bluuebunny/crossref_metadata_2025 huggingface dataset:
The expression of contextual fear conditioning involves the dorsal hippocampus TRPV1 receptor interacting with the NMDA/NO/cGMP signalling pathway
Authors: Bertacchini Gabriela L. , Sonego Andreza B. , Lisboa Sabrina F. , Lagatta Davi C. , Resstel Leonardo B. M.
Published: November 2024

Background and Purpose

The dorsal hippocampus (dHIP) is pivotal for learning, memory, and defensive responses. Transient receptor potential vanilloid type 1 (TRPV1) receptors in the dHIP modulate contextual fear conditioning by triggering a cascade involving glutamate release, nitric oxide (NO) formation and cyclic guanosine monophosphate (cGMP) production. The present study investigated the involvement of dHIP TRPV1 receptors and their interaction with the glutamate/NO/cGMP signalling pathway in modulating the expression of contextual fear conditioning (CFC).

Experimental Approach

Male Wistar rats were submitted to an aversive contextual conditioning session and, 48 h later, were re‐introduced to the same aversive environment where the freezing response and autonomic activity (evidenced by increased arterial pressure and heart rate and a decrease in tail temperature) were measured.

Key Results

The results demonstrated that the TRPV1 antagonist 6‐I‐CPS in dHIP reduced the expression of CFC, whereas the agonist capsaicin had the opposite effect. Furthermore, dHIP pre‐treatment with an NMDA receptor antagonist (AP7), neuronal NO synthase inhibitor (N‐propyl‐L‐arginine), NO scavenger (c‐PTIO) or guanylate cyclase inhibitor (ODQ) attenuated capsaicin‐induced increases in CFC. Finally, we observed that re‐exposure to the aversive chamber increased dHIP NO levels in conditioned animals compared with a non‐conditioned group, which was prevented by the administration of the TRPV1 antagonist, 6‐I‐CPS.

Conclusion and Implications

Our study revealed that TRPV1 receptors in the dHIP play a crucial role in modulating contextual fear expression by acting through the NMDA receptor/NO/cGMP signalling pathway, providing important insights into the underlying mechanisms and potential therapeutic avenues associated with these pathways.
Determinants of socioemotional and behavioral well‐being among First Nations children living off‐reserve in Canada: A cross‐sectional study
Authors: Owais Sawayra , Ospina Maria B. , Ford Camron D. , Hill Troy , Lai Jessica , Krzeczkowski John , Burack Jacob A. , Van Lieshout Ryan J.
Published: November 2024

Few studies have focused on off‐reserve Indigenous children and families. This nationally representative, cross‐sectional study (data collected from 2006 to 2007) examined Indigenous‐ and non‐Indigenous‐specific determinants associated with positive socioemotional and behavioral well‐being among First Nations children living off‐reserve in Canada. The parents or other caregivers of 2990 two‐to‐five‐year‐old children (M = 3.65; 50.6% male) reported on their children's socioemotional and behavioral well‐being and a range of child, parent, and housing characteristics. Being taught an Indigenous culture, greater community cohesion, caregiver nurturance, good parental/other caregiver health, and fewer household members were associated with better socioemotional and behavioral well‐being. These results highlight the importance of leveraging Indigenous‐specific determinants and acknowledging non‐Indigenous‐specific factors, to promote the well‐being of First Nations children living off‐reserve.
“This place is fake:” green capitalism and the production of scarcity in Kigali, Rwanda
Authors: Shearer Samuel
Published: November 2024

This article is about green capitalism, demolition, and the production of housing scarcity in Kigali, Rwanda. It follows Kiyovu cy'abakene—a real place that was near zero‐carbon, built with renewable resources, owned and operated by Kigali residents—as it was first reimagined as a rhetorical “slum” and then converted into an actual one by force. And it follows the design and construction of Batsinda Housing estate, a sustainable solution to a fictional “crisis” of inadequate housing in Kigali. Drawing on several years of ethnographic research, I argue that in Kigali, and many cities like it, the destruction of built environments is not only about local elites who wish to demolish “slums” or “informal settlements” to build “world‐class” luxury cities. The demolition of neighborhoods and the displacement of people who live there is also done in the service of making new markets for green commodities through the production of scarcity. To manufacture effective demand for green commodities while maintaining their monopoly over what constitutes “sustainable,” Kigali's international teams of managers and consultants must render alternative, ecologically sound, African‐owned neighborhoods and building technologies “unsustainable.”
The risk of inbreeding versus outbreeding depression in managing an endangered and locally adapted population of a sedentary bird
Authors: Walsh Grace , McMahon Barry J. , Thörn Filip , Rödin‐Mörch Patrik , Irestedt Martin , Höglund Jacob
Published: November 2024

A debate in conservation genomics centers on whether to conserve small, fragmented populations independently or blend them through translocations from larger populations. Translocations of red grouse (Lagopus scotica) from Great Britain to supplement the Irish population have been suggested. We incorporate a variety of genetic datasets to address this. We used genome wide data from 23 contemporary and historic red grouse from Great Britain and Ireland. We also investigate microsatellite data, sequence candidate pigmentation genes, and assess phenotypic color variation. Genomic data indicate higher inbreeding in Irish grouse relative to an English population and significant divergence for genomic (FST = 0.095) and microsatellite (FST = 0.03) markers. Contemporary Ne was seven times smaller in the Irish population compared to the English. We identified divergent regions linked to pigmentation, immune response, and food intake. We show phenotypic differences in plumage color and sequence divergence among coding regions in the melanin pathway including MC1R (FST from genomic data of 0.3). The two populations thus appear locally adapted and this divergence between the source and target population when used for conservation translocations can swamp locally adapted alleles and/or introduce maladapted genotypes, leading to outbreeding depression. While it is important to avoid inbreeding by sustaining larger populations, our research emphasizes the need for practitioners to consider population divergence and local adaptation. We advocate against translocations between Ireland and Britain as a conservation strategy in this particular case and underscore the importance of prioritizing local populations where possible.
A randomized, placebo‐controlled first‐in‐human study of oral TQS‐168 in healthy volunteers: Assessment of safety, tolerability, pharmacokinetics, pharmacodynamics, and food effect
Authors: Hannestad Jonas , Smith Steven , Lam Andrew , Hurt Janet , Harada Nicole , Kim Richard , Das Abhirup , Brunello Juliana , Whitaker Gareth , Chalmers David , Senjoti Faria , Lin Wu , Coghill James , Bansal Yogesh , Sidhu Sharan , Zann Vanessa , Liu Enchi
Published: November 2024

TQS‐168, a first‐in‐class small‐molecule inducer of peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha gene expression, is in development for the treatment of amyotrophic lateral sclerosis. A single‐ascending‐dose (SAD) and multiple‐ascending‐dose (MAD) study of TQS‐168 was carried out in healthy male subjects to investigate safety, tolerability, pharmacokinetics (PK), food effect, and preliminary pharmacodynamic effects (PD). Since solubility enhancement could be beneficial, assessment of three formulations was incorporated into the study using an integrated rapid manufacturing and clinical testing approach. Dosing in the SAD part was initiated with a crystalline methylcellulose (MC) suspension, and then spray‐dried dispersion (SDD) and hot‐melt extrusion (HME) suspensions were evaluated. The HME and SDD formulations showed two and fourfold higher exposure than the MC suspension, respectively, and the SDD formulation was selected for progression to subsequent SAD and MAD cohorts, in which there was further investigation of the food effect on exposure in addition to assessments of safety, tolerability, PK, and PD. Cmax and AUC plasma exposures of TQS‐168 were supra‐proportional at higher doses, irrespective of formulation. Median Tmax for TQS‐168 occurred between 0.5 and 4.0 h post‐dose and occurred later with higher doses. Geometric mean half‐lives (T1/2) for TQS‐168 were independent of formulation and food, ranging from 3.2 to 10.5 h following single doses and 4.1 to 7.3 h following multiple doses. Food blunted TQS‐168 Cmax but had minimal impact on AUC. TQS‐168 was considered to be safe and generally well tolerated following single and multiple oral doses. The SDD formulation was selected for future patient studies.
Fine‐tuning of artificial intelligence managers' logic in a supply chain with competing retailers
Authors: Li Yue , Zhao Ruiqing , Li Xiang , Choi Tsan‐Ming
Published: November 2024

Today, with the advance of artificial intelligence, companies in the real world are using AI as managers to make operational decisions, who can respond quickly to market shocks and whose logic can be fine‐tuned to programmed pessimism/optimism, that is, underestimating/overestimating the market. The introduction of AI managers poses new challenges to supply chain management, and how to manage AI managers warrants further exploration. We investigate the optimal AI manager fine‐tuning strategies in a supply chain consisting of one manufacturer and two competing retailers, each operated by an AI manager in the face of an uncertain market shock. We establish the manufacturer–retailer AI manager fine‐tuning game, where the manufacturer and two retailers endogenously decide whether to fine‐tune their AI managers' logic. The market may suffer an uncertain shock, and once the shock occurs, the AI managers' logic settings and price decisions can be quickly adjusted. We find that the manufacturer would never fine‐tune the AI manager, while the retailers may fine‐tune their AI managers to programmed optimism. Notably, AI manager's fine‐tunability only benefits the retailers and harms the manufacturer, entire supply chain, consumers, and social welfare. To make AI manager's fine‐tunability beneficial to all participants, that is, to reach a win–win–win situation, we design two incentive mechanisms, retailer pessimism incentive mechanism and mutual pessimism incentive mechanism (MPIM), where MPIM can lead to the win–win–win situation. Further, we endogenize the compensation, endogenous retailer pessimism compensation and endogenous mutual pessimism compensation, both achieving the win–win–win outcome. We also make several extensions and provide suggestions for supply chain firms to fine‐tune their AI managers' logic.
Anatomical Significance of the Patent Foramen Ovale by Real‐Time 3D TEE in Cryptogenic Stroke and Migraine
Authors: Wang Li , Sun Haibo , Shen Han
Published: November 2024

Background

The transesophageal echocardiogram (TEE) is the standard imaging modality for confirming the presence or absence of patent foramen ovale. PFO is a flap valve depending on the pressure change between the left and right atrium, which can help determine whether to open. 3D‐TEE was shown to optimize the visualization of PFO. There is a causal association between PFO and unexplained stroke. It seems that 3D‐TEE can present a high‐risk PFO morphological feature, which seems to show more than just being easier to open.

Methods

In total, 134 consecutive patients with cryptogenic stroke or migraine who had suspected PFO and underwent c‐TCD, TTE, and c‐TEE were included in this study. TEE confirmed the PFO. The right‐to‐left shunt (RLS) grade of PFO at rest and abdominal compression Valsalva maneuver was detected by c‐TEE.

Results

The long diameter of FO (1.74 ± 0.3 vs. 1.60 ± 0.4, p = 0.039), the short diameter of FO (1.12 ± 0.3 vs. 1.00 ± 0.3, p = 0.036), perimeter of FO (4.62 ± 0.7 vs. 4.22 ± 1.0, p = 0.026), and area (1.80 ± 0.8 vs. 1.35 ± 0.8, p = 0.05) of the FO were significantly larger in the larger RLS group. In group of CS, a larger proportion of Eustachian valve or a Chiari's network (14.3% vs. 3.5%, p = 0.036), a larger proportion of in the left funnelform (55.1% vs. 16.3%, p < 0.001), a longer length of the PFO tunnel (13.4 ± 4.4 vs. 7.8 ± 2.5, p < 0.001), a lower IVC‐PFO angle (16.4 ± 3.4 vs. 20.3 ± 7.7, p = 0.001), a higher proportion of LA multiple exits of the tunnel (46.9% vs. 14.3%, p < 0.001). Multivariate regression analysis showed that male gender (HR: 4.026, 95% CI: 0.883–18.361, p = 0.072), age (HR: 1.076, 95% CI: 1.002–1.155, p = 0.045), the left funnelform (HR: 7.299, 95% CI: 1.585–33.618, p = 0.011), a longer length of the PFO tunnel (HR: 1.843, 95% CI: 1.404–2.418, p < 0.001) and multiple exits of the tunnel of LA (HR: 8.544, 95% CI: 1.595–45.754, p = 0.012) increased the risk of cerebral infarction. The cut‐off value calculated by ROC for the diagnosis of high‐risk PFO was that the length of the PFO tunnel was 12 mm and the left funnelform combined with multiple exits of the left atrial (sensitivity was 92%, specificity was 90%). The area under the curve of the combined index versus PoPE score (0.932 vs. 0.736) relative to the RoPE score was statistically significant.

Conclusions

TEE has shown outstanding advantages in displaying the specific morphological characteristics of PFO. The left funnelform, a longer length of the PFO tunnel, and multiple exits of the tunnel of LA are associated with an increasing risk of CS in anatomical PFO respect.
Unveiling the Genetic and Clinical Differences of Acute Myeloid Leukemia (AML) in Obese Patients
Authors: Yalniz Fevzi F. , Johnson Anna , Alnimer Yanal , Chahine Zena , Morris Trevor , Yadav Rina , Taj Hiffsa , Iragavarapu Chaitanya , Munker Reinhold , Monohan Gregory , Wai Sainan , Zhang Shulin , Nozad Sahar , Qasrawi Ayman
Published: November 2024

Background

The molecular architecture of acute myeloid leukemia (AML) is heterogeneous. Obesity has been identified as a risk factor for the development of AML. There remains a scarcity of data elucidating the specific genetic profile of AML in obese patients.

Methods

We conducted a review of adult patients treated at our institution for newly diagnosed AML from January 1, 2017, to January 1, 2023. Obesity is defined as BMI > 30 kg/m2. Demographic, clinical, laboratory, and pathologic data were collected retrospectively. The primary outcome of interest was the molecular features of obese compared to non‐obese AML patients. The secondary outcome was overall survival (OS). Inverse probability of treatment weights (IPTW) used to balance both groups on several confounding variables.

Results

A total of 185 patients were included in the analysis. 90 (49%) were obese. Compared with non‐obese patients, obese patients were younger and more likely to be females (55 vs. 63, p = 0.04, 55% vs. 38%, p value, p = 0.02, respectively). After matching on age, gender, and ethnicity, obese patients exhibit lower rates of total number of gene mutations (median 2.7 vs. 3.2, p = 0.05), significantly lower rates of mutations in transcriptional factor genes (15.7% vs. 33.2%, p = 0.01), and near‐significant in spliceosome genes (12% vs. 22.3%, p = 0.08), and higher rates of NPM1 mutation (23.3% vs. 12.6%, p = 0.08). Median OS was not significantly different in the matched cohort.

Conclusions

The molecular features of obese AML patients significantly differ from non‐obese counterparts. These findings suggest distinct underlying mechanisms in leukemogenesis in obese patients.
Allogeneic Hematopoietic Stem Cell Transplantation in Refractory Multiple Myeloma—A Retrospective Multicenter Analysis
Authors: Richardson T. , Kobbe G. , Fenk R. , Schroeder T. , Crysandt M. , Neuerburg C. , Holderried Tobias A.W. , Schütte D. , Gödel P. , Hallek M. , Scheid C. , Holtick U.
Published: November 2024

A growing list of therapies available for patients with multiple myeloma (MM) results in deep response rates, but eventually almost all patients relapse. Allogeneic hematopoietic cell transplantation (allo‐SCT) is a familiar approach for MM, but responses are often short and side effects burdensome. Simultaneously, allo‐SCT provides a unique platform on which novel immune therapies can be employed to improve clinical outcomes. Our work describes the characteristics and outcomes of 128 refractory myeloma patients who underwent allo‐SCT at five German centers between 2010 and 2021. The median number of therapies before the transplant was 6. With a median follow‐up of 6, 4 years, the median progression‐free survival and overall survival were 7 and 19 months, respectively. NRM was 28% after 6 years. OS and PFS were 61% and 45% at 1 year, 49% and 34% at 2 years, and 38% and 25% at 6 years. Achieving a CR before transplant was the single most significant variable before transplant. Allo‐SCT yet remains an option for fit patient's refractory to all other treatments available. It is potentially curative for a subset of patients. Finding the characteristics of patients with durable remissions is key to sparing unnecessary toxicity for those unlikely to benefit.
A survey of ocular pathology in Warmblood horses in South Africa
Authors: Allen Ramona , Goodhead Antony D.
Published: November 2024

Background

Warmblood horses are a popular breed around the world for equestrian sports. Previous studies have investigated ocular findings in other breeds of horses; however, no studies exist for the Warmblood breed.

Objectives

To determine the prevalence of ocular abnormalities in a convenience sample of Warmblood horses in South Africa and to determine if the prevalence of lens and chorioretinal lesions increase with age.

Study design

Descriptive, observational study.

Methods

Warmblood horses underwent a full ophthalmic examination which included a Schirmer tear test (STT), tonometry, fluorescein dye testing, slit lamp biomicroscopy and indirect ophthalmoscopy. Age was categorised into three groups namely <8 years old, 8–13 years old and 14+ years old for statistical analysis. Prevalence of lens and chorioretinal lesions were compared between age categories.

Results

One hundred and four horses (208 eyes) were examined. The age range was 5 months to 30 years (mean 11 years, standard deviation [SD] 6 years). Ocular pathology was noted in 125 eyes (60.1%) and 79 horses (76%). The highest number of lesions were noted in the choroid and retina, iris and lens. Chorioretinal lesions were seen in 100 eyes (48.1%) and in 65 horses (62.5%). Iridial lesions were seen in 19 eyes (9.1%) and 12 horses (11.5%). Cataracts were seen in 19 eyes (9.1%) and in 13 horses (12.5%). The presence of total chorioretinal lesions (eye level [p = 0.002]; horse level [p = 0.004]), focal chorioretinal lesions (eye level [p = 0.004]; horse level [p = 0.008]) and cataract (eye [p = 0.03]; horse level [p = 0.02]) were all shown to statistically increase with age.

Main limitations

A small sample size and limited geographic area.

Conclusions

There was a high prevalence of ocular pathology in this population of Warmblood horses in South Africa. This reiterates the importance of an ocular examination as a part of routine health checks, as well as during prepurchase examinations.
Quantifying head and withers movement asymmetry in sound and naturally forelimb lame horses trotting on a circle on hard and soft surfaces
Authors: Taddey Caroline M. , Roecken Michael , Kreling Kai M. , Cruz Antonio M.
Published: November 2024

Background

Reliable lameness thresholds for vertical head displacement for trotting on a circular path and on different surfaces have yet to be defined. Withers movement in lame horses could help improve the diagnostic accuracy of sensor technology.

Objectives

To define head movement lameness threshold ranges and describe the relationship between head and withers movement during trotting under different circumstances in sound and forelimb lame horses.

Study design

Retrospective analysis of clinical data and comparison with control group.

Methods

Fifty‐five sound and thirty‐four naturally lame horses were trotted under field conditions on a hard surface on a straight line and on both directions on soft and hard surfaces. Movement asymmetry was analysed by measuring differences in displacement minima for head and withers using an inertial measurement unit sensor‐based gait analysis system. Receiver operating characteristic (ROC) analysis was performed to define threshold ranges. Relationships between head and withers data were identified by calculating the correlation with linear regression analysis.

Results

Estimated lameness threshold values for vertical head movement asymmetry ranged from 11.5 to 12.5 mm. On both surfaces, a head movement asymmetry threshold range from 24.5 to 26.5 mm could be found for the circle. Lame horses showed significant correlations between head and withers movement on hard ground straight line (R2 0.714, p < 0.001) and inner leg lame horses on the lunge (R2 0.915, p < 0.001).

Main limitations

Different sources of lameness were not distinguished. Radius and speed during lungeing could not be perfectly controlled. Inclusion in the sound group was based on a subjective examination by one clinician and in the lame group two clinicians subjectively determined inner and outer leg lameness creating an extra amount of uncertainty.

Conclusions

Lameness thresholds for quantifying head movement asymmetry on the lunge were proposed. A significant correlation was observed between head and withers movement asymmetry under several conditions.
The Burden of Seasonal Influenza and Its Potential Complications Among Older Japanese Adults: A Real‐World Database Study
Authors: Arashiro Takeshi , Tajima Yuki , Ban Yohei , Loiacono Matthew M. , Ideguchi Masayo , de Courville Caroline
Published: November 2024

Background

Seasonal influenza may lead to severe complications, including respiratory and cardiovascular disease, that result in considerable healthcare resource utilization (HCRU) and mortality, particularly in older individuals. This real‐world study assessed the burden of influenza and its potential complications in older Japanese adults.

Methods

This retrospective claims database analysis (April 2015 to June 2019) included insured individuals aged ≥ 60 years at the start of four consecutive influenza seasons in Japan (October 1 to April 30). The primary endpoint was the incidence of influenza‐related emergency room (ER) and outpatient visits, the incidence of hospitalizations, the probability of 30‐day inpatient mortality, and 60‐day medical costs of influenza or its potential complications.

Results

Of 8,974,708 individuals (43.2% male, mean ± standard deviation age 73.8 ± 8.9 years), 370,430 (4.13%) were diagnosed with influenza. Overall, 17.18 (95% confidence interval [CI] 16.32–18.04) and 3893.53 (3880.87–3906.19) per 100,000 individuals had influenza‐related ER and outpatient visits, respectively, and 181.50 (178.71–184.28) per 100,000 individuals were hospitalized for influenza. The incidence of influenza‐related ER visits and hospitalizations for influenza or potential complications and the probability of 30‐day inpatient mortality increased with age.

Conclusions

Seasonal influenza and its potential complications represent a substantial burden that increases with age in Japanese individuals.
Precision medicine in diabetes prediction: Exploring a subgroup‐specific biomarker strategy for risk stratification
Authors: Yen I‐Weng , Chen Szu‐Chi , Lin Chia‐Hung , Fan Kang‐Chih , Yang Chung‐Yi , Hsu Chih‐Yao , Kuo Chun‐Heng , Lin Mao‐Shin , Lyu Ya‐Pin , Juan Hsien‐Chia , Heng‐Huei Lin , Li Hung‐Yuan
Published: November 2024

Introduction

The early detection of high‐risk individuals is crucial to delay and reduce the incidence of type 2 diabetes. In this study, we aimed to explore the performance of a novel subgroup‐specific biomarker strategy in the prediction of incident diabetes.

Materials and Methods

In the Taiwan Lifestyle Cohort Study, adult subjects without diabetes were included and followed for the incidence of diabetes in 2006–2019. The biomarkers measured included blood secretogranin III (SCG3), vascular adhesion protein‐1 (VAP‐1), fibrinogen‐like protein 1 (FGL1), angiopoietin‐like protein 6 (ANGPTL6), and angiopoietin‐like protein 4 (ANGPTL4).

Results

Among the 1,287 subjects, 12.2% developed diabetes during a 6 year follow‐up. Blood VAP‐1 was significantly associated with incident diabetes in the overall population (HR = 0.724, P < 0.05), participants under 65 years old (HR = 0.685, P < 0.05), those with a BMI of ≥24 kg/m2 (HR = 0.673, P < 0.05), and females (HR = 0.635, P < 0.05). Blood ANGPTL6 was significantly correlated with incident diabetes in participants aged 65 and older (HR = 0.314, P < 0.05), and blood SCG3 was associated with incident diabetes in those with a BMI of <24 kg/m2 (HR = 1.296, P < 0.05). Two subgroup‐specific biomarker strategies were developed. The gender and BMI‐specific biomarker strategy, using traditional risk factors and blood SCG3 or VAP‐1 in different subgroups, could improve prediction performance, especially the specificity and positive prediction value, compared with the whole‐population strategy using only traditional risk factors or traditional risk factors plus blood VAP‐1.

Conclusion

Gender‐ and BMI‐specific biomarker strategy can improve the prediction of incident diabetes. A subgroup‐specific biomarker strategy is a novel approach in the prediction of incident diabetes.
In vivo reflectance confocal microscopy role for early to advanced lentigo maligna melanoma spectrum: A systematic review and pooled analysis
Authors: Melhoranse Gouveia Bruna , Ferguson Peter M. , Lo Serigne N. , Collgros Helena , Martin Linda K. , Sinz Christoph , Smit Amelia K. , Gallo Bruna , Ho Genevieve , Glanz Amanda , Scolyer Richard A. , Cust Anne E. , Guitera Pascale
Published: November 2024

Background

Lentigo maligna (LM) is a growing problem worldwide and the main type of melanoma in situ in some Caucasian populations. It presents as a spectrum from atypical intraepidermal melanocytic proliferation (AIMP) to invasive lentigo maligna melanoma (LMM). Accurate diagnosis and staging are crucial for determining appropriate management strategies.

Objectives

To assess the role of in vivo reflectance confocal microscopy (RCM) in differentiating early and advanced stages of lentigo maligna.

Methods

A systematic search was conducted on Medline, PubMed, Scopus, Web of Science, Proquest Central, Embase, Cochrane and Google Scholar. References of included and excluded studies were reviewed for additional sources. Studies involving RCM for AIMP, LM and LMM diagnosis published until 1 December 2023, were selected for analysis. Publications on other non‐invasive imaging techniques, other skin diseases or those addressing only RCM surgical margins and therapeutic response without reporting RCM features were excluded. Each article was reviewed by two experts, with disagreements resolved by a third expert. Data for each RCM feature were pooled, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Features were stratified for architecture, cellular morphology and distribution.

Results

Twenty‐seven articles involving 303 lesions were included. Features favouring LM over AIMP included (1) Architecture: the presence of non‐edged papillae (OR 4.50, 95% CI 1.92–10.52) and (2) Cellular distribution: widespread pagetoid cells and junctional atypical cells (OR 25.06, 95% CI 4.19–148.45) and junctional nests (OR 18.06, 95% CI 3.04–106.32). Features favouring LMM over LM included (1) Architecture: epidermal disarray (OR 5.03, 95% CI 1.90–13.22), junctional disarray (OR 4.19, 95% CI 1.54–11.33) and destroyed collagen fibres (OR 3.91, 95% CI 1.80–8.44) and (2) cellular distribution: widespread pagetoid and junctional atypical cells (OR 2.71, 95% CI 1.27–5.75) and junctional nests (OR 4.48, 95% CI 2.12–9.43).

Conclusions

This study identifies the RCM features associated with the LM/LMM spectrum.
Adipocyte Apoptosis Following a Novel Method for Double Chin Reduction: A Pilot Human Histology Study
Authors: Goldberg David J.
Published: November 2024

Background

Submental fullness is perceived as unattractive by both men and women. The noninvasive simultaneous delivery of HIFES and synchronized radiofrequency+ (Sync RF+) technologies aims to address the submental fullness by concurrently targeting the skin, adipose tissue, and weakened anterior belly of the digastric muscle, the three contributing layers to the double chin appearance.

Aims

This study aims to investigate the histological changes to adipose tissue related to cell morphology, caspase‐7, and Bcl‐2 levels to detect adipocyte apoptosis following the HIFES and Sync RF+ treatment on human subjects.

Methods

The active group (n = 6) received single 20‐min treatment on the submental area, while the control group (n = 2) did not receive any treatment. Biopsies of subcutaneous fat tissue were obtained at baseline, and 24 h and 7 days posttreatment. The specimens were histologically and immunohistochemically analyzed for changes in morphology, caspase‐7, and Bcl‐2 levels.

Results

Observed caspase‐7 levels increased by 511% at 24‐h posttreatment, and 101% at 7 days (p < 0.0001), while the Bcl‐2 levels decreased by 89% at 24 h and 24% at 7 days posttreatment (p < 0.0001). The control group had no statistically significant relative changes in the activity of caspase‐7. Posttreatment adipocytes were shrunken in size, and shapes lost their uniformity compared to baseline. Five of six subjects reported the treatment as being comfortable. No adverse events were observed during the study.

Conclusions

The results of this human histology study indicate that noninvasive HIFES and Sync RF+ technologies have a favorable safety profile for submental fat reduction through the induction of adipocyte apoptosis.

Trial Registration

ClinicalTrials.gov identifier: NCT06282172
Characteristics of Temporomandibular Joint Osteoarthritis Patients With Condylar Erosion: A Retrospective Cross‐Sectional Study
Authors: Chen Yifan , Zhang Xiao , Xia Chenlong , Tang Liangchen , Chen Min‐er , Huang Sirong , He Jianxiang , Li Zhiyong
Published: November 2024

Background

Condylar erosion (CE) may indicate an active progressive stage of temporomandibular joint osteoarthritis (TMJOA), but no studies have analysed the characteristics of this population.

Objective

This cross‐sectional study analysed the characteristics of TMJOA patients with CE.

Methods

A total of 267 patients were included. The severity of CE of all joints was evaluated using cone beam computed tomography (CBCT) and scored using a four‐point rating scale (0–III). Patients were categorised into mild (grade I), moderate (grade II) and severe (grade III) groups. Demographic and clinical characteristics were summarised and stratified by age and erosion severity. Univariate and multivariate logistic regression analyses were performed based on the assignment of the variables.

Results

The proportion of patients under 30 years old is much higher than other age groups. Compared to adults (≥ 20 years old), a higher proportion of adolescent patients (10–19 years old) choose orthodontics department for their first consultation (p < 0.01). And adolescent patients have a higher proportion of temporomandibular joint (TMJ) noise (p < 0.05) and a lower proportion of arthralgia (p < 0.001). Significant differences exist in CE severity between adolescents and adults (p < 0.001). The severe group had the youngest patients (p < 0.05) and the highest proportion of mandibular deviation and abnormal postural habits.

Conclusions

Patients under 30 years of age constitute a significant proportion of TMJOA cases with CE. Compared to adults, adolescent patients have more severe CE and less arthralgia. Due to obvious dental and maxillofacial deformities and milder TMJ symptoms, adolescent patients may not be aware that they have TMJ disease, potentially leading to delayed treatment.
EH6 enstatite chondrites Northwest Africa 7976 and Northwest Africa 12945: Implications for EH chondrite metamorphism
Authors: Gray Mabel L. , Weisberg Michael K. , Jaret Steven J. , Ebel Denton S.
Published: November 2024

The enstatite chondrite class is known to have complex thermal histories, often interpreted to include impact melting and shock metamorphism. Highly equilibrated (type 6) EH group enstatite chondrites are rare and thought to have formed through collisional heating. We studied two EH6 chondrites, NWA 7976 and NWA 12945, for their textural, chemical, and mineralogical characteristics. The samples we studied contain subhedral to anhedral grains of enstatite and plagioclase, suggesting solid‐state recrystallization. They show low degrees of shock and no evidence of shock melting. Additionally, the ubiquitous occurrence of daubréelite exsolution lamellae in troilite and the Ni content of schreibersite suggest slow cooling at greater burial depths in the parent body, rather than rapid cooling as a result of an impact event. Based on the characteristics and scarcity of type 6 EH chondrites, and the ubiquitous shock effects and melt rocks in the enstatite chondrite class, we conclude that the unshocked NWA 7976 and NWA 12945 were formed by heat derived from impact melt sheets, analogous to contact metamorphism.
Objective Structured Clinical Examination Perception Scale (OSCEPS) for Health Sciences Students: A Psychometric Evaluation Study
Authors: Sengul Tuba , Semerci Remziye , Güney Seda , Karakaya Çataldaş Seda
Published: November 2024

Objective Structured Clinical Examinations (OSCE) is an objective assessment approach that enables the evaluation of students' practical skills by simulating real clinical scenarios. This scale is specifically designed to evaluate the attributes and characteristics of the OSCE from the perspective of health sciences students, thereby filling a crucial gap in the existing assessment methods. This research conducted a methodological design involving 220 students from the faculties of medicine and nursing between 2022 and 2023. Data were gathered using a “Descriptive Form” and “OSCEPS.” Factor analyses were performed for research and validation to ascertain the scale's factorial structure. The factorial analysis was used to test the structural validity of the scale. A structure consisting of 19 items was developed. The Cronbach's alpha coefficient was 0.943. Fit indices resulting from the study were RMSEA = 0.084; GFI = 0.839; CFI = 0.902; IFI = 0.902; RFI = 0.824; NFI = 0.843; TLI = 0.889. This study proves that the OSCEPS is a highly reliable and valid scale with strong psychometric properties. It effectively assesses health sciences students' perceptions of OSCE, thereby enhancing the credibility and usefulness of this assessment tool.
Corneal asymmetry contributes decentration in both spherical and toric orthokeratology lenses
Authors: Zhang Ronghan , Chen Shengwen , Ye Anqi , Peng Lulu , Chen Minfeng , Zhu Chengwei , Wang Yanli , Zhao Sijun , Qu Jia , Mao Xinjie
Published: November 2024

Purpose

To discuss the characteristics of anterior corneal elevation asymmetry in myopic eyes and clarify which kind of asymmetry most influenced lens position.

Methods

In this retrospective study of 199 consecutive myopic participants, corneal topography was used to analyse asymmetry in anterior corneal elevation. Amongst them, 65 participants (65 eyes) who underwent orthokeratology (31 and 34 with spherical and toric lenses, respectively) were re‐evaluated. Stepwise multiple linear regression analysis was used to identify the contributing factors that influenced lens decentration. Receiver operating characteristic curve (ROC) analysis was employed to assess how the corneal asymmetry vector could predict decentration.

Results

There were no significant differences in treatment zone decentration (TZDec) between participants wearing toric and spherical lenses (p = 0.60 and 0.64 for 1 week and 1 month of wear, respectively). Amongst the underlying factors, the magnitude of TZDec was only correlated with the amount of corneal asymmetry vector (standardised β = 0.44, 0.48, p < 0.001 for all) after 1 week and 1 month of wear, and the direction of TZDec after 1 month of lens wear was associated with the angle of the asymmetry vector (r = 0.25, p = 0.04). ROC analysis showed that the magnitude of corneal asymmetry vector produced accurate discrimination between non‐severe and severe decentration for 1 week and 1 month of wear (area under the curve was 0.93 ± 0.04 and 0.89 ± 0.05, respectively, p < 0.001). Amongst participants whose corneal asymmetry vector exceeded 41.06 μm and was oriented inferiorly, 35.29% showed severe decentration after 1 month of lens wear.

Conclusions

In myopic participants, corneal asymmetry existed in the 8.0 mm chord diameter. If the asymmetry vector >41.06 μm and the direction was oriented inferiorly, then practitioners must be vigilant about severe decentration which would not be alleviated by a toric design.
Geography: The Geopolitics of China–Pakistan Relations
Authors: Ali Ghulam , Peng Nian
Published: November 2024

This article argues that Pakistan's strategic location provides a strong foundation for the durability of its relations with China. In support of this claim, it assesses the impact of other key factors, including the “Indian factor,” in this bilateral relationship. The article illustrates Pakistan's “advantageous” location compared to China's inherent geographical limitations. The Chinese elite realized geographical realities from the beginning and pursued a long‐term partnership with Pakistan. This was evident from China's investment in megaprojects in Pakistan, which were all premised on geography. Pakistan's geographical location has served China's interests in various ways, including breaking China's encirclement, acting as a gateway to the outside world, and preventing the infiltration of militancy into the mainland during the Cold War. Pakistan can potentially act as a hub between China and other regional countries in the context of the Belt and Road Initiative. The article diverts emphasis from the “Indian factor” to enduring geographical conditions as the basis for the durable Beijing–Islamabad partnership.
Creeping Stem 1 regulates directional auxin transport for lodging resistance in soybean
Authors: Xu Zhiyong , Zhang Liya , Kong Keke , Kong Jiejie , Ji Ronghuan , Liu Yi , Liu Jun , Li Hongyu , Ren Yulong , Zhou Wenbin , Zhao Tao , Zhao Tuanjie , Liu Bin
Published: November 2024

Soybean, a staple crop on a global scale, frequently encounters challenges due to lodging under high planting densities, which results in significant yield losses. Despite extensive research, the fundamental genetic mechanisms governing lodging resistance in soybeans remain elusive. In this study, we identify and characterize the Creeping Stem 1 (CS1) gene, which plays a crucial role in conferring lodging resistance in soybeans. The CS1 gene encodes a HEAT‐repeat protein that modulates hypocotyl gravitropism by regulating amyloplast sedimentation. Functional analysis reveals that the loss of CS1 activity disrupts polar auxin transport, vascular bundle development and the biosynthesis of cellulose and lignin, ultimately leading to premature lodging and aberrant root development. Conversely, increasing CS1 expression significantly enhances lodging resistance and improves yield under conditions of high planting density. Our findings shed light on the genetic mechanisms that underlie lodging resistance in soybeans and highlight the potential of CS1 as a valuable target for genetic engineering to improve crop lodging resistance and yield.
Changes in SWEET‐mediated sugar partitioning affect photosynthesis performance and plant response to drought
Authors: Aubry Emilie , Clément Gilles , Gilbault Elodie , Dinant Sylvie , Le Hir Rozenn
Published: November 2024

Sugars, produced through photosynthesis, are at the core of all organic compounds synthesized and used for plant growth and their response to environmental changes. Their production, transport, and utilization are highly regulated and integrated throughout the plant life cycle. The maintenance of sugar partitioning between the different subcellular compartments and between cells is important in adjusting the photosynthesis performance and response to abiotic constraints. We investigated the consequences of the disruption of four genes coding for SWEET sugar transporters in Arabidopsis (SWEET11, SWEET12, SWEET16, and SWEET17) on plant photosynthesis and the response to drought. Our results show that mutations in both SWEET11 and SWEET12 genes lead to an increase of cytosolic sugars in mesophyll cells and phloem parenchyma cells, which impacts several photosynthesis‐related parameters. Further, our results suggest that in the swt11swt12 double mutant, the sucrose‐induced feedback mechanism on stomatal closure is poorly efficient. On the other hand, changes in fructose partitioning in mesophyll and vascular cells, measured in the swt16swt17 double mutant, positively impact gas exchanges, probably through an increased starch synthesis together with higher vacuolar sugar storage. Finally, we propose that the impaired sugar partitioning, rather than the total amount of sugars observed in the quadruple mutant, is responsible for the enhanced sensitivity upon drought. This work highlights the importance of considering SWEET‐mediated sugar partitioning rather than global sugar content in photosynthesis performance and plant response to drought. Such knowledge will pave the way to design new strategies to maintain plant productivity in a challenging environment.
Pupil size correlates with heart rate, skin conductance, pulse wave amplitude, and respiration responses during emotional conflict and valence processing
Authors: Chang Yi‐Hsuan , Yep Rachel , Wang Chin‐An
Published: November 2024

Pupil size is a non‐invasive index for autonomic arousal mediated by the locus coeruleus–norepinephrine (LC‐NE) system. While pupil size and its derivative (velocity) are increasingly used as indicators of arousal, limited research has investigated the relationships between pupil size and other well‐known autonomic responses. Here, we simultaneously recorded pupillometry, heart rate, skin conductance, pulse wave amplitude, and respiration signals during an emotional face–word Stroop task, in which task‐evoked (phasic) pupil dilation correlates with LC‐NE responsivity. We hypothesized that emotional conflict and valence would affect pupil and other autonomic responses, and trial‐by‐trial correlations between pupil and other autonomic responses would be observed during both tonic and phasic epochs. Larger pupil dilations, higher pupil size derivative, and lower heart rates were observed in the incongruent condition compared to the congruent condition. Additionally, following incongruent trials, the congruency effect was reduced, and arousal levels indexed by previous‐trial pupil dilation were correlated with subsequent reaction times. Furthermore, linear mixed models revealed that larger pupil dilations correlated with higher heart rates, higher skin conductance responses, higher respiration amplitudes, and lower pulse wave amplitudes on a trial‐by‐trial basis. Similar effects were seen between positive and negative valence conditions. Moreover, tonic pupil size before stimulus presentation significantly correlated with all other tonic autonomic responses, whereas tonic pupil size derivative correlated with heart rates and skin conductance responses. These results demonstrate a trial‐by‐trial relationship between pupil dynamics and other autonomic responses, highlighting pupil size as an effective real‐time index for autonomic arousal during emotional conflict and valence processing.
Exploring the experience of family members caring for a relative with alcohol use disorder: A phenomenological inquiry
Authors: Brown‐King Clarene E. , Pratt Beth A. , Mammah Kyndall , Morancy Wanda
Published: November 2024

Introduction

Alcohol use disorder (AUD) is a global concern with negative physical, psychological and social consequences. The ramifications of AUD extend beyond the individual and affect their family caregivers. Yet, the majority of existing research has primarily focused on individuals with AUD and interventions to encourage their abstinence rather than on their support systems.

Aim

In order to advance a holistic approach, research to address this gap is imperative to understand family caregiver concerns and needs for added support.

Method

We conducted a qualitative study using van Manen's hermeneutic phenomenological approach to uncover the meaning of family caregivers' lived experiences and capture the essence of their involvement in caring for a relative with AUD. A purposeful and snowball sample of family members (N = 10) living within the United States participated in a face‐to‐face or virtual, one‐on‐one audio‐recorded interview and a second meeting for member checking the transcribed data. Participants received a $20.00 gift card as a token for their participation.

Results

Six major themes emerged from the description of participants' lived experiences: (1) traversing the peaks and valleys, (2) wandering in the unknown, (3) pointing fingers, (4) weathering the storm, (5) drawing a line and (6) looking back, looking in. Although participants experienced many challenges, they never relinquished and remained committed to their caregiver role. Steadfastly staying with their relatives through crises exemplifies commitment as described by Sister Simone Roach's Theory of Caring. Through the ups and downs, each participant found meaning from the experience, which aligned closely with Starck's Theory of Meaning.

Conclusion

This study has implications for nursing practice, public health policy and highlights the need for collaboration to address the existing challenges for family caregivers of relatives with AUD.
Estimating the Social Visibility of Abortions in Uganda and Ethiopia Using the Game of Contacts
Authors: Giorgio Margaret , Shiferaw Solomon , Makumbi Fredrick , Seme Assefa , Kibira Simon Peter Sebina , Nabukeera Sarah , Anjur‐Dietrich Selena , Yihdego Mahari , Tadele Niguse , Sully Elizabeth
Published: November 2024

Social network–based data collection methods that rely on third‐party reporting have emerged as a promising approach for measuring abortion in restrictive settings. In order for these methods to accurately measure abortion incidence, they must also assess the visibility of abortions within social networks. Failure to do so may result in estimates affected by transmission bias, caused by imperfect knowledge of all abortions within one's social network. In this paper, we present exploratory research that uses respondent‐driven sampling (RDS) and the game of contacts method to measure abortion visibility in four sites in Uganda and Ethiopia. We assess the existence of potential biases in the game of contacts estimate of abortion visibility in each site by conducting several internal and external validity tests. While these tests provided some promising results, other factors such as the representativeness of the RDS samples, direct versus indirect abortion knowledge transfers, and the generalizability of the study sites may have introduced biases into the final estimates of abortion visibility in this study. We conclude by making recommendations on how applications of this methodology could be improved to better estimate abortion‐related transmission bias.