bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Antibiotic on Efficacy and Adverse Reactions of Chemoimmunotherapy in Non‐small Cell Lung Cancer Patients: A Retrospective Cohort Study
Authors: Deng Fang , Du Xiuwei , Zhang Ping , Xu Jing , Li Yu , Yang Zhongfei
Published: November 2024

Background

This study aimed to evaluate the impact of antibiotic exposure on efficacy and adverse reactions in non‐small cell lung cancer (NSCLC) patients receiving chemoimmunotherapy, and to explore any specific associations on the basis of antibiotic class.

Methods

A retrospective study was conducted on NSCLC patients who received chemoimmunotherapy in two Shandong hospitals between January 2018 and October 2023. The association between antibiotic exposure and progression‐free survival (PFS), overall survival (OS), objective response rate (ORR) and incidence of immune related adverse reactions (irAE) of patients were evaluated.

Results

Of the 316 patients, 134 (42.41%) received antibiotics (ATB group), and 182 (57.59%) did not (N‐ATB group). There was no significant difference in PFS (aHR = 1.009, 95% CI: 0.770–1.323; p = 0.946) or OS (aHR = 1.420, 95% CI: 0.986–2.047; p = 0.060) between ATB and N‐ATB groups. The impact on efficacy was related to the type of antibiotic. β‐Lactams (aHR = 1.737, 95% CI: 1.148–2.629; p = 0.009), in particular β‐lactam/β‐lactamase inhibitor combinations (BLBLIs) (aHR = 1.885, 95% CI: 1.207–2.944, p = 0.005) were associated with poorer OS. However, quinolones (aHR = 1.192, 95% CI: 0.861–1.650; p = 0.291) were not associated with OS. The incidence of irAEs was not significantly different between ATB and N‐ATB groups (p = 0.073), but was higher with BLBLIs (p = 0.013).

Conclusions

In NSCLC patients receiving chemoimmunotherapy, no significant difference was observed in efficacy and incidence of irAEs between the ATB and the n‐ATB groups. In antibiotic class analysis, β‐lactams and specifically BLBLIs were observed to be associated with worse OS.
Proximal antecedents and acute outcomes of simultaneous alcohol and cannabis use: Systematic review of daily‐ and event‐level studies
Authors: Farrelly Kyra N. , Amini Tahmina , Coelho Sophie G. , Fox Nicolle , Dimitrova Nicole , Hendershot Christian S. , Wardell Jeffrey D.
Published: November 2024

Many studies have revealed that individuals who engage in simultaneous use of alcohol and cannabis report elevated substance‐related consequences relative to those who use only alcohol or cannabis; however, evidence from emerging studies examining within‐person differences across simultaneous use and single substance use occasions is less consistent. This systematic review aimed to synthesize findings from existing day‐ and event‐level studies of within‐person differences in the proximal antecedents and acute outcomes associated with simultaneous use versus single substance use episodes. Our search strategy revealed 30 eligible articles. Two categories of antecedents (i.e., internal [e.g., motives] and external [e.g., social context]) and three categories of outcomes (i.e., consumption behavior, general positive and negative consequences, and specific consequences) were identified. The current literature consistently suggests that greater day‐ or event‐level social and enhancement motives, as well as being in a social context, predict greater likelihood of engaging in simultaneous use compared with alcohol‐ or cannabis‐only use. However, there was heterogeneity in findings regarding the role of other person‐level antecedents. Further, while most evidence pointed to heavier alcohol consumption on simultaneous use occasions versus alcohol‐only occasions, findings for elevations in acute negative and positive substance‐related consequences on simultaneous use versus single substance use occasions were mixed. Additionally, four studies found that increased consequences on simultaneous use occasions depended on the level of alcohol consumed. This review identifies several antecedents for simultaneous use events but suggests that simultaneous use occasions are not always associated with more acute harms than single substance use occasions. Given the extent to which the current literature is mixed, this review emphasizes the importance of methodological improvements and future research examining the mechanisms linking simultaneous use with substance‐related consequences to help reconcile findings across within‐person and between‐person studies.
Artificial intelligence‐based drug repurposing with electronic health record clinical corroboration: A case for ketamine as a potential treatment for amphetamine‐type stimulant use disorder
Authors: Gao Zhenxiang , Winhusen T. John , Gorenflo Maria P. , Dorney Ian , Ghitza Udi E. , Kaelber David C. , Xu Rong
Published: November 2024

Background and aims

Amphetamine‐type stimulants are the second‐most used illicit drugs globally, yet there are no US Food and Drug Administration (FDA)‐approved treatments for amphetamine‐type stimulant use disorders (ATSUD). The aim of this study was to utilize a drug discovery framework that integrates artificial intelligence (AI)‐based drug prediction, clinical corroboration and mechanism of action analysis to identify FDA‐approved drugs that can be repurposed for treating ATSUD.

Design and setting

An AI‐based knowledge graph model was first utilized to prioritize FDA‐approved drugs in their potential efficacy for treating ATSUD. Among the top 10 ranked candidate drugs, ketamine represented a novel candidate with few studies examining its effects on ATSUD. We therefore conducted a retrospective cohort study to assess the association between ketamine and ATSUD remission using US electronic health record (EHR) data. Finally, we analyzed the potential mechanisms of action of ketamine in the context of ATSUD.

Participants and Measurements

ATSUD patients who received anesthesia (n = 3663) or were diagnosed with depression (n = 4328) between January 2019 and June 2022. The outcome measure was the diagnosis of ATSUD remission within one year of the drug prescription.

Findings

Ketamine for anesthesia in ATSUD patients was associated with greater ATSUD remission compared with other anesthetics: hazard ratio (HR) = 1.58, 95% confidence interval (CI) = 1.15–2.17. Similar results were found for ATSUD patients with depression when comparing ketamine with antidepressants and bupropion/mirtazapine with HRs of 1.51 (95% CI = 1.14–2.01) and 1.68 (95% CI = 1.18–2.38), respectively. Functional analyses demonstrated that ketamine targets several ATSUD‐associated pathways including neuroactive ligand‐receptor interaction and amphetamine addiction.

Conclusions

There appears to be an association between clinician‐prescribed ketamine and higher remission rates in patients with amphetamine‐type stimulant use disorders.
Prevalence of pharmacotherapy for attention‐deficit/hyperactivity disorder and prescription stimulant misuse: A national study of US college students
Authors: Summit Alynna G. , Moseley Madison C. , Chaku Natasha , Elam Kit K. , Jacobs Wura , Lederer Alyssa M. , Vaughan Ellen L. , Quinn Patrick D.
Published: November 2024

Background and aims

Increasing rates of attention‐deficit/hyperactivity disorder (ADHD) pharmacotherapy may simultaneously benefit patients and increase the availability of stimulants for misuse. We measured the association between university‐level prevalence of ADHD medication treatment and prevalence of prescription stimulant misuse (PSM) among college students.

Design, setting and participants

This was an observational study using cross‐sectional data from the American College Health Association–National College Health Assessment III. Data included 395 participating universities between Fall 2019 and Fall 2022. Our sample included 224 469 undergraduates aged 18–25 years (65.2% cisgender female; 58.7% White).

Measurements

Students self‐reported any life‐time clinical ADHD diagnosis, past‐year ADHD medication treatment and past‐3‐month PSM. We defined university‐level ADHD medication prevalence as the proportion of included students endorsing past‐year ADHD medication treatment. Secondary outcomes included life‐time PSM and moderate‐ to high‐risk alcohol and cannabis use. We also measured university‐level depression medication prevalence as a negative control exposure.

Findings

Among the included students, 9.6% reported a life‐time clinical ADHD diagnosis, 5.1% reported past‐year medication treatment and 2.4% reported past‐3‐month PSM. The prevalence of ADHD medication treatment varied among universities [mean = 5.3%, standard deviation (SD) = 2.8%]. In adjusted models, prevalence of PSM was 7% relatively greater for every 1% increase in university‐level medication prevalence [adjusted prevalence ratio (aPR) = 1.07; 95% confidence interval (CI) = 1.04–1.09]. Further, individuals with non‐medication‐treated ADHD were 40% more likely to report PSM than those without ADHD (aPR = 1.40; 95% CI = 1.25–1.56). There was no statistically significant difference in PSM among individuals with ADHD who did or did not receive medication (aPR = 0.90; 95% CI = 0.78–1.04). Results for secondary outcomes and the negative control partially supported the specificity of the findings.

Conclusions

Among university students in the United States, there appears to be a positive association between attending universities with a greater prevalence of attention deficit/hyperactivity disorder (ADHD) medication treatment and risk of prescription stimulant misuse (PSM). This study provides further support for the possibility that ADHD medication treatment prevalence is a risk factor for PSM.
Surgical treatment of hypospadias with lichen sclerosus: Long‐term outcomes from a single center
Authors: Yang Bo , Wang Xue‐Jun , Bo‐Ya Li , Chen Shao‐Ji , Li Jiao , Deng Yan‐Mei , Bai Li‐Shuang , Song Lin‐Hong , Qin Dao‐Rui , Mao Yu , Tang Yun‐Man
Published: November 2024

Background

Hypospadias with lichen sclerosus (LS) poses surgical challenges due to lack of materials for urethral reconstruction and coverage and the limited number of reports on this clinical condition.

Objectives

To report surgical strategies and outcomes for primary and redo hypospadias patients with LS.

Materials and methods

We conducted a retrospective observational descriptive study with 31 patients with primary/redo hypospadias and LS between 2013 and 2023. Of these patients, 9 had primary hypospadias with 7 distal types and 2 proximal types, and 22 were redo patients. Nineteen of the 31 patients underwent various surgical techniques, and 12 underwent the oral mucosa onlay procedure (OMOP). Postoperative uroflowmetry, hypospadias objective scoring evaluation (HOSE), and complications were evaluated.

Results

For primary distal hypospadias with LS‐affected skin, five patients underwent circumcision; these patients had normal postoperative urinary flow, and only one patient had an inconspicuous penis after surgery. For the patients with primary proximal hypospadias with an LS‐affected urethra, one patient required perineal urethrostomy following a modified Koyanagi procedure for recurrent stricture; the other patient underwent two‐stage transverse preputial island flap urethroplasty with no postoperative lower urinary tract symptoms (LUTS) and satisfactory aesthetic scores. In two remaining cases of primary distal hypospadias with meatus/urethral LS, no LUTS or postoperative complications occurred following meatoplasty/circumcision and penile basal fixation. During reoperations, compared with those of patients who underwent other redo procedures, twelve patients who underwent OMOP had better Qmax and uroflowmetry (p = 0.002) and higher HOSE scores (p = 0.01).

Conclusions

For primary hypospadias patients with LS, enhanced exposure of the penile shaft and glans may benefit distal hypospadias, whereas staged surgery may be suitable for proximal hypospadias. The oral mucosa is favored for urethral augmentation in patients with redo hypospadias complicated with LS, and the OMOP can address neourethra coverage effectively.
An estimation of lysine requirements of fattening pigs maintained and raised in Japan
Authors: Tsuchino Naoya , Takahashi Katsuaki , Ueno Takashi , Ozeki Teruo , Katsumata Masaya
Published: November 2024

This study aimed to update the first‐liming amino acid (lysine) requirements of fattening pigs maintained and raised in Japan using 146 fattening pigs with an average weight of 62 kg. Five diets were prepared with total lysine concentrations of 0.45%, 0.65%, 0.85%, 0.95%, and 1.05%. Six replicates were used for each lysine concentration. The feeding trial lasted for 4 weeks until the average weight of the pigs reached 92 kg. The total lysine concentration of the diets affected feed efficiency throughout the 4 weeks and was lowest in pigs fed diets with a total lysine concentration of 0.45% and highest in pigs fed 0.85%. The total lysine requirement was estimated using feed efficiency as the response index. The linear and quadratic models estimated 0.68% and 0.75% of the requirement for the first 2 weeks and 0.66% and 0.72% for the 4‐week period, respectively. These estimates were equivalent to the total lysine requirement of 0.72% for the 50–70 kg body weight (expected gain of 850 g/d) in the Japanese Feeding Standard for Swine 2013 and higher than the 0.59% for the 70–115 kg body weight (expected gain of 1000 g/d).
Steroids' Neuroprotective Potential in Severe Cerebral Venous Thrombosis: Experimental and Clinical Exploration of NLRP3 Inflammasome Inhibition
Authors: Hu Shuyuan , Gu Yaqin , Hou Limin , Liu Jia , Zhao Haiping , Luo Yumin , Wang Chunxiu , Ji Xunming , Liu Guiyou , Duan Jiangang
Published: November 2024

Background

NLRP3 inflammasome‐related inflammation might play an important role in the pathophysiology of severe CVT. The use of steroids as anti‐inflammatory agents in improving severe CVT prognosis remains controversial.

Methods

A total of 94 male Sprague–Dawley rats were used. We evaluated the dynamic and association between NLRP3 inflammasome in brain, blood, and CSF and severity in severe CVT rats and/or patients. We also explored the effect of steroids on NLRP3 activation, neurological injury, and CSF circulation disturbance after CVT in animals and/or patients.

Results

In rats, compared with the sham group, NLRP3‐related factors rose on day 1, peaked on day 2 (NLRP3, Sham: 0.79 ± 0.22; day 2: 1.25 ± 0.08, p < 0.01; pro‐Caspase‐1, Sham: 0.58 ± 0.13, day 2: 1.20 ± 0.44, p < 0.05; GSDMD, Sham: 0.94 ± 0.22, day 2: 1.72 ± 0.46, p < 0.05; pro‐IL‐1β, Sham: 0.74 ± 0.15, day 2: 1.35 ± 0.09, p < 0.01), decreased on day 7 in rats (n = 4 per group). Thrombus (Sham: 0.00 ± 0.00, day 2: 3.44 ± 0.70, p < 0.0001), infarct size (Sham: 0.00 ± 0.00, day 2: 11.99 ± 6.26, p < 0.01) and neurological deficits appeared similar trend. In 50 patients, serum NLRP3 and IL‐6 levels correlated positively with NIHSS (r = 0.4273, p = 0.0020; r = 0.4938, p = 0.0029) and mRS (r = 0.5349, p = 0.0125; r = 0.6213, p = 0.026), while CSF IL‐6 correlated positively with mRS on admission (r = 0.5349, p = 0.0125). Compared with baseline, NLRP3 (0.36 (0.36, 0.36) vs. 0.41 (0.37, 0.84), p < 0.0001) and IL‐6 decreased (4.06 ± 1.48 vs. 12.03 ± 7.80, p < 0.05), accompanying by improvement of neurological deficits and CSF circulation (all p < 0.01) after steroids therapy in severe CVT patients at discharge and 3 months follow‐up. No significant steroid‐related adverse effects were observed.

Conclusion

Short‐term steroid therapy may improve prognosis of severe CVT by suppressing NLRP3 inflammasome‐related inflammation.
The Pseudoinflammatory Pattern Revisited
Authors: Shea Christopher R.
Published: November 2024

In 1973, Dr. Martin C. Mihm, Jr. presented the finding that congenital melanocytic nevi, when viewed at low magnification, resemble superficial and deep perivascular dermatitis, forming the so‐called “pseudoinflammatory” pattern. One year earlier, Dr. Richard A. Sagebiel had put forward the concept of “pseudovascular spaces” in melanocytic nevi. A retrospective look at these early studies confirms that alert observation at the microscope can lead to a deeper understanding of the fundamental biology underlying melanocytic tumors.
Genotype‐by‐environment interactions for mean performance and trait variation in house fly larvae reared on two diets
Authors: Laursen Stine Frey , Hansen Laura Skrubbeltrang , Bahrndorff Simon , Nielsen Hanne Marie , Sahana Goutam , Sørensen Jesper Givskov , Ørsted Michael , Kristensen Torsten Nygaard
Published: November 2024

Some insect species have been proposed as a sustainable alternative to traditional animal‐based food and feed sources. Optimisation of insect production can generally be achieved using two main approaches: optimising environmental conditions and improving traits of interest through selective breeding. These avenues are not inseparable as performance of a genotype might differ between environments due to phenotypic plasticity and because genotypes can respond differently to environmental changes, that is genotype‐by‐environment interactions (G × E). In insect production, diets can be of variable quality and consist of waste‐ and by‐products of low nutritional value, which might result in decreased performance and/or increased trait variability within a population. Therefore, it is of interest to investigate how genotypes perform across various diets. Here, we investigated plasticity and G × E for mean performance and trait variation, which we define as the ability of a genotype to produce consistent phenotypes within and across environments. We did this by rearing 190 full‐sib families of house fly larvae, Musca domestica L. (Diptera: Muscidae), on two diets based on either alfalfa, Medicago sativa L. (Fabales: Fabaceae), or deproteinated grass. Four larval traits were assessed: egg‐to‐larva viability, surface area, dry weight and relative lipid content. Reaction norms were used to investigate the effects of diet on full‐sib family mean and trait variation within and across environments. We found that families reared on the grass‐based diet had higher performance across all investigated traits than families reared on the alfalfa‐based diet. For both mean performance and trait variation, we found G × E for all investigated traits. These findings suggest that there is genetic variation for plasticity (slope of reaction norms) for both trait mean and trait variation, and thus that there is a potential to breed for genotypes with high performance as well as for genotypes with low trait variation within and across diets.
Loss of neuropeptide signalling alters temporal expression of mouse suprachiasmatic neuronal state and excitability
Authors: Wegner Sven , Belle Mino D. C. , Chang Pi‐Shan , Hughes Alun T. L. , Conibear Alexandra E. , Muir Charlotte , Samuels Rayna E. , Piggins Hugh D.
Published: November 2024

Individual neurons of the hypothalamic suprachiasmatic nuclei (SCN) contain an intracellular molecular clock that drives these neurons to exhibit day‐night variation in excitability. The neuropeptide vasoactive intestinal polypeptide (VIP) and its cognate receptor, VPAC2, are synthesized by SCN neurons and this intercellular VIP‐VPAC2 receptor signal facilitates coordination of SCN neuronal activity and timekeeping. How the loss of VPAC2 receptor signalling affects the electrophysiological properties and states of SCN neurons as well as their responses to excitatory inputs is unclear. Here we used patch‐clamp electrophysiology and made recordings of SCN neurons in brain slices prepared from transgenic animals that do not express VPAC2 receptors (Vipr2−/− mice) as well as animals that do (Vipr2+/+ mice). We report that while Vipr2+/+ neurons exhibit coordinated day‐night variation in their electrical state, Vipr2−/− neurons lack this and instead manifest a range of states during both day and night. Further, at the population level, Vipr2+/+ neurons vary the membrane threshold potential at which they start to fire action potentials from day to night, while Vipr2−/− neurons do not. We provide evidence that Vipr2−/− neurons lack a component of voltage‐gated sodium currents that contribute to SCN neuronal excitability. Moreover, we determine that this aberrant temporal control of neuronal state and excitability alters neuronal responses to a neurochemical mimic of the light‐input pathway to the SCN. These results highlight the critical role VIP‐VPAC2 receptor signalling plays in the temporal expression of individual neuronal states as well as appropriate ensemble activity and input gating of the SCN neural network.
Behavioural phenotypes of Dicer knockout in the mouse SCN
Authors: Du Ngoc‐Hien , Kompotis Konstantinos , Sato Miho , Pedron Erica , Androvic Sabrina , Brown Steven
Published: November 2024

The suprachiasmatic nucleus (SCN) is the master clock that directly dictates behavioural rhythms to anticipate the earth's light/dark cycles. Although post‐transcriptional regulators called microRNAs have been implicated in physiological SCN function, how the absence of the entire mature miRNome impacts SCN output has not yet been explored. To study the behavioural consequences of miRNA depletion in the SCN, we first generated a mouse model in which Dicer is inactivated in the SCN by crossing Syt10Cre mice with Dicerflox mice to study behavioural consequences of miRNA depletion in the SCN. Loss of all mature miRNAs in the SCN shortened the circadian period length by ~37 minutes at the tissue level and by ~45 minutes at the locomotor activity level. Moreover, knockout animals exhibited a reduction in the precision of the circadian rhythm with more variable activity onsets under both LD 12:12 and DD conditions. We also observed that knockouts with higher onset variations were inclined to develop ultradian rhythms under constant light. In a second mouse model, recombination of Dicerflox via Cre delivery specifically in the SCN resulted in loss of behavioural rhythms in some animals depending on the injection efficiency. Together, our observations highlight the importance of microRNAs for a physiological SCN function and their pivotal role in robust circadian oscillations.
The political and economic environment promoting growth in American wealth inequality
Authors: Ackert Lucy F. , Ramirez Gabriel G.
Published: November 2024

Wealth inequality around the world is high and rising. In this paper, we argue that wealth inequality in the United States has been exacerbated by an environment favourable to the ultra‐wealthy. Three distinctive changes in the economic and political landscape have fostered the increase in inequality. First, campaign finance law abruptly changed after the Citizens United Supreme Court decision. This decision gave the ultra‐wealthy an outsized influence on American politics. Second, an increase in competition for executive talent drove CEO salaries to new heights. Demand increased for executives with general leadership skills as corporations grew larger, increasing competition in the market for executive talent. Third, because tax policy in the United States is subject to lobbying influences, those at the top of the wealth distribution are favoured, leading to further concentration in wealth. Our empirical results are consistent with the view that these changes resulted in an increase in disparity, shifting wealth from the 99% to the 1%.
Changing Bird Migration Patterns Have Potential to Enhance Dispersal of Alien Plants From Urban Centres
Authors: Deshpande Purabi , Johansson Niko , Kluen Edward , Lehikoinen Aleksi , Thorogood Rose
Published: November 2024

There is increasing recognition that alien species may be ‘sleepers’, becoming invasive with favourable changes in conditions, yet these changes remain difficult to predict. As populations of frugivorous birds shift with urbanisation and climate change, they could provide dispersal services for introduced fruiting plants that have previously been considered benign. This is likely to be especially problematic at higher latitudes where bird migration phenologies are altering rapidly. However, any consequences for fruit dispersal have not yet been explored. Here, we use Helsinki, Finland, to investigate whether (i) streetscapes provide birds with a fruit resource that differs from urban forest fragments and (ii) the chances for dispersal of alien species (i.e., preferential consumption of native fruits). While there were both more fruits and birds in streetscapes (replicated across multiple years), fruits were not consumed preferentially according to origin. Additionally, seed analysis from faecal samples of blackbird Turdus merula L., a previously migratory but increasingly resident species, suggested that alien and native plants are equally likely to be dispersed. These results indicate that birds could be dispersing alien species more frequently than previously thought and highlight the complex effects of changing climates on potentially invasive species.
A Proposed Coupling Framework of Biological Invasions: Quantifying the Management Prioritization in Mealybugs Invasion
Authors: Zhao Haoxiang , Xian Xiaoqing , Yang Nianwan , Chen Ting , Li Jianyu , Sheppard Andy , Wan Fanghao , Qi Guojun , Liu Wanxue
Published: November 2024

Prioritizing potential invasive alien species, introduction pathways, and likely places susceptible to biological invasions is collectively critical for developing the targeting of management strategies at pre‐border, border, and post‐border. A framework for prioritizing the invasion management that considered all these elements in combination is lacking, particularly in the context of potential coinvasion scenarios of multispecies. Here, for the first time, we have constructed a coupling framework of biological invasions to evaluate and prioritize multiple invasion risks of 35 invasive alien mealybugs (IAMs) that posed a significant threat to the agri‐horticultural crops in China. We found that the imported tropical fruits from free trade areas of the Association of Southeast Asian Nations to entry ports of southern China were the primary introduction pathway for IAMs, vectored on various fruit commodities. There was also a high probability for cointroductions of potential multi‐IAMs with a single imported tropical fruit. The potential distribution of such IAMs with dissimilar net relatedness were mainly located in southern China. These distributions, however, are likely to expand to the higher latitudes of northern China under future climate and land use/land cover changes. Temperature and anthropogenic factors were both independently and collectively determining factors for the diversity and distribution patterns of imported IAMs under near‐current climate conditions. Our findings highlight that these multiple components of global change have and will continue to facilitate the introduction and establishment risks of IAMs in southern China, as well as the spread risk into northern China. Additionally, our findings, for the first time, demonstrated management prioritization across the continuous invasion stages of 35 IAMs in China, and provide additional insights into the development of targeting of their biosecurity and management decisions.
Shared Decision‐Making and Body Mass Index in Australian Antenatal Care: An Exploratory OPTION12 Evaluation
Authors: Hawke Madeline , Sweet Linda , Considine Julie
Published: November 2024

Background

Shared decision‐making is recommended as a person‐centred approach to decision‐making in antenatal care. Little is known about the implementation of shared decision‐making in antenatal care.

Objective

An exploratory study to understand how shared decision‐making is implemented in antenatal clinics and whether body mass index influences maternity clinicians’ use of shared decision‐making when providing antenatal care for women.

Methods

Twenty‐six antenatal clinic consultations were audio‐recorded with maternity clinicians and women with body mass index ≥ 35 kg/m2, and a comparison group of women with body mass index 18.5–24.9 kg/m2. Data were analysed quantitatively using the OPTION12 scale. Narrative case studies are presented to compare shared decision‐making behaviour related to induction of labour.

Results

Twelve clinicians and 26 pregnant women were recruited to the study. The total scores ranged from 0 to 24, with a mean score of 9 and a median of 9.5 indicating low implementation of shared decision‐making by clinicians and limited involvement of women in decision‐making. No difference was observed in OPTION12 scores in decision‐making for women by body mass index.

Conclusion

This study suggests that shared decision‐making is limited in the antenatal clinic setting for all women, regardless of body mass index. Further research is required to confirm the findings of this exploratory study.

Patient or Public Contribution

The perspectives of women with body mass index ≥ 35 kg/m2 informed many aspects of this study including the language/terminology adopted by researchers. A consumer group reviewed the language used in the study materials, to ensure readability and avoidance of stigmatising terminology.
Gender‐specific genetic influence of rs1111875 on diabetes risk: Insights from the Taiwan biobank study
Authors: Chiang Chih‐Wei , Chou Ying‐Hsiang , Huang Chien‐Ning , Lu Wen‐Yu , Liaw Yung‐Po
Published: November 2024

Background

This study investigates the gender‐specific genetic influence of the single nucleotide polymorphism (SNP) rs1111875 on diabetes risk within the Taiwanese population using data from the Taiwan Biobank. Diabetes mellitus, particularly type 2 diabetes (T2D), is influenced by genetic factors, and the rs1111875 SNP near the hematopoietically expressed homeobox (HHEX) gene has been linked to T2D susceptibility.

Methods

The study included 69,272 participants after excluding those from arsenic‐polluted areas and those with incomplete data. Logistic regression models were used for analyses.

Results

The analyses revealed that the CT genotype of rs1111875 was associated with an increased risk of diabetes (OR = 1.092, 95% CI = 1.030–1.157, P = 0.003), as was the TT genotype (OR = 1.280, 95% CI = 1.165–1.407, P < 0.001). The effect was more pronounced in women (CT: OR = 1.118, 95% CI = 1.036–1.207, P = 0.004; TT: OR = 1.404, 95% CI = 1.243–1.585, P < 0.001). Men exhibited a higher overall risk of diabetes (OR = 1.565, 95% CI = 1.445–1.694, P < 0.001) and had a higher prevalence (12.71% vs 7.80%, P < 0.001) compared to women.

Conclusions

The findings underscore the importance of considering gender differences in genetic studies of diabetes and suggest that personalized diabetes management strategies should account for both genetic and gender‐specific risk factors. This research contributes to the broader understanding of genetic determinants of diabetes and their interaction with gender, aiming to enhance personalized healthcare strategies for diabetes prevention and treatment.
Inhibition of iron‐induced cofilin activation and inflammation in microglia by a novel cofilin inhibitor
Authors: Shehjar Faheem , James Antonisamy William , Mahajan Reetika , Shah Zahoor A.
Published: November 2024

Neuroinflammatory conditions linked to iron dysregulation pose significant challenges in neurodegenerative diseases. Iron‐loaded microglia are observed in the brains of patients with various neuroinflammatory conditions, yet how iron overload affects microglial function and contributes to various neuroinflammatory processes is poorly understood. This in vitro study elucidates the relationship between excess iron, cofilin activation, and microglial function, shedding light on potential therapeutic avenues. Iron overload was induced in Human Microglial Clone 3 cells using ferrous sulfate, and the expressions of ferritin heavy chain, ferritin light chain, divalent metal transporter 1, cofilin, p‐cofilin, nuclear factor‐κB (NF‐κB), and various inflammatory cytokines were analyzed using real‐time quantitative polymerase chain reaction, immunocytochemistry, Western blotting, and enzyme‐linked immunosorbent assay. Results revealed a notable increase in cofilin, NF‐κB, and inflammatory cytokine expression levels following excess iron exposure. Moreover, treatment with deferoxamine (DFX), a known iron chelator, and a novel cofilin inhibitor (CI) synthesized in our laboratory demonstrate a mitigating effect on iron‐induced cofilin expression. Furthermore, both DFX and CI exhibit promising outcomes in mitigating the inflammatory consequences of excess iron, including the expression of pro‐inflammatory cytokines and NF‐κB activation. These findings suggest that both DFX and CI can potentially alleviate microglia‐induced neuroinflammation by targeting both iron dysregulation and cofilin‐mediated pathways. Overall, this study provides valuable insights into iron‐induced cofilin activation and microglial activation, offering avenues for potential targeted therapies for neuroinflammatory conditions associated with iron and cofilin dysregulation in neurodegenerative diseases.

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QuPath Edu and OpenMicroanatomy: Open‐source virtual microscopy tools for medical education
Authors: Yli‐Hallila Aaron , Bankhead Peter , Arends Mark J. , Lehenkari Petri , Palosaari Sanna
Published: November 2024

Virtual microscopy is becoming increasingly common in both medical education and routine clinical practice. Virtual microscopy software is typically designed either for (1) training students in anatomy, histology, and histopathology, or (2) quantitative analysis—but not both simultaneously. QuPath is one of the most widely used software applications for histopathology image analysis in research and provides a comprehensive set of computational tools to evaluate histology slides. We have enhanced QuPath by developing a new extension, QuPath Edu, which adapts the software to function as an intuitive microanatomy learning environment. Additionally, we have created an entirely new, complementary software platform called OpenMicroanatomy, which provides an alternative way to access QuPath Edu teaching content through a web interface. These tools have been used in teaching of first year medical and dentistry students at the University of Oulu Medical Faculty, and we conducted a user survey for the Class of 2023 to assess the usability and student experience. In general, the introduced annotation and quiz features were appreciated by the students and the system usability of OpenMicroanatomy was considered excellent (SUS score 84.8). Together, these freely available tools enable teachers to develop and deploy innovative training material for anatomy, histopathology, quantitative analysis, and artificial intelligence in a wide range of contexts. This unique combination can provide the next generation of students with essential multidisciplinary skills.
Cyclin‐dependent kinase 13 is indispensable for normal mouse heart development
Authors: Waheed‐Ullah Qazi , Wilsdon Anna , Abbad Aseel , Rochette Sophie , Bu'Lock Frances , Saed Asma Ali , Hitz Marc‐Phillip , Brook J. David , Loughna Siobhan
Published: November 2024

Congenital heart disease (CHD) has an incidence of approximately 1%. Over the last decade, sequencing studies including large cohorts of individuals with CHD have begun to unravel the genetic mechanisms underpinning CHD. This includes the identification of variants in cyclin‐dependent kinase 13 (CDK13), in individuals with syndromic CHD. CDK13 encodes a serine/threonine protein kinase. The cyclin partner of CDK13 is cyclin K; this complex is thought to be important in transcription and RNA processing. Pathogenic variants in CDK13 cause CDK13‐related disorder in humans, characterised by intellectual disability and developmental delay, recognisable facial features, feeding difficulties and structural brain defects, with 35% of individuals having CHD. To obtain a greater understanding for the role that this essential protein kinase plays in embryonic heart development, we have analysed a presumed loss of function Cdk13 transgenic mouse model (Cdk13tm1b). The homozygous mutants were embryonically lethal in most cases by E15.5. X‐gal staining showed Cdk13 expression localised to developing facial regions, heart and surrounding areas at E10.5, whereas at E12.5, it was more widely present. In the E15.5 heart, staining was seen throughout. RT‐qPCR showed significant reduction in Cdk13 transcript expression in homozygous compared with WT and heterozygous hearts at E10.5 and E12.5. Detailed morphological 3D analysis of embryonic and postnatal hearts was performed using high‐resolution episcopic microscopy, which affords a more detailed analysis of structures such as cardiac valve leaflets and endocardial cushions, compared with more traditional histological techniques. We show that both the homozygous and heterozygous Cdk13tm1b mutants exhibit a range of CHD, including ventricular septal defects, bicuspid aortic valve, double outlet right ventricle and atrioventricular septal defects. 100% (n = 4) of homozygous hearts displayed CHD. Differential expression was seen in Cdk13tm1b homozygous mutants for two genes known to be necessary for normal heart development. The types of defects, and the presence of CHD in heterozygous mice (17.02%, n = 8/47), are consistent with the CDK13‐related disorder phenotype in humans. This study provides important insights into the effects of reduced function of CDK13 in the mouse heart and contributes to our understanding of the mechanism behind this disorder as a cause of CHD.
Development of a Tactile Vocabulary Based on Suitability and Perceptual Intensity
Authors: Ikejima Toshiki , Mizukoshi Koji , Nonomura Yoshimune
Published: November 2024

A vocabulary of tactile perception is essential for the evaluation of the feel of materials. Different tactile vocabulary has been established by various industries, making the understanding and comparison of tactile perceptions challenging. In this study, we developed a universal tactile vocabulary applicable across various industries. Based on our participants' tactile evaluations of 32 materials, we compiled a vocabulary of 273 words, categorizing them into a perceptual hierarchy: sensory and affective. Additionally, we recorded and analyzed the word use frequencies, suitability, intensity, and similarities of the tactile evaluations. Finally, we selected 31 words that each accurately expresses a particular tactile perception and can be applied to materials and products in diverse industries. The vocabulary developed in this study is expected to be a useful aid in designing the tactile aspects of various products.
Barriers Experienced by Psychiatric Nurses to Facilitate Therapeutic Relationships With Mental Healthcare Users With Dual Diagnosis in a Psychiatric Hospital in South Africa
Authors: Mathebula Thomas , van der Wath Anna Elizabeth , Ramavhoya Thifhelimbilu Irene
Published: November 2024

Background

Psychiatric nurses are in a unique position to build therapeutic relationships with mental healthcare users with dual diagnoses to foster trust and recovery. However, a dual diagnosis poses barriers to establishing and maintaining a therapeutic nurse–patient relationship.

Aim

The overall aim of this study was to explore and describe barriers experienced by psychiatric nurses to facilitate therapeutic relationships with mental healthcare users with dual diagnosis in a psychiatric hospital in Limpopo province, South Africa.

Design

A qualitative, explorative, descriptive and contextual design was followed.

Method

Semi‐structured interviews were conducted with 12 purposively selected participants who cared for mental healthcare users with dual diagnoses. Tech's method of open coding was used to analyse the data.

Findings

Disruptive and disrespectful behaviour and mental healthcare users' substance use during hospitalisation resulted in nurses harbouring ambivalent feelings that impaired therapeutic nurse–patient relationships.

Conclusion

The barriers affecting therapeutic relationships with mental healthcare users with dual diagnosis should be addressed to enhance recovery and treatment compliance.

Recommendations

An integrated approach with the involvement of the interprofessional team, debriefing and training for nurses may help to foster therapeutic nurse–patient relationships, empower nurses and enhance the recovery of mental healthcare users with dual diagnosis.
Fibre Sources on Performance and Carcass and Meat Characteristics of Feedlot Nellore Young Bulls
Authors: Niwa Marcus Vinicius Garcia , Ítavo Luís Carlos Vinhas , Brandão Ferreira Ítavo Camila Celeste , de Nadai Bonin Gomes Marina , Longhini Vanessa Zirondi , Cunha Camila Soares , Dias Alexandre Menezes , dos Santos Difante Gelson , Vedovatto Marcelo , da Costa Gomes Rodrigo , Gurgel Antonio Leandro Chaves , Dias‐Silva Tairon Pannunzio , da Costa Leite Lopes Brenda Farias , de Moraes Gabriella Jorgetti
Published: November 2024

We evaluated the replacement of neutral detergent fibre levels from forage (NDFfor) by cottonseed cake on the performance, and carcass and meat traits of Nellore young bulls finished in a feedlot. Individual data from 24 Nellore young bulls with 330 ± 4.54 kg of body weight (BW) and 18 ± 1 months old were used. The animals were randomly distributed in four nutritional treatments containing 9.5%; 5.5%; 2.5%; and 0.0% NDF from whole corn plant silage (forage source), replaced by cottonseed cake, in the total diet. Animal performance and carcass and meat characteristics were analysed by orthogonal polynomial regression. A positive quadratic effect was observed for DM, CP, EE, NDF, and physically effective NDF intake (peNDFI8 mm, and peNDFI1.18 mm). There was no NDFfor‐level effect for final weight, hot carcass weight, carcass yield, internal and external depth, carcass length, pH, subcutaneous fat thickness, and loin eye area. A positive quadratic effect was detected for average daily gain. Feed efficiency demonstrated a positive quadratic trend, reaching an optimum peak level when young bulls 4.01% of NDFfor. There was no NDFfor‐level effect for meat and fat colour variables. The NDFfor‐level with the highest DM intake (2.01% BW) was 5.15%, and the highest ADG (1.54 kg/day) was 4.91% of NDFfor. Thus, although NDFfor levels did not affect carcass characteristics, fat, and meat colour, levels between 4.50% and 5.15% NDF from forage replaced by cottonseed cake are recommended to enhance the productive performance of feedlot Nellore young bulls. Cottonseed cake as a source of fibre can partially or totally replace corn plant silage.
Recent advances in stochastic simulation algorithms create opportunities to study new ecological and eco‐evolutionary problems
Authors: Kummel Misha T. , Vasseur David A.
Published: November 2024

Incorporating stochasticity into ecological modeling is vital for understanding the structure and function of ecological systems, but stochasticity has been challenging to consistently introduce into foundational ecological theory. The Gillespie stochastic simulation algorithm (herein SSA) provides a key method to represent demographic stochasticity, but due to its foundational assumptions is inadequate for problems involving intra‐population variation and extrinsically/environmentally‐driven rapid changes in demographic rates. Two recent extensions to the SSA address these limitations: one augments the SSA with individual‐linked trait distributions that let us track trait changes across individuals and populations and the other introduces a methodological innovation to allow demographic rates to change between events; in four case studies we demonstrate the utility of these advances and highlight that simultaneously integrating both extensions into a single framework allows us to tackle a new class of ecological and evolutionary questions that have typically not been explored in continuous time modeling.
Leaf Transpirational Cooling and Thermal Tolerance Vary Along the Spectrum of Iso‐Anisohydric Stomatal Regulation in Sand‐Fixing Shrubs
Authors: Guo Jing‐Jing , Gong Xue‐Wei , Hao Guang‐You
Published: November 2024

Transpirational cooling is crucial for plant thermal regulation to avoid overheating; however, during prolonged and/or acute heat stress it often necessitates stomatal closure to reduce the risk of hydraulic failure due to dehydration. The intricate interplay between thermal regulation, water transport and use may govern plant performance in water‐limited and simultaneously heat‐stressed environments, yet this remains inadequately understood. Here, in a common garden, we evaluated the functional associations among physiological characteristics related to leaf thermoregulation, heat tolerance, xylem water transport, and stomatal regulation in eight shrub species commonly used for fixing active sand dunes in northern China. Our study showed that traits associated with heat adaptation and xylem hydraulics were closely related to stomatal regulation. More isohydric shrub species with higher water transport efficiency possessed stronger transpirational cooling capacity; whereas the more anisohydric species demonstrated greater tolerance to overheating. Moreover, leaf heat tolerance was strongly coordinated with drought tolerance reflected by leaf turgor loss point. These results underscore the importance of stomatal regulation in shaping plant thermal adaptive strategies and provide valuable insights into the coupling of water and heat‐related physiological processes in plants adapted to sandy land environments prone to combined drought and heat stresses.
Diurnal Rhythmicity in the Rhizosphere Microbiome—Mechanistic Insights and Significance for Rhizosphere Function
Authors: Bending Gary D. , Newman Amy , Picot Emma , Mushinski Ryan M. , Jones Davey L. , Carré Isabelle A.
Published: November 2024

The rhizosphere is a key interface between plants, microbes and the soil which influences plant health and nutrition and modulates terrestrial biogeochemical cycling. Recent research has shown that the rhizosphere environment is far more dynamic than previously recognised, with evidence emerging for diurnal rhythmicity in rhizosphere chemistry and microbial community composition. This rhythmicity is in part linked to the host plant's circadian rhythm, although some heterotrophic rhizosphere bacteria and fungi may also possess intrinsic rhythmicity. We review the evidence for diurnal rhythmicity in rhizosphere microbial communities and its link to the plant circadian clock. Factors which may drive microbial rhythmicity are discussed, including diurnal change in root exudate flux and composition, rhizosphere physico‐chemical properties and plant immunity. Microbial processes which could contribute to community rhythmicity are considered, including self‐sustained microbial rhythms, bacterial movement into and out of the rhizosphere, and microbe‐microbe interactions. We also consider evidence that changes in microbial composition mediated by the plant circadian clock may affect microbial function and its significance for plant health and broader soil biogeochemical cycling processes. We identify key knowledge gaps and approaches which could help to resolve the spatial and temporal variation and functional significance of rhizosphere microbial rhythmicity. This includes unravelling the factors which determine the oscillation of microbial activity, growth and death, and cross‐talk with the host over diurnal time frames. We conclude that diurnal rhythmicity is an inherent characteristic of the rhizosphere and that temporal factors should be considered and reported in rhizosphere studies.