bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of necroptosis‐related genes in ankylosing spondylitis by bioinformatics and experimental validation
Authors: Wen Pengfei , Zhao Yan , Yang Mingyi , Yang Peng , Nan Kai , Liu Lin , Xu Peng
Published: July 2024

The pathogenesis of ankylosing spondylitis (AS) remains unclear, and while recent studies have implicated necroptosis in various autoimmune diseases, an investigation of its relationship with AS has not been reported. In this study, we utilized the Gene Expression Omnibus database to compare gene expressions between AS patients and healthy controls, identifying 18 differentially expressed necroptosis‐related genes (DENRGs), with 8 upregulated and 10 downregulated. Through the application of three machine learning algorithms—least absolute shrinkage and selection operation, support vector machine‐recursive feature elimination and random forest—two hub genes, FASLG and TARDBP, were pinpointed. These genes demonstrated high specificity and sensitivity for AS diagnosis, as evidenced by receiver operating characteristic curve analysis. These findings were further supported by external datasets and cellular experiments, which confirmed the downregulation of FASLG and upregulation of TARDBP in AS patients. Immune cell infiltration analysis suggested that CD4+ T cells, CD8+ T cells, NK cells and neutrophils may be associated with the development of AS. Notably, in the group with high FASLG expression, there was a significant infiltration of CD8+ T cells, memory‐activated CD4+ T cells and resting NK cells, with relatively less infiltration of memory‐resting CD4+ T cells and neutrophils. Conversely, in the group with high TARDBP expression, there was enhanced infiltration of naïve CD4+ T cells and M0 macrophages, with a reduced presence of memory‐resting CD4+ T cells. In summary, FASLG and TARDBP may contribute to AS pathogenesis by regulating the immune microenvironment and immune‐related signalling pathways. These findings offer new insights into the molecular mechanisms of AS and suggest potential new targets for therapeutic strategies.
Simultaneous mutations in ITPK4 and MRP5 genes result in a low phytic acid level without compromising salt tolerance in Arabidopsis
Authors: Ren Yuying , Jiang Mengdan , Zhu Jian‐Kang , Zhou Wenkun , Zhao Chunzhao
Published: July 2024

Generation of crops with low phytic acid (myo‐inositol‐1,2,3,4,5,6‐hexakisphosphate (InsP6)) is an important breeding direction, but such plants often display less desirable agronomic traits. In this study, through ethyl methanesulfonate‐mediated mutagenesis, we found that inositol 1,3,4‐trisphosphate 5/6‐kinase 4 (ITPK4), which is essential for producing InsP6, is a critical regulator of salt tolerance in Arabidopsis. Loss of function of ITPK4 gene leads to reduced root elongation under salt stress, which is primarily because of decreased root meristem length and reduced meristematic cell number. The itpk4 mutation also results in increased root hair density and increased accumulation of reactive oxygen species during salt exposure. RNA sequencing assay reveals that several auxin‐responsive genes are down‐regulated in the itpk4‐1 mutant compared to the wild‐type. Consistently, the itpk4‐1 mutant exhibits a reduced auxin level in the root tip and displays compromised gravity response, indicating that ITPK4 is involved in the regulation of the auxin signaling pathway. Through suppressor screening, it was found that mutation of Multidrug Resistance Protein 5 (MRP5)5 gene, which encodes an ATP‐binding cassette (ABC) transporter required for transporting InsP6 from the cytoplasm into the vacuole, fully rescues the salt hypersensitivity of the itpk4‐1 mutant, but in the itpk4‐1 mrp5 double mutant, InsP6 remains at a very low level. These results imply that InsP6 homeostasis rather than its overall amount is beneficial for stress tolerance in plants. Collectively, this study uncovers a pair of gene mutations that confer low InsP6 content without impacting stress tolerance, which offers a new strategy for creating “low‐phytate” crops.
Ultrasound diagnostic of intrauterine adhesions: Systematic review and meta‐analysis
Authors: Ding Caiyun , Wei Wei , Ding Fengzhi , Ding Jin , Li Bozheng , Ma Qiang
Published: July 2024

Purpose

To summarize and compare the accuracy of transvaginal ultrasound (TVS), 3D‐TVS, and sonohysterography (SHG) for the diagnosis of intrauterine adhesions (IUA).

Methods

The computer searches databases such as web of science, Medline, EMBASE, and PubMed collecting diagnostic studies of IUA via ultrasound. The retrieval time was included from inception to January 1, 2023. Two researchers independently screened the literature, extracted information, and used RevMan 5.3 to complete an assessment of the risk of bias in the included literature. Meta‐analysis of included studies using Stata 16.0 and Meta Disc 1.4 software.

Results

Thirteen studies were included. The analysis results of 2D‐TVS are The sensitivity (SEN): 0.54 (95% CI [0.28078]), specificity (SPE): 0.96 (95% CI [0.78, 0.99]), and the area (AUC) under the operating characteristic curve (SROC): 0.83 (95% CI [0.80, 0.86]); the SEN, SPE, and AUC of 3D‐TVS are: 0.96 (95% CI [0.90, 0.98]), 0.84 (95% CI [0.68, 0.93]), 0.97 (95% CI [0.95, 0.98]); and the SEN, SPE, and AUC of SHG are: 0.74 (95% CI [0.53, 0.88]), 0.97 (95% CI [0.94, 0.99]), 0.95 (95% CI [0.93, 0.97]).

Conclusion

The current results show that the diagnostic value of 3D‐TVS for IUA is better than SHG and significantly higher than that of 2D‐TVS. However, the analysis of subgroups is still limited by the number of included studies. In order to better explore the application of ultrasound in intrauterine adhesion, more high‐quality studies are needed in the future.
Assessing pet owners' willingness to embrace insects in pet food
Authors: Baptista da Silva Camila , Santos Neto Elias Leocádio dos , Broeckx Bart J. G. , Ruiz‐Suárez Norberto , Eeckhout Mia , Hesta Myriam
Published: July 2024

Alternative diets for pets have gained attention in recent years due to concerns about sustainability and environmental impact. One emerging option is the inclusion of edible insects in pet food. This study aimed to survey dog (DO) and cat (CO) owners regarding their willingness to feed insect‐based pet food (IBPF) to their pets and to identify potential motivating factors. A total of 435 valid responses were evaluated, with 66% being DO and 58% CO. Of those, 24% owned both dogs and cats. About half of DO (52%) and 62% of CO were positive about IBPF. CO had a higher acceptance of IBPF than DO (p < 0.05). Moreover, both DO and CO showed a significant increase in acceptance if IBPF has been proven to provide sustainable and nutritional benefits (p < 0.01). CO adhering to a specific diet themselves showed a significantly higher acceptance of IBPF (p < 0.05), however it was independent of the type of diet. Additionally, 32% of DO and 34% of CO reported prior experience with eating edible insects themselves, and a positive entomophagy experience increased DO's (p = 0.108) and CO's (p < 0.01) acceptance of IBPF. Furthermore, the interest in entomophagy resulted in increased acceptance of IBPF by both DO and CO who had not yet tried insects (p < 0.01). In conclusion, pet owners demonstrated a favourable perception of IBPF and showed a willingness to incorporate these products into their pets' diets. CO displayed a more positive perception compared to DO, suggesting a beneficial focus on the feline niche. To enhance overall acceptance, emphasizing sustainability and conducting further research to establish the nutritional benefits of IBPF are crucial. The findings of this study provide valuable insights for pet food manufacturers and marketers to develop strategies and products aligned with the preferences and needs of pet owners.
An Assessment of Local People's Knowledge and Management Practices of Freshwater Macrophytes in Three Kenyan Lakes
Authors: Onwong'a Rebeccah Kwamboka , Oduor Ayub M. O. , Sitoki Lewis , Handa Collins
Published: July 2024

It is increasingly being recognised that local people's knowledge can contribute to the ecological and socioeconomic goals of natural resource management programmes. Yet, few studies have examined local people's knowledge concerning freshwater macrophyte diversity. Consequently, the extent to which local people's knowledge can contribute to mitigating freshwater macrophyte degradation and supporting their management remains largely unknown. To contribute towards filling this knowledge gap, we investigated local people's knowledge, perceptions and management practices of freshwater macrophyte species. Data collection involved conducting face‐to‐face in‐depth interviews and focus group discussions among local people who lived in areas adjacent to Lake Baringo, Nyanza Gulf of Lake Victoria and the Kenyan side of Lake Jipe. The sociodemographic characteristics of the respondents were summarised using descriptive statistics. Then, generalised linear mixed‐effect models were used to test whether the respondent's sociodemographic characteristics were associated with their macrophyte species recognition skills, benefits and problems associated with macrophytes and management practices. Our respondents named a total of 35 macrophyte species, with each respondent naming an average of six species. Our results showed that respondents who were not involved in fishing and fish‐related activities identified more macrophytes than those who participated in such activities. Additionally, individuals who frequently visited the lake named more macrophyte species compared to those who visited either daily or occasionally. While our respondents acknowledged various benefits and problems associated with macrophytes, there was a higher recognition rate for those that directly impacted humans. Regarding local management practices, it was observed that macrophytes were not conserved, with management efforts focusing solely on problematic species. Overall, macrophyte naming skills, knowledge on provisioning and supporting ecosystem services, direct adverse macrophyte impacts and management methods increased with age. We identified knowledge gaps regarding alien species and the indirect impacts of macrophytes. Addressing these gaps is crucial.
Online shopping and rural‐urban wage inequality
Authors: Pi Jiancai , Liu Xinyi
Published: July 2024

This paper takes online shopping into consideration, and constructs general equilibrium models to analyze how consumers' dependence on online shopping affects rural‐urban skilled‐unskilled wage inequality. We find that when consumers' dependence on online shopping increases, wage inequality can be conditionally narrowed down, depending on the unskilled labor intensity in the urban manufacturing sector and the possible elasticity of the contract price.
A mixed methods evaluation of the breastfeeding memory aide CHINS
Authors: Shotton Lynette , Collins Tracy , Cordier Reinie , Chikwava Fadzai , Steen Mary
Published: July 2024

Breastfeeding rates remain persistently low in the United Kingdom (UK) despite wide‐scale rollout of UNICEF Baby Friendly Initiative training and accreditation. More must be done to ensure breastfeeding practitioners can provide effective support. The memory aide CHINS (Close, Head free, In‐line, Nose to Nipple and Sustainable) could help practitioners remember, recall, and apply breastfeeding theory in practice and this paper presents a UK evaluation of its impact. A concurrent, convergent mixed methods approach was adopted using Normalisation Process Theory (NPT) as an overarching framework. An online survey targeted breastfeeding practitioners and academics from the UK (n = 115). A sub‐set (n = 16) of respondents took part in qualitative focus groups. Survey data was subjected to descriptive and inferential statistical analysis, and the focus group data was analysed, using NPT. CHINS is widely used in breastfeeding education and practice largely because of its simplicity and ease of integration in everyday practice, as well as its sustained inclusion in UNICEF Baby Friendly Initiative training. CHINS has introduced a standardised approach to the principles of positioning for effective breastfeeding. Doing so has helped address inconsistencies and poor practice in this area, and CHINS plays a role in assisting practitioners in building confidence in their breastfeeding practice. More needs to be done to ensure the breastfeeding workforce develop and maintain the requisite skills to promote and support breastfeeding, including the role of memory aides such as CHINS in achieving this.
Dissecting the role of the MS‐ring protein FliF in Bacillus cereus flagella‐related functions
Authors: Mazzantini Diletta , Gherardini Guendalina , Rossi Virginia , Celandroni Francesco , Calvigioni Marco , Panattoni Adelaide , Massimino Mariacristina , Lupetti Antonella , Ghelardi Emilia
Published: July 2024

The flagellar MS‐ring, uniquely constituted by FliF, is essential for flagellar biogenesis and functionality in several bacteria. The aim of this study was to dissect the role of FliF in the Gram‐positive and peritrichously flagellated Bacillus cereus. We demonstrate that fliF forms an operon with the upstream gene fliE. In silico analysis of B. cereus ATCC 14579 FliF identifies functional domains and amino acid residues that are essential for protein functioning. The analysis of a ΔfliF mutant of B. cereus, constructed in this study using an in frame markerless gene replacement method, reveals that the mutant is unexpectedly able to assemble flagella, although in reduced amounts compared to the parental strain. Nevertheless, motility is completely abolished by fliF deletion. FliF deprivation causes the production of submerged biofilms and affects the ability of B. cereus to adhere to gastrointestinal mucins. We additionally show that the fliF deletion does not compromise the secretion of the three components of hemolysin BL, a toxin secreted through the flagellar type III secretion system. Overall, our findings highlight the important role of B. cereus FliF in flagella‐related functions, being the protein required for complete flagellation, motility, mucin adhesion, and pellicle biofilms.
The everyday phenomenology of bedside insight: Response to Paley's critique of phenomenological research in nursing
Authors: Birnbaum Shira
Published: July 2024

The quality of phenomenological research in nursing has been a subject of long‐standing debate and critique, but conversation took a particularly contentious turn following publication of John Paley's 2017 Phenomenology as Qualitative Research (Routledge), which elicited strong reactions. Faculty in nursing doctoral programs now face a challenge: in light of current controversies, what can we teach that is appropriately labeled phenomenological, and is there a way to present philosophical concepts that might equip students to avoid the most egregious mistakes of the past? In this article, I suggest that ordinary clinical nursing practice is an inherently phenomenological enterprise, and creative bedside insights belong at the center of our teaching, as they embody an everyday phenomenology which exemplifies core elements of the phenomenological method. Instead of following ever‐more‐precisely elaborated instructional manuals, I propose, our students should begin their studies of phenomenology by returning attention to the way creative insight emerges during routine care. Bedside insights have been rendered invisible by our discipline's valuing of technical proceduralism over artistry in research and by the turn to evidence‐based practice in clinical work, but they are a valuable pathway to learning and should be part of our response to the current crisis.
Gastric slow‐wave modulation via power‐controlled, irrigated radio‐frequency ablation
Authors: Matthee Ashton , Aghababaie Zahra , Nisbet Linley A. , Simmonds Sam , Dowrick Jarrah M. , Sands Gregory B. , Angeli‐Gordon Timothy R.
Published: July 2024

Background

Recently, radio‐frequency ablation has been used to modulate slow‐wave activity in the porcine stomach. Gastric ablation is, however, still in its infancy compared to its history in the cardiac field, and electrophysiological studies have been restricted to temperature‐controlled, non‐irrigated ablation. Power‐controlled, irrigated ablation may improve lesion formation at lower catheter‐tip temperatures that produce the desired localized conduction block.

Methods and Results

Power‐controlled, irrigated radio‐frequency ablation was performed on the gastric serosal surface of female weaner pigs (n = 5) in vivo. Three combinations of power (10–15 W) and irrigation settings (2–5 mL min−1) were investigated. A total of 12 linear lesions were created (n = 4 for each combination). Slow waves were recorded before and after ablation using high‐resolution electrical mapping.

Key Results

Irrigation maintained catheter‐tip temperature below 50°C. Ablation induced a complete conduction block in 8/12 cases (4/4 for 10 W at 2 mL min−1, 1/4 for 10 W at 5 mL min−1, 3/4 for 15 W at 5 mL min−1). Blocks were characterized by a decrease in signal amplitude at the lesion site, along with changes in slow‐wave propagation patterns, where slow waves terminated at and/or rotated around the edge of the lesion.

Conclusions and Inferences

Power‐controlled, irrigated ablation can successfully modulate gastric slow‐wave activity at a reduced catheter‐tip temperature compared to temperature‐controlled, non‐irrigated ablation. Reducing the irrigation rate is more effective than increasing power for blocking slow‐wave activity. These benefits suggest that irrigated ablation is a suitable option for further translation into a clinical intervention for gastric electrophysiology disorders.
Acute hemorrhagic edema of infancy: 20‐year experience from an Italian tertiary referral center
Authors: Fiordelisi Adele , Soldovieri Sara , Pagnini Ilaria , Marrani Edoardo , Simonini Gabriele , Indolfi Giuseppe , Trapani Sandra
Published: July 2024

Purpose

Data on acute hemorrhagic edema of infancy (AHEI) are derived from small case series or case reports. We report a 20‐year experience at a national referral center.

Methods

We performed a single‐center retrospective study including patients who were diagnosed with AHEI from January 1, 2004, to June 30, 2023.

Results

We identified 21 patients (57.1% females) with a median age of 18 months (range 7–33 months). Thirteen (61.9%) patients were admitted to the pediatric ward, the remaining eight (38.1%) presented to the emergency department and were discharged for outpatient management. The median length of hospitalization was 5 days (range 3–9 days). Twenty patients (95.2%) had prodromal symptoms. The most common cutaneous findings were targetoid purpuric plaques. The lesions were most localized on the face (13, 61.9%) and on the upper limbs (18 patients, 85.7%). Sixteen (76%) patients presented with nonpitting and tender edema, localized on the feet (9/16, 56%) and hands (6/16, 37.5%). Systemic involvement was rare, and no patients experienced complications or sequelae. Twelve (57.1%) patients underwent infectious disease investigations, with positive results in only four (33.3%). None of the patients diagnosed after the SARS‐CoV‐2 outbreak (March 2020) had positive nasopharyngeal swabs for the virus. For the 13 patients who were admitted to the pediatric ward, the median length of hospitalization was five days (3–9 days).

Conclusions

The 21‐patient single‐center cohort of children affected by AHEI confirmed a generally benign course of AHEI, despite a 62% rate of hospitalization.
Analysis of physical traits, clinical parameters, and energy metabolism of in vivo‐ and in vitro‐derived Flemish newborn calves during the first day of life
Authors: Schütz Luís Fernando , Zago Fabiano Carminatti , de Aguiar Luís Henrique , Forell Fabiana , Martins Leonardo Tondello , Urio Monica , Neto Pedro Claudino dos Santos , Junior Jamir Machado , Tavares Kaio Cesar Simiano , Gaudêncio Neto Saul , Feltrin Cristiano , Mezzalira Alceu , Bertolini Marcelo
Published: July 2024

Studies investigating physiological deviations from normality in newborn calves derived from in vitro fertilization procedures remain important for the understanding of factors that reduce calf survival after birth. The aim of this study was to investigate parameters affecting health and welfare of newborn Flemish calves derived from in vitro embryo production (IVP) in the first hours of life in comparison to in vivo‐derived calves. Physical traits of newborn calves and fetal membranes (FM) were recorded soon after birth. Newborn venous blood samples were collected at several time points within the first 24 h of life for analyses of energy substrates, electrolytes, blood gases, acid–base balance, blood chemistry, and haematology. A liver biopsy was taken within the first hour after birth for analysis of gene expression of key enzymes of the fructolytic and glycolytic pathways. Newborn IVP calves were heavier and larger at birth, which was associated with heavier FM. At several time points during the first 24 h of life, IVP‐derived calves had altered rectal temperature, blood gases, electrolyte concentrations, blood parameters for liver, kidney and muscle function, and acid–base balance, plasma lipid metabolism, and hemogram parameters. The relative mRNA abundances for triokinase and lactate dehydrogenase‐B were greater in IVP calves. In summary, IVP‐derived newborn calves were at higher risk of clinical problems after birth, which was markedly greater in heavier and larger calves. Such animals take longer to adapt to extrauterine life and should receive a special attention during the immediate neonatal period.
Targeting conserved TIM3
+
VISTA
+
tumor-associated macrophages overcomes resistance to cancer immunotherapy
Authors: Vanmeerbeek Isaure , Naulaerts Stefan , Sprooten Jenny , Laureano Raquel S. , Govaerts Jannes , Trotta Rosa , Pretto Samantha , Zhao Shikang , Cafarello Sarah Trusso , Verelst Joren , Jacquemyn Maarten , Pociupany Martyna , Boon Louis , Schlenner Susan M. , Tejpar Sabine , Daelemans Dirk , Mazzone Massimiliano , Garg Abhishek D.
Published: July 2024

Despite the success of immunotherapy, overcoming immunoresistance in cancer remains challenging. We identified a unique niche of tumor-associated macrophages (TAMs), coexpressing T cell immunoglobulin and mucin domain–containing 3 (TIM3) and V-domain immunoglobulin suppressor of T cell activation (VISTA), that dominated human and mouse tumors resistant to most of the currently used immunotherapies. TIM3
+
VISTA
+
TAMs were sustained by IL-4–enriching tumors with low (neo)antigenic and T cell–depleted features. TIM3
+
VISTA
+
TAMs showed an anti-inflammatory and protumorigenic phenotype coupled with inability to sense type I interferon (IFN). This was established with cancer cells succumbing to immunogenic cell death (ICD). Dying cancer cells not only triggered autocrine type I IFNs but also exposed HMGB1/VISTA that engaged TIM3/VISTA on TAMs to suppress paracrine IFN-responses. Accordingly, TIM3/VISTA blockade synergized with paclitaxel, an ICD-inducing chemotherapy, to repolarize TIM3
+
VISTA
+
TAMs to proinflammatory TAMs that killed cancer cells via tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) signaling. We propose targeting TIM3
+
VISTA
+
TAMs to overcome immunoresistant tumors.
From “forever chemicals” to fluorine-free alternatives
Authors: Ateia Mohamed , Scheringer Martin
Published: July 2024

Identifying alternatives to PFAS requires weighing trade-offs and uncertainties
Dynamics of high-speed electrical tree growth in electron-irradiated polymethyl methacrylate
Authors: Sturge Kathryn M. , Hoppis Noah , Bussio Ariana M. , Barney Jonathan , Beaudoin Brian , Brown Cameron , Carlsten Bruce , Chun Carolyn , Clifford Bryson C. , Cumings John , Dallmann Nicholas , Fitzgibbon Jack , Frashure Emily H. , Hammell Ashley E. , Hannan José , Henderson Samuel L. , Hiebert Miriam E. , Krutzler James , Lichthardt Joseph , Marr-Lyon Mark , Montano Thomas , Moody Nathan , Mueller Alexander , O’Shea Patrick , Schneider Ryan , Smith Karl , Tappan Bryce , Tiemann Clayton , Walter David , Koeth Timothy W.
Published: July 2024

Dielectric materials are foundational to our modern-day communications, defense, and commerce needs. Although dielectric breakdown is a primary cause of failure of these systems, we do not fully understand this process. We analyzed the dielectric breakdown channel propagation dynamics of two distinct types of electrical trees. One type of these electrical trees has not been formally classified. We observed the propagation speed of this electrical tree type to exceed 10 million meters per second. These results identify substantial gaps in the understanding of dielectric breakdown, and filling these gaps is paramount to the design and engineering of dielectric materials that are less susceptible to electrostatic discharge failure.
Cross-talk between ILC2 and Gata3
high
T
regs
locally constrains adaptive type 2 immunity
Authors: Stockis Julie , Yip Thomas , Moreno-Vicente Julia , Burton Oliver , Samarakoon Youhani , Schuijs Martijn J. , Raghunathan Shwetha , Garcia Celine , Luo Weike , Whiteside Sarah K. , Png Shaun , Simpson Charlotte , Monk Stela , Sawle Ashley , Yin Kelvin , Barbieri Johanna , Papadopoulos Panagiotis , Wong Hannah , Rodewald Hans-Reimer , Vyse Timothy , McKenzie Andrew N. J. , Cragg Mark S. , Hoare Matthew , Withers David R. , Fehling Hans Jörg , Roychoudhuri Rahul , Liston Adrian , Halim Timotheus Y. F.
Published: July 2024

Regulatory T cells (T
regs
) control adaptive immunity and restrain type 2 inflammation in allergic disease. Interleukin-33 promotes the expansion of tissue-resident T
regs
and group 2 innate lymphoid cells (ILC2s); however, how T
regs
locally coordinate their function within the inflammatory niche is not understood. Here, we show that ILC2s are critical orchestrators of T
reg
function. Using spatial, cellular, and molecular profiling of the type 2 inflamed niche, we found that ILC2s and T
regs
engage in a direct (OX40L-OX40) and chemotaxis-dependent (CCL1-CCR8) cellular dialogue that enforces the local accumulation of Gata3
high
T
regs
, which are transcriptionally and functionally adapted to the type 2 environment. Genetic interruption of ILC2-T
reg
communication resulted in uncontrolled type 2 lung inflammation after allergen exposure. Mechanistically, we found that Gata3
high
T
regs
can modulate the local bioavailability of the costimulatory molecule OX40L, which subsequently controlled effector memory T helper 2 cell numbers. Hence, ILC2-T
reg
interactions represent a critical feedback mechanism to control adaptive type 2 immunity.
CD5 deletion enhances the antitumor activity of adoptive T cell therapies
Authors: Patel Ruchi P. , Ghilardi Guido , Zhang Yunlin , Chiang Yi-Hao , Xie Wei , Guruprasad Puneeth , Kim Ki Hyun , Chun Inkook , Angelos Mathew G. , Pajarillo Raymone , Hong Seok Jae , Lee Yong Gu , Shestova Olga , Shaw Carolyn , Cohen Ivan , Gupta Aasha , Vu Trang , Qian Dean , Yang Steven , Nimmagadda Aditya , Snook Adam E. , Siciliano Nicholas , Rotolo Antonia , Inamdar Arati , Harris Jaryse , Ugwuanyi Ositadimma , Wang Michael , Carturan Alberto , Paruzzo Luca , Chen Linhui , Ballard Hatcher J. , Blanchard Tatiana , Xu Chong , Abdel-Mohsen Mohamed , Gabunia Khatuna , Wysocka Maria , Linette Gerald P. , Carreno Beatriz , Barrett David M. , Teachey David T. , Posey Avery D. , Powell Daniel J. , Sauter C. Tor , Pileri Stefano , Pillai Vinodh , Scholler John , Rook Alain H. , Schuster Stephen J. , Barta Stefan K. , Porazzi Patrizia , Ruella Marco
Published: July 2024

Most patients treated with US Food and Drug Administration (FDA)–approved chimeric antigen receptor (CAR) T cells eventually experience disease progression. Furthermore, CAR T cells have not been curative against solid cancers and several hematological malignancies such as T cell lymphomas, which have very poor prognoses. One of the main barriers to the clinical success of adoptive T cell immunotherapies is CAR T cell dysfunction and lack of expansion and/or persistence after infusion. In this study, we found that CD5 inhibits CAR T cell activation and that knockout (KO) of CD5 using CRISPR-Cas9 enhances the antitumor effect of CAR T cells in multiple hematological and solid cancer models. Mechanistically, CD5 KO drives increased T cell effector function with enhanced cytotoxicity, in vivo expansion, and persistence, without apparent toxicity in preclinical models. These findings indicate that CD5 is a critical inhibitor of T cell function and a potential clinical target for enhancing T cell therapies.
An aldolase-dependent phloroglucinol degradation pathway in
Collinsella
sp. zg1085
Authors: Li Yating , Xu Tong , Tu Yanqin , Li Tong , Wei Yifeng , Zhou Yan
Published: July 2024

Phloroglucinol (1,3,5-trihydroxybenzene) is a key intermediate in the degradation of polyphenols such as flavonoids and hydrolysable tannins and can be used by certain bacteria as a carbon and energy source for growth. The identification of enzymes that participate in the fermentation of phloroglucinol to acetate and butyrate in
Clostridia
was recently reported. In this study, we present the discovery and characterization of a novel metabolic pathway for phloroglucinol degradation in the bacterium
Collinsella
sp. zg1085, from marmot respiratory tract. In both the
Clostridial
and
Collinsella
pathways, phloroglucinol is first reduced to dihydrophoroglucinol by the NADPH-dependent phloroglucinol reductase (PGR), followed by ring opening to form (
S
)-3-hydroxy-5-oxohexanoate by a Mn
2+
-dependent dihydrophloroglucinol cyclohydrolase (DPGC). In the
Collinsella
pathway, (
S
)-3-hydroxy-5-oxohexanoate is then cleaved to form malonate semialdehyde and acetone by a newly identified aldolase (HOHA). Finally, a NADP
+
-dependent malonate-semialdehyde dehydrogenase converts malonate semialdehyde to CO
2
and acetyl-CoA, an intermediate in carbon and energy metabolism. Recombinant expression of the
Collinsella
PGR, DPGC, and HOHA in
E. coli
enabled the conversion of phloroglucinol into acetone, providing support for the proposed pathway. Experiments with
Olsenella profusa
, another bacterium containing the gene cluster of interest, show that the PGR, DPGC, HOHA, and MSDH are induced by phloroglucinol. Our findings add to the variety of metabolic pathways for the degradation of phloroglucinol, a widely distributed phenolic compound, in the anaerobic microbiome.

IMPORTANCE

Phloroglucinol is an important intermediate in the bacterial degradation of polyphenols, a highly abundant class of plant natural products. Recent research has identified key enzymes of the phloroglucinol degradation pathway in butyrate-producing anaerobic bacteria, which involves cleavage of a linear triketide intermediate by a beta ketoacid cleavage enzyme, requiring acetyl-CoA as a co-substrate. This paper reports a variant of the pathway in the lactic acid bacterium
Collinsella
sp. zg1085, which involves cleavage of the triketide intermediate by a homolog of deoxyribose-5-phosphate aldolase, highlighting the variety of mechanisms for phloroglucinol degradation by different anaerobic bacterial taxa.
Age, sedimentology, and deformational history of the Mesozoic Franciscan accretionary complex, Angel Island, California, USA
Authors: Das Meghomita , Anfinson Owen , Rowe Christie , Schroeder Nicolas
Published: July 2024

The Franciscan Complex represents the forearc accretionary wedge that formed during late Mesozoic–Cenozoic subduction in California, USA, and preserves detailed records of long-lived subduction and exhumation of high-pressure, low-temperature rocks. As one of the world’s largest exposed subduction complexes, it records the evolution of subduction dynamics that correspond to the tectonic development of the western USA.

Lithotectonic units within the Franciscan Complex represent different stages, mechanisms, and depths of accretion in the subduction history. Previous authors have proposed subdivisions for the Franciscan Complex, but as the metasedimentary units are very similar over large spatial and temporal scales, they have been difficult to map except on the broadest scales. This restricts the potential for researchers to characterize past tectonic events and subduction/exhumation mechanisms.

Angel Island in the San Francisco Bay has previously been mapped as an undivided blueschist-facies metasedimentary unit thrust over lower-grade metasediments along the Quarry Point thrust, but we find that the Angel Island units include lithologic and metamorphic diversity spanning nearly the entire range of variability for the Franciscan Complex. We present new mapping, lithologic descriptions, and detrital zircon U-Pb geochronology to propose a new lithostratigraphy for Angel Island consisting of seven structurally juxtaposed units ranging from sub-metamorphic to low blueschist. The structurally highest and structurally lowest units are sub-blueschist grade, and the center of the fault-bounded stack consists of blueschist-grade metasediments separated by a thin sliver of sodic-amphibole metabasalt. The blueschist units and structurally higher sub-blueschist–grade units have maximum depositional ages of ca. 108–110 Ma, which is consistent with similar grade units from across the Bay Area, and they match well with respect to lithology and metamorphic grade. The structurally lowest units below the Quarry Point thrust have similar provenance but younger maximum depositional ages of ca. 97 Ma. These units have been suggested by previous authors to be affiliated with either Alcatraz or Marin Headlands rocks, which have similar depositional ages but show much more diversity in detrital zircon age spectra, which makes their association debatable.

These results offer the first high-resolution detrital zircon U-Pb geochronologic dataset from the Franciscan Complex that allows definition of the diversity of age and provenance within a previously defined regional unit, which should be considered in future work attempting regional correlations with regional sample distribution.
Supplemental Material: Cretaceous magnetostratigraphy of the southern Simao Basin, SE Tibetan Plateau and its paleogeographic implications
Authors: Zhang Dawen , Yan maodu , al. et
Published: July 2024

Tables S1–S3 and Figures S1–S8.
Ovarian hyperstimulation syndrome without gonadotropin stimulation: an unusual response to a GnRH agonist
Authors: Petch Sarah , Bauman Renato , Hatunic Mensud , Allen Cathy
Published: July 2024

Ovarian hyperstimulation syndrome (OHSS) is a well-known iatrogenic complication of ovarian stimulation with gonadotropins. We present the case of a woman in her 30s who developed OHSS without the administration of gonadotropins. She was due to undergo intracytoplasmic sperm injection (ICSI) for primary subfertility. After taking a gonadotropin-releasing hormone (GnRH) receptor agonist for 3 weeks, she presented with abdominal pain, nausea and bloating. She was diagnosed with moderate to severe OHSS, requiring management as an inpatient.

Investigations included a pelvic ultrasound scan showing an enlarged ovary, serum oestradiol >30 000 pmol/L and an MRI of the brain with an incidental finding of a 5 mm pituitary microadenoma.

She recovered rapidly and was referred for endocrinology evaluation and multidisciplinary team discussion. The OHSS was felt to be explained by an unusual ‘flare’ response to a GnRH agonist. A further ICSI cycle with an antagonist protocol is planned.
Assessment of neuropathy subtypes in type 1 diabetes
Authors: Karlsson Pall , Sjogaard Marie Balle , Schousboe Karoline , Mizrak Hatice Isik , Kufaishi Huda , Staehelin Jensen Troels , Randel Nyengaard Jens , Hansen Christian Stevns , Yderstræde Knud Bonnet , Buhl Christian Selmer
Published: July 2024

Introduction

Diabetic polyneuropathy (DPN), a common complication of diabetes, can manifest as small, large, or mixed fiber neuropathy (SFN, LFN, and MFN, respectively), depending on the type of fibers involved. Despite evidence indicating small fiber involvement prior to large fiber involvement in type 1 diabetes mellitus (T1DM)-associated DPN, no evidence has been produced to determine the more prevalent subtype. We aim to determine the more prevalent type of nerve fiber damage—SFN, LFN, and MFN—in T1DM-associated DPN, both with and without pain.

Research design and methods

In this cross-sectional study, participants (n=216) were divided into controls; T1DM; T1DM with non-painful DPN (NP-DPN); and T1DM with painful DPN (P-DPN). DPN was further subgrouped based on neuropathy severity. The more prevalent type of fiber damage was determined applying small and large fiber-specific tests and three diagnostic models: model 1 (≥1 abnormal test); model 2 (≥2 abnormal tests); and model 3 (≥3 abnormal tests).

Results

MFN showed the highest prevalence in T1DM-associated DPN. No differences in neuropathy subtype were found between NP-DPN and P-DPN. DPN, with prevalent SFN plateaus between models 2 and 3. All models showed increased prevalence of MFN according to DPN severity. Model 3 showed increased DPN with prevalent LFN in early neuropathy. DPN with prevalent SFN demonstrated a similar, but non-significant pattern.

Conclusions

DPN primarily manifests as MFN in T1DM, with no differentiation between NP-DPN and P-DPN. Additionally, we propose model 2 as an initial criterion for diagnosing DPN with a more prevalent SFN subtype in T1DM. Lastly, the study suggests that in mild stages of DPN, one type of nerve fiber (either small or large) is more susceptible to damage.
Individual and geospatial factors associated with receipt of colorectal cancer screening: a state-wide mixed-level analysis
Authors: Bayly Jennifer E , Schonberg Mara A , Castro Marcia C , Mukamal Kenneth J
Published: July 2024

Background

Colorectal cancer (CRC) is the second leading cause of cancer death in US adults but can be reduced by screening. The roles of individual and contextual factors, and especially physician supply, in attaining universal CRC screening remains uncertain.

Methods

We used data from adults 50–75 years old participating in the 2018 New York (NY) Behavioural Risk Factor Surveillance System linked to county-level covariates, including primary care physician (PCP) density and gastroenterologist (GI) density. Data were analysed in 2023–2024. Our analyses included (1) ecological and geospatial analyses of county-level CRC screening prevalence and (2) individual-level Poisson regression models of receipt of screening, adjusted for socioeconomic and county-level contextual variables.

Results

Mean prevalence of up-to-date CRC screening was 71% (95% CI 70% to 73%) across NY’s 62 counties. County-level CRC screening demonstrated significant spatial patterning (Global Moran’s I=0.14, p=0.04), consistent with the existence of county-level contextual factors. In both county-level and individual-level analyses, lack of health insurance was associated with lower likelihood of up-to-date screening (ß=−1.09 (95% CI −2.00 to –0.19); adjusted prevalence ratio 0.68 (95% CI 0.60 to 0.77)), even accounting for age, race/ethnicity and education. In contrast, county-level densities of both PCPs and GIs were completely unassociated with screening at either the county or individual level. As expected, other determinants at the individual level included education status and age.

Conclusion

In this state-wide representative analysis, physician density was completely unassociated with CRC screening, although health insurance status remains strongly related. In similar screening environments, broadened insurance coverage for CRC screening is likely to improve screening far more effectively than increased physician supply.
Pretreatment CT-based machine learning radiomics model predicts response in unresectable hepatocellular carcinoma treated with lenvatinib plus PD-1 inhibitors and interventional therapy
Authors: Hua Yonglin , Sun Zhixian , Xiao Yuxin , Li Huilong , Ma Xiaowu , Luo Xuan , Tan Wenliang , Xie Zhiqin , Zhang Ziyu , Tang Chenwei , Zhuang Hongkai , Xu Weikai , Zhu Haihong , Chen Yajin , Shang Changzhen
Published: July 2024

Background

Lenvatinib plus PD-1 inhibitors and interventional (LPI) therapy have demonstrated promising treatment effects in unresectable hepatocellular carcinoma (HCC). However, biomarkers for predicting the response to LPI therapy remain to be further explored. We aimed to develop a radiomics model to noninvasively predict the efficacy of LPI therapy.

Methods

Clinical data of patients with HCC receiving LPI therapy were collected in our institution. The clinical model was built with clinical information. Nine machine learning classifiers were tested and the multilayer perceptron classifier with optimal performance was used as the radiomics model. The clinical-radiomics model was constructed by integrating clinical and radiomics scores through logistic regression analysis.

Results

151 patients were enrolled in this study (2:1 randomization, 101 and 50 in the training and validation cohorts), of which three achieved complete response, 69 showed partial response, 46 showed stable disease, and 33 showed progressive disease. The objective response rate, disease control rate, and conversion resection rates were 47.7, 78.1 and 23.2%. 14 features were selected from the initially extracted 1223 for radiomics model construction. The area under the curves of the radiomics model (0.900 for training and 0.893 for validation) were comparable to that of the clinical-radiomics model (0.912 for training and 0.892 for validation), and both were superior to the clinical model (0.669 for training and 0.585 for validation). Meanwhile, the radiomics model can categorize participants into high-risk and low-risk groups for progression-free survival (PFS) and overall survival (OS) in the training (HR 1.913, 95% CI 1.121 to 3.265, p=0.016 for PFS; HR 4.252, 95% CI 2.051 to 8.816, p=0.001 for OS) and validation sets (HR 2.347, 95% CI 1.095 to 5.031, p=0.012 for PFS; HR 2.592, 95% CI 1.050 to 6.394, p=0.019 for OS).

Conclusion

The promising machine learning radiomics model was developed and validated to predict the efficacy of LPI therapy for patients with HCC and perform risk stratification, with comparable performance to clinical-radiomics model.
Matrix attachment regions enhance transgene expression by manipulating position-dependent effects in stably transfected CHO-K1 cells
Authors: Zhang Jihong , Wang Lin , Zhang Xi , Sun Qiuli , Zhang Junhe
Published: July 2024

We previously found that the position of matrix attachment regions (MARs) within the vector significantly affects its ability to enhance transgenic expression in the recombinant protein production. This study aims to systematically investigate the position-dependent impacts of MAR on transgene expression. We observed a significant increase in enhanced green fluorescent protein (eGFP) expression levels in stably transfected CHO-K1 cells with either MAR 1-68 or MAR X-29 when MARs located upstream of the promoter. This increase was especially evident with MAR flanked the expression cassette. Concurrently, a substantial increase was observed in the percentage of eGFP-expressing cells, with 97.8% and 96.0% in MAR-containing constructs versus 73.7% in MAR-absent constructs. Further analysis of erythropoietin (EPO) expression revealed that constructs with flanking MARs induced the highest EPO productivity. Bioinformatics analysis revealed that certain specific transcription factors are important in modulating the transcription process. In conclusion, vectors harboring both MARs around the expression cassette constitute an optimal construct for enhanced recombinant protein production in CHO-K1 cells. This insight underscores the importance of strategic MAR incorporation in vector design for optimized recombinant protein expression.
The adaptive sliding mode control based on U–K theory for foot trajectory following of hexapod robot
Authors: Wei Junying , Li Xiang , Liu Yu , Zhang Haowei , Yang Lei , Li Xueyi
Published: July 2024

This paper addresses the control of a hexapod robot’s foot trajectory tracking using an adaptive sliding mode control (SMC) approach based on Udwadia–Kalaba theory. Unlike the traditional control approach, the Udwadia–Kalaba theory allows for the transformation of the hexapod robot foot trajectory tracking control problem into a system servo binding solution problem. This method eliminates the requirement to linearize the nonlinear system. The system may contain uncertainties, such as less-than-ideal initial circumstances and vibration disturbances during operation, which have an impact on the control precision due to mistakes in modeling, measurements, and changes in operational states. To deal with the uncertainty, the adaptive SMC controller was developed. The stability analysis is carried out using the second Lyapunov function method. By modeling the hexapod robot’s legs and running simulations to compare the simulated tracking route to the planned trajectory, the precision and stability of the control approach suggested in this study are finally demonstrated, and by comparing with the simulation results of adaptive robust control strategy, the advantages of RBF neural network adaptive SMC strategy are obtained.
Efficient EEG Feature Learning Model Combining Random Convolutional Kernel with Wavelet Scattering for Seizure Detection
Authors: Liu Yasheng , Jiang Yonghui , Liu Jie , Li Jie , Liu Mingze , Nie Weiwei , Yuan Qi
Published: July 2024

Automatic seizure detection has significant value in epilepsy diagnosis and treatment. Although a variety of deep learning models have been proposed to automatically learn electroencephalography (EEG) features for seizure detection, the generalization performance and computational burden of such deep models remain the bottleneck of practical application. In this study, a novel lightweight model based on random convolutional kernel transform (ROCKET) is developed for EEG feature learning for seizure detection. Specifically, random convolutional kernels are embedded into the structure of a wavelet scattering network instead of original wavelet transform convolutions. Then the significant EEG features are selected from the scattering coefficients and convolutional outputs by analysis of variance (ANOVA) and minimum redundancy-maximum relevance (MRMR) methods. This model not only preserves the merits of the fast-training process from ROCKET, but also provides insight into seizure detection by retaining only the helpful channels. The extreme gradient boosting (XGboost) classifier was combined with this EEG feature learning model to build a comprehensive seizure detection system that achieved promising epoch-based results, with over 90% of both sensitivity and specificity on the scalp and intracranial EEG databases. The experimental comparisons showed that the proposed method outperformed other state-of-the-art methods for cross-patient and patient-specific seizure detection.
An investigation of inflationary and bounce cosmology within the context of f(Q) gravity
Authors: Ghosh Moli , Chattopadhyay Surajit
Published: July 2024

In this work, we have examined the metric affine-based geometric model [Formula: see text] to investigate inflationary cosmology and bouncing cosmology. The four bouncing models we have examined are the exponential, matter, symmetric and super-bounce models. Furthermore, in the inflationary situation, we have employed a scalar field to test whether or not kinetic energy is dominated and whether or not all of the bouncing models are consistent with inflationary conditions. We have investigated various energy conditions for various scale factors and verified whether or not these scale factors are consistent with inflationary scenarios within the framework of inflationary cosmology under [Formula: see text]. In the end, we have shown that the bouncing scale factor under the polynomial model ([Formula: see text]) of [Formula: see text] gravity in a single scalar field is compatible with the inflationary scenario.