bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysfunctional CD11c
−
CD21
−
extrafollicular memory B cells are enriched in the periphery and tumors of patients with cancer
Authors: Ruffin Ayana T. , Casey Allison N. , Kunning Sheryl R. , MacFawn Ian P. , Liu Zhentao , Arora Charu , Rohatgi Anjali , Kemp Felicia , Lampenfeld Caleb , Somasundaram Ashwin , Rappocciolo Giovanna , Kirkwood John M. , Duvvuri Umamaheswar , Seethala Raja , Bao Riyue , Huang Yufei , Cillo Anthony R. , Ferris Robert L. , Bruno Tullia C.
Published: February 2025

Many patients with recurrent and metastatic cancer fail to produce a durable response to immunotherapy, highlighting the need for additional therapeutic targets to improve the immune landscape in tumors. Recent studies have highlighted the importance of B cells in the antitumor response, with memory B cells (MBCs) being prognostic in a variety of solid tumors. MBCs are a heterogenous B cell subset and can be generated through both germinal center reactions and extrafollicular (EF) responses. EF-derived MBCs have been recently linked to poor prognosis and treatment resistance in solid tumors and thus may represent candidate biomarkers or immunotherapy targets. EF-derived MBCs, termed “double-negative” (DN) MBCs may be further classified on the basis of surface expression of CD11c and CD21 into DN1, DN2, and DN3 MBCs. CD11c
−
CD21
+
DN1 MBCs and CD11c
+
CD21
−
DN2 MBCs have been well studied across inflammatory diseases; however, the biology and clinical relevance of CD11c
−
CD21
−
DN3 MBCs remain unknown. Here, we report an accumulation of DN3 MBCs in the blood and tumors of patients with head and neck squamous cell carcinoma (HNSCC) and an increase in DN3 MBCs in locally advanced HNSCC tumors. Circulating and intratumoral DN3 MBCs were hyporesponsive to antigen stimulation, had low antibody production, and failed to differentiate into antibody-secreting cells. Moreover, DN3 MBCs accumulated selectively outside of tertiary lymphoid structures. Last, circulating DN3 MBCs correlated with poor therapeutic response, advanced disease, and worse outcomes in patients with HNSCC and melanoma, supporting further assessment of EF-derived MBCs as potential biomarkers and therapeutic targets.
β cell dedifferentiation, the underlying mechanism of diabetes in Wolfram syndrome
Authors: Amo-Shiinoki Kikuko , Tanabe Katsuya , Nishimura Wataru , Hatanaka Masayuki , Kondo Manabu , Kagawa Syota , Zou Meng , Morikawa Shuntaro , Sato Yoshihiko , Komatsu Mitsuhisa , Mizukami Hiroki , Nishida Naoki , Asahara Shun-Ichiro , Masutani Hiroshi , Tanizawa Yukio
Published: February 2025

Insulin-dependent diabetes in patients with Wolfram syndrome (WS; OMIM 222300) has been linked to endoplasmic reticulum (ER) stress caused by
WFS1
gene mutations. However, the pathological process of ER stress–associated β cell failure remains to be fully elucidated. Our results indicate loss of β cell lineage and subsequent dedifferentiation as the mechanisms underlying functional and mass deficits in WS. An immunohistochemical analysis of human pancreatic sections from deceased individuals with WS revealed a near-complete loss of β cells and subsequent decrease in α cells, suggesting loss of endocrine function.
Wfs1
-deficient mice displayed dysfunction, gradual loss, and dedifferentiation of β cells, leading to permanent hyperglycemia. Impairment of the β cell lineage was observed after weaning, leading to the mixed phenotype of insulin- and glucagon-producing cells in a subset of the lineage-traced β cells. Islets of
Wfs1
-deficient mice increased the number of dedifferentiated cells that maintained general endocrine features but were no longer reactive with antisera against pancreatic hormones. Mechanistically,
Wfs1
-null islets had a lower adenosine triphosphate content and impaired oxidative glycolysis, although mitochondrial oxidative function was maintained. The functional and metabolic alterations of WS β cells were recovered by deletion of thioredoxin-interacting protein (Txnip), an ER stress–induced protein up-regulated in
Wfs1
deficiency.
Txnip
deletion preserved functional β cells and prevented diabetes progression in
Wfs1
-deficient mice. Together, this study deciphered pathological mechanisms of β cell dedifferentiation in β cell failure and has implications for Txnip inhibition in WS therapy.
Antibodies targeting Crimean-Congo hemorrhagic fever virus GP38 limit vascular leak and viral spread
Authors: Pahmeier Felix , Monticelli Stephanie R. , Feng Xinyi , Hjorth Christy K. , Wang Albert , Kuehne Ana I. , Bakken Russell R. , Batchelor Thomas G. , Lee Saeyoung E. , Middlecamp Marissa , Stuart Lauren , Duarte-Neto Amaro N. , Abelson Dafna M. , McLellan Jason S. , Biering Scott B. , Herbert Andrew S. , Chandran Kartik , Harris Eva
Published: February 2025

Crimean-Congo hemorrhagic fever virus (CCHFV) is a priority pathogen transmitted by tick bites, with no vaccines or specific therapeutics approved to date. Severe disease manifestations include hemorrhage, endothelial dysfunction, and multiorgan failure. Infected cells release the viral glycoprotein GP38, whose extracellular function is presently unknown. GP38 is considered an important target for vaccine and therapeutic design because GP38-specific antibodies can protect against severe disease in animal models, albeit through an unknown mechanism of action. Here, we showed that GP38 induces endothelial barrier dysfunction in vitro by disrupting the endothelial glycocalyx layer and triggering hyperpermeability. We also demonstrated that GP38 alone can cause vascular leak in a mouse model. We found that CCHFV infection leads to vascular leak in vivo, which was exacerbated by exogenous administration of GP38, facilitating dissemination of CCHFV into target tissues such as the liver. Protective antibodies that recognized specific antigenic sites on GP38, but not a protective neutralizing antibody binding the structural protein Gc, potently inhibited endothelial hyperpermeability in vitro and vascular leak in vivo during CCHFV infection. This work uncovers a function of the circulating viral protein GP38 as a viral toxin in CCHFV pathogenesis and elucidates a potential mode of action of nonneutralizing yet protective GP38-specific antibodies.
Inhibiting mechanotransduction prevents scarring and yields regeneration in a large animal model
Authors: Mascharak Shamik , Griffin Michelle , Talbott Heather E. , Guo Jason L. , Parker Jennifer , Morgan Annah Grace , Valencia Caleb , Kuhnert Maxwell Michael , Li Dayan J. , Liang Norah E. , Kratofil Rachel M. , Daccache Joseph A. , Sidhu Ikjot , Davitt Michael F. , Guardino Nicholas , Lu John M. , Abbas Darren B. , Deleon Nestor M. D. , Lavin Christopher V. , Adem Sandeep , Khan Anum , Chen Kellen , Henn Dominic , Spielman Amanda , Cotterell Asha , Akras Deena , Downer Mauricio , Tevlin Ruth , Lorenz H. Peter , Gurtner Geoffrey C. , Januszyk Michael , Naik Shruti , Wan Derrick C. , Longaker Michael T.
Published: February 2025

Modulating mechanotransduction by inhibiting yes-associated protein (YAP) in mice yields wound regeneration without scarring. However, rodents are loose-skinned and fail to recapitulate key aspects of human wound repair. We sought to elucidate the effects of YAP inhibition in red Duroc pig wounds, the most human-like model of scarring. We show that one-time treatment with verteporfin, a YAP inhibitor, immediately after wounding is sufficient to prevent scarring and to drive wound regeneration in pigs. By performing single-cell RNA sequencing (scRNA-seq) on porcine wounds in conjunction with spatial proteomic analysis, we found perturbations in fibroblast dynamics with verteporfin treatment and the presence of putative pro-regenerative/profibrotic fibroblasts enriched in regenerating/scarring pig wounds, respectively. We also identified differences in enriched myeloid cell subpopulations after treatment and linked this observation to increased elaboration of interleukin-33 (IL-33) in regenerating wounds. Finally, we validated our findings in a xenograft wound model containing human neonatal foreskin engrafted onto nude mice and used scRNA-seq of human wound cells to draw parallels with fibroblast subpopulation dynamics in porcine wounds. Collectively, our findings provide support for the clinical translation of local mechanotransduction inhibitors to prevent human skin scarring, and they clarify a YAP/IL-33 signaling axis in large animal wound regeneration.
Necrosis drives susceptibility to
Mycobacterium tuberculosis
in Polg
D257A
mutator mice
Authors: Mabry C. J. , Weindel C. G. , Stranahan L. W. , VanPortfliet J. J. , Davis J. R. , Martinez E. L. , West A. P. , Patrick K. L. , Watson R. O.
Published: February 2025

The genetic and molecular determinants that underlie the heterogeneity of
Mycobacterium tuberculosis
(Mtb) infection outcomes in humans are poorly understood. Multiple lines of evidence demonstrate that mitochondrial dysfunction can exacerbate mycobacterial disease severity, and mutations in some mitochondrial genes confer susceptibility to mycobacterial infection in humans. Here, we report that mutations in mitochondria DNA (mtDNA) polymerase gamma potentiate susceptibility to Mtb infection in mice. Polg
D257A
mutator mtDNA mice fail to mount a protective innate immune response at an early infection time point, evidenced by high bacterial burdens, reduced M1 macrophages, and excessive neutrophil infiltration in the lungs. Immunohistochemistry reveals signs of enhanced necrosis in the lungs of Mtb-infected Polg
D257A
mice, and Polg
D257A
mutator macrophages are hypersusceptible to extrinsic triggers of necroptosis
ex vivo
. By assigning a role for mtDNA mutations in driving necrosis during Mtb infection, this work further highlights the requirement for mitochondrial homeostasis in mounting balanced immune responses to Mtb.
Immunostimulatory effects of
Streptococcus sanguinis
extracellular membrane vesicles protect oral gingival epithelial cells from periodontal pathobiont damage
Authors: Helliwell Emily , Rauch Isabella , Nice Tim , Merritt Justin , Kreth Jens
Published: February 2025

The commensal
Streptococcus sanguinis
is highly prevalent in the oral cavity and characterized for its ability to inhibit growth of oral pathogens. Like many other cell types, streptococci produce extracellular membrane vesicles (EMVs), which contain specific molecular cargo and facilitate interactions with host cells. We previously demonstrated that EMVs from
S. sanguinis
are internalized by gingival epithelial cells (GECs) without causing cell death. Our aim is to characterize the effects of vesicles on eukaryotic cells. Microscopy studies of gingival epithelial cells inoculated with EMVs from wild-type and specific deletion mutants show differential uptake, with decreased uptake of ΔSSA1099 EMVs and increased uptake of ΔSSA1882 EMVs relative to SK36 EMVs. However, EMVs from wild-type and deletion mutants showed similar patterns in cytokine and chemokine secretion. Transcriptomic analysis of gingival epithelial cells inoculated with SK36 EMVs showed a downregulation of genes implicated in apoptosis as well as interferon signaling, while showing an upregulation of genes involved in cytokine production. Gelatin zymography results show that SK36 EMVs have a contrasting result on production of MMP2/9; MMP2 production is decreased while MMP9 is increased by 48 hours post-inoculation (hpi). Dual-inoculation studies demonstrate that prior internalization of
S. sanguinis
EMVs protects gingival epithelial cells from exposure to pathobiont
Porphyromonas gingivalis
outer membrane vesicles (OMVs), preventing dissociation and cell death. Our overall findings suggest that
S. sanguinis
EMVs trigger an immune response on gingival epithelial cells; however, this response suggests inhibition of some immune signaling pathways. Our results highlight an important role in commensalism, in which a microbe induces an immune response but avoids damage to host cells, thus discouraging infection by pathobionts.
HSP90 interacts with VP37 to facilitate the cell-to-cell movement of broad bean wilt virus 2
Authors: Kim Myung-Hwi , Jang Seok-Yeong , Choi Ji-Soo , Kim Sora , Lee Yubin , Park Suejin , Kwon Sun-Jung , Seo Jang-Kyun
Published: February 2025

The systemic spread of viruses in plants requires successful viral cell-to-cell movement through plasmodesmata (PD). Viral movement proteins (MPs) interact with cellular proteins to modify and utilize host transport routes. Broad bean wilt virus 2 (BBWV2) moves from cell to cell as a virion through the PD gated by VP37, the MP of BBWV2. However, the host proteins that function in the cell-to-cell movement of BBWV2 remain unclear. In this study, we identified cellular heat shock protein 90 (HSP90) as an interacting partner of VP37. The interaction between HSP90 and VP37 was assessed using the yeast two-hybrid assay, co-immunoprecipitation, and bimolecular fluorescence complementation. Tobacco rattle virus-based virus-induced gene silencing analysis revealed that
HSP90
silencing significantly inhibited the systemic spread of BBWV2 in
Nicotiana benthamiana
plants. Furthermore,
in planta
treatment with geldanamycin (GDA), an inhibitor of the chaperone function of HSP90, demonstrated the necessity of HSP90 in successful cell-to-cell movement and systemic infection of BBWV2. Interestingly, GDA treatment inhibited the HSP90-VP37 interaction at the PD, resulting in the inhibition of VP37-derived tubule formation through the PD. Our results suggest that the HSP90-VP37 interaction regulates VP37-derived tubule formation through the PD, thereby facilitating the cell-to-cell movement of BBWV2.

IMPORTANCE

This study highlights the regulatory role of heat shock protein 90 (HSP90) in facilitating the cell-to-cell movement of broad bean wilt virus 2 (BBWV2). HSP90 interacted with VP37, the movement protein of BBWV2, specifically at plasmodesmata (PD). This study demonstrated that the HSP90-VP37 interaction is crucial for viral cell-to-cell movement and the formation of VP37-derived tubules, which are essential structures for virus transport through the PD. The ATP-dependent chaperone activity of HSP90 is integral to this interaction, as demonstrated by the inhibition of virus movement upon treatment with geldanamycin, which disrupts the function of HSP90. These findings elucidate the molecular mechanisms underlying the cell-to-cell movement of plant viruses and highlight the role of HSP90 in viral infection. This study suggests that the chaperone activity of HSP90 may function in changing the conformational structure of VP37, thereby facilitating the assembly and function of virus-induced structures required for viral cell-to-cell movement.
Investigating the influence of
Diadematidae
scuticociliatosis on host microbiome composition
Authors: Vilanova-Cuevas Brayan , DeRito Christopher M. , Ritchie Isabella T. , Kellogg Christina A. , Evans James S. , Zimmerman Alizee , Williams Stacey M. , Brandt Marilyn , Sevier Moriah , Gittens Samuel , Budd Kayla A. , Warham Matthew , Sharp William C. , Delgado Gabriel A. , Hylkema Alwin , Kitson-Walters Kimani , Quod Jean-Pascal , Breitbart Mya , Hewson Ian
Published: February 2025

Mass mortality of Diadematidae urchins, caused by the
Diadema antillarum
scuticociliatosis Philaster clade (DScPc)
,
affected the Caribbean in spring 2022 and subsequently spread to the eastern Mediterranean, Red Sea, and western Indian Ocean. A key question around Diadematidae scuticociliatosis (DSc), the disease caused by the scuticociliate, is whether the urchin microbiome varies between scuticociliatosis-affected and grossly normal urchins. Tissue samples from both grossly normal and abnormal
Diadema antillarum
were collected in the field during the initial assessment of the DSc causative agent and from an experimental challenge of DScPc culture on aquacultured
D. antillarum
. Specimens were analyzed using 16S rRNA gene amplicon sequencing. Additional abnormal urchin samples were collected from the most recent outbreak site in the western Indian Ocean (Réunion Island). At reference (i.e., unaffected by DSc) sites,
Kistimonas
spp.
, Propionigenium
spp., and
Endozoicomonas
spp. were highly represented in amplicon libraries. DSc-affected urchin amplicon libraries had lower taxonomic richness and a greater representation of taxa related to
Fangia hongkongensis
and
Psychrobium
spp. Amplicon libraries of urchins experimentally challenged with the DSc pathogen had some shifts in microbial composition, but
F. hongkongensis
was not a part of the core bacteria in DSc-challenged specimens. DSc-affected
Echinothrix diadema
from Réunion Island showed a similar high representation of
F. hongkongensis
as that seen on Caribbean
D. antillarum
. Our results suggest that DSc alters
Diadematidae
microbiomes and that
F. hongkongensis
may be a candidate bacterial biomarker for DSc in environmental samples. The mechanism driving microbiome variation in host–pathogen interactions remains to be explored.

IMPORTANCE

The mass mortality of Diadematidae urchins due to
Diadema antillarum
scuticociliatosis (DSc) has had significant ecological impacts, spreading from the Caribbean to the eastern Mediterranean, Red Sea, and western Indian Ocean. This study investigates whether the microbiome of urchins varies between those affected by DSc and those that are not. Using 16S rRNA gene amplicon sequencing, researchers found that DSc-affected urchins had lower taxonomic richness and a greater representation of
Fangia hongkongensis
and
Psychrobium
spp. The findings indicate that
F. hongkongensis
could serve as a bacterial biomarker for DSc in environmental samples, providing a potential tool for early detection and management of the disease. Understanding these microbiome changes is crucial for developing strategies to mitigate the spread and impact of DSc on marine ecosystems.
Lipid alterations in acute myocardial infarction are associated with gut microbiota
Authors: Zuo Jiebin , Wang Panpan , Xue Kewen , Tan Yuwen , Zhang Ting , Li Yang , He Feixiang , Wu Weikun , Yan Zhixiang , Cong Li , Li Gang
Published: February 2025

Although lipid metabolism and gut microbiota dysregulation are known to participate in cardiovascular disease, few studies have examined these alterations and associations in acute myocardial infarction (AMI) patients. This study reveals altered and associated lipid metabolism and gut microbiome based on proteomic and lipidomic analyses of fecal and plasma samples from 30 patients with AMI and 33 healthy volunteers. Twenty-three differential plasma lipids, nine altered fecal lipids, and nine differential fecal bacterial species were identified in AMI patients relative to healthy volunteers, with nine plasma lipids, three fecal lipids, and two fecal bacteria as potential biomarkers. Correlation analysis revealed that the abundances of
Stenotrophomonas
and
Bilophila
were positively correlated with sphingosine and ceramide levels, respectively.
Alistipes indistinctus
and
Porphyromonas
were correlated with blood lipid indicators (total cholesterol, triglycerides, and low-density lipoprotein-C), and
A. indistinctus
,
Bilophila
, and
Stenotrophomonas
were associated with myocardial injury indicators (cTnI, CK, CK-MB, LDH, and BNP). This study identified potential lipid and gut microbe biomarkers and their associations in AMI patients.

IMPORTANCE

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. While lipid metabolism and gut microbiota are known to play important roles in cardiovascular diseases, their interactions in the context of AMI are not fully understood. In this study, we explore the lipidomic and microbiome alterations in AMI patients, identifying key biomarkers associated with myocardial injury. By correlating specific lipid changes with bacterial species in fecal samples, we highlight the potential of lipid–microbe interactions in the pathogenesis of AMI. These findings provide novel insights into the complex mechanisms underlying AMI and suggest potential targets for early diagnosis and therapeutic interventions aimed at modulating lipid and microbial profiles to improve patient outcomes.
New insights into the testicular tropism of porcine reproductive and respiratory syndrome virus
Authors: Durazo-Martínez Kassandra , Osorio Fernando A. , Delhon Gustavo , Hernández Jesús , Vu Hiep L. X.
Published: February 2025

Porcine reproductive and respiratory syndrome virus (PRRSV) has a restricted host specificity, primarily infecting porcine macrophages. Notably, an exception to such macrophage-restricted tropism has been observed in sexually active boars, where the virus infects and induces apoptosis in the germinal epithelium, resulting in viral dissemination in the ejaculate. Whether this phenomenon occurs in prepubertal animals remains unclear. In this study, we isolated spermatogonia stem cells (SSCs) from neonatal pigs and cultured them
in vitro
. These SSC cultures formed morula-like colonies, exhibited alkaline phosphatase activity—a characteristic of stem cells—and expressed protein gene product 9.5, a marker of SSCs. Notably, the SSC cultures supported PRRSV replication with kinetics similar to that observed in porcine alveolar macrophages. To assess the testicular tropism of PRRSV in prepuberal animals, 28-day-old male pigs were infected with a virulent PRRSV strain. Testicular tissues were sequentially analyzed using a combination of
in situ
hybridization for PRRSV RNA and immunohistochemistry for specific cellular markers. Unlike in sexually active boars, PRRSV did not infect the spermatogonia cells within the seminiferous tubules of prepubertal pigs. Instead, the virus primarily infected macrophages and myoid cells located in the interstitium and peritubular areas. It appeared that the anatomical separation of spermatogonia from the basal membrane of the seminiferous tubules in prepubertal pigs prevents these cells from being infected by PRRSV. Overall, our findings offer valuable insights into the age-dependent testicular tropism of PRRSV.

IMPORTANCE

Contaminated boar semen used in artificial insemination has significantly contributed to the global spread of porcine reproductive and respiratory syndrome virus (PRRSV), a virus that typically infects only cells within the monocyte and macrophage lineages. Our study reveals that spermatogonia stem cells (SSCs) from neonatal piglets are also susceptible to PRRSV, suggesting that non-macrophage cells can be infected by the virus. However, despite this susceptibility, PRRSV-infected cells were not found in the seminiferous tubules of prepubertal male pigs inoculated with a virulent PRRSV strain. This contrasts with sexually mature boars, where PRRSV-infected cells were prominently observed within the seminiferous tubules. The discrepancy is likely due to anatomical differences between the seminiferous tubules of sexually mature boars and prepubertal pigs. These findings provide new insights into PRRSV pathogenesis. Additionally, the
ex vivo
SSC culture provides a valuable model for identifying new viral receptors necessary for PRRSV infection and for investigating the virus’s impact on spermatogenesis.
Development of Australian mental health guidelines for community sport
Authors: Vella Stewart Anthony , Liddelow Caitlin , Rice Simon M , Keegan Richard , Hall Kate , Jones Mark A , Lubans David Revalds , McLeod Samantha , Okely Anthony David , Olive Lisa S , Purcell Rosemary , Reece Lindsey J , Rosenbaum Simon , Schweickle Matthew J , Singh Kelsey , Stewart Damien , Stimpson Leisl , Sutcliffe Jordan T , Teychenne Megan , Walton Courtney C , Swann Christian
Published: February 2025

Objective

The need for clear and actionable guidelines for the promotion and protection of mental health in organised community sport has previously been identified. This study aimed to provide guidelines to promote and protect mental health in organised community sport in Australia.

Methods

Guideline development was informed by (1) systematic reviews of the evidence pertaining to existing mental health guidelines in sport and mental health interventions in community sport; (2) an expert Delphi consensus study and (3) key stakeholder input via focus groups. A Guideline Development Committee comprising experts and key stakeholder representatives articulated nine distinct guidelines.

Results

These guidelines address the areas of: mental health literacy training; mental health support pathways and processes; responding to mental health emergencies; responding to major events that may impact mental health; having a mental health plan in place; reducing stigmatising attitudes; appointing a dedicated mental health champion; coach education and promoting well-being within the organisation.

Conclusions

We provide guidance for promoting and protecting mental health in community sport. Monitoring uptake and measuring the effectiveness of the guidelines are important areas of future work to advance positive mental health for everybody involved in community sport.
Perineuromal hydrodissection for acute postamputation pain? An observational study in a time of war
Authors: Dmytriiev Dmytro , Liu Winnie , Barsa Maksym , Khomenko Andreii , Strokan Andreii , Pasquina Paul F , Cohen Steven P
Published: February 2025

Introduction

This exploratory study investigates the potential of perineuromal hydrodissection as an adjunct to opioid therapy for postamputation pain, specifically focusing on residual limb and phantom limb pain (PLP). Given the correlations between acute pain and the development of chronic pain, the primary aims were to estimate the effect size of early hydrodissection of scar tissue around residual limb neuroma(s) and to identify the best time frame for treatment.

Methods

Seventy-four patients with war-related limb amputations and painful neuromas were included in this observational analysis. Thirty-eight Ukrainian patients with war-related limb amputation and a painful neuroma(s) who underwent hydrodissection and opioid therapy within 6 months of amputation were compared with 36 patients who received opioids alone. Co-primary outcome measures were median reduction from baseline in average residual limb and PLP at 12 weeks. The composite positive outcome was designated as a ≥2-point decrease or 30% reduction in average residual limb and PLP, satisfaction with treatment, and not requiring an increase in analgesics.

Results

Hydrodissection as an add-on to opioids resulted in a greater reduction in average residual limb pain at 12 weeks (−2.00±1.00 vs −1.00±1.00; p<0.001) and earlier time periods, but PLP only through 4 weeks. At 12 weeks, Hospital Anxiety and Depression Scale anxiety (10.00±2.00 vs 11.00±1.00; p<0.001) but not depression score was lower in the hydrodissection group. Opioid use in the hydrodissection group significantly declined from 41.32±9.63 to 33.42±8.78 morphine equivalents per day (p=0.001) over the study, but not in the opioid-only group (p=0.20). Differences in 12-week satisfaction rates were not significant.

Conclusions

This exploratory study suggests perineuromal hydrodissection may improve residual limb pain and to a lesser degree phantom limb pain, particularly when implemented early in the course of postamputation pain. The study provides preliminary effect size estimates and identifies acute pain as a potential characteristic of patients who may respond more favorably to this intervention. Randomized controlled trials are needed to confirm these findings and control for the confounding variables identified.
Estimating Tangential Heave Stress on Solar Piles in the Northern United States
Authors: Emami Ahari Hossein , Ajmera Beena , Pant Rohit , Huang Chang , Liu Yuqing
Published: February 2025

Construction of solar panel piles in the Northern US is challenging due to soil freezing in winter. Freezing causes volumetric expansion and movement of soil along the pile applying a tangential heave stress (THS) that jacks up the pile. Relying on averaged values of the THS in building codes based on state/county conditions can lead to inaccurate THS estimates at specific project sites. In this study, the THS and adfreeze shear strength (AFSS) of soil samples collected from Indiana were measured using a temperature-controlled direct shear device at different temperatures and normal stresses. AFSS refers to the strength of the initial bond between the frozen soil and a foundation, while the THS is the residual upward force that remains after this bond breaks. This distinction is vital as the use of the THS can result in more economical and realistic foundations. A decrease in temperature led to an increase in the AFSS due to the amount of unfrozen water available at the interface. The obtained THSs were lower than those recommended by codes. In addition, it was found that the AFSS stems from the bonding of the ice to steel, while the THS results from friction. AFSS was not significantly influenced by the normal stress, while the THS increased with an increase in the normal stress.
A Novel Analog Electronic Circuit for Versatile Fractional Exponentiation
Authors: Cen Xiaoliang , Li Chunbiao , Liu Wangyu , Yang Yong , Minati Ludovico
Published: February 2025

The presence of nonlinear feedback is an effective method for generating chaos in dynamical systems. Although physics provides a plethora of nonlinear relationships that can be exploited for this purpose, engineering chaotic electronic circuits with prescribed nonlinear terms remain a formidable challenge. In particular, the implementation of fractional exponentiation represents a particularly challenging task. In this paper, we present a solution to this problem in the form of a new circuit topology, which we have designated as the “444 circuit”, comprising only four transistors, four operational amplifiers, and four resistor pairs. In addition to multiplication and division, this circuit can perform complex algebraic operations, including the calculation of fractional powers. After introducing its operating principles and some conceptual aspects of its implementation, we demonstrate the performance of this unifying circuit structure by realizing a family of Lorenz-like systems.
A Class of Two-Dimensional Offset-Boostable Chaotic Systems with Transcendental Functions
Authors: Huang Heqing , Li Chunbiao , Cen Xiaoliang , Gao Yikai , Liu Wangyu
Published: February 2025

Chaos regulation, including polarity control and offset boosting, is a new topic with active research for chaos-related applications. Chaotic systems with multiple offset-boostable variables provide more signal candidates with desired polarities and average values for application of chaos to secure communication. In this paper, we propose a new class of two-dimensional offset-boostable chaotic systems with exponential or logarithmic feedback functions. These systems provide two independent constants for nonbifurcating offset boosting in different regimes. The systems with transcendental functions are realized under the combinations of transistor and operational amplifiers, proving directly two-dimensional offset boosting.
Program Merge: What's Deep Learning Got to Do with It?
Authors: Lahiri Shuvendu K , Svyatkovskiy Alexey , Bird Christian , Miejer Erik , Coatta Terry
Published: February 2025

A discussion with Shuvendu Lahiri, Alexey Svyatkovskiy, Christian Bird, Erik Meijer and Terry Coatta
A Glimpse Into the Pandora's Box
Authors: West Jack , Li Jingjie , Fawaz Kassem
Published: February 2025

Demystifying on-device AI on Instagram and TikTok.
A Heterogeneous Chiplet Architecture for Accelerating End-to-End Transformer Models
Authors: Sharma Harsh , Dhingra Pratyush , Doppa Jana , Ogras Umit , Pande Partha Pratim
Published: February 2025

Transformers have revolutionized deep learning and generative modeling, enabling advancements in natural language processing tasks. However, the size of transformer models is increasing continuously, driven by enhanced capabilities across various deep learning tasks. This trend of ever-increasing model size has given rise to new challenges in terms of memory and compute requirements. Conventional computing platforms, including GPUs, suffer from suboptimal performance due to the memory demands imposed by models with millions/billions of parameters. The emerging chiplet-based platforms provide a new avenue for compute- and data-intensive machine learning (ML) applications enabled by a Network-on-Interposer (NoI). However, designing suitable hardware accelerators for executing Transformer inference workloads is challenging due to a wide variety of complex computing kernels in the Transformer architecture. In this paper, we leverage chiplet-based heterogeneous integration (HI) to design a high-performance and energy-efficient multi-chiplet platform to accelerate transformer workloads. We demonstrate that the proposed NoI architecture caters to the data access patterns inherent in a transformer model. The optimized placement of the chiplets and the associated NoI links and routers enable superior performance compared to the state-of-the-art hardware accelerators. The proposed NoI-based architecture demonstrates scalability across varying transformer models and improves latency and energy efficiency by up to 11.8 × and 2.36 ×, respectively when compared with the existing state-of-the-art architecture HAIMA
.
Automatic Quantification of Serial PET/CT Images for Pediatric Hodgkin Lymphoma Using a Longitudinally Aware Segmentation Network
Authors: Tie Xin , Shin Muheon , Lee Changhee , Perlman Scott B. , Huemann Zachary , Weisman Amy J. , Castellino Sharon M. , Kelly Kara M. , McCarten Kathleen M. , Alazraki Adina L. , Hu Junjie , Cho Steve Y. , Bradshaw Tyler J.
Published: February 2025

“Just Accepted” papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To develop a longitudinally-aware segmentation network (LAS-Net) that can quantify serial PET/CT images for pediatric patients with Hodgkin lymphoma. Materials and Methods This retrospective study included baseline (PET1) and interim (PET2) PET/CT images from 297 pediatric patients enrolled in two Children’s Oncology Group clinical trials (AHOD1331 and AHOD0831). The internal dataset included 200 patients (enrolled between March 2015-August 2019; median age, 15.4 [IQR: 5.6, 22.0] years; 107 male), and the external testing dataset included 97 patients (enrolled between December 2009-January 2012; median age, 15.8 [IQR: 5.2, 21.4] years; 59 male). LAS-Net incorporates longitudinal cross-attention, allowing relevant features from PET1 to inform the analysis of PET2. The model’s lesion segmentation performance on PET1 images was evaluated using Dice coefficients and lesion detection performance on PET2 images was evaluated using F1 scores. Additionally, quantitative PET metrics, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in PET1, as well as qPET and ∆SUVmax in PET2, were extracted and compared against physician-derived measurements. Agreement between model and physician-derived measurements was quantified using Spearman correlation, and bootstrap resampling was employed for statistical analysis. Results LAS-Net detected residual lymphoma on PET2 scans with an F1 score of 0.61 (precision/recall: 0.62/0.60), outperforming all comparator methods ( P < .01). For baseline segmentation, LAS-Net achieved a mean Dice score of 0.77. In PET quantification, LAS-Net’s measurements of qPET, ∆SUVmax, MTV and TLG were strongly correlated with physician measurements, with Spearman’s ρ values of 0.78, 0.80, 0.93 and 0.96, respectively. The quantification performance remained high, with a slight decrease, in an external testing cohort. Conclusion LAS-Net demonstrated significant improvements in quantifying PET metrics across serial scans in pediatric patients with Hodgkin lymphoma, highlighting the value of longitudinal awareness in evaluating multitime-point imaging datasets. ©RSNA, 2025
Bluetooth Three‐Dimensional AOA Positioning Method Based on the AMA‐SDM
Authors: Cai Xiaowen , Yang Jinjin , Chen Yangzhuo , Long Rongliang , Dai Siling , Li Pinchun
Published: February 2025

In order to solve the highly nonlinear nonconvex problem of the mathematical model in Bluetooth (angle of arrival (AOA)) localization, this paper proposes an alternating minimization algorithm for three‐dimensional AOA localization. The algorithm method converts the solving error minimization solving three‐dimensional coordinate problem in Bluetooth three‐dimensional AOA localization model to solving four single‐variable problems and alternately optimizes each variable to get the global optimal solution, which reduces the complexity of the model solving and achieves the high‐precision localization performance without auxiliary information. The test is carried out in two states: dynamic line of sight (LOS) and static non–line of sight (NLOS), and the results show that the proposed method meets the demand for indoor positioning accuracy with a positioning error of 16 cm in LOS environment and 34 cm in NLOS environment.
Elimination of Escherichia coli in a Packed Column Containing Jujube Seed Kernel Granular Activated Carbon Coated With Silver Nanoparticles (Ag‐NPs/GAC)
Authors: Kameni Ngounou M. , Nsoe Mengue , Amba Esegni V. , Kofa Guillaume , Ndi Koungou S. , Kayem Guifo J.
Published: February 2025

This study aims to develop a filter material capable of inhibiting bacterial growth and eliminating microorganisms from filtered water. Granular activated carbon (GAC) was prepared from jujube seed kernels by a chemical activation method whereby the kernels were heated at 650°C for 3 h in the presence of varied concentrations of phosphoric acid (H3PO4) (1, 2 and 3 M). Silver nanoparticles (Ag‐NPs) were prepared using the polysaccharide reduction method with AgNO3 at two concentrations (2 and 4 mmol). The Ag‐NPs obtained were characterised by a UV–visible spectrophotometer, optical microscope and microorganism inhibition test. GAC was coated with Ag‐NPs by impregnating it with a fixed concentration of Ag‐NPs in a supersaturated solution. The resulting GAC and Ag‐NPs/GAC were characterised using several methods (pH, point zero charge and FTIR). The leakage of Ag fixed on GAC was evaluated. The antimicrobial properties of the synthesised Ag‐NPs/GAC were investigated using inhibition zone, impregnation and column techniques against E. coli. The best nanoparticle shape with a large reactive surface was obtained after treatment with 2 mmol of AgNO3. There was no leaching of Ag ions in the treated water after passage through the bed. Except for the GAC not impregnated with Ag‐NPs, no E. coli CFU/mL was found in the filtered water obtained from Ag‐NPs/GAC beds at all tested pHs after 2–3 days of operation.
Gender‐Specific Effects on Quality of Life and Physical Activity After Pulmonary Vein Isolation: A Secondary Analysis of a Randomized Controlled Trial
Authors: Meretz Daniel , Seifert Martin , Haase-Fielitz Anja , Georgi Christian , Bannehr Marwin , Moeller Viviane , Minden Hans-Heinrich , Meininghaus Dirk Große , Janßen Gerhard , Butter Christian
Published: February 2025

Background: Gender differences exist in atrial fibrillation (AF) regarding epidemiology, mechanisms, management, and outcomes. There are limited data regarding gender‐specific outcomes after pulmonary vein isolation (PVI) including AF recurrence, physical activity, and health‐related quality of life.

Methods: In this secondary analysis of a randomized controlled trial (BE‐ACTION study: investigating 200 patients with paroxysmal or persistent AF undergoing PVI), a gender‐specific analysis of the primary endpoint (recurrence of atrial arrhythmia > 30s, additional ablation procedure, or new onset of antiarrhythmic drugs) was performed. Quality of life was assessed using the AFEQT and SF‐36 questionnaires, while physical activity was measured via step counts recorded at baseline, 6 months, and 12 months. The Mann–Whitney U test and Fisher exact test were used to compare continuous and categorical variables, respectively.

Results: 33.5% were women. Women and men were comparable in demographics, comorbidities, and steps per day before and after PVI. There was no statistically significant difference in the primary composite endpoint between women (37.3%) and men (25.6%) (p = 0.085). Before PVI, women had lower quality of life scores than men (median AFEQT scores: 43.5 points [25th to 75th percentiles 25.9–63.9] vs. 62.0 points [47.2–76.4], respectively, p < 0.001) as well as in the physical (40.22 points [33.98–46.69] vs. 46.30 points [39.21–51.60], p = 0.002) and mental domains (42.33 points [27.34–51.59] vs. 49.59 points [36.02–55.64], p = 0.001) of the SF‐36 questionnaire. The overall improvement in the quality of life was significant for both men and women (p < 0.001). Using AFEQT, women exhibited lower quality of life scores compared to men at 6 months post‐PVI (p = 0.001); however, this difference was no longer statistically significant at 12 months (p = 0.077).

Conclusion: These data emphasize the importance of AF recurrence after PVI and motivate future research to explore the causes and clinical consequences of a gender gap in quality of life in women after PVI.

Trial Registration: BE‐ACTION Study ClinicalTrials.gov identifier: DRKS00012914
A Before–After Study With a Novel Educational Tool for Reducing Non–Heart‐Beating Donation Hesitancy in High Schools
Authors: Terzoni Stefano , Milani Sara , Lusignani Maura , Ruta Federico , Ricci Cristian , Ferrara Paolo , Turrioni Tania
Published: February 2025

Background: Non–heart‐beating donors have great potential for organ donation, which still needs to be used. Young adults aged 18–30 years are often hesitant to donate their organs; high schools are ideal places for education aimed at fostering donations, but effective strategies still need to be developed in the literature.

Objective: To build an educational intervention targeted at high school students aged 18+, also developing dedicated tools.

Materials and Methods: A before–after study on a non‐randomized sample of students from eight schools of two campuses in Northern Italy. A questionnaire was built and validated (Cronbach’s alpha, exploratory factor analysis). An educational interactive game was created to involve the students.

Results: One hundred and eighty‐seven students were enrolled (M = 108 = 57.75%, F = 67 = 35.8%, nonbinary = 5 = 2.7%, nonresponders n = 7 = 3.75%). The questionnaire proved valid and reliable (alpha = 0.889, all factor loadings above Stevens’ cutoff). Intention to donate raised significantly from 33.0% to 42.6% (p < 0.05); so did knowledge about non–heart‐beating donations. There was a significant increase in those who would have wanted to ask such questions to healthcare personnel (p < 0.001) (n = 87, 47.3% vs. n = 84, 70.59%, p < 0.05). The main reasons for not expressing the willingness to donate were “it’s too early in my life,” lack of information, and fear that the organs could be stolen or sold.

Conclusion: This educational game proved engaging; the questionnaire was successfully validated and can be used in future studies on education about organ donation.
Extrachromosomal DNA dynamics contribute to intratumoural receptor tyrosine kinase genetic heterogeneity and drug resistance in gastric cancer
Authors: Kanayama Kazuki , Imai Hiroshi , Hashizume Ryotaro , Matsuda Chise , Usugi Eri , Hirokawa Yoshifumi S. , Watanabe Masatoshi
Published: February 2025

Chromosomal instability in gastric cancer cells is associated with the amplification of oncogenes that encode receptor tyrosine kinases (RTKs), such as HER2 and FGFR2; such gene amplification varies from cell to cell and manifests as genetic heterogeneity within tumours. The intratumoural genetic heterogeneity of RTK gene amplification causes heterogeneity in RTK protein expression, which has been suggested to be associated with therapeutic resistance to RTK inhibitors; however, the underlying mechanism is not fully understood. Here, we show that extrachromosomal DNA (ecDNA) causes intratumoural genetic heterogeneity in RTKs and drug resistance due to diverse dynamic changes. We analysed the dynamics of FGFR2 and MYC ecDNA in a gastric cancer cell line after single-cell cloning. Similar to those in parental cells, the copy numbers of FGFR2 and MYC in subclones differed significantly between cells, indicating intraclonal genetic heterogeneity. Furthermore, the ecDNA composition differed between subclones, which affected FGFR2 protein expression and drug sensitivity. Interestingly, clone cells that were resistant to the FGFR2 inhibitor AZD4547 presented diverse changes in ecDNA, including chimeric ecDNA, large ecDNA and increased ecDNA numbers; these changes were associated with high expression and rephosphorylation of FGFR2. Conversely, when resistant clone cells were cultured under conditions that excluded AZD4547, the ecDNA status became similar to that of the original clone cells, and the inhibitory effect on cell growth was restored. Implications: Our results show that dynamic quantitative and qualitative changes in ecDNA can drive the intratumoural genetic heterogeneity of RTKs and resistance to RTK inhibitors.
Changes in body water composition and severity of respiratory disease in very preterm infants
Authors: Allanore Alexandra , Bonsante Francesco , Lorrain Simon , Lapillonne Alexandre , Iacobelli Silvia
Published: February 2025

Introduction
Acute respiratory disorders and bronchopulmonary dysplasia (BPD) are frequent and serious complications in very preterm infants (VPI). These conditions are influenced by several factors, including fluid imbalances and abnormal postnatal changes in body water composition (BWC). We aimed to investigate the association between BWC and the severity of respiratory disease in VPI using bioelectrical impedance analysis (BIA).

Material and Methods
We conducted an observational study in a level III NICU at Reunion Island University Hospital. Infants born before 32 weeks of gestation, with BWC monitoring during hospital stay were included. The severity of respiratory disease was assessed using Mean Airway Pressure (MAP) recorded at the same time as BIA. Secondary outcomes included the Lung Ultrasound Score (LUS), measured weekly from 28 days of life, and BDP occurrence and severity at 36 weeks of postconceptional age.

Results
We included 34 VPI (BW 1131±352g, GA 28.0±2.2) and performed 267 BWC analyses (average: 8 BIA/patient). MAP was directly associated with extracellular water (ECW, % of body weight) (p<0.001), even after adjustment for confounding variables at multivariate analysis (p< 0.02). No significant association was observed between total body water measures and the LUS. ECW was significantly associated with the occurrence of severe BPD (p< 0.003).

Conclusion
These results highlight the protective effect of the contraction of total body water and in particular of the ECW on the severity of acute and chronic respiratory pathology in VPI. They also indicate the interest of monitoring BWC by BIA throughout hospitalization in critically ill neonates.