bluuebunny/crossref_metadata_2025 huggingface dataset:
A pilot study of novel ultrahigh‐frequency dorsal root ganglia stimulation for chronic lower limb pain: Focusing on safety and feasibility
Authors: Lee Shang‐Yi , Hsiung Nai‐Huan , Chapman Kenneth B. , Cheng Yu‐Kai , Huang Chieh‐Liang , Chen Kuen‐Bao , Chang Chi‐Heng , Wen Yeong‐Ray
Published: November 2024

Objectives

This single‐arm, open‐label, single‐center observational pilot study assessed the safety and efficacy of ultrahigh‐frequency dorsal root ganglia (UHF‐DRG) stimulation in patients with chronic leg pain with or without low back pain. Such high‐frequency electrostimulation had not been conducted in the human central nervous system previously.

Materials and Methods

The primary objective was to evaluate the safety of UHF‐DRG stimulation (2 Hz pulses with 50 msec pulse‐width and 500 kHz intrapulse sine waves, 5‐min duration per stimulation) by identifying incident adverse events (AE) and severe adverse events (SAE) during the trial. The secondary objectives included assessment of pain reduction using a numerical rating score (NRS), presence of paraesthesia, and changes in four pain medications (weak opioids, anticonvulsants, antidepressants, and non‐steroid‐anti‐inflammatory drugs). One DRG lead was implanted for one day then removed, and the patients received maximal three times of UHF stimulation in total.

Results

The study focused on ten cases. Two of them did not complete the study due to difficulty of lead implantation. There was no SAE in this trial. Among the ten cases, AEs occurred in eight, three experienced injection‐related local pain and one of them had a post‐dural‐puncture headache, others had symptoms un‐related to implantation procedure or UHF stimulation. The average NRS was reduced from 6.4 ± 1.1 at baseline to 2.9 ± 1.1 on the second‐day post‐implantation, and it was striking that the NRS was maintained at 3.6 ± 2.8 until 2 days after lead removal. The results showed a trend of lower frequency in medication use for all types of analgesics.

Conclusions

In this first‐in‐human pilot study, we discovered that intermittent pulsed UHF‐DRG stimulations ameliorated chronic lower limb pain for an extended period in humans. Our finding opens up a new neuromodulatory concept and may initiate a novel paradigm for treating intractable pain.
A Key R2R3‐MYB Transcription Factor Activates Anthocyanin Biosynthesis and Leads to Leaf Reddening in Poplar Mutants
Authors: Li Weinan , Li Qianqian , Che Jiahang , Ren Jie , Wang Aike , Chen Jinhuan
Published: November 2024

Colorful woody plants are highly valued for their ornamental qualities, and are commonly used in garden landscape design. We previously cultivated several ornamental poplar varieties from bud mutants of Populus sp. Linn. ‘2025’ (ZL2025), each with different leaf colors. Based on transcriptome data from these varieties with varying anthocyanin pigmentation, we identified and named an R2R3‐MYB gene, PdMYB113. The mRNA of PdMYB113 accumulated in the leaves of the red‐leaf mutants ‘QHY’ and ‘LHY’, but barely expressed in the leaves of ‘ZL2025’. The anthocyanin biosynthesis genes were upregulated, resulting in high levels of red anthocyanins (particularly Peonidin‐3‐O‐rutinoside, Cyanidin‐3‐O‐rutinoside, and Cyanidin‐3‐O‐glucoside) in both OE‐PdMYB113 tobacco and poplar plants. This upregulation caused a color change in the tissues from green to red or dark purple. Yeast one‐hybrid and luciferase assays demonstrated that PdMYB113 activates the expression of anthocyanin biosynthesis genes, including the early anthocyanin biosynthetic gene PdCHS and the late anthocynin biosynthetic gene PdANS. Consequently, PdMYB113 is identified as a key regulator of red coloration in poplar. Additionally, PdMYB113 does not dwarf transgenic plants under normal lighting conditions. This study elucidates the regulatory mechanisms of color change in ZL2025 and highlights a crucial gene for breeding new varieties of woody plants.
Cytosolic fructose‐1,6‐bisphosphatase isoform mediates metabolic adjustments in bean fruit pericarp to support seed growth
Authors: Bernal Lilia , Coello Patricia , Padilla‐Chacón Daniel , Martínez‐Barajas Eleazar
Published: November 2024

Seed development requires substantial metabolic resources and is influenced by adverse environmental conditions. However, the ability of plants to produce viable seeds under restrictive conditions suggests the existence of mechanisms that make this process less sensitive to environmental stress. Uncovering their regulation could lead to the development of genotypes better adapted to stressful conditions. Plant response to stress is complex, and the contribution of organs such as the fruit pericarp to stress tolerance mechanism may have been underestimated. The bean fruit pericarp, a photosynthetic structure that contributes to seed development, can synthesize starch from surplus sucrose, which is later degraded during the rapid seed growth phase. This metabolic flexibility may be crucial for supporting seed growth when the photosynthate supply is reduced. To explore this possibility, we disrupted phloem continuity at the pedicel level in fruits about to enter the seed reserve accumulation stage. We used the capacity of the pericarp to incorporate 14CO2 to investigate changes in its metabolism. Our findings reveal that, in response to reduced photosynthate availability, the fruit pericarp did not increase 14CO2 fixation. However, the amount of 14C used for starch synthesis decreased, while the proportion used for soluble sugars synthesis increased. This shift resulted in an increase in 14C‐products transported to seeds was accompanied by a significant increase in the activity of cytosolic fructose 1,6‐bisphosphatase. Our results indicate that photosynthate restriction accelerates the degradation of pericarp storage proteins, and the increase in cFBPase activity could be crucial in converting the carbon produced in carbohydrates.
Interlocal learning mechanisms and policy diffusion: The case of new energy vehicles finance in Chinese cities
Authors: Liu Weixing , Ma Liang , Wang Xuan , Yi Hongtao
Published: November 2024

Policy diffusion based on learning mechanisms has fascinated political science and public administration scholars for a long time. A robust and growing body of studies have identified the existence and importance of learning mechanisms in policy diffusion. However, there are still some gaps that need to be further improved. First, scholars identify the learning mechanism mainly based on indirect evidence, such as geographical proximity and successful innovation policies adopted by other jurisdictions, which lacking direct and systematic evidence. Second, little is known about how the hierarchical power structure affects the leap from learning behavior to policy adoption. This study provides direct evidence for the promoting effect of intergovernmental learning on policy diffusion by analyzing case of Chinese local financial subsidy policies for new energy vehicles. The empirical results reveal that policy learning in the form of site visits among local governments significantly promotes the policy diffusion, but superior government policy strategy attenuates the influence of interlocal learning on policy diffusion. Also, the initiators and themes of policy learning affect the learning–diffusion linkage, portraying the conditional effects and nuanced dynamics of interlocal policy learning in eliciting policy diffusion.
Expressed emotion and help‐seeking behaviours among elderly adults with depression symptoms in northeast Malaysia: qualitative findings from a mixed methods investigation
Authors: Sanggar Arunah , Razak Asrenee Ab , Phoa Picholas Kian Ann
Published: November 2024

Background

Stressful life events greatly increase the risk of depression, which affects about 22% of older persons in northeast Malaysia. But how emotional distress manifests itself in reaction to these stressful events differs from person to person. Therefore, this study aims to delve into the nuances of emotional expression among older adults with depression symptoms in northeast Malaysia, alongside their help‐seeking behaviours and utilisation of professional support.

Methods

Using a qualitative interpretative phenomenological approach, we conducted in‐depth face‐to‐face interviews with participants, guided by Kleinman's explanatory model of illness. Nineteen older adults who screened positive for depression were included in the research.

Results

None of the participants explicitly acknowledged experiencing depression. However, they articulated their distress through three primary themes: ‘Life is miserable,’ ‘Depression is a sign of weakness,’ and ‘Belief in pre‐determination.’ Remarkably, despite screening positive for depression, participants demonstrated a lack of awareness regarding available professional mental health services. Moreover, they expressed a reluctance to seek such services, citing reasons related to stigma and misconceptions. The predominant themes that emerged concerning help‐seeking behaviours were ‘Self‐efficacy,’ ‘Social support,’ and ‘Formal assistance from non‐mental healthcare professionals.’

Conclusion

The expression of emotion among older adults is restricted by socio‐cultural influences. Thus, there is a need to improve mental health literacy among older adults in Malaysia, and their preferred source of support such as religious leaders and non‐mental healthcare physicians.
Fifteen years of tillage and straw returning promotes soil structure and carbon sequestration under rice–rice–oilseed rape rotation in Central China
Authors: Zhang Yanke , Wang Kunkun , Wang Jinlong , Zhong Zijing , Ren Tao , Li Xiaokun , Cong Rihuan , Lu Jianwei
Published: November 2024

Straw returning and tillage measures are one of the key measures to improve soil structure and fertilize soil. Different rotation systems and tillage methods (no‐tillage or conventional tillage) affect the physical structure and the C sequestration efficiency of soil. Here, we examined the response of soil organic C stocks, soil C fractions and soil structure to straw returning and tillage management based on a 15‐year rice–rice–oilseed rape rotation. Our results indicated that the soil carbon stock reached C equivalent within 10 years with straw returning and 5–6 years without straw returning. No‐tillage improve the C sequestration efficiency only in the early stage. Soil organic C (SOC) fractions significantly increased after straw returning, that is, dissolved organic carbon (DOC) increased by 10.3%–21.4%, particulate organic carbon (POC) increased by 32.0%–44.2%, light fraction organic carbon (LFOC) increased by 37.9%–61.2%, and microbial biomass carbon (MBC) increased by 7.1%–12.1%. Except for LFOC, no significant difference was observed between no‐tillage and tillage for the other SOC fractions. Straw returning significantly improved the proportion of >2 mm aggregates (+40.0%) and the SOC content of >0.25 mm aggregates. Meanwhile, straw returning with conventional tillage (CTS) enhanced the SOC content of <0.25 mm aggregates. The soil structure became irregular (anisotropy increased by 115.0%), more complex (fractal dimension increased by 10.2%) and the number of soil pores increased by 108.5% after straw returning. LFOC and MBC played important roles in promoting the changes in the soil structure and the formation of macro‐aggregates. Overall, straw returning was more effective in increasing the SOC, the accumulation of macro‐aggregates, and the number of soil macropores, as well as improving the soil structure compared with tillage under the triple upland‐paddy rotation system.
Long‐term conservation tillage practices affect total carbon and contribute to the formation of soil aggregates in the semi‐arid North China Plain
Authors: Wu Hongliang , Timilsina Arbindra , Chen Suying , Li Xiaoxin , Zhang Yuming , Hu Chunsheng , Dong Wenxu
Published: November 2024

The soil aggregates characteristics and organic carbon (SOC) distribution under various tillage practices have been widely studied, but the changes in inorganic carbon (SIC) and their effect on soil aggregate formation are not clear. This study evaluated how long‐term tillage affects total carbon (both organic and inorganic) and contributes to forming aggregates in a fluvo‐aquic soil derived from limestone alluvial fans in the North China Plain. The four tillage practices that were used in a maize (Zea mays)/wheat (Triticum aestivum) double‐cropping system were moldboard plough without residues (CK), moldboard plough with residue retention (CT), rotary tillage with residue retention (RT) and no tillage with residue retention (NT). CT treatment, compared with NT treatment, decreased the SIC concentration at 0–300 mm and SOC concentration at 0–50 mm but increased the SOC concentration at 100–300 mm. Thus, there were no differences in the total carbon storage in the 0–300 mm layer because of the changes in SOC and SIC concentrations among four tillage practices. NT and RT practices increased the large macro‐aggregates (LM>2mm) and the mean weight diameter (MWD) only within the 0–50 mm layer, while the CT practice increased the LM>2mm and the MWD within the 100–250 mm layer. Correlation analysis revealed a significant link between LM>2mm and SOC, while small macroaggregates (SM0.25–2mm) were closely correlated with SIC. SOC and SIC had a relay cementation effect on the formation of large aggregates under long‐term tillage, and therefore, the effects of these two types of carbon should be comprehensively considered in the study of carbon sequestration and aggregate formation in calcareous soil.
Cutting the sap: First molecular phylogeny of twig‐girdler longhorn beetles (Coleoptera: Cerambycidae: Lamiinae: Onciderini) suggests shifts in host plant attack behaviours contributed to morphological evolution
Authors: Souza Diego de S. , French Rowan L. K. , Júnior José O. Silva , Nearns Eugenio H. , Marinoni Luciane , Swift Ian P. , Miller Kelly B. , Sperling Felix A. H. , Monné Marcela L.
Published: November 2024

Understanding how novel adaptive traits arise, evolve and impact other aspects of an organism's phenotype is a foundational question in evolutionary biology. We explore this by focusing on Onciderini (Coleoptera: Cerambycidae: Lamiinae), a tribe of longhorn beetles commonly referred to as twig girdlers because the females of some species girdle live trees to deposit their eggs. We reconstructed the first time‐calibrated phylogeny of the Onciderini, based on three genetic markers (cytochrome c oxidase subunit 1 ‘cox1’, Wingless ‘Wg’ and carbamoyl‐phosphate synthase domain of the CAD locus ‘CPS’), and used morphometric data, employing multiple models of trait evolution and phylogenetic regressions, to assess whether girdling behaviour predicts head size or head size sexual dimorphism. Our results indicate that onciderines originated c. 49 million years ago ‘Ma’ (95% highest posterior densities ‘HPD’: 44.1–54.57 Ma) and consist of two major lineages, which we formalize as subtribes Hypsiomatina and Onciderina. Additionally, our analyses revealed several taxonomic inconsistencies within the tribe, which we rectify by proposing new synonymies, including Jamesia Jekel as a synonym of Hypselomus Perty, Cipriscola Dillon & Dillon of Hypsioma Audinet‐Serville and Psyllotoxus Thomson and Taricanus Thomson as a synonym of Oncideres Lacordaire, and a new combination for Periergates kenjii Nearns & Swift as Oncideres kenjii (Nearns & Swift) comb. nov. Using this new phylogenetic framework, we identified five independent unidirectional origins of girdling behaviour within the tribe. Overall, our results suggest that girdling influences head size evolution in Onciderini, as it is associated with an increase in both male and female head size of girdler species. Despite this, girdling and non‐girdling lineages do not consistently differ in head size sexual dimorphism. This study refines the classification of Onciderini and marks a significant step in understanding the evolutionary dynamics shaping the diversity of twig‐girdler beetles, a group with notable ecological and economic importance.
Quantitative Identification of Mixed Urban Functions: A Probabilistic Approach Based on Physical and Social Sensing Data
Authors: Zhang Yan , Kwan Mei‐Po , Yu Boting , Liu Yanjun , Song Liuyi , Chen Nengcheng
Published: November 2024

This paper proposes a diversity identification method based on information fusion for quantitatively identifying mixed urban functional zones (UFZ), addressing the critical need for better city planning and management. This method integrates both social and physical sensing data, considering the frequency of urban functional occurrences and the intensity of human activity. Specifically, we extract “dynamic” human activity features from crowdsourced smart device data and “static” visual features from street view images. Based on the fused multi‐modal data, our method infers the large‐scale distribution of UFZs more accurately. We also create a standardized mixed UFZ dataset for model training and testing, which includes residential, commercial, public services, industrial, and ecological categories. In general, the method transforms the functional label recognition task into a probability distribution recognition task. It addresses complex land use distributions rather than simply assigning a single label to each zone. The result shows that our method could achieve a Cosine similarity of (0.542 ± 0.143), the lowest Chebyshev of (0.785 ± 0.043), and L1 distances of (0.264 ± 0.080), indicating more accurate and consistent predictions and closer match to true distributions.
Confronting the neoliberal challenge: Recognition, social freedom and depth realism
Authors: Agar Jolyon Charles
Published: November 2024

This article explores how Axel Honneth's critical theory, when adapted to a materialist depth realism, can be utilised as a critique of Fredrick Hayek's ‘neoliberalism’, an antipolitics influenced by Karl Popper's neo‐positivism. In response to the neoliberal challenge, it is proposed that Axel Honneth's theories of recognition, when grounded in anthropological (‘critical’) materialism, provides a robust defence of an irreducible social agency. When interpreted through this lens, recognition is one aspect of the system of human needs based on subject–subject interactions, the other being a subject–object interaction of humans with non‐human objects. By contrast, Honneth's more recent theory of social freedom relies on a Hegelian process of historical reconstruction and so remains vulnerable to the same epistemic errors that inform neoliberal attempts to universalise homo economicus, that is, of reducing reality to various ways in which it is conceptualised. In this regard, anthropological materialism must presuppose depth realism. The importance of this can be seen when the implications for Honneth's move towards a more orthodox Hegelianism in his more recent works are considered.
Molecular hydrogen positively influences root gravitropism involving auxin signaling and starch accumulation
Authors: Zhang Yingying , Liu Ziyu , Huang Huize , Li Longna , Xu Sheng , Shen Wenbiao
Published: November 2024

Although geoscience of natural hydrogen (H2), hydrogen‐producing soil bacteria, and especially plant‐based H2, has been observed, it is not clear whether or how above H2 resources influence root gravitropic responses. Here, pharmacological, genetic, molecular, and cell biological tools were applied to investigate how plant‐based H2 coordinates gravity responses in Arabidopsis roots. Since roots show higher H2 production than shoots, exogenous H2 supply was used to mimic this function. After H2 supplementation, the asymmetric expression of the auxin‐response reporter DR5 driven by auxin influx and efflux carriers, and thereafter positive root gravitropism were observed. These positive responses in root gravitropism were sensitive to auxin polar transport inhibitors, and importantly, the defective phenotypes observed in aux1‐7, pin1, and pin2 mutants were not significantly altered by exogenous H2. The observed starch accumulation was matched with the reprogramming gene expression linked to starch synthesis and degradation. Transgenic plants expressing hydrogenase1 (CrHYD1) from Chlamydomonas reinhardtii not only displayed higher endogenous H2 concentrations, the inducible AUX1 gene expression and starch accumulation, but also showed pronounced root gravitropism. Collectively, above evidence preliminarily provides a framework for understanding the molecular basis of the possible functions of both plant/soil‐based and nature H2 in root architecture.
Imagining post‐war futures amid cycles of destruction and efforts of reconstruction
Authors: Carr Constance , Kryvets Olga
Published: November 2024

This commentary brings forward Ukrainian voices to this journal's conversation on the invasion of Ukraine and the dilemmas it poses to scholars in geography. We argue that there needs to be space in this discussion for the viewpoints of Ukrainians themselves who are on the ground, confronting the atrocities every day, and who can provide experiential knowledge about (i) the immediate cycles of destruction and efforts of reconstruction; (ii) the systemic impediments to reconstruction; and (iii) the diverse sets of post‐war imagined futures. These signpost to scholars the sheer scope of the conflict and the multitude of research avenues to explore in order to understand the realities of the war more deeply. They thus provide information and inspiration to geographers wondering about how to orient and where to respond.
Improving RBC inventory by optimizing preoperative ordering and eliminating crossmatch and hold
Authors: Virk Mrigender Singh , Cederlof Kathleen , Howard Emily , Panigrahi Anil
Published: November 2024

Background

Blood product constraints have increased the focus on inventory management as blood banks have faced challenges that impact supply chains and donor availability. Solutions often include a reduction in transfusion volumes through multidisciplinary improvements, but this is often coupled with a reduction in blood bank inventory to match reduced demand. We sought to improve inventory availability within the blood bank without modification of transfusion rates through solutions that prevented unnecessary RBC orders and crossmatching.

Study Design and Methods

Improvements were focused on reduction of duplicate orders, preoperative blood orders, excess volume of blood orders, and crossmatching in advance of perioperative needs. The study monitored the improvement of the crossmatch to transfusion ratio as the primary outcome and days of shelf life until expiration as a secondary outcome.

Results

The CT ratio of RBCs decreased from 2.03 (16,044/7922) pre‐implementation to 1.67 (12,321/7375) post‐implementation (p < 0.05). Our inventory was managed more efficiently following our interventions as demonstrated through the day of shelf life of RBCs issued. Pre‐implementation, RBCs were issued an average of 17.5 days before expiration, which increased to 20.4 days post‐implementation (p < 0.05).

Conclusion

Modification of preoperative order sets and education of clinical staff to ensure appropriate blood product ordering can significantly impact available inventory. Although this was also identified within our study, we found that the largest impact comes from a change in crossmatching workflow to reduce unnecessary reserving of RBCs. These changes can be implemented without significant impact to turnaround time.
The prevalence of murmurs and gallop sounds in anemic cats
Authors: Matson Hannah , Fuentes Virginia Luis , Humm Karen
Published: November 2024

Background

There is little information on the prevalence of auscultatory abnormalities in anemic cats. This study aimed to describe the prevalence of cardiac murmurs and gallop sounds in a population of anemic and nonanemic cats presenting to an emergency room (ER) and to assess whether the prevalence of auscultatory abnormalities was influenced by the severity of anemia.

Key Findings

Records of cats presenting to an ER between May 2021 and May 2022 or receiving a blood transfusion between September 2019 and January 2022 were retrospectively analyzed for presence of a murmur or gallop sound. Cats with known structural heart disease were excluded. A murmur was found in 56 of 185 (30%) anemic cats compared with 11 of 102 (11%) nonanemic cats (p < 0.001), with a higher proportion in cats with PCV <16% (p < 0.001). Twenty‐five of 185 (14%) anemic cats had a gallop compared with 4 of 102 (4%) nonanemic cats (p = 0.009), with the highest proportion in cats with PCV 11%–20% (p < 0.001). Echocardiography was performed on 17 of 185 anemic cats; 8 had normal echocardiograms and 9 demonstrated evidence of chamber dilation without left ventricular wall thickening, consistent with anemia.

Conclusions

Abnormalities on auscultation are common in anemic cats presenting to the ER, with a higher prevalence in more severely anemic cats.
Comparison of intranasal atipamezole by atomization or drops with intramuscular injection for reversing sedative effects of medetomidine in healthy dogs
Authors: Jafarbeglou Majid , Marjani Mehdi , Oghbaei Mohammadreza , Paryani Mohammadreza , Bakhshi‐Khanghah Reza
Published: November 2024

Objective

To determine and compare the efficacy of intranasal (IN) atomization, IN drops, and IM injection of atipamezole for reversal of medetomidine‐induced sedation in healthy dogs.

Design

Prospective, randomized, blinded study.

Setting

University teaching hospital.

Animals

Forty mixed‐breed, shelter‐owned dogs with an average weight of 29.9 ± 5.6 kg (mean ± SD) that required sedation for minor diagnostic or therapeutic procedures.

Interventions

Atipamezole was administered by a dog handler at 200 µg/kg via IN atomization (ATI‐INA, n = 10), IN drops (ATI‐IND, n = 10), or IM injection (ATI‐IM, n = 10) 20 minutes following medetomidine administration (40 µg/kg). A control group (n = 10) received no atipamezole.

Measurements and Main Results

Ease of atipamezole administration was evaluated. Sedation score, heart rate (HR), respiratory rate (RR), and blood pressure (BP) were recorded pre‐medetomidine administration (T0), pre‐atipamezole administration (T20), and at multiple intervals following atipamezole administration. ATI‐IM resulted in the fastest recovery, followed by ATI‐INA, with ATI‐IND being the slowest. The adverse cardiovascular impacts of medetomidine were not completely mitigated. ATI‐IM showed initial HR restoration followed by a decline. HR in both IN groups showed a slower increase compared to ATI‐IM, but no subsequent decline was observed. ATI‐IM resulted in a transient decrease in BP, though dogs remained normotensive. A gradual reduction in BP was noted in the IN groups. At T50, RR of all atipamezole groups differed from control, and a significant increase in RR was observed in ATI‐IM dogs compared to pre‐atipamezole value. No adverse effects were observed.

Conclusions

All routes for atipamezole administration effectively reversed medetomidine‐induced sedation, with ATI‐IM being fastest. IN routes were easy for the dog handler to administer, making them viable alternatives in cases of accidental drug exposure, particularly outside a hospital setting.
An integrative species delimitation approach uncovers eriophyoid mite Diptilomiopus ligustri species complex (Acariformes: Eriophyoidea)
Authors: Gao Wei‐Nan , Zhang Qi , Xue Xiao‐Feng
Published: November 2024

Eriophyoid mites (Acari: Eriophyoidea) are among the smallest terrestrial arthropods possessing simplified morphological characters, which challenges the traditional morphology‐based species delimitation. The Diptilomiopus spp. exhibit further morphological degeneration (e.g., lack of genus on both legs and some opisthosoma setae). Especially, they possess high similarity in the reticulate prodorsal shield patterns, leading to cryptic species complex and hampering our understanding of species diversity. In this study, we implemented an integrated approach, including genetic distance analysis, phylogenetic analysis, population genetic structure construction, introgression test, and morphometric analysis, to delimitate the Diptilomiopus ligustri complex. We obtained 52 mitochondrial COI gene sequences and 19 whole‐genome sequences across 18 sample sites of this complex. All samples were collected from Ligustrum plants in China, which may cover their main distribution ranges. Our results demonstrate that the D. ligustri complex consists of at least four distinct species (i.e., D. ligustri, D. cf. ligustri sp1., D. cf. ligustri sp2., and D. cf. ligustri sp3.), which are genetically divergent but do not differ morphologically, assessed by principal component analysis of 27 morphological characteristics. No significant gene flow was observed among this complex. Divergence time estimates further showed that most Diptilomiopus species diverged in a short time interval at the Paleogene–Neogene boundary, indicating a rapid radiation. Our results highlight the integrated approaches in eriophyoid mite species complex delimitation.
Purkinje cell ablation and Purkinje cell‐specific deletion of Tsc1 in the developing cerebellum strengthen cerebellothalamic synapses
Authors: Nishiyama Hiroshi , Nishiyama Naoko , Zemelman Boris V.
Published: November 2024

Cerebellar damage early in life often causes long‐lasting motor, social and cognitive impairments, suggesting the roles of the cerebellum in developing a broad spectrum of behaviours. This recent finding has promoted research on how cerebellar damage affects the development of the cerebral cortex, the brain region responsible for higher‐order control of all behaviours. However, the cerebral cortex is not directly connected to the cerebellum. The thalamus is a major direct target of the cerebellar nuclei, conveying cerebellar signals to the cerebral cortex. Despite its crucial position in cerebello–cerebral interaction, thalamic susceptibility to cerebellar damage remains largely unclear. Here, we studied the consequences of early cerebellar perturbation on thalamic development. Whole‐cell patch‐clamp recordings showed that the synaptic organization of the cerebellothlamic circuit is similar to that of the primary sensory thalamus, in which aberrant sensory activity alters synaptic circuit formation. The ablation of Purkinje cells in the developing cerebellum strengthened cerebellothalamic synapses and enhanced thalamic suprathreshold activities. Purkinje‐cell specific deletion of tuberous sclerosis complex subunit 1 (Tsc1), an autism‐associated gene for which the protein product negatively regulates the mammalian target of rapamycin, also strengthened cerebellothalamic synapses. However, this strengthening occurred only in homozygous deletion, whereas both homozygous and hemizygous deletion are known to cause autism‐like behaviours. These results suggest that, although the cerebellothalamic projection is vulnerable to disturbances in the developing cerebellar cortex, other changes may also drive the behavioural consequences of early cerebellar perturbation.

image

Key points

Cerebellar damage early in life often causes motor, social and cognitive impairments, suggesting the roles of the cerebellum in developing a broad spectrum of behaviours.

Recent studies focus on how the developing cerebellum affects the formation and function of the cerebral cortex, the higher‐order centre for all behaviours. However, the cerebellum does not directly connect to the cerebral cortex.

Here, we studied the consequences of early cerebellar perturbation on the thalamus because it is a direct postsynaptic target of the cerebellum, sending cerebellar signals to the cerebral cortex.

Loss of cerebellar Purkinje cells, which are commonly associated with various neurological disorders, strengthened cerebellothalamic synapses, suggesting the vulnerability of the thalamus to substantial disturbance in the developing cerebellum.

Purkinje cell‐specific loss of tuberous sclerosis complex‐1, a negative regulator of mammalian target of rapamycin, is an established mouse model of autism. This mouse model also showed strengthened cerebellothalamic synapses.
The React–Predict–Manipulate Model: A Proposed Theoretical Hierarchy of Decision Making in Competitive Environments
Authors: Maier Torsten , Alzahabi Reem , Sharpe Benjamin T. , Maier Hillary
Published: November 2024

The competitive environment, high stakes, and intense time pressure inherent in esports underscore the necessity for superior decision-making abilities under pressure. The React–Predict–Manipulate (RPM) Model offers a theoretical framework to enhance understanding and training of decision making in competitive gaming environments. Based on cognitive psychology and decision theory, the RPM Model delineates a hierarchy of cognitive processes: React, Predict, and Manipulate. Each level represents a progressive refinement in the decision-making capabilities of players—from instinctual reactions to strategic foresight and tactical manipulation. This paper explores how esports athletes can leverage this model to cultivate higher cognitive agility and strategic acumen, thus potentially improving their performance in high-stakes scenarios.
Metagenome-based diversity and functional analysis of culturable microbes in sugarcane
Authors: Lin Haidong , Wu Liang , Zhang Lijun , Ta Quang Kiet , Liu Peng , Song Jinkang , Yang Xiping
Published: November 2024

Sugarcane is a key crop for sugar and energy production, and understanding the diversity of its associated microbes is crucial for optimizing its growth and health. However, there is a lack of thorough investigation and use of microbial resources in sugarcane. This study conducted a comprehensive analysis of culturable microbes and their functional features in different tissues and rhizosphere soil of four diverse sugarcane species using metagenomics techniques. The results revealed significant microbial diversity in sugarcane’s tissues and rhizosphere soil, including several important biomarker bacterial taxa identified, which are reported to engage in several processes that support plant growth, such as nitrogen fixation, phosphate solubilization, and the production of plant hormones. The Linear discriminant analysis Effect Size (LEfSe) studies identified unique microbial communities in different parts of the same sugarcane species, particularly
Burkholderia
, which exhibited significant variations across the sugarcane species. Microbial analysis of carbohydrate-active enzymes (CAZymes) indicated that genes related to sucrose metabolism were mostly present in specific bacterial taxa, including
Burkholderia
,
Pseudomonas
,
Paraburkholderia
, and
Chryseobacterium
. This study improves understanding of the diversities and functions of endophytes and rhizosphere soil microbes in sugarcane. Moreover, the approaches and findings of this study provide valuable insights for microbiome research and the use of comparable technologies in other agricultural fields.

IMPORTANCE

This work utilized metagenomics techniques for conducting a comprehensive examination of culturable microbes and their functional characteristics in various tissues and rhizosphere soil of four distinct sugarcane species. This study enhances comprehension of the diversity and functions of endophytes and rhizosphere soil microbes in sugarcane. Furthermore, the methodologies and discoveries of this work offer new perspectives for microbiome investigation and the use of similar technologies in other agricultural fields.
Performance of deep learning models in predicting the nugent score to diagnose bacterial vaginosis
Authors: Watanabe Naoki , Watari Tomohisa , Akamatsu Kenji , Miyatsuka Isao , Otsuka Yoshihito
Published: November 2024

The Nugent score is a commonly used diagnostic tool for bacterial vaginosis. However, its accuracy depends on the skills of laboratory technicians. This study aimed to evaluate the performance of deep learning models in predicting the Nugent score to improve diagnostic consistency and accuracy. In total, 1,510 vaginal smear images collected from a hospital in Japan between 2021 and 2023 were assessed. Each image was annotated by laboratory technicians into one of four categories based on the Nugent score—normal vaginal flora, no vaginal flora, altered vaginal flora, or bacterial vaginosis. Deep learning models were developed to predict these categories, and their performance was compared to that of technician annotations. The deep learning models demonstrated 84% accuracy at 400× magnification and 89% at 1,000× magnification. The 1,000× model was further optimized and tested on an independent set of 106 images. After optimization, the advanced model achieved 94% accuracy, outperforming the average 92% accuracy of the technicians. The agreement between the advanced model predictions and technicians was 92% for normal vaginal flora, 100% for no vaginal flora, 91% for altered vaginal flora, and 100% for bacterial vaginosis. Overall, our findings suggest that deep learning models have the potential to diagnose bacterial vaginosis with an accuracy comparable to that of laboratory technicians.

IMPORTANCE

Bacterial vaginosis is a global health issue affecting women, causing symptoms such as abnormal vaginal discharge and discomfort. The Nugent score is a standard method for diagnosing bacterial vaginosis and is based on the manual interpretation of Gram-stained vaginal smears. However, this method relies on the skill and experience of trained professionals, leading to variability in results and poses significant challenges for settings with limited access to experienced technicians. The results of this study indicate that deep learning models can predict the Nugent score with high accuracy, offering the potential to standardize the diagnosis of bacterial vaginosis. By reducing observer variability, these models can facilitate reliable diagnoses, even in settings where experienced personnel are scarce. Although validation is needed on a larger scale, our results suggest that deep learning models may represent a new approach for diagnosing bacterial vaginosis.
6-(Pyrazol-1-yl)pyrazolo[3,4-b]pyridines: Synthesis, Structure, and Wheat Growth Regulating Activity
Authors: Dmitrieva I. G. , Vasilin V. K. , Dotsenko V. V. , Aksenov N. A.
Published: November 2024

4-Methyl-6-pyrazolyl-2-chloronicotinonitriles were synthesized by the reaction of 6-hydrazino-4-methyl-2-chloronicotinonitriles with 1,3-diketones. Upon treatment with hydrazine and methylhydrazine, 4-methyl-6-pyrazolyl-2-chloronicotinonitriles were converted into the corresponding 3-amino-4-methyl-6-pyrazolyl-1H-pyrazolo[3,4-b]pyridines. A similar reaction involving 1,1-dimethylhydrazine and ethylhydrazine was accompanied by elimination of the alkyl substituent and also led to the formation of 3-amino-6-pyrazolyl-1H-pyrazolo[3,4-b]pyridines. Acylation and carbamoylation of the prepared compounds proceeded regioselectively at the amino group. One of the new compounds, N-[6-(3,5-dimethylpyrazol-1-yl)-1,4-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanoylamide, showed a growth-stimulating effect in the field experiments on winter wheat crops.
Preclinical evaluation of antigen-sensitive B7-H3-targeting nanobody-based CAR-T cells in glioblastoma cautions for on-target, off-tumor toxicity
Authors: Meeus Fien , Funeh Cyprine Neba , Awad Robin Maximilian , Zeven Katty , Autaers Dorien , De Becker Ann , Van Riet Ivan , Goyvaerts Cleo , Tuyaerts Sandra , Neyns Bart , Devoogdt Nick , De Vlaeminck Yannick , Breckpot Karine
Published: November 2024

Background

Glioblastoma is the most common lethal primary brain tumor, urging evaluation of new treatment options. Chimeric antigen receptor (CAR)-T cells targeting B7 homolog 3 (B7-H3) are promising because of the overexpression of B7-H3 on glioblastoma cells but not on healthy brain tissue. Nanobody-based (nano)CARs are gaining increasing attention as promising alternatives to classical single-chain variable fragment-based (scFv)CARs, because of their single-domain nature and low immunogenicity. Still, B7-H3 nanoCAR-T cells have not been extensively studied in glioblastoma.

Methods

B7-H3 nanoCAR- and scFvCAR-T cells were developed and evaluated in human glioblastoma models. NanoCAR-T cells targeting an irrelevant antigen served as control. T cell activation, cytokine secretion and killing capacity were evaluated in vitro using ELISA, live cell imaging and flow cytometry. Antigen-specific killing was assessed by generating B7-H3 knock-out cells using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-genome editing. The tumor tracing capacity of the B7-H3 nanobody was first evaluated in vivo using nuclear imaging. Then, the therapeutic potential of the nanoCAR-T cells was evaluated in a xenograft glioblastoma model.

Results

We showed that B7-H3 nanoCAR-T cells were most efficient in lysing B7-H3posglioblastoma cells in vitro. Lack of glioblastoma killing by control nanoCAR-T cells and lack of B7-H3negglioblastoma killing by B7-H3 nanoCAR-T cells showed antigen-specificity. We showed in vivo tumor targeting capacity of the B7-H3 nanobody—used for the nanoCAR design—in nuclear imaging experiments. Evaluation of the nanoCAR-T cells in vivo showed tumor control in mice treated with B7-H3 nanoCAR-T cells in contrast to progressive disease in mice treated with control nanoCAR-T cells. However, we observed limiting toxicity in mice treated with B7-H3 nanoCAR-T cells and showed that the B7-H3 nanoCAR-T cells are activated even by low levels of mouse B7-H3 expression.

Conclusions

B7-H3 nanoCAR-T cells showed promise for glioblastoma therapy following in vitro characterization, but limiting in vivo toxicity was observed. Off-tumor recognition of healthy mouse tissue by the cross-reactive B7-H3 nanoCAR-T cells was identified as a potential cause for this toxicity, warranting caution when using highly sensitive nanoCAR-T cells, recognizing the low-level expression of B7-H3 on healthy tissue.
Successful treatment of in-transit metastatic melanoma with combination intralesional T-VEC and topical imiquimod immunotherapy
Authors: Lenga Marisa , Choi Esther , Sosman Jeffrey , Chandra Sunandana , Lam Danielle , Johnson Kirsten , Schiemann Lauren , Choi Jennifer
Published: November 2024

In-transit metastases of malignant melanoma pose a significant clinical challenge, particularly in patients with contraindications to systemic therapies. While surgical excision and systemic immunotherapies remain standard treatments, localized therapies such as intralesional talimogene laherparepvec (T-VEC) and topical imiquimod, which stimulate tumor-specific T-cell responses, have garnered increasing attention for their potential efficacy and tolerability. Although the individual efficacy of these therapies is well-documented, their combined use and their synergistic effects have not been well-documented. This case series reports on five patients with in-transit melanoma metastases treated with T-VEC and imiquimod at Northwestern Memorial Hospital from November 2018 to May 2023. Patients received a median of 13 (range 8–20) T-VEC injections over a median of 6 months (range 5–9), of which 4 of those months were with concurrent T-VEC and imiquimod cream. Four of the five patients achieved complete response (CR) by the end of the treatment course. One patient developed systemic progression during therapy, leading to early cessation of treatment. All patients with CR elected to continue topical imiquimod applications as maintenance following T-VEC for a median of 6 months (range 2–14 months). Only one of the four patients who achieved CR developed metastatic nodal disease 10 months after the last T-VEC injection. The three other patients are free of cutaneous and systemic disease 2–57 months after their last injection. All patients tolerated treatment well with zero patients discontinuing treatment due to side effects. These findings suggest that the combination of intralesional T-VEC and topical imiquimod can be an effective and safe treatment of in-transit metastases of malignant melanoma.
Analytical solution for rainwater infiltration in monolithic soil covers under heavy rainfall and its implications for practice
Authors: Li Guangyao , Liu Zhaolong , Jiao Weiguo , Feng Song , Zhan Liangtong , Du Xiuli
Published: November 2024

Global warming has caused frequent occurrences of extreme rainfall events worldwide. Studying the rainwater infiltration in monolithic soil covers (MSCs) and associated slope stability under heavy rainfall presents practical significance for landfill management. This study established an analytical solution for rainwater infiltration in MSCs during heavy rainfall assuming that the soil hydraulic properties follow exponential forms. The analytical solution was used to calculate the factor of safety (FOS) of MSCs after the verification with numerical simulations. It is found that the FOS for the potential slip surface at the cover bottom remained the lowest during and after heavy rainfall. The percolation and FOS might present pronounced “lag effects”, meaning that the maximum percolation rate and minimum FOS occurred after heavy rainfall. A parametric study was conducted to reveal the influencing factors on the hydraulic response and slope stability of MSCs based on the analytical solution. Relevant results demonstrate that the hydraulic performance and slope stability could be improved by decreasing soil saturated hydraulic conductivity, increasing soil desaturation coefficient, and lowering water level in landfills. The results also reveal the existence of a threshold of soil saturated hydraulic conductivity (1 × 10−8 m/s for this study) for controlling the hydraulic performance and slope stability of MSCs. Furthermore, the analytical solution was applied to determine the rainfall intensity–duration threshold curves of MSCs. The results indicate that the obtained curves of MSCs satisfied exponential forms. This study provides an effective tool and valuable guidance for the design and maintenance of MSCs.
Evaluating the concordance of ChatGPT and physician recommendations for bariatric surgery
Authors: Kahlon Sunny , Sleet Mary , Sujka Joseph , Docimo Salvatore , DuCoin Christopher , Dimou Francesca , Mhaskar Rahul
Published: November 2024

Integrating artificial intelligence (AI) into healthcare prompts the need to measure its proficiency relative to human experts. This study evaluates the proficiency of ChatGPT, an OpenAI language model, in offering guidance concerning bariatric surgery compared to bariatric surgeons. Five clinical scenarios representative of diverse bariatric surgery situations were given to American Society for Metabolic and Bariatric Surgery (ASMBS)-accredited bariatric surgeons and ChatGPT. Both groups proposed medical or surgical management for the patients depicted in each scenario. The outcomes from both the surgeons and ChatGPT were examined and matched with the clinical benchmarks set by the ASMBS. There was a high degree of agreement between ChatGPT and physicians on the three simpler clinical scenarios. There was a positive correlation between physicians’ and ChatGPT answers for not recommending surgery. ChatGPT’s advice aligned with ASMBS guidelines 60% of the time, in contrast to bariatric surgeons, who consistently aligned with the guidelines 100% of the time. ChatGPT showcases potential in offering guidance on bariatric surgery, but it does not have the comprehensive and personalized perspective that doctors exhibit consistently. Enhancing AI’s training on intricate patient situations will bolster its role in the medical field.