bluuebunny/crossref_metadata_2025 huggingface dataset:
GIMAP7 inhibits epithelial‐mesenchymal transition and glycolysis in lung adenocarcinoma cells via regulating the Smo/AMPK signaling pathway
Authors: Cui Liyuan , Shen Yumei , Duan Shanzhou , Ding Qifeng , Wang Yifei , Yang Wentao , Chen Yongbing
Published: December 2023

Background

GTPase immunity‐associated protein 7 (GIMAP7) has been previously recognized as a prognostic marker in pan‐cancer. Our objective was to explore the function of GIMAP7 in the progression of lung adenocarcinoma (LUAD).

Methods

GIMAP7 was overexpressed by transfection with GIMAP7 plasmid, and knocked down using siRNAs. The biological functions of GIMAP7 were examined by employing CCK‐8, EdU, colony formation, flow cytometry, wound healing, and transwell assays. The effects of GIMAP7 on the extracellular acidification rate (ECAR), oxygen consumption rate (OCR), lactate production, and glucose uptake were evaluated. In addition, the related mRNA and protein expression was detected employing immunohistochemical, western blot, and qRT‐PCR. A xenograft tumor model was established in nude mice to evaluate the effects of GIMAP7 on tumor growth.

Results

GIMAP7 was lowly expressed in LUAD tissues and cells. GIMAP7 inhibited the proliferation, mobility, EMT, glycolysis, but promoted apoptosis in LUAD cells. Moreover, we also confirmed that GIMAP7 suppressed Smo/AMPK signaling in LUAD cells. By adding the Smo agonist SAG and AMPK agonist GSK621, the results of rescue experiments further verified that GIMAP7 played a role in LUAD inhibition through inhibition of the Smo/AMPK signaling pathway. Furthermore, the role of GIMAP7 in inhibiting tumor growth was verified in vivo.

Conclusions

These results demonstrate that GIMAP7 could inhibit cell proliferation, mobility and glycolysis, but accelerate apoptosis via repressing the Smo/AMPK signaling pathway in LUAD.
The maturing of anthropology
Authors: Miller Daniel
Published: December 2023

As anthropology reaches maturity, its contributions are likely to grow. This is because the discipline's practitioners, in writing parochial ethnography, can link a respect for individual difference to our understanding of global humanity. Such a practice aligns with the growing political struggle to retain meaning in an expanding world. Moreover, anthropology's commitment to life as lived research, including private domains and engagement with digital worlds, will also become more significant, while anthropology's ethos of empathy will expand beyond the human. Reaching maturity will require a further repudiation of inequality and colonialism, developing a different relationship to theory, philosophy, and engaged anthropology, as well as fostering a much wider commitment to global education.
Health care professionals' experiences of pain management in the intensive care unit: a qualitative study
Authors: Bhattacharyya A. , Laycock H. , Brett S. J. , Beatty F. , Kemp H. I.
Published: December 2023

Despite the existence of evidence‐based guidelines for the assessment and management of pain in the critical care setting, the prevalence of acute pain remains high. Inadequate pain management is associated with longer duration of mechanical ventilation, reduced capacity for rehabilitation and long‐term psychological sequelae. This study aimed to describe the experiences of pain management from healthcare professionals working in intensive care units. Healthcare professionals were recruited from intensive care units in London, UK using a purposive sampling technique. Semi‐structured interviews were transcribed verbatim. Transcripts were analysed using an inductive thematic analysis technique. Thirty participants were recruited from eight diverse intensive care units. Five themes were identified. First, there was a lack of consensus in pain assessment in the ICU where nursing staff described more knowledge and confidence of validated pain measures than physicians, and concerns over validity and usability were raised. Second, there was a universal perception of resource availability impacting the quality of pain management including high clinical workload, staff turnover and availability of certain pain management techniques. Third, acknowledgement of the importance of pain management was highest in those with experience of interacting with critical care survivors. Fourth, participants described their own emotional reaction to managing those in pain which influenced their learning. Finally, there was a perception that, due to the complexity of the intensive care unit population, pain was de‐prioritised and there were conflicting views as to whether standardised analgosedation algorithms were useful. This study provides evidence to suggest interdisciplinary training, collaboratively designed decision‐making tools, prioritisation initiatives and research priorities are areas that could be targeted to improve pain management in critical care.
Editorial: The evolving paradigms and treatments for primary biliary cholangitis
Authors: Vuppalanchi Raj , Kowdley Kris V.
Published: December 2023

LINKED CONTENT

This article is linked to Mayo et al papers. To view these articles, visit https://doi.org/10.1111/apt.17755 and https://doi.org/10.1111/apt.17798
Editorial: Does knowledge about liver disease enhance adherence to lifestyle recommendations?
Authors: Michel Maurice , Schattenberg Jörn M.
Published: December 2023

LINKED CONTENT

This article is linked to Petroni et al papers. To view these articles, visit https://doi.org/10.1111/apt.17768 and https://doi.org/10.1111/apt.17810
Editorial: The evolving paradigms and treatments for primary biliary cholangitis—Authors' reply
Authors: Mayo Marlyn J. , Vierling John M. , Bowlus Christopher L.
Published: December 2023

LINKED CONTENT

This article is linked to Mayo et al papers. To view these articles, visit https://doi.org/10.1111/apt.17755 and https://doi.org/10.1111/apt.17779
Letter: interpretation of the BESST trial in the context of baseline antidepressant and neuromodulator use
Authors: Hiramoto Brent , Chan Walter W.
Published: December 2023

LINKED CONTENT

This article is linked to Parkman et al papers. To view these articles, visit https://doi.org/10.1111/apt.17479 and https://doi.org/10.1111/apt.17838
Editorial: Does knowledge about liver disease enhance adherence to lifestyle recommendations? Authors' reply
Authors: Petroni Maria Letizia , Colosimo Santo , Marchesini Giulio
Published: December 2023

LINKED CONTENT

This article is linked to Petroni et al papers. To view these articles, visit https://doi.org/10.1111/apt.17768 and https://doi.org/10.1111/apt.17789
A newly developed surgeon‐controlled suction device in robotic‐assisted thoracoscopic surgery
Authors: Nakagawa Tatsuo , Murakami Hiroaki , Ohsumi Yuki , Miyamoto Ei , Gotoh Masashi
Published: December 2023

Introduction

Assistant surgeons usually clean the surgical field with a suction cannula in robotic‐assisted surgery. This manipulation requires skill and experience to avoid interfering with the operation of the console surgeon. Recently, we created a new suction device that a console surgeon can manipulate with the robotic arms.

Materials and Surgical Technique

A small metal suction tip with as a lumen and small side pores for suction and can be connected to a silicone tube connected to wall suction. The tip of the silicone tube can be grasped with robotic forceps and used for organ retraction as well as suction. The suction device has been used in eight lung lobectomy cases and four lung segmentectomy cases to date. There were no major difficulties related to the new suction device except for metal tip disconnection and blood clots clogging.

Discussion

Our newly developed surgeon‐controlled suction device is inexpensive, easy to handle, and useful for suction, blunt dissection, and organ retraction in robotic‐assisted thoracoscopic surgery, especially when performing lymph node dissection.
Global standards and the philosophy of consumption: Toward a consumer‐driven governance of global value chains
Authors: Karimova Guli‐Sanam , Heidbrink Ludger , Brinkmann Johannes , LeMay Stephen Arthur
Published: December 2023

This study delves into the significant ethical criteria in the context of global standards. It addresses the moral wrongdoings and adverse side effects associated with global value chains as discussed in the business ethics literature. The methodology involves theoretical application and synthesis. The study employs ethical principles from deontology, consequentialism, and political cosmopolitanism to establish normative criteria such as “injustice and harm to others” and “bad outcomes.” It further investigates how these criteria should influence consumers' decisions, actions, and responsibilities. These criteria are then used to examine the moral wrongdoings and negative effects mentioned in global standards. The study explores how global standards implicitly express consumers' roles in governing global value chains. It scrutinizes consumers' actions and decisions by applying ethical frameworks to global standards. The study outlines consumers' individual and political responsibilities in achieving the goals of global standards. The research findings have implications for governments, consumers, and organizations in practicing shared responsibility. The aim of this research is to provide normative guidance for responsible actions.
Enhancing early language and literacy skills for racial/ethnic minority children with low incomes through a randomized clinical trial: The mediating role of cognitively stimulating parent–child interactions
Authors: Miller Elizabeth B. , Canfield Caitlin F. , Roby Erin , Wippick Helena , Shaw Daniel S. , Mendelsohn Alan L. , Morris‐Perez Pamela A.
Published: December 2023

Parenting is a critical mediator of children's school readiness. In line with this theory of change, data from the randomized clinical trial of Smart Beginnings (tiered Video Interaction Project and Family Check‐Up; N = 403, treatment arm n = 201) were used to examine treatment impacts on early language and literacy skills at child age 4 years (nLatinx = 168, nBlack = 198, nMale = 203), as well as indirect impacts through parental support of cognitive stimulation at child age 2 years. Although results did not reveal direct effects on children's early skills, there were significant indirect effects for early literacy (β = .03, p = .05) and early language (β = .04, p = .04) via improvements in parental cognitive stimulation. Implications for interventions targeting parenting to improve children's school readiness beginning at birth are discussed.
SAM domain variants of EPHB4 associated with aberrant signaling are linked to lymphatic‐related fetal hydrops and facial dysmorphology
Authors: Vanden Broek Kara , Ryu Jae‐Ryeon , Perrier Renee , Tyndall Amanda V. , Childs Sarah J. , Au Ping Yee Billie
Published: December 2023

Variants in EPHB4 (Ephrin type B receptor 4), a transmembrane tyrosine kinase receptor, have been identified in individuals with various vascular anomalies including Capillary Malformation‐Arteriovenous Malformation syndrome 2 and lymphatic‐related (non‐immune) fetal hydrops (LRHF). Here, we identify two novel variants in EPHB4 that disrupt the SAM domain in two unrelated individuals. Proband 1 presented within the LRHF phenotypic spectrum with hydrops, and proband 2 presented with large nuchal translucency prenatally that spontaneously resolved in addition to dysmorphic features on exam postnatally. These are the first disease associated variants identified that do not disrupt EPHB4 protein expression or tyrosine‐kinase activity. We identify that EPHB4 SAM domain disruptions can lead to aberrant downstream signaling, with a loss of the SAM domain resulting in elevated MAPK signaling in proband 1, and a missense variant within the SAM domain resulting in increased cell proliferation in proband 2. This data highlights that a functional SAM domain is required for proper EPHB4 function and vascular development.
Are child custody evaluations beneficial to family law judges? A study from the judicial perspective
Authors: Axelson Tammi , Gentile Jennifer
Published: December 2023

There is a long history of dissension among legal and mental health professionals about the value of child custody evaluations. Despite frequent use by the courts, the lack of adequate empirical research impedes the ability to validate the efficacy of child custody evaluations. This study investigated the overall value of court‐ordered child custody evaluations by surveying a diverse, national sample of judges to gather data regarding the usefulness, and validity of child custody evaluations. Two hundred and sixty‐eight judges from 42 states completed an anonymous survey. The results indicated that judges find information voiced by the child in question, data obtained from the parent–child observations, and collateral data obtained about the litigants as most useful. Survey findings suggested judges perceived there to be a shortage of trained evaluators and also consider child custody evaluations too expensive and too time‐consuming. Overall, judges find child custody evaluations useful and clearly desire experts to include recommendations on legal custody and parenting time schedules in their reports.
Rock magnetic analyses as a tool to investigate diversity of drift pumice clasts: An example from Japan's 2021 Fukutoku‐Oka‐no‐Ba (FOB) eruption
Authors: Carlut Julie , Isambert Aude , Carvallo Claire , Garcia da Fonseca Geoffrey , Moussissa Nelly‐Wangue , Bouis Arthur , Yoshida Kenta
Published: December 2023

The crystallization of nanolites within magma chambers has recently raised a strong interest due to their impact on increasing melt viscosity and triggering magmatic eruptions. In 2021, the Fukutoku‐Oka‐no‐Ba (FOB) underwater eruption produced large quantities of pumices that eventually formed rafts drifting at the surface of the ocean to the East coasts of Japan. Pumices collected along the shore shortly after grounding show various colors, microscopic and Raman analyses made by Yoshida et al. (Island Arc, 31, 1, 2022) revealed the presence of magnetite nanolites in some of them. In this study, we explore the magnetic properties of a batch of pumices of different colors from the FOB eruption, aiming to refine characterization of iron oxide nanolites. We used various analytical techniques such as SEM and FEG‐SEM observations, EDS‐X analyses, and rock magnetic experiments, including thermomagnetic analyses, hysteresis curves, coercivity analyses and FORC measurements. Our findings reveal that the iron oxides present in the FOB samples are Ti‐magnetite, with minor amounts of Mg and Al. The magnetic crystals show a wide range of sizes, from extra small iron oxide nanolites (ESION) in the pumices with the lighter colors, to more bulky grains reaching the micrometer size in some of the dark color samples, significant diffusion is inferred in that case. Consequently, the magnetic characterization of iron oxide crystals within the Fukutoku‐Oka‐no‐Ba pumices reveals varying stages of nucleation, dissolution, growth, and diffusion processes, providing evidences for the heterogeneous state of the magma during the eruption.
Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real‐life clinical practice
Authors: Muñoz‐Aceituno E. , Butrón‐Bris B. , Ovejero‐Benito M. C. , Sahuquillo‐Torralba A. , Baniandrés Rodríguez O. , Herrera‐Acosta E. , Rivera‐Diaz R. , Ferran M. , Sánchez‐Carazo J. L. , Riera‐Monroig J. , Pujol‐Montcusí J. , Vidal D. , de la Cueva P. , García‐Bustinduy M. , Ruiz‐Villaverde R. , Ballescà F. , Llamas‐Velasco M. , Navares M. , Palomar‐Moreno I. , Sánchez‐García I. , García‐Martínez J. , Novalbos J. , Zubiaur P. , Abad‐Santos F. , Daudén‐Tello E. , de la Fuente H.
Published: December 2023

Background

Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation.

Objective

To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting.

Methods

We studied 180 SNPs in patients with moderate‐to‐severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed.

Results

A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR‐146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83–0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes.

Conclusion

We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non‐response to this drug in patients with plaque psoriasis.
Strategies to combat heat stress in poultry production—A review
Authors: Mangan Modou , Siwek Maria
Published: December 2023

The effects of heat stress (HS) caused by high temperatures continue to be a global concern in poultry production. Poultry birds are homoeothermic, however, modern‐day chickens are highly susceptible to HS due to their inefficiency in dissipating heat from their body due to the lack of sweat glands. During HS, the heat load is higher than the chickens' ability to regulate it. This can disturb normal physiological functioning, affect metabolism and cause behavioural changes, respiratory alkalosis and immune dysregulation in birds. These adverse effects cause gut dysbiosis and, therefore, reduce nutrient absorption and energy metabolism. This consequently reduces production performances and causes economic losses. Several strategies have been explored to combat the effects of HS. These include environmentally controlled houses, provision of clean cold water, low stocking density, supplementation of appropriate feed additives, dual and restricted feeding regimes, early heat conditioning and genetic selection of poultry lines to produce heat‐resistant birds. Despite all these efforts, HS still remains a challenge in the poultry sector. Therefore, there is a need to explore effective strategies to address this long‐lasting problem. The most recent strategy to ameliorate HS in poultry is early perinatal programming using the in ovo technology. Such an approach seems particularly justified in broilers because chick embryo development (21 days) equals half of the chickens' posthatch lifespan (42 days). As such, this strategy is expected to be more efficient and cost‐effective to mitigate the effects of HS on poultry and improve the performance and health of birds. Therefore, this review discusses the impact of HS on poultry, the advantages and limitations of the different strategies. Finally recommend a promising strategy that could be efficient in ameliorating the adverse effects of HS in poultry.
Introgression of a dominant phototropin1 mutant enhances carotenoids and boosts flavour‐related volatiles in genome‐edited tomato RIN mutants
Authors: Nizampatnam Narasimha Rao , Sharma Kapil , Gupta Prateek , Pamei Injangbuanang , Sarma Supriya , Sreelakshmi Yellamaraju , Sharma Rameshwar
Published: December 2023

The tomato (Solanum lycopersicum) ripening inhibitor (rin) mutation is known to completely repress fruit ripening. The heterozygous (RIN/rin) fruits have extended shelf life, ripen normally, but have inferior taste/flavour. To address this, we used genome editing to generate newer alleles of RIN (rinCR) by targeting the K‐domain.

Unlike previously reported CRISPR alleles, the rinCR alleles displayed delayed onset of ripening, suggesting that the mutated K‐domain represses the onset of ripening. The rinCR fruits had extended shelf life and accumulated carotenoids at an intermediate level between rin and progenitor line. Besides, the metabolites and hormonal levels in rinCR fruits were more akin to rin.

To overcome the negative attributes of rin, we crossed the rinCR alleles with Nps1, a dominant‐negative phototropin1 mutant, which enhances carotenoid levels in tomato fruits. The resulting Nps1/rinCR hybrids had extended shelf life and 4.4–7.1‐fold higher carotenoid levels than the wild‐type parent.

The metabolome of Nps1/rinCR fruits revealed higher sucrose, malate, and volatiles associated with tomato taste and flavour. Notably, the boosted volatiles in Nps1/rinCR were only observed in fruits bearing the homozygous Nps1 mutation. The Nps1 introgression into tomato provides a promising strategy for developing cultivars with extended shelf life, improved taste, and flavour.
Clinical, histological, and molecular differences in melanoma due to different TERT promoter mutations subtypes. A retrospective cross‐sectional study in 684 melanoma patients
Authors: Manrique‐Silva Esperanza , David Millán‐Esteban , Maider Aguerralde‐Martin , García‐Casado Zaida , Moro Ruggero , Requena Celia , Través Victor , Virós Amaya , Kumar Rajiv , Nagore Eduardo
Published: December 2023

Differences in survival according to the pTERT mutation subtypes (−124C > T, −146C > T, and tandem −138_139CC > TT) have been observed. The present study aimed to describe the clinical as the histopathological and molecular cutaneous melanoma features according to the presence of the three most prevalent pTERT mutation subtypes (−124C > T, −146C > T, and tandem −138_139CC > TT). A retrospective cross‐sectional study including 684 patients was designed, and a Partial Least‐Squares Discriminant Analysis (PLS‐DA) was performed. After the PSL‐DA, it was observed that the tandem −138_139CC > TT subtype differs from the other subtypes. The model demonstrated that the −124C > T and the −138_139 CC > TT subtypes were associated with fast‐growing melanomas (OR 0.5, CI 0.29–0.86, p = .012) and with Breslow >2 mm (OR 0.6, CI 0.37–0.97, p = .037), compared to the −146C > T mutation. Finally, the −124C > T appeared to be more associated with the presence of TILs (non‐brisk) than the −146C > T (OR 0.6, CI 0.40–1.01, p = .05). These findings confirmed that the −124C > T and the tandem −138_139 CC > TT subtypes are both highly associated with the presence of features of aggressiveness; however, only the −124C > T was highly associated with TILs. This difference could explain the worse survival rate associated with the tandem −138_139CC > TT mutations.
Growth and photosynthetic physiology of holopelagic Sargassum (Phaeophyceae) under laboratory conditions
Authors: Vásquez‐Elizondo Román Manuel , Vázquez‐Delfín Erika , Robledo Daniel
Published: December 2023

Species of holopelagic Sargassum are responsible for Caribbean golden tides, commonly known as ‘Sargassum events’. These events mainly comprise Sargassum fluitans and Sargassum natans I, which are exposed to high levels of irradiance, but also self‐shading within their floating masses. In this study, we grew S. fluitans and S. natans I and acclimated them to low‐light conditions at 23°C in the laboratory to explore their responses to increasing light intensities. Photosynthesis, respiration, growth, and pigment content were evaluated over 3 weeks. S. fluitans and S. natans I photoacclimate to higher irradiances by decreasing their chlorophyll a and c contents. An increase in maximum photosynthesis and respiration rates was observed under high light, although differences occurred in the saturation irradiance and the initial slope of the photosynthesis versus irradiance curve. These adjustments were reflected in S. fluitans daily growth (from 2% to 7% d−1 at low to high light, respectively) and tissue nitrogen content (1.6–2.7%) but were absent in S. natans I (~1% d−1). The photosynthetic physiology of S. fluitans under these conditions suggests lower light requirements without compromising growth; however, under high light a higher photosynthetic performance was observed. Combining physiological and growth studies in holopelagic Sargassum species will serve as a baseline to understand and explain the success and overgrowth of these species along the Caribbean coast.
Utility of the Japanese version of the Clinical Dementia Rating® plus National Alzheimer's Coordinating Centre Behaviour and Language Domains for sporadic cases of frontotemporal dementia in Japan
Authors: Taomoto Daiki , Sato Shunsuke , Kanemoto Hideki , Suzuki Maki , Hirakawa Natsuho , Takasaki Akihiro , Akimoto Miu , Satake Yuto , Koizumi Fuyuki , Yoshiyama Kenji , Takahashi Rei , Shigenobu Kazue , Hashimoto Mamoru , Miyagawa Toji , Boeve Bradley , Knopman David , Mori Etsuro , Ikeda Manabu
Published: December 2023

Background

We aimed to validate the Clinical Dementia Rating (CDR®) dementia staging instrument plus the National Alzheimer's Coordinating Centre Behaviour and Language Domains (CDR® plus NACC FTLD) for use in clinical settings in Japan and in the Japanese language.

Methods

This prospective observational study enrolled 29 patients with frontotemporal dementia (FTD) and 21 patients with Alzheimer's disease (AD) dementia from the Departments of Psychiatry at Osaka University Hospital and Asakayama General Hospital and the Brain Function Centre at Nippon Life Hospital. CDR® plus NACC FTLD, CDR®, Mini‐Mental State Examination (MMSE), Western Aphasia Battery (WAB), Neuropsychiatric Inventory‐plus (NPI‐plus), Stereotypy Rating Inventory (SRI), and frontal behavioural symptom scores obtained from items of NPI‐plus and SRI, were conducted to assess inter‐ and intra‐rater reliability, validity, and responsiveness. We performed receiver operating characteristic (ROC) curve analysis to evaluate the discriminating power of the Behaviour/Comportment/Personality (BEHAV) and Language (LANG) domains of the CDR® plus NACC FTLD and the MEMORY domain of the CDR® in patients AD dementia and FTD.

Results

The CDR® plus NACC FTLD showed good inter‐ and intra‐rater reliabilities. In patients with FTD, the BEHAV domain of the CDR® plus NACC FTLD was significantly correlated with all clinical measures except for the SRI total score, while the LANG domain of the CDR® plus NACC FTLD was significantly correlated with the MMSE and the WAB‐Aphasia quotient. In addition, the CDR® plus NACC FTLD sum of boxes significantly changed after 6 months and after 1 year. ROC curve analysis showed that the BEHAV and LANG domains of the CDR® plus NACC FTLD distinguished between patients with AD dementia and FTD better than the MEMORY domain of the CDR®.

Conclusions

This study validated the Japanese version of the CDR® plus NACC FTLD with good reliability, validity, and responsiveness.
Nationalistic bias in collusion prosecution: the case for international antitrust agreements
Authors: Garcia Filomena , Paz y Miño Jose Manuel , Torrens Gustavo
Published: December 2023

We study the incentives of competition authorities to prosecute collusive practices of domestic and foreign firms in a multimarket contact model between two firms operating in two countries. In equilibrium, the country of origin of the firms might prefer to delay prosecution to protect profits in foreign markets. This strategic delay is valuable because prosecution in the country of origin of the firms activates an information spillover that triggers prosecution in the foreign country. Prosecution delays, however, are suboptimal under global welfare. With multiple industries, both countries can be better off under integration or signing an international antitrust agreement.
Refractory supraventricular fetal tachycardia as a cause of non-immune hydrops: management conundrum
Authors: Agarwal Akanksha , Saha Subash Chandra , Kaur Amanjot , Naganur Sanjeev
Published: December 2023

Supraventricular tachyarrhythmia (SVT) is the most common form of fetal tachyarrhythmias. The presentation can vary from ill-defined, non-sustained episodes of tachyarrhythmia to frank non-immune hydrops. The standard of care is transplacental therapy by treating the mother with oral antiarrhythmic drugs, followed by direct fetal therapy in refractory cases. We report a case of primigravida in her late 20s, who presented at 28.1 weeks of gestation with fetal hydrops and SVT. She was initially managed with oral digoxin and flecainide, but due to worsening hydrops, risk of fetal demise and extreme prematurity, further management by direct fetal therapy was given in terms of intramuscular digoxin and intraperitoneal flecainide. Following which, the fetus had a favourable outcome. This case highlights the possible role of direct fetal therapy in refractory cases of SVT.
Endomyocardial fibrosis: a tragic conundrum or a mere negligence?
Authors: Shah Bhavik Sandip , Lanjewar Charan
Published: December 2023

Often termed as ‘vanishing mystery’ epidemiologically, endomyocardial fibrosis (EMF) continues to be the the most common cause of restrictive cardiomyopathy in Africa and some parts of the Indian subcontinent, where it is considered a significant public health problem. On the other hand, in developed countries, it is considered a rare phenomenon. This entity is considered incurable due to lack of targeted therapies, even after 75 years since its discovery. The authors describe here a case of an Indian male, in his early 30s who presented with complaints of dyspnoea on minimal daily activities, swelling of both legs and abdominal fullness for 3 months. The clinical features were suggestive of isolated right heart failure. He was diagnosed with EMF on echocardiography and the findings were confirmed on cardiac MRI. The patient has progressed to develop biventricular dysfunction and is being managed symptomatically with diuretics due to unavailability of targeted treatment options at present.
Endomyocardial fibrosis with ischaemic stroke
Authors: Mays Hugo , Durand Rory , Sulaiman Habitha , Murphy Ross
Published: December 2023

A Caucasian man in his mid-50s presented to the emergency department with sudden onset right-sided weakness and dysarthria. CT angiogram demonstrated a small volume of left middle cerebral artery territory infarction after which the patient underwent successful thrombolysis. Initial ECG showed diffuse T wave inversion. He was admitted to an acute stroke ward where 72 hours of telemetry demonstrated normal sinus rhythm without arrhythmia. Transthoracic echocardiogram showed a reduced ejection fraction of 47% in the absence of any regional wall motion abnormality. An echogenic mass was noted in the apical inferior septal wall. Cardiac MRI demonstrated circumferential mid to apical endocardial thickening with characteristic appearances consistent with endomyocardial fibrosis (EMF). Furthermore, a visible hypointensity in the apex confirmed left ventricular thrombus adherent to the area of EMF. The patient was started on anticoagulation and heart failure therapy. He has recovered from the ischaemic stroke and is currently under outpatient surveillance.
Structure, electronic and magnetic properties of the Al12N12 clusters encapsulated with transition metals
Authors: Li Zhi , Zhao Zhen
Published: December 2023

The metal-doped aluminum nitrides have attracted special attention as new technology-related materials owing to their combination of fullerene-like and metallic properties. The structure, electronic and magnetic properties of the TM@Al[Formula: see text]N[Formula: see text] clusters have been investigated by using first principles. The results indicate that the V@Al[Formula: see text]N[Formula: see text], Ni@Al[Formula: see text]N[Formula: see text], Zr@Al[Formula: see text]N[Formula: see text], Rh@Al[Formula: see text]N[Formula: see text], Ta@Al[Formula: see text]N[Formula: see text] and Pt@Al[Formula: see text]N[Formula: see text] clusters display more structural stability than their neighbors. The Sc@Al[Formula: see text]N[Formula: see text], V@Al[Formula: see text]N[Formula: see text], Mn@Al[Formula: see text]N[Formula: see text], Zn@Al[Formula: see text]N[Formula: see text], Y@Al[Formula: see text]N[Formula: see text], Nb@Al[Formula: see text]N[Formula: see text], Tc@Al[Formula: see text]N[Formula: see text], Ag@Al[Formula: see text]N[Formula: see text], Lu@Al[Formula: see text]N[Formula: see text], W@Al[Formula: see text]N[Formula: see text] and Hg@Al[Formula: see text]N[Formula: see text] clusters are more dynamically stable than their neighbors. The amount of charge transfer between the TM (TM=Ti, Y and Os) atoms and Al[Formula: see text]N[Formula: see text] clusters is the most. The maximum spin densities (3.025 [Formula: see text], 2.779 [Formula: see text] and 3.231 [Formula: see text]) of the TM@Al[Formula: see text]N[Formula: see text] clusters occur at the subgroup VIIB TM@Al[Formula: see text]N[Formula: see text] clusters.
Dislocation-based mechanical responses and deformation mechanisms of Al/Cu heterointerfaces: A computational study via molecular dynamics simulations
Authors: Gao Qing , Li Wei , Ren Junqiang , Guo Xin , Li Qilun , Lu Xuefeng , Qiao Jisen
Published: December 2023

Layered metal composites have been widely used in various industries fields because of their excellent properties and are responsible for mechanical behavior of materials. This paper focuses on analyzing the deformation mechanism of the (110) interface under different loading states by MD. The results show that there are two yield points in the stress–strain curve under both Z- and Y-axis loading states. The first yield is the nucleation of dislocations at the interface, meantime the slip of dislocations and the extension of stacking faults begin at the Al layer. The second one, the dislocation passes through the interface, nucleates and emits toward the Cu layer at the interface, leading to a stress mutation. It is worth noting that during the stable rheological stage, the deformation mechanisms vary under different loading directions. Under Y-axis tensile loading, the phase transformation of FCC–HCP is present due to the interaction of dislocation movement and stacking fault. On the contrary, there are two twin paths A and B, improving the strength, during Z-axis compression loading. For other loading modes, there are three zones, namely the elastic stage, the release of energy, and strain hardening and dynamic softening. The interface plays the role of nucleation, annihilation and penetration of dislocations, and this interface-dislocation mechanism is reflected in the whole stage of plastic deformation. The results have an insight into the design and control in heterointerface.
Rationalizing Graph Neural Networks with Data Augmentation
Authors: Liu Gang , Inae Eric , Luo Tengfei , Jiang Meng
Published: December 2023

Graph rationales are representative subgraph structures that best explain and support the graph neural network (GNN) predictions. Graph rationalization involves the joint identification of these subgraphs during GNN training, resulting in improved interpretability and generalization. GNN is widely used for node-level tasks such as paper classification and graph-level tasks such as molecular property prediction. However, on both levels, little attention has been given to GNN rationalization and the lack of training examples makes it difficult to identify the optimal graph rationales. In this work, we address the problem by proposing a unified data augmentation framework with two novel operations on environment subgraphs to rationalize GNN prediction. We define the environment subgraph as the remaining subgraph after rationale identification and separation. The framework efficiently performs rationale–environment separation in therepresentation spacefor a node’s neighborhood graph or a graph’s complete structure to avoid the high complexity of explicit graph decoding and encoding. We conduct experiments on 17 datasets spanning node classification, graph classification, and graph regression. Results demonstrate that our framework is effective and efficient in rationalizing and enhancing GNNs for different levels of tasks on graphs.
Computational modeling of cardiac electrophysiology and arrhythmogenesis: toward clinical translation
Authors: Trayanova Natalia A. , Lyon Aurore , Shade Julie , Heijman Jordi
Published: December 2023

The complexity of cardiac electrophysiology, involving dynamic changes in numerous components across multiple spatial (from ion channel to organ) and temporal (from milliseconds to days) scales, makes an intuitive or empirical analysis of cardiac arrhythmogenesis challenging. Multiscale mechanistic computational models of cardiac electrophysiology provide precise control over individual parameters, and their reproducibility enables a thorough assessment of arrhythmia mechanisms. This review provides a comprehensive analysis of models of cardiac electrophysiology and arrhythmias, from the single cell to the organ level, and how they can be leveraged to better understand rhythm disorders in cardiac disease and to improve heart patient care. Key issues related to model development based on experimental data are discussed, and major families of human cardiomyocyte models and their applications are highlighted. An overview of organ-level computational modeling of cardiac electrophysiology and its clinical applications in personalized arrhythmia risk assessment and patient-specific therapy of atrial and ventricular arrhythmias is provided. The advancements presented here highlight how patient-specific computational models of the heart reconstructed from patient data have achieved success in predicting risk of sudden cardiac death and guiding optimal treatments of heart rhythm disorders. Finally, an outlook toward potential future advances, including the combination of mechanistic modeling and machine learning/artificial intelligence, is provided. As the field of cardiology is embarking on a journey toward precision medicine, personalized modeling of the heart is expected to become a key technology to guide pharmaceutical therapy, deployment of devices, and surgical interventions.
A Theoretical Design of Angular-Phased Broadband Antenna Array for Submillimeter Wave Applications
Authors: Goel Tushar , Sonker Anuradha , Gautam A. K. , Patnaik Amalendu
Published: December 2023

In this article, a broadband semicircular antenna array geometry was examined, along with its design and configuration in the submillimeter wave range (9.35-42.89 GHz). The work has been divided into two prime phases; in the first phase of work, an innovative angular-phased 1 : 4 broadband power divider has been presented in which its isolation, insertion, and return losses are investigated. In the next phase, the proposed power divider was used to configure a 4-element antenna array, and its theoretical analysis was carried out. The angular path difference in the array was used to introduce phase difference in between the antenna elements to minimize the mutual coupling and to optimize the narrow beamwidth. Using geometry and fundamental array theory, the array factor of a novel broadband array configuration has been derived and analytically investigated.
Protective Activity of Alpha-Mangostin against UVB-Induced Injury in HaCaT Cells by Modulating the Ceramide and MAPK and NF-κB Signaling Pathways
Authors: Jin Jiahui , Bao Yan , Wang Yan , Zheng Huimin , Guo Hao , Zhang Lei , Guo Ruoxi , Yang Lei
Published: December 2023

This study investigated the potential protective effects of alpha-mangostin (α-MG) on ultraviolet B (UVB)-induced damage in HaCaT cells. The results showed that α-MG less than 10 μM had no significant cytotoxicity and exposure to UVB (50 mJ/cm2) reduced cell viability by approximately 50% compared with the control. The 2 μM α-MG upregulated cell viability and downregulated the expression of metal matrix proteases (MMPs). The results of flow cytometry, real-time quantitative PCR (RT-qPCR), and immunoblotting manifested that α-MG relieved the extent of apoptosis and reduced the levels of apoptosis-associated mRNAs and proteins, respectively. The results of RT-qPCR and ELISA indicated that α-MG suppressed the generation of IL-6 and TNF-α. Furthermore, α-MG effectively downregulated activation of the UVB-induced nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Finally, lipidomics profiling demonstrated that α-MG significantly reduced UVB radiation-increased ceramide. Overall, these results demonstrated that α-MG has beneficial effects against photoaging by reducing the ceramide content and inhibiting MAPK and NF-κB signaling pathways.
A Novel Scale to Assess Humidification during Noninvasive Ventilation: A Prospective Observational Study
Authors: Pan Longfang , Hong Yueling , Zhong Xiaoqing , He Jiao , Zhang Zuli , Zhao Qianru , Bai Linfu , Ma Mengyi , Duan Jun
Published: December 2023

Objective. To develop a novel scale to assess humidification during noninvasive ventilation (NIV). Methods. This study was performed in an ICU of a teaching hospital. Three ICU practitioners with more than 10 years of clinical experience developed an oral humidification scale with a range of 1–4 points. Each studied the current literature on humidification and examined 50 images of mouths of NIV patients with different levels of humidification. Then, through discussion, a consensus scale was developed. Next, 10 practitioners and 33 NIV patients were recruited to validate the scale. Finally, the patients rated the dryness of their mouths using the 1–4 visual scale just after the practitioners’ assessment. Talking and discussion were forbidden during the assessment, and the scorers were blinded to each other. Results. We performed 36 assessments in 33 NIV patients. Three patients were assessed twice each more than 2 days apart. The interitem correlation coefficients between the 10 practitioners ranged from 0.748 to 0.917. Fleiss’s kappa statistic was 0.516, indicating moderate agreement among practitioners. Of the 33 patients, 5 (15%) were unable to make an assessment using the 1–4 visual scale. Among the remainder, 55.7% provided scores that matched those given by the practitioners; 13.7% of scores were 1 point higher than that rated by the practitioners, and 20.7% were 1 point lower. Only 10% were beyond a 1-point difference. The kappa coefficient was 0.483 between patients and practitioners. Conclusions. The oral humidification scale showed moderate agreement between practitioners. It was also highly accurate in reflecting the level of humidification assessed by patients.
Supplementary Data from Sphingosine Kinase-1 Enhances Resistance to Apoptosis through Activation of PI3K/Akt/NF-κB Pathway in Human Non–Small Cell Lung Cancer
Authors: Song Libing , Xiong Huaping , Li Jun , Liao Wenting , Wang Lan , Wu Jueheng , Li Mengfeng
Published: December 2023

Supplementary Figures S1-S5; Supplementary Tables S1-S4.
Supplementary Figure 7 from BATF2 Deficiency Promotes Progression in Human Colorectal Cancer via Activation of HGF/MET Signaling: A Potential Rationale for Combining MET Inhibitors with IFNs
Authors: Liu Zebing , Wei Ping , Yang Yu , Cui Wenli , Cao Bing , Tan Cong , Yu Baohua , Bi Rui , Xia Kaiqin , Chen Weixiang , Wang Yiqin , Zhang Youyuan , Du Xiang , Zhou Xiaoyan
Published: December 2023

IFN-β and MET inhibitors enhance apoptosis but inhibit the proliferation of CRC cells.
Supplemental Tables 1, 2 and 3 from Absence of Cytomegalovirus in Glioblastoma and Other High-grade Gliomas by Real-time PCR, Immunohistochemistry, and In Situ Hybridization
Authors: Holdhoff Matthias , Guner Gunes , Rodriguez Fausto J. , Hicks Jessica L. , Zheng Qizhi , Forman Michael S. , Ye Xiaobu , Grossman Stuart A. , Meeker Alan K. , Heaphy Christopher M. , Eberhart Charles G. , De Marzo Angelo M. , Arav-Boger Ravit
Published: December 2023

Tables with (1) real-time PCR data of fresh frozen samples, (2) IHC and FISH data of FFPE samples and (3) IHC data of tissue micro arrays.
Data from Pharmacodynamic Analysis of BTK Inhibition in Patients with Chronic Lymphocytic Leukemia Treated with Acalabrutinib
Authors: Alsadhan Anfal , Cheung Jean , Gulrajani Michael , Gaglione Erika M. , Nierman Pia , Hamdy Ahmed , Izumi Raquel , Bibikova Elena , Patel Priti , Sun Clare , Covey Todd , Herman Sarah E.M. , Wiestner Adrian
Published: December 2023

AbstractPurpose:
To determine the pharmacodynamic relationship between target occupancy of Bruton tyrosine kinase (BTK) and inhibition of downstream signaling.
Patients and Methods:
Patients with chronic lymphocytic leukemia (CLL) enrolled in a phase II clinical trial (NCT02337829) with the covalent, selective BTK inhibitor acalabrutinib donated blood samples for pharmacodynamic analyses. Study design included randomization to acalabrutinib 100 mg twice daily or 200 mg once daily and dose interruptions on day 4 and 5 of the first week. BTK occupancy and readouts of intracellular signaling were assessed sequentially between 4 and 48 hours from last dose.
Results:
Four hours from last dose, BTK occupancy exceeded 96% and at trough, was higher with twice daily, median 95.3%, than with once daily dosing, median 87.6% (P < 0.0001). By 48 hours from last dose, median free BTK increased to 25.6%. Due to covalent binding of acalabrutinib, free BTK is generated by de novo synthesis. The estimated rate of BTK synthesis varied widely between patients ranging from 3.6% to 31.4% per day. Acalabrutinib reduced phosphorylation of BTK and inhibited downstream B-cell receptor (BCR) and NFκB signaling. During dosing interruptions up to 48 hours, expression of BCR target genes rebounded, while phosphorylation of signaling molecules remained repressed. In vitro cross-linking of IgM on CLL cells obtained 36 to 48 hours from last dose upregulated CD69, with high correlation between cellular free BTK and response (R = 0.7, P ≤ 0.0001).
Conclusions:
Higher BTK occupancy was achieved with twice daily over once daily dosing, resulting in deeper and more sustained inhibition of BCR signaling.
Figure S3 from Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors
Authors: Kazi Aslamuzzaman , Ranjan Alok , Kumar M.V. Vasantha , Agianian Bogos , Garcia Chavez Martin , Vudatha Vignesh , Wang Rui , Vangipurapu Rajanikanth , Chen Liwei , Kennedy Perry , Subramanian Karthikeyan , Quirke Jonathan C.K. , Beato Francisca , Underwood Patrick W. , Fleming Jason B. , Trevino Jose , Hergenrother Paul J. , Gavathiotis Evripidis , Sebti Said M.
Published: December 2023

KRAS switch-I/II allosteric pocket is dynamic.
Figure S2 from Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors
Authors: Kazi Aslamuzzaman , Ranjan Alok , Kumar M.V. Vasantha , Agianian Bogos , Garcia Chavez Martin , Vudatha Vignesh , Wang Rui , Vangipurapu Rajanikanth , Chen Liwei , Kennedy Perry , Subramanian Karthikeyan , Quirke Jonathan C.K. , Beato Francisca , Underwood Patrick W. , Fleming Jason B. , Trevino Jose , Hergenrother Paul J. , Gavathiotis Evripidis , Sebti Said M.
Published: December 2023

KRB-456 binds to KRAS G12DGCP at a switch-I/II allosteric site.
Two new records of Fissidens (Fissidentaceae, Bryophyta) for South Africa
Authors: BRUGGEMAN-NANNENGA MARIA A. , ROOY JACQUES VAN
Published: December 2023

Two pluripapillose semilimbate species of Fissidens, the East African F. ferrugineus and the wide-spread African F. schweinfurthii are for the first time recorded from the Republic of South Africa.