bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher-order connectomics of human brain function reveals local topological signatures of task decoding, individual identification, and behavior
Authors: Santoro Andrea , Battiston Federico , Lucas Maxime , Petri Giovanni , Amico Enrico
Published: December 2023

Traditional models of human brain activity often represent it as a network of pairwise interactions between brain regions. Going beyond this limitation, recent approaches have been proposed to infer higher-order interactions from temporal brain signals involving three or more regions. However, to this day it remains unclear whether methods based on inferred higher-order interactions outperform traditional pairwise ones for the analysis of fMRI data. To address this question, we conducted a comprehensive analysis using fMRI time series of 100 unrelated subjects from the Human Connectome Project. We show that higher-order approaches greatly enhance our ability to decode dynamically between various tasks, to improve the individual identification of unimodal and transmodal functional subsystems, and to strengthen significantly the associations between brain activity and behavior. Overall, our approach sheds new light on the higher-order organization of fMRI time series, improving the characterization of dynamic group dependencies in rest and tasks, and revealing a vast space of unexplored structures within human functional brain data, which may remain hidden when using traditional pairwise approaches.
Polymer Model Unveils Quantitative Association of Chromatin Conformation and Gene Regulation
Authors: Senapati Swayamshree , Irshad Inayat Ullah , Sharma Ajeet K. , Kumar Hemant
Published: December 2023

The spatial organization of chromatin in the nucleus is of essence for regulating gene transcription. However, the mechanisms governing the intricate interplay of chromatin structure and gene transcription remain poorly understood. Hi-C experiments have unveiled a multiscale chromatin organization, significantly enriching our understanding of the structural control of gene expression. We introduce a computational framework to link chromatin structural modifications to gene regulation. This framework generates an ensemble of three-dimensional conformations of a given genomic locus using a bead-spring polymer model where the cHiC contact map is used as an input. We then correlate such chromatin conformations to the transcription level of the encoded genes using a Markov chain-based model, where binding/unbinding rates extracted from the molecular dynamics trajectories are used. By considering a specific example, we have demonstrated that the deletion of the CTCF binding domain between two consecutive TADs leads to a significant change in the enhancer-promoter interaction and gene transcription of the encoded genes, namely sox9 and kcnj2, responsible for limb development. Such a change in gene expression level is quantitatively consistent with experiments. Further insight from the polymer-based 3D conformation reveals that the higher gene expression level of the kcnj2 gene is caused by the specific enhancers of kcnj2, present in the sox9 TAD, which become accessible after boundary deletion. By quantifying the impact of these enhancers, our model can also be used to identify the functional enhancers. Together, the present computational framework not only advances our understanding of the relationship between the spatial architecture of the chromosome and the function of the cell but also provides invaluable insights into potential therapeutic interventions targeting aberrant gene regulation in pathological contexts.
Global analysis of the RNA-RNA interactome inAcinetobacter baumanniiAB5075 uncovers a small regulatory RNA repressing the virulence-related outer membrane protein CarO
Authors: Hamrock Fergal J. , Ryan Daniel , Shaibah Ali , Ershova Anna S. , Mogre Aalap , Sulimani Maha M. , Reichardt Sarah , Hokamp Karsten , Westermann Alexander J. , Kröger Carsten
Published: December 2023

Acinetobacter baumanniiis an opportunistic Gram-negative pathogen that infects critically ill patients. The emergence of antimicrobial resistantA. baumanniihas exacerbated the need to functionally characterise environmental adaptation, antibiotic resistance and pathogenicity of this organism and their genetic regulators to inform intervention strategies. Critical to rapid adaptation to changing environments in bacteria are small regulatory RNAs (sRNAs), however, the role that sRNAs play in the biology ofA. baumanniiis poorly understood. To assess the regulatory function of sRNAs and to uncover their RNA interaction partners inA. baumannii, we employed an RNA proximity ligation and sequencing method (Hi-GRIL-seq) in three different environmental conditions. We found that 40 sRNA candidates were ligated to sRNA-RNA chimeric sequencing reads, suggesting that sRNA-mediated gene regulation is pervasive inA. baumanniiand that sRNAs act as direct regulators of mRNA molecules through antisense base-pairing. In-depth characterisation uncovered the sRNA Aar to be a post-transcriptional regulator of four mRNA targets including that of the outer membrane protein CarO and the siderophore receptor BfnH. We show that Aar initiates base-pairing with these mRNA molecules using a conserved seed region of nine nucleotides, sequestering the ribosome binding sites and inhibiting translation. Aar is differentially expressed in response to multiple stress stimuli suggesting a role in fine-tuning translation of the Aar-target molecules inA. baumanniiunder hostile conditions. Together, our study provides mechanistic insights into sRNA-mediated gene expression control inA. baumanniiand represents a valuable resource for future RNA-centric research endeavours in this ESKAPE pathogen.
ADPKD-Causing Missense Variants in Polycystin-1 Disrupt Cell Surface Localization or Polycystin Channel Function
Authors: Ha Kotdaji , Loeb Gabriel B. , Park Meyeon , Gupta Mohona , Akiyama Yukako , Argiris Jillian , Pinedo Aide , Park Christine Haewon , Brandes Nadav , Ritu F. , Ye Chun Jimmie , Reiter Jeremy F. , Delling Markus
Published: December 2023

Autosomal dominant polycystic kidney disease (ADPKD) is the leading monogenic cause of kidney failure and affects millions of people worldwide. Despite the prevalence of this monogenic disorder, our limited mechanistic understanding of ADPKD has hindered therapeutic development. Here, we successfully developed bioassays that functionally classify missense variants in polycystin-1 (PC1). Strikingly, ADPKD pathogenic missense variants cluster into two major categories: 1) those that disrupt polycystin cell surface localization or 2) those that attenuate polycystin ion channel activity. We found that polycystin channels with defective surface localization could be rescued with a small molecule. We propose that small-molecule-based strategies to improve polycystin cell surface localization and channel function will be effective therapies for ADPKD patients.
Molecular mechanisms and energetics of lipid droplet formation and directional budding†
Authors: Sabet Fatemeh Kazemi , Bahrami Arash , Ghosh Rikhia , Różycki Bartosz , Bahrami Amir H.
Published: December 2023

The formation and budding of lipid droplets (LDs) are known to be governed by the LD size and by membrane tensions in the Endoplasmic Reticulum (ER) bilayer and LD-monolayers. Using coarse-grained simulations of an LD model, we first show that ER-embedded LDs of different sizes can form through a continuous transition from wide LD lenses to spherical LDs at a fixed LD size. The ER tendency to relax its bilayer modulates the transition via a subtle interplay between the ER and LD lipid densities. By calculating the energetic landscape of the LD transition, we demonstrate that this size-independent transition is regulated by the mechanical force balance of ER and LD-tensions, independent from membrane bending and line tension whose energetic contributions are negligible according to our calculations. Our findings explain experimental observation of stable LDs of various shapes. We then propose a novel mechanism for directional LD budding where the required membrane asymmetry is provided by the exchange of lipids between the LD-monolayers. Remarkably, we demonstrate that this budding process is energetically neutral. Consequently, LD budding can proceed by a modest energy input from proteins or other driving agents. We obtain equal lipid densities and membrane tensions in LD-monolayers throughout budding. Our findings indicate that unlike LD formation, LD budding by inter-monolayer lipid exchange is a tension-independent process.
Universal Heater Industries: managing conflict with a distributor
Authors: Chintaluri Manoj Gour , Subramanian R. Bala
Published: December 2023

Learning outcomes

This case study exposes students to conflicts with distributors, escalated scenarios of a trade association and the possible repercussions of such a scenario. Upon completion of this case study, the students will be able to understand the critical success factors for a distribution setup and alignment of channels for driving growth; understand and manage the power dynamics with a stakeholder, like trade associations, distribution reach, fallacies in managing the distributors and identifying the gaps; critically evaluate negotiation opportunities when a trade association is not directly related to the principal organization.

Case overview/synopsis

This case study showcased a conflict between the distributor and Universal Heater Industries (UHI), a leading player in the water heater business in India. In 2015, the global leadership of UHI identified India as an emerging market and undertook a complete management overhaul to implement a new growth plan. Several measures were put in place that leveraged the global product portfolio and new people were appointed to push the agenda. Manish Singhal, the national sales head of UHI, selected Kerala as the pilot state to implement the new plan. However, the projects failed, as the distributor escalated the treatment meted out by UHI to the Electrical Trade Association (ETA). Trade associations have had a history of playing truant with players like UHI, and because of this, business came to a complete halt. The UHI and ETA teams met once; however, the suggested closure by ETA needed to be aligned with UHI’s interests. Singhal’s dilemma deepened, and they had to decide the next steps.

Complexity academic level

This case study is suitable for a postgraduate marketing course in a segment on managing channels, intermediaries, distribution management and channel conflicts. The uniqueness of this case is in the dimension of the trade association and managing the stakeholders.

Supplementary material

Teaching notes are available for educators only.

Subject code

CSS8: Marketing.
Tata International Limited: expanding leather footwear in India
Authors: Mehdi Mokhalles Mohammad , Nafees Lubna , Kapoor Shivani , Kalia Shalini
Published: December 2023

Learning outcomes

The case study aims to provide students with an understanding of the challenges businesses face expanding into the home market after having an international presence through exports. It also throws light on operations in an emerging market economy – both rural and urban. The key objectives are to understand the leather footwear business operation in India, understand the challenges of expanding business in India, analyse strategies adopted to sustain and compete in India and identify the possible distribution strategies for the leather footwear business in India.

Case overview/synopsis

The case study focuses on Tata International Limited’s (TIL) leather and leather products business in India. The leather and leather products division was present in India since 1973 (Anand, 2020) and exported to more than 35 countries across the world (Anand, 2020). TIL did not want to miss the opportunity available in India and planned to expand its leather footwear business in the country. The company opened retail outlets in major Indian cities and an experience store in Dewas (Madhya Pradesh) in 2019. It aimed for a domestic presence along with the existing export business. However, the biggest challenge that was in front of V. Muthukumaran, head of leather products division at TIL, was how to go ahead with the idea of domestic expansion (Anand, 2020). Should the company expand the market through sister companies (Westside and Tata CliQ) in India? How and in what way should TIL plan for going through Westside and Tata CLiQ? Should Muthukumaran think of either the brick-and-mortar route or the online route or both?

Complexity academic level

This case study is designed for use in undergraduate and graduate early-stage programmes. This case study is primarily designed for use in Master of Business Administration and/or Bachelor of Business Administration programmes. The case study is ideal for courses on understanding the expansion in the domestic market, strategy, retail and international marketing. The teaching note discusses theoretical frameworks such as external environment analysis and SWOT analysis to devise distribution strategies. The case study mapped the distribution channel and decision alternatives for the company.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 8: Marketing.
Implications of competitive tendering on consulting engineering services in South Africa: a thematic analysis
Authors: Govender Neil , Laryea Samuel , Watermeyer Ron
Published: December 2023

Purpose

Competitive tendering in South Africa is often associated with procurement based on the lowest fee tendered. Previous research on this topic did not provide in-depth examinations of how pricing within consulting engineering companies was affected by competitive tendering nor did it illuminate the extent to which professional services were impacted by competitive tendering. This paper aims to examine the implications of competitive tendering on pricing and delivery of consulting engineering services in South Africa.

Design/methodology/approach

A survey research strategy with a questionnaire as the research instrument elicited qualitative data from 28 experienced consulting engineers in South Africa. Thematic analysis was used to analyse qualitative data from the questionnaires.

Findings

Three key themes were identified, namely: considerations when determining consulting engineering fees on competitively tendered projects; the impact of reduced fees due to competitive tendering on the delivery of consulting engineering services; and interventions to prevent unsustainably “low” professional fees. Many consulting engineers in South Africa still determine fees using fee scales, while other considerations include resources, project complexity, risk, etc. Most participants asserted that design optimisation/value engineering, training, meetings and construction monitoring were adversely impacted by “low” fees.

Originality/value

This paper provides in-depth qualitative feedback from experienced consulting engineers (most having more than 20 years’ experience) on a topical issue in the South African construction industry. Thematic analysis was a novel method of analysis that was not used previously in this area of study.
The role of user-generated content in tourism decision-making: an exemplary study of Andalusia, Spain
Authors: Sánchez-Franco Manuel J. , Rey-Tienda Sierra
Published: December 2023

Purpose

This research proposes to organise and distil this massive amount of data, making it easier to understand. Using data mining, machine learning techniques and visual approaches, researchers and managers can extract valuable insights (on guests' preferences) and convert them into strategic thinking based on exploration and predictive analysis. Consequently, this research aims to assist hotel managers in making informed decisions, thus improving the overall guest experience and increasing competitiveness.

Design/methodology/approach

This research employs natural language processing techniques, data visualisation proposals and machine learning methodologies to analyse unstructured guest service experience content. In particular, this research (1) applies data mining to evaluate the role and significance of critical terms and semantic structures in hotel assessments; (2) identifies salient tokens to depict guests' narratives based on term frequency and the information quantity they convey; and (3) tackles the challenge of managing extensive document repositories through automated identification of latent topics in reviews by using machine learning methods for semantic grouping and pattern visualisation.

Findings

This study’s findings (1) aim to identify critical features and topics that guests highlight during their hotel stays, (2) visually explore the relationships between these features and differences among diverse types of travellers through online hotel reviews and (3) determine predictive power. Their implications are crucial for the hospitality domain, as they provide real-time insights into guests' perceptions and business performance and are essential for making informed decisions and staying competitive.

Originality/value

This research seeks to minimise the cognitive processing costs of the enormous amount of content published by the user through a better organisation of hotel service reviews and their visualisation. Likewise, this research aims to propose a methodology and method available to tourism organisations to obtain truly useable knowledge in the design of the hotel offer and its value propositions.
Values and information publicity shape tourists' intentions to visit green hotels: an application of the extended value-belief norms theory
Authors: Waris Idrees , Iqbal Asif , Ahmed Riaz , Hashim Sharizal , Ahmed Adeel
Published: December 2023

Purpose

The unsustainable practices of hotels have greatly contributed to ecological imbalances, encompassing excessive energy and water consumption, improper waste disposal and inadequate resource management. Information publicity (IP) plays an effective role in influencing tourists' intentions to visit green hotels. Therefore, the current study has incorporated IP into the value-belief norm (VBN) framework to examine tourists' intentions to visit green hotels.

Design/methodology/approach

This study is a correlational research design, and the purposive sampling technique was employed for the data collection. The study used 355 valid data and analyzed them via partial least squares structural equation modeling (PLS-SEM).

Findings

The study results show that egoistic values have the greatest impact on pro-environmental beliefs (ENBs). In addition, the results indicate the impact of ENB and IP on personal norms (PNs), leading toward the intention to visit green hotels.

Practical implications

This study helps hotel managers devise and execute effective marketing strategies for green hotels. Hospitality marketers should pay more attention to values, orientations and IP, emphasizing the significance of these factors in increasing the visits of customers to green hotels.

Originality/value

IP, an important factor that informs tourists about hotels that are environmentally friendly, has been neglected in the tourism research. This research examines the significance of IP in developing ENBs and influencing the PN of tourists.
Leveraging community-based assets in coaching, wellness and mentorship to increase the African American and Latinx math teacher workforce
Authors: Warner Sean S.
Published: December 2023

Purpose

There is some evidence to suggest that the historical challenge associated with recruiting and retaining Black and Brown Science, Technology, Engineering and Math (STEM) collegians is tied to early their teaching and learning experiences in Mathematics. This paper describes an National Science Foundation (NSF) funded project (NSF #2151043) whose goal is to attract, prepare and retain math teachers of color in high need school districts ensure that those teachers remain in the field long enough to make a meaningful impact on the minds and hearts of BIPOC students who are often, extrinsically, and intrinsically, discouraged from pursuing careers in STEM professions.

Design/methodology/approach

This mixed-methods study, which began in the summer of 2023, seeks to recruit, prepare, support and retain nineteen (19) Black and Brown math teachers for two (2) high need urban school districts. The expectancy value theory will be used to explain the performance, persistence, and choices of the teachers, while grounded theory will be utilized to understand the impact of the intensive mentorship and wellness coaching that applied over the first year of their preservice preparation and subsequent in-service years.

Findings

Measures of project efficacy won’t begin until 2025 and as such there are no findings or implications to draw from for the study at this time.

Originality/value

The intention of this paper is to augment the body of knowledge on recruiting and retaining Black and Brown math teachers for urban schools where the need for quality STEM teachers is critical.
When the Abu Dhabi United Group Came to Town: Constructing an Organisational Fix for State Capitalism through the Manchester Life Partnership
Authors: Goulding Richard , Leaver Adam , Silver Jonathan
Published: December 2023

For many cities, the entry of financial actors into housing opens new geopolitical relations with overseas entities, including state‐backed investors such as sovereign wealth funds. These transformations raise the question of the extent to which real estate enables the urbanisation of state capitalism, understood as the expansion of the state's role as promoter, supervisor, and owner of capital. Our paper answers this question through an analysis of Manchester Life, a residential real estate joint venture between Manchester City Council and the Abu Dhabi United Group, an investment firm linked to the Abu Dhabi royal family. In doing so it explores state capitalism as a form of extended urbanisation, with oil revenues from the Persian Gulf used to extract urban land rents in the Global North. It further highlights urban geopolitical implications, theorising Manchester Life as an organisational fix that reworks the geographies of value extraction while eroding democratic accountability.
Anti‐natalism is incompatible with Theory X
Authors: Yoshizawa Fumitake
Published: December 2023

The anti‐natalist philosopher David Benatar defends a position asserting that all life is harmful, and that it is, therefore, wrong to have children. In this paper, I critique Benatar's less‐discussed claim that his anti‐natalism provides solutions to population ethics problems, such as the Non‐Identity Problem, the Repugnant Conclusion, and the Mere Addition Problem, all of which are presented in Derek Parfit's Reasons and Persons. Since the publication of his Better Never to Have Been, Benatar has continued to claim that its provision of such solutions strengthens his defense of anti‐natalism. Although Benatar's view has received much criticism, this argument has not been discussed at length. I undertake a thorough examination of the argument and identify reasons to reject it. The central point of my critique is that the implications of Benatar's views in determining ranges of wrong and not‐wrong cases of procreation are extensionally inadequate when applied to the problems of population ethics.
The metabolic basis of inherited neutropenias
Authors: Oyarbide Usua , Crane Genevieve M. , Corey Seth J.
Published: December 2023

Neutrophils are the shortest‐lived blood cells, which requires a prodigious degree of proliferation and differentiation to sustain physiologically sufficient numbers and be poised to respond quickly to infectious emergencies. More than 107 neutrophils are produced every minute in an adult bone marrow—a process that is tightly regulated by a small group of cytokines and chemical mediators and dependent on nutrients and energy. Like granulocyte colony‐stimulating factor, the primary growth factor for granulopoiesis, they stimulate signalling pathways, some affecting metabolism. Nutrient or energy deficiency stresses the survival, proliferation, and differentiation of neutrophils and their precursors. Thus, it is not surprising that monogenic disorders related to metabolism exist that result in neutropenia. Among these are pathogenic mutations in HAX1, G6PC3, SLC37A4, TAFAZZIN, SBDS, EFL1 and the mitochondrial disorders. These mutations perturb carbohydrate, lipid and/or protein metabolism. We hypothesize that metabolic disturbances may drive the pathogenesis of a subset of inherited neutropenias just as defects in DNA damage response do in Fanconi anaemia, telomere maintenance in dyskeratosis congenita and ribosome formation in Diamond–Blackfan anaemia. Greater understanding of metabolic pathways in granulopoiesis will identify points of vulnerability in production and may point to new strategies for the treatment of neutropenias.
Telehealth services for children with neuro‐developmental disabilities in the Asia‐Pacific region: A systematic review
Authors: Devagiri Bhagya , Ariyasena Akila Dinethra K. , Siriwardhana Dhammika Deepani , Sumanasena Samanmali
Published: December 2023

Background

In recent years telehealth became a popular and a rational health service delivery approach, especially amidst multiple challenges posed while providing health care interventions during the COVID‐19 pandemic.

Aim

We synthesized available evidence on telehealth for managing children with NDDs in the Asia‐Pacific region with the aim of identifying successful methods.

Methodology

We systematically reviewed six electronic databases: MEDLINE, AMED, EMBASE, PsychInfo, Web of Science, and (CINAHL plus) using the keywords and database‐specific subject headings from their inception to 25th August 2021. Review findings were synthesized narratively, and harvest plots were used to demonstrate the effect of interventions. The protocol and reporting the findings of this review adhered to PRISMA 2020 guidelines. PROSPERO registration: CRD 340690.

Results

We harvested 30,823 records; 17,563 duplicates were removed, and 196 full‐text articles were assessed for eligibility. 16 studies with multiple research designs were included in the review. Eight were from the Pacific region and eight represented Asia. The interventions targeted families and children with a variety of NDDs (autism spectrum disorder, Down syndrome, cleft lip and palate, hearing impairment, cerebral palsy etc.) via telehealth. Telehealth packages consisted of direct and indirect methods of synchronous, asynchronous, and hybrid approaches. All studies used parent‐led intervention strategies. Telehealth reported a positive effect in 7/16 studies while five showed a neutral effect.

Conclusions

According to published evidence telehealth for children with NDDs is an evolving, evidence‐based service facilitation modality in the Asia‐Pacific region, with only a few published randomized controlled trials. The systematic review shows promising telehealth practices emerging across the region despite the diversity in NDDs studied.
Levothyroxine for a high‐normal TSH in unexplained infertility
Authors: Galbiati Francesca , Jokar Tahereh Orouji , Howell Lars M. , Li Runjia , Fourman Lindsay T. , Lee Hang , Jeong Jong‐Hyeon , Fazeli Pouneh K.
Published: December 2023

Objective

Unexplained infertility affects nearly one‐third of infertile couples. Women with unexplained infertility are more likely to have a high‐normal thyroid‐stimulating hormone level (TSH: 2.5–5 mIU/L) compared to women with severe male factor infertility. Practice guidelines vary on whether treatment should be initiated for TSH levels >2.5 mIU/L in women attempting conception because the effects of treating a high‐normal TSH level with levothyroxine are not known. We evaluated conception and live birth rates in women with unexplained infertility and high‐normal TSH levels.

Design, Patients and Measurements

Retrospective study including 96 women evaluated for unexplained infertility at a large academic medical centre between 1 January 2000 and 30 June 2017 with high‐normal TSH (TSH: 2.5–5 mIU/L and within the normal range of the assay) who were prescribed (n = 31) or not prescribed (n = 65) levothyroxine. Conception and live birth rates were assessed.

Results

The conception rate in the levothyroxine group was 100% compared to 90% in the untreated group (p = .086 unadjusted; p < .05 adjusted for age; p = .370 adjusted for TSH; p = .287 adjusted for age and TSH). The live birth rate was lower in the levothyroxine group (63%) compared to the untreated group (84%) (p = .05 unadjusted; p = .094 adjusted for age; p = .035 adjusted for TSH; p = .057 adjusted for age and TSH).

Conclusions

Women with unexplained infertility and high‐normal TSH levels treated with levothyroxine had a higher rate of conception but lower live birth rate compared to untreated women, with the limitation of a small sample size. These findings assert the need for prospective, randomized studies to determine whether treatment with levothyroxine in women with unexplained infertility and high‐normal TSH is beneficial.
Grading pancreatic adenocarcinomas on fine needle aspiration cytology. The outstanding issues
Authors: Mallik Mrinmay Kumar , Qadan Laila Rafiq , Mohanty Asit Kumar , Alali Ali , Kapila Kusum
Published: December 2023

Objective

The three‐tier grading scheme described in “The Papanicolaou Society of Cytopathology (PSC) System for reporting Pancreaticobiliary Cytopathology” (TPSCRPBC) which remained unchanged following the WHO Reporting System for Pancreaticobiliary Cytopathology (WRPBC) was evaluated on pancreatic adenocarcinomas (PACs) reported on endoscopic ultrasound‐guided fine needle aspiration cytology (EUS‐FNAC).

Methods

The Papanicolaou and May Grunwald Giemsa‐stained smears from 116 cases of PACs were graded using the three‐tier grading scheme laid down by TPSCRPBC/WRPBC. Cases exhibiting multiple grades were assigned primary, secondary and tertiary grades. Each case was assigned a grade score, either by adding the primary and secondary grades, by adding the primary and tertiary grades when the tertiary grade was 3 or by doubling the grade when only one grade existed. Necrosis was estimated semi‐quantitatively. The inter‐observer reproducibility in grading was evaluated using Kappa and Kendall's tau‐c. Correlations between the various grades, the stage of the tumour and the amount of necrosis were assessed using Spearman rho and Kendall's tau‐b.

Results

31.89% of cases showed one grade, and 68.11% showed at least two grades. 16.38% showed three grades. The two commonest grade scores were 3 and 5. The inter‐observer reproducibility for grading and grade scoring was satisfactory. A positive correlation was noted between the grades and the amount of necrosis. No significant correlation was found between the grades, grade scores and the stage of the tumours.

Conclusions

The TPSCRPBC/WRPBC grading scheme can be suitably applied to PACs with good inter‐observer reproducibility. Cases often show multiple grades in the same tumour.
Shifting hotspots: Climate change projected to drive contractions and expansions of invasive plant abundance habitats
Authors: Evans Annette E. , Jarnevich Catherine S. , Beaury Evelyn M. , Engelstad Peder S. , Teich Nathan B. , LaRoe Jillian M. , Bradley Bethany A.
Published: December 2023

Aim

Preventing the spread of range‐shifting invasive species is a top priority for mitigating the impacts of climate change. Invasive plants become abundant and cause negative impacts in only a fraction of their introduced ranges, yet projections of invasion risk are almost exclusively derived from models built using all non‐native occurrences and neglect abundance information.

Location

Eastern USA.

Methods

We compiled abundance records for 144 invasive plant species from five major growth forms. We fit over 600 species distribution models based on occurrences of abundant plant populations, thus projecting which areas in the eastern United States (U.S.) will be most susceptible to invasion under current and +2°C climate change.

Results

We identified current invasive plant hotspots in the Great Lakes region, mid‐Atlantic region, and along the northeast coast of Florida and Georgia, each climatically suitable for abundant populations of over 30 invasive plant species. Under a +2°C climate change scenario, hotspots will shift an average of 213 km, predominantly towards the northeast U.S., where some areas are projected to become suitable for up to 21 new invasive plant species. Range shifting species could exacerbate impacts of up to 40 invasive species projected to sustain populations within existing hotspots. On the other hand, within the eastern U.S., 62% of species will experience decreased suitability for abundant populations with climate change. This trend is consistent across five plant growth forms.

Main Conclusions

We produced species range maps and state‐specific watch lists from these analyses, which can inform proactive regulation, monitoring, and management of invasive plants most likely to cause future ecological impacts. Additionally, areas we identify as becoming less suitable for abundant populations could be prioritized for restoration of climate‐adapted native species. This research provides a first comprehensive assessment of risk from abundant plant invasions across the eastern U.S.
Feasibility and safety of per‐oral endoscopic septotomy for Killian‐Jamieson diverticulum: Case series with video
Authors: Tanaka Ippei , Shimamura Yuto , Inoue Haruhiro , Azuma Daisuke , Ushikubo Kei , Yamamoto Kazuki , Okada Hiroki , Kimoto Yoshiaki , Nishikawa Yohei , Owada Kaori , Tanabe Mayo , Onimaru Manabu
Published: December 2023

Background and Aims

Killian‐Jamieson diverticulum (KJD) is a relatively uncommon variant of pharyngoesophageal diverticula, distinct from the more prevalent Zenker diverticulum. However, literature on endoscopic management of KJD remains limited. This study aimed to elucidate the efficacy and safety of peroral endoscopic septotomy (POES) as a treatment approach for symptomatic KJD.

Methods

In this retrospective observational study, we investigated the outcomes of nine consecutive patients who underwent POES for KJD between January 2019 and May 2023. Follow‐up data of at least 2 months post‐treatment were analyzed. The primary outcome measure was the technical success rate of POES. Secondary outcomes encompassed the clinical success rate, defined as symptomatic improvement 2 months after POES, and the incidence of adverse events.

Results

All patients presented with dysphagia, with a median symptom duration of 6 months (interquartile range [IQR]: 3–12 months). The median diverticulum size was 32 mm (IQR: 24–42 mm). The median duration of the operation time was 66 min (IQR: 60–109). A 100% technical success rate was achieved, with complete closure of the defect in all cases. There were no adverse events related to this treatment. The median hospitalization duration was 5 days (IQR: 4–6), and the clinical success rate was 88.9%. Follow‐up barium esophagograms exhibited significant improvement in the flow of the barium for all patients.

Conclusions

Despite the relatively limited case volume, our findings underscore that POES is a safe and efficacious approach for managing symptomatic KJD.
Cx3cr1 deficiency interferes with learning‐ and direct current stimulation‐mediated neuroplasticity of the motor cortex
Authors: Gellner Anne‐Kathrin , Reis Janine , Fiebich Bernd L. , Fritsch Brita
Published: December 2023

Microglia are essential contributors to synaptic transmission and stability and communicate with neurons via the fractalkine pathway. Transcranial direct current stimulation [(t)DCS], a form of non‐invasive electrical brain stimulation, modulates cortical excitability and promotes neuroplasticity, which has been extensively demonstrated in the motor cortex and for motor learning. The role of microglia and their fractalkine receptor CX3CR1 in motor cortical neuroplasticity mediated by DCS or motor learning requires further elucidation. We demonstrate the effects of pharmacological microglial depletion and genetic Cx3cr1 deficiency on the induction of DCS‐induced long‐term potentiation (DCS‐LTP) ex vivo. The relevance of microglia–neuron communication for DCS response and structural neuroplasticity underlying motor learning are assessed via 2‐photon in vivo imaging. The behavioural consequences of impaired CX3CR1 signalling are investigated for both gross and fine motor learning. We show that DCS‐mediated neuroplasticity in the motor cortex depends on the presence of microglia and is driven in part by CX3CR1 signalling ex vivo and provide the first evidence of microglia interacting with neurons during DCS in vivo. Furthermore, CX3CR1 signalling is required for motor learning and underlying structural neuroplasticity in concert with microglia interaction. Although we have recently demonstrated the microglial response to DCS in vivo, we now provide a link between microglial integrity and neuronal activity for the expression of DCS‐dependent neuroplasticity. In addition, we extend the knowledge on the relevance of CX3CR1 signalling for motor learning and structural neuroplasticity. The underlying molecular mechanisms and the potential impact of DCS in rescuing CX3CR1 deficits remain to be addressed in the future.
Cerebral vascular and blood brain–barrier abnormalities in a mouse model of epilepsy and tuberous sclerosis complex
Authors: Guo Dongjun , Zhang Bo , Han Lirong , Rensing Nicholas R. , Wong Michael
Published: December 2023

Objective

Tuberous sclerosis complex (TSC) is a genetic disorder, characterized by tumor formation in the brain and other organs, and severe neurological symptoms, such as epilepsy. Abnormal vascular endothelial growth factor (VEGF) expression may promote angiogenesis in kidney and lung tumors in TSC and has been identified in brain specimens from TSC patients, but the role of VEGF and vascular abnormalities in neurological manifestations of TSC is poorly defined. In this study, we investigated abnormalities in brain VEGF expression, cerebral blood vessel anatomy, and blood–brain barrier (BBB) structure and function in a mouse model of TSC.

Methods

Tsc1GFAPCKO mice were used to investigate VEGF expression and vascular abnormalities in the brain by Western blotting and immunohistochemical analysis of vascular and BBB markers. In vivo two‐photon imaging was used to assess BBB permeability to normally impenetrable fluorescently labeled compounds. The effect of mechanistic target of rapamycin (mTOR) pathway inhibitors, VEGF receptor antagonists (apatinib), or BBB stabilizers (RepSox) was assessed in some of these assays, as well as on seizures by video‐electroencephalography.

Results

VEGF expression was elevated in cortex of Tsc1GFAPCKO mice, which was reversed by the mTOR inhibitor rapamycin. Tsc1GFAPCKO mice exhibited increased cerebral angiogenesis and vascular complexity in cortex and hippocampus, which were reversed by the VEGF receptor antagonist apatinib. BBB permeability was abnormally increased and BBB‐related tight junction proteins occludin and claudin‐5 were decreased in Tsc1GFAPCKO mice, also in an apatinib‐ and RepSox‐dependent manner. The BBB stabilizer (RepSox), but not the VEGF receptor antagonist (apatinib), decreased seizures and improved survival in Tsc1GFAPCKO mice.

Significance

Increased brain VEGF expression is dependent on mTOR pathway activation and promotes cerebral vascular abnormalities and increased BBB permeability in a mouse model of TSC. BBB modulation may affect epileptogenesis and represent a rational treatment for epilepsy in TSC.
Atomistic simulation of rolling contact fatigue behavior of a face‐centered cubic material (nickel)
Authors: Goswami Pragyan , Pal Snehanshu , Gupta Manoj
Published: December 2023

The atomic‐level fundamental understanding of the rolling contact fatigue (RCF) mechanism using molecular dynamics (MD) simulation is yet to be understood more clearly. In this paper, the atomistic behavior of the single‐crystal Ni is studied under dynamic rolling contact loading with the help of MD simulations at varying temperatures of the specimen. The deformed material is investigated using atomic strain analyses to evaluate the shear, volumetric strain distribution, and von Mises stress. Furthermore, dislocation and stacking–fault analyses are done to determine the deformation mechanism of the material with the oscillation cycles. Simulation studies infer that dislocation defects tend to increase with the temperature of the specimen logarithmically. The deformation majorly results in partial dislocations, indicating low stacking fault (SF) energy. The present work opens up a new field of study to understand the RCF mechanisms, which can provide the foundational work to understand other face‐centered cubic (FCC) materials.
The immune system in Down Syndrome: Autoimmunity and severe infections
Authors: Ramba Meredith , Bogunovic Dusan
Published: December 2023

Over 200,000 individuals in the United States alone live with Down Syndrome (DS), the most common genetic disorder associated with intellectual disability. DS has a constellation of features across the body, including dysregulation of the immune system. Individuals with DS have both a higher frequency of autoimmunity and more severe infections than the general population, highlighting the importance of understanding the immune system in this population. Individuals with DS present with dysregulation of both the innate and adaptive immune systems. Elevated cytokine levels, increased type I and type II IFN signaling, a shift toward memory phenotypes in T cells, and a decrease in the size of the B‐cell compartment are observed in individuals with DS, which contribute to both autoinflammation and severe infections. Herein, we discuss the current knowledge of the immune system in individuals with Down Syndrome as well as ideas of necessary further investigations to decipher the mechanisms by which trisomy 21 leads to immune dysregulation, with the ultimate goal of identifying clinical targets to improve treatment.
Three patterns of symptom communication between patients and clinicians in the intensive care unit: A fieldwork study
Authors: Nyhagen Ragnhild , Egerod Ingrid , Rustøen Tone , Lerdal Anners , Kirkevold Marit
Published: December 2023

Aim

To describe different patterns of communication aimed at preventing, identifying and managing symptoms between mechanically ventilated patients and clinicians in the intensive care unit.

Design

We conducted a fieldwork study with triangulation of participant observation and individual interviews.

Methods

Participant observation of nine patients and 50 clinicians: nurses, physiotherapists and physicians. Subsequent individual face‐to‐face interviews with nine of the clinicians, and six of the patients after they had regained their ability to speak and breathe spontaneously, were fully alert and felt well enough to sit through the interview.

Findings

Symptom communication was found to be an integral part of patient care. We identified three communication patterns: (1) proactive symptom communication, (2) reactive symptom communication and (3) lack of symptom communication. The three patterns co‐existed in the cases and the first two complemented each other. The third pattern represents inadequate management of symptom distress.

Conclusion

Recognition of symptoms in non‐speaking intensive care patients is an important skill for clinicians. Our study uncovered three patterns of symptom communication, two of which promoted symptom management. The third pattern suggested that clinicians did not always acknowledge the symptom distress.

Implications for Patient Care

Proactive and reactive symptom assessment of non‐speaking patients require patient verification when possible. Improved symptom prevention, identification and management require a combination of sound clinical judgement and attentiveness towards symptoms, implementation and use of relevant assessment tools, and implementation and skill building in augmentative and alternative communication.

Impact

This study addressed the challenges of symptom communication between mechanically ventilated patients and clinicians in the intensive care unit. Our findings may have an impact on patients and clinicians concerned with symptom management in intensive care units.

Reporting Method

We used the consolidated criteria for reporting qualitative research.

Patient Contribution

A user representative was involved in the design of the study.
Safety and efficacy of REGENDIL™ infused hair growth promoting product in adult human subject having hair fall complaints (alopecia)
Authors: Merja Apeksha , Patel Nayan , Patel Maheshvari , Patnaik Saurav , Ahmed Asrar , Maulekhi Shatakshi
Published: December 2023

Background

Hair serum is recommended therapy for the management of hair fall problems. People of all ages suffer from hair fall.

Aim

To evaluate safety and efficacy of hair growth promoting product in healthy adult subjects with hair fall complaints (Alopecia).

Methods

In this safety and efficacy clinical study, 32 healthy individuals (aged 18–45 years) experiencing hair loss were enrolled. Participants applied 0.5 mL of the product to the affected scalp area daily for 60 days. The study evaluated various factors, including hair growth rate, thickness, density, scalp condition using CASLite‐Nova, anagen‐to‐telogen ratio, hair fall reduction, overall hair and scalp appearance, hair strength, and participants' subjective perceptions of the product.

Results

Highly statistically significant improvement was observed in hair growth rate, thickness, and density at Day 30 and Day 60. Hair growth rate increased (p‐value <0.01) by 10.52% in 30 days and 31.62% in 60 days after test product application. Average hair growth increased by 424.21 μm/day and 487.31 μm/day at Day 30 and 60 respectively. The hair growth improved by up to 1.5 times after 60 days of usage in healthy subjects with hair fall complaints. No adverse events or product‐related adverse events were reported.

Conclusion

Hair serum containing REGENDIL™ (Redensyl, AnaGain, Procapil, Capilia longa), and 5 kDa hyaluronic acid was efficacious and well tolerable in reducing hair fall (Alopecia). Hair serum significantly improved hair growth, hair density, hair thickness, and hair strength within 60 days of usage, thereby demonstrating it worth as a beneficial inclusion as a daily haircare product.
Continuous genetic adaptation to high elevations of alpine bamboos in the Hengduan Mountains, Southwest China
Authors: Luo Li‐Ying , Jin Gui‐Hua , Ma Peng‐Fei , Li De‐Zhu
Published: December 2023

Many examples of phenotypic modifications resulting from high‐elevation adaptation have been documented, however, the underlying processes responsible for these modifications and whether the continuity of the adaptation process remain elusive, particularly in plants. The alpine plants distributed along wide elevational gradients provide an ideal system to address this question. Here, we collected transcriptomes from multiple tissues of three species with different elevations (~1500, ~2500, and ~3600 m in the Hengduan Mountains, Southwest China) in two genera Fargesia and Yushania of alpine bamboos, respectively, and conducted evolutionary and expressional analyses. Results showed that high‐elevation adaptation emerged earlier in the evolutionary history of both genera and evolved continuously as the elevation increased. Moreover, convergence of genetic changes was observed in the two genera, with amounts of candidate genes responsible for high‐elevation adaptation identified under positive selection. Overall, our study provides an empirical example and valuable genetic resource for further investigation of high‐elevation adaptation in plants and sheds new light on how plants adapting to high‐elevation environments in a biodiversity hotspot.