bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive review on the hepatotoxicity of herbs used in the Indian (Ayush) systems of alternative medicine
Authors: Philips Cyriac Abby , Theruvath Arif Hussain
Published: April 2024

Complementary and alternative medicine-related liver injuries are increasing globally. Alternative medicine, as an inclusive healthcare practice, is widely accepted in developing and underdeveloped countries. In this context, the traditional systems of medicine in India have been at the forefront, catering to the preventive and therapeutic spectrum in the absence of conclusive evidence for benefits and lack of data on safety. Contrary to popular belief, it is evident that apart from adverse events caused by contamination and adulteration of alternative medicines, certain commonly used herbal components have inherent hepatotoxicity. This narrative review updates our current understanding and increasing publications on the liver toxicity potential of commonly used herbs in traditional Indian systems of medicine (Ayush), such as Tinospora cordifolia (Willd.) Hook.f. & Thomson (Giloy/Guduchi), Withania somnifera (L.) Dunal (Ashwagandha), Curcuma longa L. (Turmeric), and Psoralea corylifolia L. (Bakuchi/Babchi). This review also highlights the importance of the upcoming liver toxicity profiles associated with other traditional herbs used as dietary supplements, such as Centella asiatica (L.) Urb., Garcinia cambogia Desr., Cassia angustifolia Vahl (Indian senna), and Morinda citrofolia L. (Noni fruit). Fortunately, most reported liver injuries due to these herbs are self-limiting, but can lead to progressive liver dysfunction, leading to acute liver failure or acute chronic liver failure with a high mortality rate. This review also aims to provide adequate knowledge regarding herbalism in traditional practices, pertinent for medical doctors to diagnose, treat, and prevent avoidable liver disease burdens within communities, and improve public health and education.
Impact of a Professional Development Course for Doctoral Nurses and Students on Genomic Conceptual Knowledge and Competencies
Authors: Kronk Rebecca , Kalarchian Melissa , Lutz Calvin
Published: April 2024

Background:

Universally, nurses’ limited educational opportunities to expand their genomic literacy may have implications on patient care management, research, and training.

Purpose:

To evaluate the impact of a self-paced online course on genomic knowledge and competency acquisition in a sample of nurses possessing a doctoral degree and doctoral students.

Methods:

Pre- and postcourse data were collected using the “Genomic Nursing Concept Inventory” (GNCI) (N = 129) and a self-report survey based on the Essential Genetic and Genomic Competencies for Nurses with Graduate Degrees (N = 131).

Results:

GNCI scores in all 4 topical categories and in 9 of the 16 domains significantly improved. All Genetic Competency scores significantly improved. Significant correlations were observed between Genetic Competency self-ratings and GNCI scores precourse and change of scores.

Conclusions:

The positive outcomes should encourage the development of more accessible educational opportunities for nurses and other healthcare professionals to improve genomic literacy and competency.
Yolk Sac Differentiation in Endometrial Carcinoma
Authors: Mills Anne M. , Jenkins Taylor M. , Dibbern Megan E. , Atkins Kristen A. , Ring Kari L.
Published: April 2024

Endometrial somatically derived yolk sac tumors are characterized by yolk sac morphology with AFP, SALL-4, and/or Glypican-3 immunoexpression. Yolk sac marker expression, however, is not limited to tumors with overt yolk sac histology. Three hundred consecutive endometrial malignancies were assessed for immunomarkers of yolk sac differentiation. Of these, 9% expressed ≥1 yolk sac marker, including 29% of high-grade tumors. Only 3 (1%) met morphologic criteria for yolk sac differentiation; these were originally diagnosed as serous, high-grade NOS, and dedifferentiated carcinoma. Two were MMR-intact and comprised exclusively of yolk sac elements, while the dedifferentiated case was MMR deficient and had a background low-grade endometrioid carcinoma; this case also showed BRG1 loss. All 3 were INI1 intact. Nonspecific yolk sac marker expression was seen in 14 carcinosarcomas, 4 endometrioid, 2 serous, 1 clear cell, 1 dedifferentiated, 1 mixed serous/clear cell, and 1 mesonephric-like carcinoma. INI1 was intact in all cases; one showed BRG1 loss. Twenty were MMR-intact, and 4 were MMR deficient. All MMR-deficient cases with yolk sac marker expression, both with and without true yolk sac morphology, had no evidence of residual disease on follow-up, whereas 82% of MMR-intact cases developed recurrent/metastatic disease. In summary, endometrial somatically derived yolk sac tumors were rare but under-recognized. While AFP immunostaining was specific for this diagnosis, Glypican-3 and SALL-4 expression was seen in a variety of other high-grade carcinomas. INI1 loss was not associated with yolk sac morphology or immunomarker expression in the endometrium, and BRG1 loss was rare. All patients with MMR-deficient carcinomas with yolk sac immunoexpression +/− morphology were disease-free on follow-up, whereas the majority of MMR-intact cancers showed aggressive disease.
Topical Application of TT-10 Ameliorates Impaired Wound Healing
Authors: Liu Yangdan , Ho Chiakang , Wen Dongsheng , Zhou Zhiyuan , Tsai Tingyu , Sun Jiaming , Liu Yuxin , Gao Ya , Li Qingfeng , Zhang Yifan
Published: April 2024

Background:

In recent decades, chronic wounds have become an increasingly significant clinical concern because of their increasing morbidity and socioeconomic toll. However, there is currently no product available on the market that specifically targets this intricate process. One clear indicator of delayed wound repair is the inhibition of reepithelialization. Yes-associated protein (YAP), which is a potential focal point for tissue repair and regeneration, has been shown to be prominent in several studies. In this context, the authors have identified the pharmacologic product TT-10, which is a YAP activator, as a potential candidate for the treatment of various forms of chronic wounds.

Methods:

The role of TT-10 in regulating YAP activity and subcellular localization was determined by Western blotting and immunofluorescence staining. The effect of TT-10 on the biological functions of keratinocytes was assessed by proliferation, wound healing, and apoptosis assays. The impairment of YAP activity in chronic wounds was measured in human and mouse tissues. The in vivo efficacy of TT-10 was examined by gross examination; hematoxylin and eosin staining; and measuring wound areas and gaps in normal, diabetic, and ischemic wounds.

Results:

The authors’ findings suggest that TT-10 facilitates the nuclear transport of YAP, consequently increasing YAP activity, which in turn increases the proliferation and migration of keratinocytes. Moreover, the authors showed that intracutaneous injection of TT-10 along the wound periphery promoted reepithelialization by means of YAP activation in the epidermis, culminating in accelerated wound closure in several chronic wound healing models.

Conclusion:

The authors’ research highlights the potential of TT-10 to treat chronic wounds, which is a persistent challenge in tissue repair.

Clinical Relevance Statement:

The authors’ research identifies TT-10, a small molecule YAP activator, as a novel therapeutic candidate that enhances keratinocyte function and promotes reepithelialization, offering plastic surgeons an innovative approach to addressing chronic wound challenges.
“Loss of Bone Signal” on 99mTc-Labeled Pyrophosphate Scintigraphy in a Patient With Wild-Type Transthyretin Amyloidosis
Authors: Takahashi Koji , Sasaki Daisuke , Iwamura Takaaki , Sakaue Tomoki , Okura Takafumi
Published: April 2024

99mTc-3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) scintigraphy and 99mTc-pyrophosphate (PYP) scintigraphy are highly sensitive modalities for imaging both myocardial and extracardiac amyloid transthyretin in patients with wild-type transthyretin (ATTRwt) amyloidosis. “Loss of bone signal” on planar imaging of 99mTc-DPD scintigraphy, in which the tracer uptake in bone is obscured by marked tracer uptake in the overlying skeletal muscles, is reported. However, this phenomenon has not yet been documented on 99mTc-PYP scintigraphy. We describe an 89-year-old woman with ATTRwt amyloidosis in whom “loss of bone signal” together with marked tracer uptake into the skeletal muscles was clearly demonstrated on 99mTc-PYP scan.
Genomic and Transcriptomic Landscape of RET Wild-Type Medullary Thyroid Cancer and Potential Use of Mitogen-Activated Protein Kinase-Targeted Therapy
Authors: Darabi Sourat , Adeyelu Tolulope , Elliott Andrew , Sukari Ammar , Hodges Kurt , Abdulla Farah , Zuazo Carlos E , Wise-Draper Trisha , Wang Thomas , Demeure Michael J
Published: April 2024

BACKGROUND:

About 75% of medullary thyroid cancers (MTCs) are sporadic with 45% to 70% being driven by a RET mutation. Selpercatinib is an approved treatment for RET-mutated (mutRET) MTC; however, treatments are needed for wild-type RET MTC (wtRET). Genomic alterations and transcriptomic signatures of wtRET MTC may reveal new therapeutic insights.

STUDY DESIGN:

We did a retrospective analysis of MTC samples submitted for DNA/RNA sequencing and programmed cell death ligand 1 expression using immunohistochemistry at a Clinical Laboratory Improvement Amendments/College of American Pathologists-certified laboratory. Tumor microenvironment immune cell fractions were estimated using RNA deconvolution (quanTIseq). Transcriptomic signatures of inflammation and MAP kinase pathway activation scores were calculated. Mann-Whitney U, chi-square, and Fisher’s exact tests were applied (p values adjusted for multiple comparisons).

RESULTS:

The 160-patient cohort included 108 mutRET and 52 wtRET MTC samples. wtRET tumors frequently harbored mitogen-activated protein kinase (MAPK) pathway mutations, including HRAS (42.31%), KRAS (15.7%), NF1 (6.7%), and BRAF (2%), whereas only 1 MAPK pathway mutation (NF1) was identified among mutRET MTC. Recurrent mutations seen in wtRET MTC included MGA, VHL, APC, STK11, and NFE2L2. Increased transcriptional activation of the MAPK pathway was observed in patients with wtRET harboring mutations in MAPK genes. Although the frequency of programmed cell death ligand 1 expression was similar in wtRET and mutRET (10.2% vs 7%, p = 0.531), wtRET tumors were more often tumor mutational burden high (7.7% vs 0%, p = 0.011), and wtRET MTC exhibited higher expression of immune checkpoint genes.

CONCLUSIONS:

We identified molecular alterations and immune-related features that distinguish wtRET from mutRET MTC. Although RET mutation drives MTC in the absence of other alterations, we showed that wtRET MTC frequently harbors MAPK pathway mutations. These findings may indicate a potential basis for MAPK-targeted therapy, possibly in combination with immuno-oncology agents for selected patients with wtRET MTC.
Hot and scared: how do heatwaves and predation risk impact resource acquisition and allocation?
Authors: Stahlschmidt Zachary R. , Joura Harnoor , Makarem Jenna R. , Sun Jodie L.
Published: April 2024

Heatwaves are increasingly prevalent and can constrain investment into important life-history traits. In addition to heatwaves, animals regularly encounter threats from other organisms in their environments, such as predators. The combination of these two environmental factors introduces a decision-making conflict—heat exposure requires more food intake to fuel investment into fitness-related traits, but foraging in the presence of predators increases the threat of mortality. Thus, we used female variable field crickets (
Gryllus lineaticeps
) to investigate the effects of heatwaves in conjunction with predation risk (exposed food and water sources, and exposure to scent from black widow spiders,
Latrodectus hesperus
) on resource acquisition (food intake) and allocation (investment into ovarian and somatic tissues). A simulated heatwave increased food intake and the allocation of resources to reproductive investment. Crickets exposed to high predation risk reduced food intake, but they were able to maintain reproductive investment at an expense to investment into somatic tissue. Thus, heatwaves and predation risk deprioritized investment into self-maintenance, which may impair key physiological processes. This study is an important step towards understanding the ecology of fear in a warming world.
Two-dimensional nonlocal Eshelby’s inclusion theory: eigenstress-driven formulation and applications
Authors: Ding Wei , Semperlotti Fabio
Published: April 2024

The classical Eshelby’s theory, developed based on local linear elasticity, cannot be applied to inclusion problems that involve nonlocal (long range) elastic effects often observed in micromechanical systems. In this study, we introduce the extension of Eshelby’s inclusion theory to nonlocal elasticity. Starting from Eringen’s integral formulation of nonlocal elasticity, an eigenstress-driven nonlocal Eshelby’s inclusion theory is presented. The eigenstress-driven approach is shown to be a valid mathematical extension of the classical eigenstrain-driven approach in the context of nonlocal inclusion problems. Two individual numerical approaches are developed and applied to simulate inclusion problems and numerically extract the corresponding nonlocal Eshelby tensor. The numerical results obtained from both approaches confirm the validity of the derived nonlocal Eshelby tensor and its ability to capture the non-uniform eigenstress distribution within an elliptic inclusion. These results also help reveal the fundamental difference between the mechanical behaviour of the classical local and the nonlocal inclusion problems. The eigenstress-driven nonlocal inclusion theory could provide the necessary theoretical foundation for the development of homogenization methods of nonlocal heterogeneous media.
Terrirubrum flagellatum gen. nov., sp. nov. of Terrirubraceae fam. nov. and Lichenibacterium dinghuense sp. nov. from forest soil and proposal of Rhodoblastaceae fam. nov.
Authors: Guo Xiu-yin , Zhang Qiu-mei , Fu Jia-cheng , Qiu Li-hong
Published: April 2024

Two Gram-negative, aerobic, rod-shaped bacterial strains, 7MK25T and 6Y81T, were isolated from forest soil of Dinghushan Biosphere Reserve, Guangdong Province, PR China. Based on the results of 16S rRNA gene sequence analysis, strain 7MK25T showed the highest similarity (93.6 %) to Methyloferula stellata AR4T, followed by Bosea thiooxidans DSM 9653T (93.3 %). Strain 6Y81T had the highest similarity of 97.9 % to Lichenibacterium minor RmlP026T, followed by Lichenibacterium ramalinae RmlP001T (97.2 %). Phylogenomic analysis using the UBCG and PhyloPhlAn methods consistently showed that strain 7MK25T formed a sister clade to Boseaceae, while strain 6Y81T formed an independent clade within the genus Lichenibacterium, both in the order Hyphomicrobiales. The digital DNA–DNA hybridization and average nucleotide identity values between strains 7MK25T, 6Y81T and their close relatives were in the ranges of 19.1–29.9 % and 72.5–85.5 %, respectively. The major fatty acids of 7MK25T were summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c), C19 : 0 cyclo ω8c, C16 : 0 and C17 : 0 cyclo, while those of 6Y81T were summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c), C16 : 0 and C16 : 0 3-OH. Strains 7MK25T and 6Y81T took diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine as their dominant polar lipids, and Q-10 as their major respiratory quinone. On the basis of phenotypic and phylogenetic data, strain 7MK25T is proposed to represent a novel species of a novel genus with name Terrirubrum flagellatum gen. nov., sp. nov., within a novel family Terrirubraceae fam. nov., with 7MK25T (=KCTC 62738T=GDMCC 1.1452T) as its type strain. Strain 6Y81T represents a novel species in the genus Lichenibacterium, for which the name Lichenibacterium dinghuense sp. nov. (type strain 6Y81T=KACC 21 727T=GDMCC 1.2176T) is proposed. Rhodoblastaceae fam. nov. with Rhodoblastus as the type genus is also proposed to solve the non-monophylectic problem of the family Roseiarcaceae.
MPN Transformation Is Characterized By Heterogeneous Shifts In Lineage Character Resulting In Both HSC-Like And More Differentiated Lineage Signatures
Authors: Menghrajani Kamal , Dilip Deepika , Farnoud Noushin , Famulare Chris , McGovern Erin , Sirenko Maria , Mascarenhas John , Kosiorek Heidi , Hoffman Ronald , Levine Ross , Koche Richard , Rampal Raajit , Glass Jacob
Published: April 2024

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have a propensity to transform to an accelerated or blast phase (MPN-AP/BP). The resulting disease has clinically similar manifestations to Acute Myeloid Leukemia (AML) but worse clinical outcomes. Here we present the first comprehensive description of the transcriptomic characteristics of MPN-AP/BP. Our analysis incorporates data from 261 patients of the BeatAML cohort and 56 MPN-AP/BP patients, 11 of whom had paired samples from before and after transformation. We establish that transformed MPN is a transcriptionally distinct entity from de novo AML and chronic phase MPNs. Genomic pathways traditionally associated with MPN pathogenesis, such as IL2/STAT5 signaling, IL6/JAK/STAT3 signaling, and NUP98/HOXA9 fusions, were enriched in chronic-phase MPNs but are absent in transformed disease, suggesting JAK2 directed therapy may be less effective in this disease phase. We also discovered that gene expression signatures associated with doxorubicin resistance are highly enriched in transformed MPNs, which may explain the lack of efficacy of standard AML therapies. In addition, we identify that lineage composition at the time of transformation may define distinct subsets of MPN-AP/BP patients, which may assist in the future development of novel treatment strategies.

Key Points

-

Accelerated- and blast-phase transformed MPNs are a transcriptionally entities which are distinct from de novo AML.

-

Transformed MPNs may be characterized by their lineage characteristics, which can drive clinical behavior and account for their inferior overall survival

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Gene expression signatures associated with doxorubicin resistance were highly enriched in transformed MPNs, which may explain the lack of effectiveness of anthracycline-based therapies
Developing and testing Advance Choice Document implementation resources for Black African and Caribbean people with experience of compulsory psychiatric admission
Authors: Simpson Jonathan , Babatunde Abigail , Simpson Alan , Gilbert Steven , Ruck Keene Alex , Stephenson Lucy , Chua Kia-Chong , Owen Gareth , Crowe Fiona , Edwards Pauline , Galloway Selena , Fisher Megan , Schilderman Marcela , Bignell Anita , Smith Shubulade , Henderson Claire
Published: April 2024

Background

Advance Choice Documents (ACDs) have been recommended for use in England and Wales based on evidence from trials that show that they can reduce involuntary hospitalisation, which disproportionately affects Black African and Caribbean people. Our aim was therefore to develop and test ACD implementation resources and processes for Black people who have previously been involuntarily hospitalised and the people that support them.

Methods

Resource co-production workshops were held to inform the development of the ACD template and two types of training for all stakeholders, comprising a Recovery College course and simulation training. An ACD facilitator then used the ACD template developed through the workshops to create personalised ACDs with service users and mental health staff over a series of meetings. Interviews were then conducted with service user and staff participants and analysed to document their experience of the process and opinions on ACDs. Other implementation strategies were also employed alongside to support and optimise the creation of ACDs.

Results

Nine ACDs were completed and were largely reported as appropriate, acceptable, and feasible to service users and staff. Both reported it being an empowering process that encouraged hope for better future treatment and therefore better wellbeing. Uncertainty was also expressed about the confidence people had that ACDs would be adhered to/honoured, primarily due to staff workload. The information provision training and the skills training were generally considered to be informative by trainees.

Conclusions

The project has developed an ACD creation resource that was reported as agreeable to all stakeholders; however, the generalisability of the findings is limited due to the small sample size. The project also highlights the importance of staff and ACD facilitator capacity and good therapeutic relationships in ACD completion. Further research is needed to determine the adjustments needed for large scale use, including for those under age 18 and those under the care of forensic mental health services; and how to include carers/supporters more in the process.
Can Large Language Models Provide Emergency Medical Help Where There Is No Ambulance? A Comparative Study on Large Language Model Understanding of Emergency Medical Scenarios in Resource-Constrained Settings
Authors: Mensah Paulina Boadiwaa , Quao Nana Serwaa , Dagadu Sesinam ,   Cohort 2, Project Genie Clinician Evaluation Group
Published: April 2024

The capabilities of Large Language Models (LLMs) have advanced since their popularization a few years ago. The healthcare sector operates on, and generates a large volume of data annually and thus, there is a growing focus on the applications of LLMs within this sector. There are a few medicine-oriented evaluation datasets and benchmarks for assessing the performance of various LLMs in clinical scenarios; however, there is a paucity of information on the real-world usefulness of LLMs in context-specific scenarios in resourceconstrained settings. In this study, 16 iterations of a decision support tool for medical emergencies using 4 distinct generalized LLMs were constructed, alongside a combination of 4 Prompt Engineering techniques: In-Context Learning with 5-shot prompting (5SP), chain-of-thought prompting (CoT), self-questioning prompting (SQP), and a stacking of self-questioning prompting and chain-of-thought (SQCT). In total 428 model responses were quantitatively and qualitatively evaluated by 22 clinicians familiar with the medical scenarios and background contexts. Our study highlights the benefits of In-Context Learning with few-shot prompting, and the utility of the relatively novel self-questioning prompting technique. We also demonstrate the benefits of combining various prompting techniques to elicit the best performance of LLMs in providing contextually applicable health information. We also highlight the need for continuous human expert verification in the development and deployment of LLM-based health applications, especially in use cases where context is paramount.
Sequential and dynamic coding of water-sucrose categorization in rat gustatory cortices
Authors: Mendoza Germán , Fonseca Esmeralda , Merchant Hugo , Gutierrez Ranier
Published: April 2024

The gustatory system enables our conscious perception of sweetness, allowing us to distinguish sweet solutions from water. However, the neural mechanisms underlying this categorization process in rats remain poorly understood. We addressed this question by designing a novel sucrose categorization task in which rats classified varying sucrose concentrations against water. We found that in the anterior insular cortex (aIC) and orbitofrontal cortex (OFC), neural activity primarily encoded the categorical distinction between sucrose and water, rather than specific sucrose concentrations. Notably, aIC neurons encoded this distinction faster than OFC neurons. Conversely, the OFC slightly preceded the aIC in encoding choice information, although both cortices maintained parallel encoding of the rat’s choices. The encoding of sensory and categorical decisions was dynamic and sequential, forming a sequence of encoding neurons throughout the trial. These findings reveal that sucrose categorization relies on dynamic coding sequences in the neuronal activity of the aIC and OFC rather than static, long-lasting (sustained) neural representations. This dynamic coding, supported by single-cell population decoding and principal component analyses, suggests that the brain continuously updates its representation of sucrose categorization as new information emerges. Additionally, both the aIC and OFC rapidly encoded reward outcomes. Our data supports the notion that gustatory cortices employ sequential and dynamic coding to compute sensorimotor transformations, from taste detection to categorical taste decisions and reward processing.

Graphical Abstract
Lightsheet microscopy integrates single-cell optical visco-elastography and fluorescence cytometry of 3D live tissues
Authors: Tomizawa Yuji , Wali Khadija H. , Surti Manav , Suhail Yasir , Kshitiz  , Hoshino Kazunori
Published: April 2024

Most common cytometry methods, including flow cytometry, observe suspended or fixed cells and cannot evaluate their structural roles in 3D tissues. However, cellular physical interactions are critical in physiological, developmental, and pathological processes. Here, we present a novel optical visco-elastography that characterizes single-cellular physical interactions by applying in-situ micro-mechanical perturbation to live microtissues under 3D lightsheet microscopy. The 4D digital image correlation (DIC) analysis of ∼20,000 nodes tracked the compressive deformation of 3D tissues containing ∼500 cells. The computational 3D image segmentation allowed cell-by-cell qualitative observation and statistical analysis, directly correlating multi-channel fluorescence and viscoelasticity. To represent epithelia-stroma interactions, we used a 3D organoid model of maternal-fetal interface and visualized solid-like, well-aligned displacement and liquid-like random motion between individual cells. The statistical analysis through our unique cytometry confirmed that endometrial stromal fibroblasts stiffen in response to decidualization. Moreover, we demonstrated in the 3D model that interaction with placental extravillous trophoblasts partially reverses the attained stiffness, which was supported by the gene expression analysis. Placentation shares critical cellular and molecular significance with various fundamental biological events such as cancer metastasis, wound healing, and gastrulation. Our analysis confirmed existing beliefs and discovered new insights, proving the broad applicability of our method.
ATG8ylation of vacuolar membrane protects plants against cell wall damage
Authors: Julian Jose , Gao Peng , Del Chiaro Alessia , De La Concepcion Juan Carlos , Armengot Laia , Somssich Marc , Duverge Heloise , Clavel Marion , Grujic Nenad , Kobylinska Roksolana , Polivka Ingo , Besten Maarten , Dank Christian , Korbei Barbara , Bachmair Andreas , Coll Nuria S. , Sprakel Joris , Dagdas Yasin
Published: April 2024

Vacuoles are essential for cellular metabolism, growth, and the maintenance of internal turgor pressure. They sequester lytic enzymes, ions, and secondary metabolites that, if leaked into the cytosol, could lead to cell death. Despite their pivotal roles, quality control pathways that safeguard vacuolar integrity remained elusive in plants. Here, we discovered a conserved vacuolar quality control (VQC) pathway that is activated upon cell wall damage in a turgor pressure dependent manner. Cell wall perturbations induce a distinct modification - ATG8ylation - on the vacuolar membrane (tonoplast) that is regulated by the V-ATPase and ATG8 conjugation machinery. Genetic disruption of tonoplast ATG8ylation impairs vacuolar integrity, leading to cell death. Together, our findings reveal a homeostatic pathway that preserves vacuolar integrity upon cell wall damage.
Engagement and factors associated with annual anal human papillomavirus screening among sexual and gender minority individuals
Authors: Nitkowski Jenna , Ridolfi Timothy J. , Lundeen Sarah J. , Giuliano Anna R. , Chiao Elizabeth , Fernandez Maria E. , Schick Vanessa , Smith Jennifer S. , Bruggink Paige , Brzezinski Bridgett , Nyitray Alan G.
Published: April 2024

Objectives

Annual screening with a provider has been recommended for groups at highest risk for anal cancer. Anal self-sampling could help address screening barriers, yet no studies have examined annual engagement with this method.

Methods

The Prevent Anal Cancer Self-Swab Study recruited sexual and gender minority individuals 25 years and over who have sex with men in Milwaukee, Wisconsin to participate in an anal cancer screening study. Participants were randomized to a home or clinic arm. Home-based participants were mailed an anal human papillomavirus self-sampling kit at baseline and 12 months, while clinic-based participants were asked to schedule and attend one of five participating clinics at baseline and 12 months. Using Poisson regression, we conducted an intention-to-treat analysis of 240 randomized participants who were invited to screen at both timepoints.

Results

58.8% of participants completed annual (median=370 days) anal screening. When stratified by HIV status, persons living with HIV had a higher proportion of home (71.1%) versus clinic (22.2%) annual screening (p<0.001). Non-Hispanic Black participants had a higher proportion of home-based annual anal screening engagement (73.1%) compared to annual clinic screening engagement (31.6%) (p=0.01). Overall, annual screening engagement was significantly higher among participants who had heard of anal cancer from an LGBTQ organization, reported “some” prior anal cancer knowledge, preferred an insertive anal sex position, and reported a prior cancer diagnosis. Annual screening engagement was significantly lower for participants reporting a medical condition.

Conclusions

Annual screening engagement among those at disproportionate anal cancer risk was higher in the home arm.
Motor Control of Distinct Layer 6 Corticothalamic Feedback Circuits
Authors: Martinetti Luis E. , Autio Dawn M. , Crandall Shane R.
Published: April 2024

Layer 6 corticothalamic (L6 CT) neurons provide massive input to the thalamus, and these feedback connections enable the cortex to influence its own sensory input by modulating thalamic excitability. However, the functional role(s) feedback serves during sensory processing is unclear. One hypothesis is that CT feedback is under the control of extra-sensory signals originating from higher-order cortical areas, yet we know nothing about the mechanisms of such control. It is also unclear whether such regulation is specific to CT neurons with distinct thalamic connectivity. Using mice (either sex) combined within vitroelectrophysiology techniques, optogenetics, and retrograde labeling, we describe studies of vibrissal primary motor cortex (vM1) influences on different CT neurons in the vibrissal primary somatosensory cortex (vS1) with distinct intrathalamic axonal projections. We found that vM1 inputs are highly selective, evoking stronger postsynaptic responses in Dual ventral posterior medial nucleus (VPm) and posterior medial nucleus (POm) projecting CT neurons located in lower L6a than VPm-only projecting CT cells in upper L6a. A targeted analysis of the specific cells and synapses involved revealed that the greater responsiveness of Dual CT neurons was due to their distinctive intrinsic membrane properties and synaptic mechanisms. These data demonstrate that vS1 has at least two discrete L6 CT subcircuits distinguished by their thalamic projection patterns, intrinsic physiology, and functional connectivity with vM1. Our results also provide insights into how a distinct CT subcircuit may serve specialized roles specific to contextual modulation of tactile-related sensory signals in the somatosensory thalamus during active vibrissa movements.

SIGNIFICANCE STATEMENT

Layer 6 corticothalamic (L6 CT) feedback circuits are ubiquitous across mammalian species and modalities, and their activities have a strong influence on thalamic excitability and information throughput to the neocortex. Despite clear evidence of CT effects on the thalamus, we know relatively little about how CT cells themselves are regulated. Our results show that input from the primary motor cortex strongly excites a subclass of CT neurons in the primary somatosensory cortex that innervate both core and higher-order somatosensory nuclei rather than those exclusively targeting core somatosensory thalamus. The cortico-cortico-thalamic pathway formed by these connections establishes a circuit-level substrate for supporting CT influence operating under the guidance of ongoing motor activities.
Mapping the environmental co-benefits of reducing low-value care: a scoping review and bibliometric analysis
Authors: Parker Gillian , Hunter Sarah , Born Karen , Miller Fiona A.
Published: April 2024

Background

Reducing low-value care (LVC) and improving healthcare’s climate readiness are critical factors to improve the sustainability of health systems across the globe. Care practices that have been deemed low or no value, in effect, generate carbon emissions, waste and pollution without improving patient or population health. There is nascent, but growing, research and evaluation to inform practice change focused on the environmental co-benefits of reducing LVC. The objective of this study was to develop foundational knowledge of this field through a scoping review and bibliometric analysis.

Methods

We searched four databases, Medline, Embase, Scopus and CINAHL, each from inception to July 2023. We followed established scoping review and bibliometric analysis methodology to collect and analyze the data. Publication characteristics, healthcare and environmental sustainability focus (scoping review); authors, institutions, institution countries, and collaborations (bibliometric analysis) data were collected.

Findings

145 publications met inclusion criteria and were published between 2013 – July 2023; with over 80% published since 2020. Empirical studies represented 21% while commentary, editorials or opinions represented 51% of publications. The majority focused on healthcare generally (27%), followed by laboratory testing (14%), and medications (14%). Empirical publications covered a broad range of environmental issues with general and practice-specific ‘Greenhouse gas (GHG) emissions’, ‘waste management’ and ‘resource use’ as most common topics. Reducing practice-specific ‘GHG emissions’ was the most common reported environmental outcome. The bibliometric analysis revealed numerous international collaboration networks of prolific authors producing work across healthcare practices and settings, studying numerous environmental sustainability issues.

Conclusions

This study reveals that research and evaluation to inform practice change on the environmental co-benefits of reducing LVC is growing internationally, across multiple healthcare and environmental areas. Results demonstrate a need and opportunity for the emerging community to clarify approaches and strengthen the evidence-base through further empirical work in the field.
Combinatorial optimization using the Lagrange primal-dual dynamics of parametric oscillator networks
Authors: Vadlamani Sri Krishna , Xiao Tianyao Patrick , Yablonovitch Eli
Published: April 2024

Coupled-bistable-oscillator machines have recently generated significant interest due to their observed ability to rapidly produce high-quality solutions to nondeterministic-polynomial-time-complete optimization problems. While the dynamics of such systems are often derived in the literature, it has hitherto been unclear why exactly the system dynamics perform optimization so well. This paper answers this question by presenting a complete equivalence between coupled-oscillator machines and the primal-dual method of Lagrange multipliers. This equivalence explains how coupled-oscillator solvers implement the correct optimization constraints and find high-quality solutions. The equivalence also provides precise mathematical meaning to each system component and enables the principled design of systems that implement more-sophisticated optimization algorithms. We simulate the system dynamics and demonstrate (1) that its performance is competitive with performance of the best-known digital algorithms, (2) that the circuit is robust with regard to large component variations, hinting that the traditional shortcomings of analog computation may be less important for these applications, and (3) that the circuit consumes extremely low amounts of power (on the order of milliwatts) and energy (approximately 100 nJ) per optimization even for problems of 2000 variables.

Published by the American Physical Society
2024
Magnetic property changes of NdGa upon hydrogen absorption
Authors: Cedervall Johan , Shtender Vitalii , Manuel Pascal , Pomjakushin Vladimir , Mathieu Roland , Häussermann Ulrich , Andersson Mikael S.
Published: April 2024

Rare earth monogallide (REGa) Zintl phases are attractive for their properties in hydrogen storage and magnetic cooling. However, the magnetic effects upon hydrogen additions in REGa are not well understood. This study aims to explore the magnetic effects in REGaHx using SQUID magnetometry and neutron powder diffraction. To avoid challenges due to absorption and high incoherent scattering in the neutron diffraction experiments, the compound NdGaDx (x = 0, 0.9, or 1.6) was chosen for examination. It was found that NdGa exhibits two ferromagnetic structures below the Curie temperature of 42 K. Just below 42 K the magnetic moments are oriented along the crystallographic c axis, and at 20 K a spin reorientation occurs where the moments turn ∼30∘ toward the a axis. Upon partial deuteration (x = 0.9), the magnetization decreases and two magnetic phases are observed, one intermediate incommensurate phase, and one canted ferromagnetic phase with the net magnetization aligning along the b axis. For the full deuteride (x = 1.6) only one incommensurate magnetic phase is observed at low temperatures. Magnetometry also reveals that there are no isotope effects when absorbing H or D. The absorption of H or D changes the Nd-Nd distances as well as the electronic structure, which results in a drastic change in the magnetic properties as compared to NdGa.

Published by the American Physical Society
2024
Scalable Entanglement Certification via Quantum Communication
Authors: Bakhshinezhad Pharnam , Mehboudi Mohammad , Carceller Carles Roch i , Tavakoli Armin
Published: April 2024

Harnessing the advantages of shared entanglement for sending quantum messages often requires the implementation of complex two-particle entangled measurements. We investigate entanglement advantages in protocols that use only the simplest two-particle measurements, namely, product measurements. For experiments in which only the dimension of the message is known, we show that robust entanglement advantages are possible but that they are fundamentally limited by Einstein-Podolsky-Rosen steering. Subsequently, we propose a natural extension of the standard scenario for these experiments and show that it circumvents this limitation. This leads us to prove entanglement advantages from every entangled two-qubit Werner state, evidence its generalization to high-dimensional systems, and establish a connection to quantum teleportation. Our results reveal the power of product measurements for generating quantum correlations in entanglement-assisted communication and they pave the way for practical semi-device-independent entanglement certification well beyond the constraints of Einstein-Podolsky-Rosen steering.

Published by the American Physical Society
2024
Wavefront analysis and phase correctors design using SHADOW
Authors: Khosroabadi Hossein , Laundy David , Dhamgaye Vishal , Sawhney Kawal
Published: April 2024

Knife-edge imaging is a successful method for determining the wavefront distortion of focusing optics such as Kirkpatrick–Baez mirrors or compound refractive lenses. In this study, the wavefront error of an imperfect elliptical mirror is predicted by developing a knife-edge program using the SHADOW/OASYS platform. It is shown that the focusing optics can be aligned perfectly by minimizing the parabolic and cubic coefficients of the wavefront error. The residual wavefront error provides precise information about the figure/height errors of the focusing optics suggesting it as an accurate method for in situ optical metrology. A Python program is developed to design a customized wavefront refractive corrector to minimize the residual wavefront error. Uniform beam at and out of focus and higher peak intensity are achieved by the wavefront correction in comparison with ideal focusing. The developed code provides a quick way for wavefront error analysis and corrector design for non-ideal optics especially for the new-generation diffraction-limited sources, and saves considerable experimental time and effort.
Inflation Targeting in South Africa
Authors: Warnock Frank , Wheat James C. , Drake Justin , Debrah Mitch , Hungwe Archie
Published: April 2024

South Africa had formally introduced a policy of inflation targeting (IT) in February 2000. By December 2001, the governor of the South African Reserve Bank, after reading the latest statistics, was concerned with the disappointing economic data. Economic activity had slowed drastically, to the point that the country appeared to be heading for a recession. The gloomy statistics forced the governor to consider whether the country had pursued the right policy. Persistently high unemployment, one legacy of the apartheid era, meant that South Africa did not have the luxury of waiting for new policies to bear fruit. With the inflation forecast to exceed the mandated target, the governor would have to tighten monetary policy, which would further restrict investment. Was it is time for South Africa to change course?
Bitcoin: Investment or Illusion?
Authors: Allayannis George (Yiorgos) , Jones Paul Tudor , Fernstrom Aaron
Published: April 2024

The case describes a hypothetical hedge fund manager who is examining whether to invest in bitcoin. The case discusses potential risks and rewards of investing in bitcoin, the role of bitcoin and digital currencies more broadly, and financial innovation in the space, such as ICOs. It can be taught as part of a second-year MBA elective course in investments, financial institutions/capital markets, or fintech.
Higher technology education and industry interface: how the theory of planned behavior applies in student work-integrated learning and job search intention link
Authors: Chukwuedo Samson Onyeluka , Okorafor Anthony Osinachi , Odogwu Ikechukwu Chidiebere , Nnajiofor Francisca Nebechi
Published: April 2024

Purpose

Within the umbrella of technology and vocational education (TVET), technology or technical education in higher institutions of learning is obligated to produce the required manpower needed in the industry. Thus, it is pertinent to explore the interaction between the industry and higher education students. Drawing on the tenets of theory of planned behavior (TPB), this study offers valuable insights into the nomological networks of work-integrated learning (WIL), perceived behavioral control (PBC), subjective norm (SBN), personal attitude (PAT) and job search intention (JSI).

Design/methodology/approach

The study applied a structurally hypothesized model that was drawn from the TPB to collect data for the constructs. Using a cross-sectional survey after the WIL experiences of the students, we collected data from technology education undergraduates (N = 214) in their final academic year from universities in Nigeria.

Findings

With structural equation modeling, the study found that WIL is directly associated with JSI, PBC, SBN and PAT. In line with the tenets of the TPB, simple mediation models were supported about the influence of WIL on JSI via PBC and PAT discretely but not via SBN. Further, the results support two paths of serial mediation models, indicating sequential indirect links between WIL and JSI via SBN and PBC, as well as via SBN and PAT.

Research limitations/implications

Our findings have implications for higher education practitioners, industry experts and employers of labor.

Originality/value

Although extant literature has relatively shown that WIL impacts employability skills, this study has remarkably shown the WIL-JSI nexuses within the variables of TPB.
Enhancing wearability: designing wearable suit platforms for industrial workers
Authors: Chung Jiwon , Won Hyunbin , Lee Hannah , Park Soah , Ahn Hyewon , Pyeon Suhyun , Yoon Jeong Eun , Koo Sumin
Published: April 2024

Purpose

The objective of this study was to develop wearable suit platforms with various anchoring structure designs with the intention of improving wearability and enhancing user satisfaction.

Design/methodology/approach

This study selected fabrics and materials for the suit platform through material performance tests. Two anchoring structure designs, 11-type and X-type are compared with regular clothing under control conditions. To evaluate the comfort level of the wearable suit platform, a satisfaction survey and electroencephalogram (EEG) measurements are conducted to triangulate the findings.

Findings

The 11-type exhibited higher values in comfort indicators such as α, θ, α/High-β and lower values in concentration or stress indicators such as β, ϒ, sensorimotor rhythm (SMR)+Mid-β/θ, and a spectral edge frequency of 95% compared to the X-type while walking. The 11-type offers greater comfort and satisfaction compared to the X-type when lifting based on the EEG measurements and the participants survey.

Originality/value

It is recommended to implement the 11-type when designing wearable suit platforms. These findings offer essential data on wearability, which can guide the development of soft wearable robots.
Advantages and disadvantages of video conferencing and direct interaction: a conceptual framework for evaluating hybrid work models
Authors: Thejls Ziegler Marianne , Lütge Christoph
Published: April 2024

Purpose

This study aims to analyse the differences between professional interaction mediated by video conferencing and direct professional interaction. The research identifies diverging interests of office workers for the purpose of addressing work ethical and business ethical issues of professional collaboration, competition, and power in future hybrid work models.

Design/methodology/approach

Based on 28 qualitative interviews conducted between November 2020 and June 2021, and through the theoretical lens of phenomenology, the study develops explanatory hypotheses conceptualising four basic intentions of professional interaction and their corresponding preferences for video conferences and working on site.

Findings

The four intentions developed on the basis of the interviews are: the need for physical proximity; the challenge of collective creativity; the will to influence; and control of communication. This conceptual framework qualifies a moral ambivalence of professional interaction. The authors identify a connectivity paradox of professional interaction where the personal dimension remains unarticulated for the purpose of maintaining professionality. This tacit human connectivity is intertwined with latent power relations. This plasticity of both connectivity and power in direct interaction can be diminished by transferring the interaction to video conferencing.

Originality/value

The application of phenomenology to a collection of qualitative interviews has enabled the identification of underlying intention structures and the system in which they affect each other. This research identifies conflicts of interests between workers relative to their different self-perceived abilities to persevere in competitive professional interaction. It is therefore able to address consequences of future hybrid work models at an existential and societal level.