom , Vermeersch Paul , Arslan Fatih , Verouden Niels , Nap Alex , Sjauw Krischan , van den Brink Floris S.
Published: November 2022

Objectives. To compare two different forms of mechanical circulatory support (MCS) in patients with complex high-risk indicated PCI (CHIP): the Impella CP system and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Background. To prevent hemodynamic instability in CHIP, various MCS systems are available. However, comparable data on different forms of MCS are not at hand. Methods. In this multicenter observational study, we retrospectively evaluated all CHIP procedures with the support of an Impella CP or VA-ECMO, who were declined surgery by the heart team. Major adverse cardiac events (MACE), mortality at discharge, and 30-day mortality were evaluated. Results. A total of 41 patients were included, of which 27 patients were supported with Impella CP and 14 patients with VA-ECMO. Baseline characteristics were well-balanced in both groups. No significant difference in periprocedural hemodynamic instability was observed between both groups (3.7% vs. 14.3%;p=0.22). The composite outcome of MACE showed no significant difference (30.7% vs. 21.4%;p=0.59). Bleeding complications were higher in the Impella CP group, but showed no significant difference (22.2% vs. 7.1%;p=0.22) and occurred more at the non-Impella access site. In-hospital mortality was 7.4% in the Impella CP group versus 14.3% in the VA-ECMO group and showed no significant difference (p=0.48). 30-Day mortality showed no significant difference (7.4% vs. 21.4%;p=0.09). Conclusions. In patients with CHIP, there were no significant differences in hemodynamic instability and overall MACE between VA-ECMO or Impella CP device as mechanical circulatory support. Based on this study, the choice of either VA-ECMO or Impella CP does not alter the outcome.
Economic Policy Uncertainty, Managerial Ability, and the Peer Effect of Corporate Investment
Authors: Yang Ningxia
Published: November 2022

How the macro-external environment, i.e., the uncertainty of economic policies, affects the peer effect of corporate investment and whether the ability of managers, as the main decision of corporate investment, affects the peer effect of enterprise investment is worthy of further study. This paper uses Baker’s economic policy uncertainty index to obtain China’s economic policy uncertainty index and uses the DEA-Tobit two-stage model to measure the ability of managers, combined with the relevant data of China’s A-share listed companies from 2010 to 2020, to study the impact of economic policy uncertainty and managers’ ability on corporate investment peer effect. We found that China’s economic policy uncertainty increases the information acquisition cost of micro-firms and deepens the degree of information asymmetry, and firms are strongly motivated to learn or even imitate the investment decisions of enterprises in the same industry, thus intensifying the peer effect of investment. For enterprises of different nature, the economic policy uncertainty has a more significant impact on the investment peer effect of non-state-owned enterprises than state-owned enterprises. Compared with large enterprises, the impact of economic policy uncertainty on the investment cohort effect of small enterprises is more significant. Then, through group regression according to the median of managerial ability, we found that the investment peer effect is more obvious in enterprises with low management ability and the effect of economic policy uncertainty on investment peer effect is more significant in the sample with low management ability. Based on the empirical research conclusions, this paper puts forward the following suggestions: improve the corporate governance mechanism and the management ability of managers. In issuing economic policies, the government should be cautious and stable to reduce the uncertainty of economic policies.
Exosomes Derived from Dermal Papilla Cells Mediate Hair Follicle Stem Cell Proliferation through the Wnt3a/β-Catenin Signaling Pathway
Authors: Li Jiali , Zhao Bohao , Dai Yingying , Zhang Xiyu , Chen Yang , Wu Xinsheng
Published: November 2022

Both hair follicle stem cells (HFSC) and dermal papilla cells (DPC) are essential for hair follicle growth and proliferation. In this study, HFSCs and DPCs that made signature proteins like KRT14, KRT15, KRT19, α-SMA, and Versican were obtained. Cell coculture systems between HFSCs and DPCs were used to measure the increased PCNA protein content in HFSCs. Additionally, exosomes from dermal papilla cells (DPC-Exos), the overexpression and silencing of Wnt3a, could regulate the Wnt/β-catenin signaling pathway downstream genes. After collecting DPC-ExosOE-Wnt3a, the treatment of HFSC with DPC-ExosOE-Wnt3a showed that DPC-ExosOE-Wnt3a could upregulate the mRNA expression of downstream genes in the Wnt/β-catenin signaling pathway and that DPC-ExosOE-Wnt3a enhanced the proliferation of HFSCs while inhibiting their apoptosis. These findings suggest that DPC-Exos could regulate HFSC cell proliferation via the Wnt3a/β-catenin signaling pathway. This research offers novel concepts for the molecular breeding and efficient production of Angora rabbits, as well as for the treatment of human hair problems.
Impact of Fiber Buildup Stacking Sequence on Thermo-Mechanical Behaviour of Natural Fiber–Reinforced Anamide Composites
Authors: Subramanian M. , Diviya M. , Kaliappan S. , Deepak A. , Saxena Kuldeep K. , Hasan Nasim
Published: November 2022

This article focuses on the viscoelastic behaviour of the anamide composites using a dynamic mechanical study developed by hot compression moulding technology at higher temperatures. The frequency range for this analysis is 1 Hz. In the nitrogen atmosphere, thermogravimetry analysis differential scanning calorimetry was used to investigate the thermal stability of composite laminates with various fiber orientations. The findings showed that a glass transition temperature close to 100°C can be achieved at 1 Hz to increase the fiber orientation of the basalt fiber-enhanced anamide compounds. Through the thermo-gravimetric analysis experiments, the excellent thermal stability of composite laminates at temperatures above 600°C was conspicuous. Analysis using the Fourier transform infrared (FTIR) spectroscopy envisioned the surface chemical properties of anamide films at various fiber orientations, and the interaction properties between fiber and matrix were determined. Scanning electron microscopy on composite laminate surfaces proclaimed that the interface relationship between the basalt fiber and the anamide material is superior with FTIR findings being assisted. The findings demonstrate that composite laminates may be a good replacement for high-performance and high-temperature applications since they are thermally extremely robust with great rigidity.
A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance
Authors: Yap Timothy A. , LoRusso Patricia M. , Wong Deborah J. , Hu-Lieskovan Siwen , Papadopoulos Kyriakos P. , Holz Josefin-Beate , Grabowska Urszula , Gradinaru Cristian , Leung Kin-Mei , Marshall Sylwia , Reader Claire S. , Russell Roslin , Sainson Richard C.A. , Seal Claire J. , Shepherd Christopher J. , Germaschewski Fiona , Gliddon Daniel , Stern Omer , Young Lesley , Brewis Neil , Kayitalire Louis , Morrow Michelle
Published: November 2022

Purpose:

This phase 1 study (NCT03440437) evaluated the safety, tolerability, pharmacokinetics (PK), and activity of FS118, a bispecific antibody–targeting LAG-3 and PD-L1, in patients with advanced cancer resistant to anti–PD-(L)1 therapy.

Patients and Methods:

Patients with solid tumors, refractory to anti–PD-(L)1–based therapy, received intravenous FS118 weekly with an accelerated dose titration design (800 μg to 0.3 mg/kg) followed by 3+3 ascending dose expansion (1 to 20 mg/kg). Primary objectives were safety, tolerability, and PK. Additional endpoints included antitumor activity, immunogenicity, and pharmacodynamics.

Results:

Forty-three patients with a median of three prior regimens in the locally advanced/metastatic setting, including at least one anti–PD-(L)1 regimen, received FS118 monotherapy. FS118 was well tolerated, with no serious adverse events relating to FS118 reported. No dose-limiting toxicities (DLT) were observed, and an MTD was not reached. The recommended phase 2 dose of FS118 was established as 10 mg/kg weekly. The terminal half-life was 3.9 days. Immunogenicity was transient. Pharmacodynamic activity was prolonged throughout dosing as demonstrated by sustained elevation of soluble LAG-3 and increased peripheral effector cells. The overall disease control rate (DCR) was 46.5%; this disease control was observed as stable disease, except for one late partial response. Disease control of 54.8% was observed in patients receiving 1 mg/kg or greater who had acquired resistance to PD-(L)1–targeted therapy.

Conclusions:

FS118 was well tolerated with no DLTs observed up to and including 20 mg/kg QW. Further studies are warranted to determine clinical benefit in patients who have become refractory to anti–PD-(L)1 therapy.

See related commentary by Karapetyan and Luke, p. 835
Genotype-Tailored ERK/MAPK Pathway and HDAC Inhibition Rewires the Apoptotic Rheostat to Trigger Colorectal Cancer Cell Death
Authors: Jenkins Laura J. , Luk Ian Y. , Fairlie W. Douglas , Lee Erinna F. , Palmieri Michelle , Schoffer Kael L. , Tan Tao , Ng Irvin , Vukelic Natalia , Tran Sharon , Tse Janson W.T. , Nightingale Rebecca , Alam Zakia , Chionh Fiona , Iatropoulos George , Ernst Matthias , Afshar-Sterle Shoukat , Desai Jayesh , Gibbs Peter , Sieber Oliver M. , Dhillon Amardeep S. , Tebbutt Niall C. , Mariadason John M.
Published: November 2022

The EGFR/RAS/MEK/ERK signaling pathway (ERK/MAPK) is hyperactivated in most colorectal cancers. A current limitation of inhibitors of this pathway is that they primarily induce cytostatic effects in colorectal cancer cells. Nevertheless, these drugs do induce expression of proapoptotic factors, suggesting they may prime colorectal cancer cells to undergo apoptosis. As histone deacetylase inhibitors (HDACis) induce expression of multiple proapoptotic proteins, we examined whether they could synergize with ERK/MAPK inhibitors to trigger colorectal cancer cell apoptosis. Combined MEK/ERK and HDAC inhibition synergistically induced apoptosis in colorectal cancer cell lines and patient-derived tumor organoids in vitro, and attenuated Apc-initiated adenoma formation in vivo. Mechanistically, combined MAPK/HDAC inhibition enhanced expression of the BH3-only proapoptotic proteins BIM and BMF, and their knockdown significantly attenuated MAPK/HDAC inhibitor–induced apoptosis. Importantly, we demonstrate that the paradigm of combined MAPK/HDAC inhibitor treatment to induce apoptosis can be tailored to specific MAPK genotypes in colorectal cancers, by combining an HDAC inhibitor with either an EGFR, KRASG12C or BRAFV600 inhibitor in KRAS/BRAFWT; KRASG12C, BRAFV600E colorectal cancer cell lines, respectively. These findings identify a series of ERK/MAPK genotype-tailored treatment strategies that can readily undergo clinical testing for the treatment of colorectal cancer.
The Bispecific Tumor Antigen-Conditional 4–1BB x 5T4 Agonist, ALG.APV-527, Mediates Strong T-Cell Activation and Potent Antitumor Activity in Preclinical Studies
Authors: Nelson Michelle H. , Fritzell Sara , Miller Robert , Werchau Doreen , Van Citters Danielle , Nilsson Anneli , Misher Lynda , Ljung Lill , Bader Robert , Deronic Adnan , Chunyk Allison G. , Schultz Lena , Varas Laura A. , Rose Nadia , Håkansson Maria , Gross Jane , Furebring Christina , Pavlik Peter , Sundstedt Anette , Veitonmäki Niina , Ramos Hilario J. , Säll Anna , Dahlman Anna , Bienvenue David , von Schantz Laura , McMahan Catherine J. , Askmyr Maria , Hernandez-Hoyos Gabriela , Ellmark Peter
Published: November 2022

4–1BB (CD137) is an activation-induced costimulatory receptor that regulates immune responses of activated CD8 T and natural killer cells, by enhancing proliferation, survival, cytolytic activity, and IFNγ production. The ability to induce potent antitumor activity by stimulating 4–1BB on tumor-specific cytotoxic T cells makes 4–1BB an attractive target for designing novel immuno-oncology therapeutics. To minimize systemic immune toxicities and enhance activity at the tumor site, we have developed a novel bispecific antibody that stimulates 4–1BB function when co-engaged with the tumor-associated antigen 5T4. ALG.APV-527 was built on the basis of the ADAPTIR bispecific platform with optimized binding domains to 4–1BB and 5T4 originating from the ALLIGATOR-GOLD human single-chain variable fragment library. The epitope of ALG.APV-527 was determined to be located at domain 1 and 2 on 4–1BB using X-ray crystallography. As shown in reporter and primary cell assays in vitro, ALG.APV-527 triggers dose-dependent 4–1BB activity mediated only by 5T4 crosslinking. In vivo, ALG.APV-527 demonstrates robust antitumor responses, by inhibiting growth of established tumors expressing human 5T4 followed by a long-lasting memory immune response. ALG.APV-527 has an antibody-like half-life in cynomolgus macaques and was well tolerated at 50.5 mg/kg. ALG.APV-527 is uniquely designed for 5T4-conditional 4–1BB–mediated antitumor activity with potential to minimize systemic immune activation and hepatotoxicity while providing efficacious tumor-specific responses in a range of 5T4-expressing tumor indications as shown by robust activity in preclinical in vitro and in vivo models. On the basis of the combined preclinical dataset, ALG.APV-527 has potential as a promising anticancer therapeutic for the treatment of 5T4-expressing tumors.
Short-term PI3K Inhibition Prevents Breast Cancer in Preclinical Models
Authors: Ku Amy T. , Young Adelaide I.J. , Ibrahim Ahmed Atef , Bu Wen , Jiang Weiyu , Lin Meng , Williams Laterrica C. , McCue Bryant Lee , Miles George , Nagi Chandandeep , Behbod Fariba , Li Yi
Published: November 2022

Antiestrogen medication is the only chemoprevention currently available for women at a high risk of developing breast cancer; however, antiestrogen therapy requires years to achieve efficacy and has adverse side effects. Therefore, it is important to develop an efficacious chemoprevention strategy that requires only a short course of treatment. PIK3CA is commonly activated in breast atypical hyperplasia, the known precancerous precursor of breast cancer. Targeting PI3K signaling in these precancerous lesions may offer a new strategy for chemoprevention. Here, we first established a mouse model that mimics the progression from precancerous lesions to breast cancer. Next, we demonstrated that a short-course prophylactic treatment with the clinically approved PI3K inhibitor alpelisib slowed early lesion expansion and prevented cancer formation in this model. Furthermore, we showed that alpelisib suppressed ex vivo expansion of patient-derived atypical hyperplasia. Together, these data indicate that the progression of precancerous breast lesions heavily depends on the PI3K signaling, and that prophylactic targeting of PI3K activity can prevent breast cancer.

Prevention Relevance:

PI3K protein is abnormally high in breast precancerous lesions. This preclinical study demonstrates that the FDA-approved anti-PI3K inhibitor alpelisib can prevent breast cancer and thus warrant future clinical trials in high-risk women.
Homozygous Val6Gly Variation in PRDM5 Gene Causing Brittle Cornea Syndrome: A New Turkish Case
Authors: Sanrı Aslıhan , Demir Selma , Gurkan Hakan
Published: November 2022

Introduction: Brittle cornea syndrome (BCS) is a rare connective tissue disorder with ocular and systemic features. Extreme corneal thinning and fragility are the main hallmarks of BCS. Case Report: A 4-year-old boy presented with recurrent spontaneous corneal perforation. He had blue sclera, corneal leucoma, irregular iris, shallow anterior chamber, corneal astigmatism, and bilateral corneal thinning. He also had several systemic features including hearing loss, skin hyperelasticity, joint hypermobility, scoliosis, and umbilical hernia. A diagnosis of BCS was confirmed with molecular analysis. A homozygous c.17T>G, p.(Val6Gly) variation was identified in the PRDM5 gene. Discussion: p.(Val6Gly) variation in PRDM5 was previously reported in 2 patients with BCS. We also considered PRDM5 c.17T>G, p.(Val6Gly) variation as pathogenic based on the following features: the absence of the variation in population databases, in silico predictions, segregation analysis, and clinical signs of our patient. Extremely thin and brittle corneas lead to corneal perforation spontaneously or after minor trauma. Nearly all patients have lost their vision because of corneal rupture and scars. The key challenge in the management of BCS is the prevention of ocular rupture which relies on early diagnosis. Early diagnosis allows for taking prompt measures to prevent ocular rupture.
Efficacy and Safety of Laparoscopic Endoscopic Cooperative Surgery in Upper Gastrointestinal Lesions: A Systematic Review and Meta-Analysis
Authors: de Brito Sara Oliveira , Libânio Diogo , Pinto Cláudia Martins Marques , Araújo Teixeira João Pedro Pinho Osório de , Araújo Teixeira João Paulo Meireles de
Published: November 2022

Background and Aims: Laparoscopic and endoscopic cooperative surgery (LECS) combines advantages of endoscopy and laparoscopy in order to resect upper gastrointestinal lesions. Our aim was to evaluate the efficacy and safety of LECS in patients with EGJ (esophagogastric junction), gastric and duodenal lesions, as well as to compare LECS with pure endoscopic and pure laparoscopic procedures. Methods: PubMed, Scopus, and ISI Web of Knowledge were searched. Efficacy (R0, recurrence) and safety (conversion rate, procedure and hospitalization time, adverse events, mortality) outcomes were extracted and pooled (odds ratio or mean difference) using a random-effects model. Study quality was assessed with Newcastle-Ottawa Scale and heterogeneity by Cochran’s Q test and I2 . Subgroup analysis according to location was performed. Results: This meta-analysis included 24 studies/1,336 patients (all retrospective cohorts). No significant differences were found between LECS and preexisting techniques (endoscopic submucosal dissection (ESD)/laparoscopy) regarding any outcomes. However, there was a trend to shorter hospitalization time, longer procedure duration, and fewer adverse events in LECS versus Laparoscopy and ESD. R0 tended to be higher in the LECS group. Hospitalization time was significantly shorter in gastric versus EGJ lesions (mean 7.3 vs. 13.7 days, 95% CI: 6.6–7.9 vs. 8.9–19.3). There were no significant differences in conversion rate, adverse events, or mean procedural time according to location. There was a trend to higher conversion rate and longer procedure durations in EGJ and higher rate of adverse events in duodenal lesions. Conclusion: LECS is a valid, safe, and effective treatment option in patients with EGJ, gastric, and duodenal lesions, although existing studies are retrospective and prone to selection bias. Prospective studies are needed to assess if LECS is superior to established techniques. Key Messages: LECS is safe and effective in the treatment of upper gastrointestinal lesions, but there is no evidence of superiority over established techniques.
Assessment of Co-Sensitization between Pollen and Food Allergen Sources among Bengali Population, West Bengal, India
Authors: Laha Arghya , Moitra Saibal , Biswas Himani , Saha Nimai Chandra , Podder Sanjoy
Published: November 2022

Introduction: Secondary food allergies due to cross-reactivity between pollen and food allergens are a significant health burden in India. Prevalence of cross-reactivity varies by region, and particularly in West Bengal, it remains unexplored. The present study investigated sensitivities of pollen-related food allergy (PFA) patients of West Bengal by empirically determining co-sensitization patterns. Methods: The present study retrospectively analysed 1,310 pollen-allergic (PA) patients from the Allergy and Asthma Research Centre, West Bengal. A questionnaire survey was performed to record patients’ demographic and clinical features and categorized into seasonal and perennial ones. All patients were subjected to the skin prick test and specific IgE for evaluation of sensitivity against 16 pollen and 16 food allergens. Co-relation and principal component analysis (PCA) was performed to determine co-sensitivity. Results: Seasonal allergic patients were comparatively higher than perennial ones. PFA patients were mostly sensitive to eggplant (n = 387), while Azadirachta indica (n = 341) was predominant sensitizer among pollen allergen sources. Cynodon dactylon showed maximum significant positive correlation with banana, orange, peanut, pineapple, cucumber, eggplant, potato, tomato, and wheat. In the seasonal group, Cynodon dactylon-specific IgE in PFA patients (median = 4.60 kU/L) was significantly higher from that of PA ones (median = 3.44 kU/L). Among 32 allergens tested, 27 were placed in first two dimensions of the PCA biplot. Conclusion: The present study established that co-sensitivity between pollen and food allergen sources were predominant in allergic patients of West Bengal. The co-sensitization patterns among unrelated allergen sources may be due to possible expression of biologic cross-reactivity to similar allergens.