bluuebunny/crossref_metadata_2025 huggingface dataset:
Posttraumatic stress disorder and insomnia in US military veterans: Prevalence, correlates, and psychiatric and functional burden
Authors: Georgescu Michael F. , Fischer Ian C. , Beydoun May A. , McCarthy Elissa , DeViva Jason C. , Pietrzak Robert H.
Published: June 2024

Military veterans have high rates of psychiatric conditions such as posttraumatic stress disorder, which can complicate the clinical management of insomnia. Population‐based data are lacking on the prevalence, characteristics and mental health burden of veterans with co‐occurring posttraumatic stress disorder and insomnia. The current cross‐sectional study analysed data from a nationally representative sample of 4069 US veterans examining the prevalence and comorbidity between posttraumatic stress disorder and insomnia, and their associations with psychiatric and medical comorbidities, suicidality, and psychosocial functioning. Results revealed that 4.0% of US veterans screened positive for posttraumatic stress disorder + insomnia, 7.4% for insomnia only, and 3.2% for posttraumatic stress disorder only. Compared with controls, higher odds of major depressive disorder and generalized anxiety disorder were observed in the posttraumatic stress disorder + insomnia and posttraumatic stress disorder only groups. Moreover, compared with the control group, posttraumatic stress disorder + insomnia and posttraumatic stress disorder only groups had higher odds of current suicidal ideation, while the posttraumatic stress disorder + insomnia group had also higher odds of attempting suicide. Relative to the posttraumatic stress disorder only group, the posttraumatic stress disorder + insomnia group scored substantially lower on measures of cognitive, emotional and social functioning (d = 1.05, 1.04 and 0.87, respectively). This study provides contemporary data regarding current prevalence, correlates, and psychiatric and functional burden of posttraumatic stress disorder + insomnia among US veterans. The results underscore the importance of assessing, monitoring and treating posttraumatic stress disorder and insomnia as part of the efforts to mitigate suicide risk and promote multi‐domain functioning in this population.
Disposition kinetics and tissue residues of tilmicosin following intravenous, subcutaneous, single and multiple oral dosing in geese (Anser anser domesticus)
Authors: Bourdo Krzysztof , Fadel Charbel , Giorgi Mario , Šitovs Andrejs , Poapolathep Amnart , Łebkowska‐Wieruszewska Beata
Published: June 2024

Tilmicosin (TMC), a semi‐synthetic macrolide antibiotic, is widely used in veterinary medicine due to its broad‐spectrum, bacteriostatic properties. Frequently administered in various birds species, it is likely used off‐label in geese as well. The study sought to investigate TMC's pharmacokinetics, tissue residues, in geese through in vivo experiments. The study involved longitudinal open studies on 15 healthy adult males, with three phases separated by one‐month washout periods. Geese were administered TMC through intravenous (IV, 5 mg/kg), subcutaneous (SC, 10 mg/kg), and oral (PO, 25 mg/kg for five consecutive days) routes, with blood samples drawn at specific intervals. Tissue samples were also collected for subsequent analysis at pre‐assigned times. TMC in goose plasma was quantified by a fully validated HPLC method. Plasma concentrations were quantified up to 4 hr for the PO and IV routes, and up to 10 hr in the SC route. Significant variations in bioavailability were observed between SC (87%) and PO (4%) routes. The body extraction ratio was low at 0.03, suggesting minimal ability of the liver and kidneys to eliminate TMC. Multiple oral doses showed no plasma accumulation, but tissue data revealed extensive distribution and prolonged residence, up to 120 h, suggesting a sustained therapeutic effect despite the brief plasma half‐life. Regarding the multiple PO doses, provisional withdrawal times of 6, 7.5, and 8 days were suggested for the liver, muscles, and kidneys, respectively, according to the MRL set for these matrices in chickens by EMA. In conclusion, while the practical oral administration is discouraged at the population level, SC administration of TMC may be appropriate for geese, albeit impractical for flock therapy.
The role of non‐base compensation in explaining the motherhood wage gap: Evidence from Italy
Authors: Badaoui Eliane , Matteazzi Eleonora , Prete Vincenzo
Published: June 2024

This paper underlines the importance of accounting for non‐base compensation in explaining the motherhood wage gap. We consider two alternative measures of hourly wage using Italian EU‐SILC data from 2007 to 2019: the base‐wage and the full‐wage. The former refers to the contractual base wage, while the latter includes performance‐based bonuses, productivity bonuses, commissions, pay incentives, and other extra payments. We address the endogeneity issues of motherhood and examine the effect of motherhood status across various quantiles of the wage distribution for the two hourly wage measures. Empirical findings provide evidence of a motherhood base‐wage premium, which becomes nonsignificant when using the full‐wage measure, suggesting that non‐base compensation is a source of inequality for mothers. These findings are consistent across the wage distribution. Exploring potential heterogeneity across macro‐regions and periods, we find no notable regional disparities except minor distinctions for the Southern regions, alongside a decline in the base‐wage premium over time and the emergence of a full‐wage penalty in recent years. A comparative analysis with a sample of men reveals that fathers enjoy a premium with both wage measures. Nevertheless, fatherhood is also associated with reduced extra remunerations, yet to a lesser extent than motherhood.
Exercise improves surrogate measures of liver histological response in metabolic dysfunction‐associated steatotic liver disease
Authors: Cuthbertson Daniel J. , Keating Shelley E. , Pugh Christopher J. A. , Owen Patrick J. , Kemp Graham J. , Umpleby Margot , Geyer Nathaniel G. , Chinchilli Vernon M. , Stine Jonathan G.
Published: June 2024

Background and Aims

Exercise is recommended for the management of metabolic dysfunction‐associated steatotic liver disease (MASLD), yet effects on liver histology remain unknown, especially without significant weight loss. We aimed to examine changes in surrogate measures of liver histological response with exercise training.

Methods

We conducted a post hoc pooled analysis of three randomised controlled trials (duration: 12–20 weeks) comparing aerobic exercise interventions with controls. The primary outcome measure was a ≥30% relative reduction in (MRI‐measured) liver fat, as a surrogate measure of liver histological response (the threshold necessary for fibrosis improvement). Secondary outcome measures were changes in other biomarkers of liver fibrosis, anthropometry, body composition and aerobic fitness.

Results

Eighty‐eight adults (exercise: 54, control: 34; male: 67%) were included with mean (SD) age 51 (11) years and body mass index 33.3 (5.2) kg/m2. Following the intervention, exercise had ~5‐fold (OR [95%CI]: 4.86 [1.72, 13.8],p = .002) greater odds of ≥30% relative reduction in MRI‐measured liver fat compared with control. This paralleled the improvements in anthropometry (waist and hip circumference reduction), body composition (body fat, visceral and subcutaneous adipose tissue) and aerobic fitness (V̇O2peak, ventilatory threshold and exercise capacity). Importantly, these effects were independent of clinically significant body weight loss (<3% body weight).

Conclusion

Exercise training led to clinically meaningful improvements in surrogate serum‐ and imaging‐based measures of liver histological change, without clinically meaningful body weight reduction. These data reinforce the weight‐neutral benefit of exercise training and suggest that aerobic training may improve liver fibrosis in patients with MASLD.
LNCHC directly binds and regulates YBX1 stability to ameliorate metabolic dysfunction‐associated steatotic liver disease progression
Authors: Lu Kaikai , Cheng Xiaona , He Lei , Li Mengda , Chen Qian , Qian Chen , Zhao Rong , Yang Luyun , Liu Fangtong , Liu Sitong , Zhang Tianyun , Feng Lina , Wu Litao , Wu Xiaodan , Xu Nan , Li Ya , Wang Jun , Han Yu , Yuan Haiyang , Liu Tiemin , Zheng Minghua , Lu Shemin , Li Dongmin
Published: June 2024

Background and Aims

Metabolic dysfunction‐associated steatotic liver disease (MASLD) represents the foremost cause of chronic liver disease, yet its underlying mechanisms remain elusive. Our group previously discovered a novel long non‐coding RNA (lncRNA) in rats, termed lncHC and its human counterpart, LNCHC. This study aimed to explore the role of LNCHC in the progression of MASLD.

Methods

RNA‐binding proteins bound to LNCHC were searched by mass spectrometry. The target genes of LNCHC and Y‐Box binding protein 1 (YBX1) were identified by RNA‐seq. MASLD animal models were utilised to examine the roles of LNCHC, YBX1 and patatin‐like phospholipase domain containing 3 (PNPLA3) in MASLD progression.

Results

Here, we identified LNCHC as a native restrainer during MASLD development. Notably, LNCHC directly binds YBX1 and prevents protein ubiquitination. Up‐regulation of YBX1 then stabilises PNPLA3 mRNA to alleviate lipid accumulation in hepatocytes. Furthermore, both cell and animal studies demonstrate that LNCHC, YBX1 and PNPLA3 function to improve hepatocyte lipid accumulation and exacerbate metabolic dysfunction‐associated steatohepatitis development.

Conclusions

In summary, our findings unveil a novel LNCHC functionality in regulating YBX1 and PNPLA3 mRNA stability during MASLD development, providing new avenues in MASLD treatment.
Beneficial effects of hepatic cyclooxygenase‐2 expression against cholestatic injury after common bile duct ligation in mice
Authors: Brea Rocío , Casanova Natalia , Alvarez‐Lucena Carlota , Fuertes‐Agudo Marina , Luque‐Tevar María , Cucarella Carme , Capitani María C. , Marinochi María V. , Fusini Matías E. , Lahoz Agustín , Nogueroles Marina López , Fraile Juan , Ronco María T , Boscá Lisardo , González‐Rodríguez Águeda , García‐Monzón Carmelo , Martín‐Sanz Paloma , Casado Marta , Francés Daniel E.
Published: June 2024

Background and Aims

Cyclooxygenase‐2 (COX‐2) is involved in different liver diseases, but little is known about the significance of COX‐2 in cholestatic injury. This study was designed to elucidate the role of COX‐2 expression in hepatocytes during the pathogenesis of obstructive cholestasis.

Methods

We used genetically modified mice constitutively expressing human COX‐2 in hepatocytes. Transgenic mice (hCOX‐2‐Tg) and their wild‐type (Wt) littermates were either subjected to a mid‐abdominal laparotomy or common bile duct ligation (BDL) for 2 or 5 days. Then, we explored the mechanisms underlying the role of COX‐2 and its derived prostaglandins in liver function, and the synthesis and excretion of bile acids (BA) in response to cholestatic liver injury.

Results

After BDL, hCOX‐2‐Tg mice showed lower grades of hepatic necrosis and inflammation than Wt mice, in part by a reduced hepatic neutrophil recruitment associated with lower mRNA levels of pro‐inflammatory cytokines. Furthermore, hCOX‐2‐Tg mice displayed a differential metabolic pattern of BA synthesis that led to an improved clearance after BDL‐induced accumulation. In addition, an enhanced response to the BDL‐induced oxidative stress and hepatic apoptosis was observed. In vitro experiments using hepatic cells that stably express hCOX‐2 confirmed the cytoprotective role of prostaglandin E2 against BA toxicity.

Conclusions

Taken together, our data indicate that constitutive expression of COX‐2 in hepatocytes ameliorates cholestatic liver injury in mice by reducing inflammation and cell damage and by modulating BA metabolism, pointing to a role for COX‐2 as a defensive response against cholestasis‐derived BA accumulation and injury.
Hepatic manifestations of hereditary haemorrhagic telangiectasia
Authors: Kelly Claire , Buscarini Elisabetta , Manfredi Guido , Gregory Stephen , Heneghan Michael A.
Published: June 2024

Hereditary haemorrhagic telangiectasia is a genetic condition of abnormal blood vessel formation resulting from an imbalance of pro‐ and anti‐angiogenic products of the transforming growth factor β/bone morphogenetic protein signalling pathway which contributes to vascular remodelling and maintenance. Hepatic vascular malformations are common although less frequently symptomatic, but may result in high‐output cardiac failure, portal hypertension and biliary ischaemia. Whilst the understanding of the genetic and cell signalling pathways that are the hallmark of hereditary haemorrhagic telangiectasia have been clarified, there remain challenges in therapy for these patients. Only patients with symptomatic hepatic vascular malformations require treatment, with most (63%) responding to first‐line medical therapy. For non‐responders, bevacizumab is effective in reducing cardiac output in those with heart failure secondary to hepatic vascular malformations as well as other manifestations of the disease. Although liver transplantation is the only curative option, optimal timing is critical. Novel anti‐angiogenetic drugs and those that target aberrant cell signalling pathway are being explored.
Clinical characteristics and prognosis of early diagnosed Wilson's disease: A large cohort study
Authors: Li Simin , Lin Yunting , Chen Shehong , Zhang Wen , Chen Yu‐ming , Lu Xinshuo , Shao Yongxian , Lu Zhikun , Sheng Huiying , Guan Zhihong , Zheng Ruidan , Liang Cuili , Chen Yaoyong , Liu Li , Zeng Chunhua
Published: June 2024

Background and Aims

Few studies have focused on the outcomes of Wilson's disease (WD) diagnosed before age of 5 years. This study aimed to summarize the clinical features of early diagnosed WD and analyse treatment outcomes and the risk factors associated with treatment failure.

Methods

A total of 139 children confirmed with WD before 5 years were enrolled in this study. Only patients with follow‐up over 1 year were analysed with Kaplan–Meier survival analysis. The composite outcomes included death, progression to liver failure or acute hepatitis, development of renal or neurological symptoms and persistent elevation of alanine aminotransferase (ALT). The treatment failure was defined as occurrence of at least one of above outcomes.

Results

Among 139 WD patients at diagnosis, two (1.4%) WD patients presented with symptomatic liver disease, whereas 137 (98.6%) were phenotypically asymptomatic, including 135 with elevated ALT and 2 with normal liver function. Median serum ceruloplasmin (Cp) was 3.1 mg/dL, and urinary copper excretion was 87.4 μg/24‐h. There were 71 variants identified in the the copper‐transporting ATPase beta gene, and 29 were loss of function (LOF). 51 patients with LOF variant were younger at diagnosis and had lower Cp than 88 patients without LOF. Among 93 patients with over 1 year of follow‐up, 19 (20.4%) received zinc monotherapy, and 74 (79.6%) received a zinc/D‐penicillamine combination therapy. 14 (15.1%) patients underwent treatment failure, and its occurrence was associated with poor compliance (p < .01).

Conclusions

Cp is a reliable biomarker for early diagnosis, and zinc monotherapy is an effective treatment for WD during early childhood. Good treatment compliance is critical to achieve a favourable outcome.
Taxonomic assessment, conservation status, and future perspectives for New World Marsupials
Authors: Martin Gabriel M. , Carmignotto Ana Paula
Published: June 2024

New World Marsupials (NWMs) comprise over 135 species ranging from Patagonia (Argentina) to northern North America, classified within the orders Didelphimorphia, Microbiotheria and Paucituberculata.

This study examines recent taxonomic revisions and conservation priorities for NWMs, based on the IUCN Red List assessments and current literature.

NWMs are included in the following IUCN Red List categories: 2 (1.5%) Critically Endangered (CR), 9 (6.6%) Vulnerable (VU), 7 (5.1%) Near Threatened (NT), 15 (11%) Data Deficient (DD), and 72 (53%) Least Concern (LC), with 32 (23%) species awaiting formal assessments.

Population trends remain unknown for more than half of the 137 species (n = 82; 60%), with 34 stable species (25%), 30 declining (22%), and only three showing increasing trends (2.2%). Of the 105 IUCN assessed species, 45 (43%) have unknown population trends.

Identified threats for assessed species (n = 32) include ecosystem conversion and degradation as the main threats, with habitat loss through fragmentation and/or land conversion potentially affecting 26 additional species. When analysed in detail with the proposed classification ‘Habitat loss, fragmentation, and conversion’ were identified as the main threat to 61 species.

Research needs were identified for 85 species (62%), across five categories: Taxonomy (9 species), Life History and Ecology (75 species), Population size, Distribution and Trends (80 species), Threats (78 species), and Actions (2 species).

We propose four key steps to enhance the conservation of NWMs: 1) update assessments to include all valid species, 2) identify priority areas for NWM conservation, 3) encourage research collaboration, and 4) integrate data into conservation strategies at various spatial and political scales.
Facilitated introgression from domestic goat into Alpine ibex at immune loci
Authors: Münger Xenia , Robin Mathieu , Dalén Love , Grossen Christine
Published: June 2024

Hybridization can result in the transfer of adaptive genetic material from one species to another, known as adaptive introgression. Bottlenecked (and hence genetically depleted) species are expected to be particularly receptive to adaptive introgression, since introgression can introduce new or previously lost adaptive genetic variation. The Alpine ibex (Capra ibex), which recently recovered from near extinction, is known to hybridize with the domestic goat (Capra aegagrus hircus), and signals of introgression previously found at the major histocompatibility complex were suggested to potentially be adaptive. Here, we combine two ancient whole genomes of Alpine ibex with 29 modern Alpine ibex genomes and 31 genomes representing six related Capra species to investigate the genome‐wide patterns of introgression and confirm the potential relevance of immune loci. We identified low rates of admixture in modern Alpine ibex through various F statistics and screening for putative introgressed tracts. Further results based on demographic modelling were consistent with introgression to have occurred during the last 300 years, coinciding with the known species bottleneck, and that in each generation, 1–2 out of 100 Alpine ibex had a domestic goat parent. The putatively introgressed haplotypes were enriched at immune‐related genes, where the adaptive value of alternative alleles may give individuals with otherwise depleted genetic diversity a selective advantage. While interbreeding with domestic species is a prevalent issue in species conservation, in this specific case, it resulted in putative adaptive introgression. Our findings highlight the complex interplay between hybridization, adaptive evolution, and the potential risks and benefits associated with anthropogenic influences on wild species.
What's your experience?: A duoethnographic dialogue to advance disability inclusion in medical education
Authors: Jain Neera R. , Alwazzan Lulu
Published: June 2024

Background

Although disability inclusion in medical education is gaining interest internationally, scholarship and policy recommendations on this topic largely hail from the US, Canada, Australia and the UK. Existing scholarship, while calling for medical education to enact cultural and attitudinal change related to disability, has yet to exemplify how educators might critically examine their understandings.

Approach

As two medical educators and researchers, one based in New Zealand and the other based in Saudi Arabia, we took a duoethnographic approach to explore tensions, possibilities and assumptions regarding disability and disability inclusion in medical education. Through a year‐long synchronous and asynchronous dialogue, we examined our experiences in relation to literature from critical disability studies and disability inclusion in medical education.

Findings

We present recurrent themes from our dialogue. We consider what disability means, explore definitions and models of disability in our contexts, as well as our lived curriculum of disability. We grapple with the applicability of disability inclusion practices across borders. We explore the complexity of supporting access without a clear roadmap, while recognising educators' potential in this work. Finally, we recognise that, if disability is relational, we have the power and responsibility to address ableism in medical education. Throughout, we return to the importance of local consultation with disabled people (learners, physicians) to better understand how services ought to be oriented.

Conclusion

Duoethnographic dialogue is a fruitful approach to critically examine understandings of disability with others and represents a necessary start to work in education that seeks to advance justice. We share possible actions to take the work forward beyond dialogue and suggest that readers engage in such dialogues with others in their own contexts.
When I say … non‐technical skills
Authors: O'Connor Paul , O'Dea Angela
Published: June 2024

In the latest edition of When I Say… @poc_doctor outline why they prefer "nontechnical skills" to alternative terminology.
Hybrid structural analysis integrating physical model and continuous‐time state‐space neural network model
Authors: Li Hong‐Wei , Hao Shuo , Ni Yi‐Qing , Wang You‐Wu , Xu Zhao‐Dong
Published: June 2024

The most likely scenario for civil engineering structures is that only some components or parts of a structure are complex, while the rest of the structure can be well physically modeled. In this case, utilizing powerful neural networks to model these complex components or parts only and embedding the neural network models into the structure might be a viable choice. However, few studies have considered the real‐time interaction between the neural network model and another model. In this paper, a new hybrid structural modeling strategy that incorporates the neural network model is proposed. Structures installed with energy dissipation devices (EDDs) are investigated, where continuous‐time state‐space neural network (CSNN) models are adopted to represent EDDs and to couple with the physical model of the structure excluding EDDs through the state‐space substructuring method. First, CSNN models with an identical model configuration are trained to represent different physical models of EDDs and fit the experimental results of a damper to evaluate the CSNN model at the model level. Then, to demonstrate the hybrid structural analysis method, the CSNN‐based structural models of the interfloor‐damped and base‐isolated structures are established for seismic analyses. It is observed that CSNN‐based models exhibit high prediction performance and are easy to implement. Therefore, the developed hybrid structural analysis method that adopts CSNN models for EDDs is engineering practical.
Urban risk assessment model to quantify earthquake‐induced elevator passenger entrapment with population heatmap
Authors: Gu Donglian , Zhang Ning , Xu Zhen , Wu Yongjingbang , Tian Yuan
Published: June 2024

The seismic resilience of cities plays a crucial role in achieving the United Nations Sustainability Development Goal. However, despite the occurrence of elevator passenger entrapment in numerous earthquakes, there is a notable lack of studies addressing this sophisticated issue. This study aims to bridge this gap by proposing a novel urban risk assessment model designed to evaluate city‐scale earthquake‐induced elevator passenger entrapment. The model integrates big data and physics‐based approaches. A novel mapping method was developed to estimate city‐scale elevator traffic level based on population heatmap data and deep learning. A process‐based parallel computing scheme was designed to accelerate the assessment. The applicability was demonstrated based on a real‐world urban area comprising 619 buildings. The findings reveal that as the time of the earthquake varies, the risk exhibits significant fluctuations. Additionally, this study highlights that a simplistic correspondence between seismic intensity and passenger entrapment risk can lead to erroneous estimations.
The impact of packaging attributes on portion decisions: Consumer values are important
Authors: Chu Ruiqi , Tang Tang , Hetherington Marion M.
Published: June 2024

Research shows that features of food packaging can help to promote healthy food choices. Laboratory‐based studies demonstrate that smart design of packaging facilitates portion control. However, the extent to which consumers notice packaging features for portion control is not known. Therefore, this study investigated how individuals interact with food packaging, how they utilise the on‐pack serving‐size guidelines and how they make portion decisions. To do this, 25 adult participants were recruited to participate in an online semi‐structured interview. Data were analysed using thematic analysis until saturation was achieved. Participants reported that they rarely attend to on‐pack serving recommendations and indicated some resistance to them. Some structural features (small/single serving, pre‐portioned and resealable packaging) were identified as facilitators of portion control. In contrast, the healthiness evaluation of the product from packaging cues was described as a permissive cue to eat more of the product. Participants in this study value their autonomy and control, preferring convenient behavioural choices over recommended portion servings. They also reported future concerns about the effects of their diet on health, but that current context (hunger, convenience) sometimes presented a barrier to healthy eating. Packaging does more than protect its contents, packaging can affect eating decisions to support portion control, and for some, offers permission to overconsume. This study identified ways that participants use packaging to make portion decisions, revealing the role of habits, current context and future health considerations. The interviews revealed the importance of consumer values on food choice in general and portion control in particular. In conclusion, smart food packaging design could use these findings to nudge healthy portion decisions by incorporating consumer values and by recognising consumer needs for habitual, current and future concerns.
Low‐frequency dorsal root stimulation is effective for various pain etiologies and pain locations
Authors: Tabatabaei Pedram , Kakas Pavlina , Bredemo Linda , Salomonsson Josef
Published: June 2024

Background

Dorsal root ganglion stimulation (DRG‐S) has emerged as a novel therapeutic approach for managing chronic neuropathic pain.

Aims

This study aims to compare the effectiveness of 4–20 Hz DRG‐S through a retrospective analysis of a cohort of 28 patients with various neuropathic pain etiologies and pain locations.

Materials and Methods

Patient responses to both stimulation frequencies were examined using the Numeric Rating Scale (NRS) and Patient Global Impression of Change (PGIC) assessments. Factors such as patient preference and satisfaction were also evaluated.

Results

The results indicate that 4 Hz DRG‐S is not only as effective as 20 Hz stimulation but may also surpass it. Among the 28 patients, 26 assessed 4 Hz stimulation to be at least as effective as 20 Hz, with the majority (22 out of 26) considering 4 Hz stimulation superior. After trying 4 Hz stimulation, 24 out of 28 patients chose it over 20 Hz, while two patients opted for a combination of both settings. Only two patients reverted to their original 20 Hz stimulation program. A statistically significant pain reduction of 24% was observed when comparing the effects of 4 Hz versus 20 Hz.

Discussion

The study highlights the broader applicability of low‐frequency DRG‐S, extending its benefits beyond the realm of low back pain. Patients with diverse pain etiologies and locations experienced comparable positive outcomes, suggesting that the advantages of low‐frequency stimulation are not confined to specific pain types or locations.

Conclusion

This study emphasizes the potential of 4 Hz DRG‐S as a valuable alternative to the standard 20 Hz stimulation. Although the exact mechanisms require further investigation, the observed clinical benefits and patient preferences for low‐frequency stimulation suggest its viability across diverse pain indications and locations. Additional research is necessary to substantiate these findings and assess the durability and economic implications of low‐frequency DRG‐S.
PagKNAT2/6b promotes shoot branching by attenuating auxin‐strigolactone signalling in poplar
Authors: Zhao Yan‐Qiu , Song Xue‐Qin , Guo Wei , Jiang Cheng , Zhang Jin , Lu Meng‐Zhu
Published: June 2024

Shoot branching from axillary bud (AB) directly determines plant architecture. However, the mechanism through which AB remains dormant or emerges to form branches as plants grow remains largely unknown. Here, the auxin‐strigolactone (IAA‐SL) pathway was first shown to regulate shoot branching in poplar, and we found that PagKNAT2/6b could modulate this pathway. PagKNAT2/6b was expressed mainly in the shoot apical meristem and AB and was induced by shoot apex damage. PagKNAT2/6b overexpressing poplar plants (PagKNAT2/6b OE) exhibited multiple branches that mimicked the branching phenotype of nontransgenic plants after decapitation treatment, while compared with nontransgenic controls, PagKNAT2/6b antisense transgenic poplar and Pagknat2/6b mutant lines exhibited a significantly decreased number of branches after shoot apex damage treatment. In addition, we found that PagKNAT2/6b directly inhibits the expression of the key IAA synthesis gene PagYUC6a, which is specifically expressed in the shoot apex. Moreover, overexpression of PagYUC6a in the PagKNAT2/6b OE background reduced the number of branches after shoot apex damage treatment. Overall, we conclude that PagKNAT2/6b responds to shoot apical injury and regulates shoot branching through the IAA‐SL pathway. These findings may provide a theoretical basis and candidate genes for genetic engineering to create new forest tree species with different crown types.
Kidney Transplantation in ≤15 kg Children: Outcomes and Prognostic Indicators—A Review of the Organ Procurement and Transplantation Database
Authors: Melikian Raffi , Kwon Yong , Kohrman Nathan , Lo Mary , Emamaullee Juliet , Zielsdorf Shannon , Lestz Rachel , Sher Linda , Etesami Kambiz
Published: June 2024

Background

Approximately 2500 pediatric patients are awaiting kidney transplantation in the United States, with <5% comprising those ≤15 kg. Transplant in this cohort is often delayed by center‐based growth parameters, often necessitating transplantation after the initiation of dialysis. Furthermore, prognostication remains somewhat ambiguous. In this report, we scrutinize the Organ Procurement and Transplantation Network (OPTN) data from 2001 to 2021 to help better understand specific variables impacting graft and patient outcomes in these children.

Methods

The OPTN kidney transplant dataset from 2001 to 2021 was analyzed. Inclusion criteria included age <18 years, weight ≤15 kg, and recipient of primary living donor kidney transplantation (LDKT) or deceased donor kidney transplantation (DDKT). Patient and graft survival probabilities were calculated using the Kaplan–Meier method. The Cox proportional hazards model was used to calculate hazard ratio (HR) and identify variables significantly associated with patient and graft survival.

Results

Two thousand one hundred sixty‐eight pediatric transplant recipients met inclusion criteria. Patient survival at 1 and 3 years was 98% and 97%, respectively. Graft survival at 1 and 3 years was 95% and 92%, respectively. Dialysis was the sole significant variable impacting both patient and graft survival. Graft survival was further impacted by transplant era, recipient gender and ethnicity, and donor type. Infants transplanted at Age 1 had better graft survival compared with older children, and nephrotic syndrome was likewise associated with a better prognosis.

Conclusion

Pediatric kidney transplantation is highly successful. The balance between preemptive transplantation, medical optimization, and satisfactory technical parameters seems to suggest a “Goldilocks zone” for many children, favoring transplantation between 1 and 2 years of age.
Feed particle size matters for the larval growth of Alphitobius diaperinus (Panzer) but not for Tenebrio molitor L. (Coleoptera: Tenebrionidae)
Authors: Baliota Georgia V. , Rigopoulou Marianna , Rumbos Christos I. , Athanassiou Christos G.
Published: June 2024

The effect of the particle size of the feed on the larval growth and feed utilization parameters of two mealworm species, Alphitobius diaperinus (Panzer) and Tenebrio molitor L. (Coleoptera: Tenebrionidae), was examined under laboratory conditions. Wheat bran of four different particle sizes (100–250, 500–650, 850–1000 and >2000 μm) was provided as feed to larvae of both species. The larval growth and survival, as well as time to pupation and the amount of feed consumed, were monitored to determine differences among the wheat bran particle sizes within each insect species. Our research results suggest that a finely ground feed with a particle size below 650 μm significantly impact the growth and development of A. diaperinus, as opposed to a feed containing particles larger than 850 μm. Contrariwise, the larvae of T. molitor exhibited no discernible response to the various feed particle sizes that were evaluated. Overall, it was observed that the two mealworm species did not exhibit identical responses for the tested feed particle size, suggesting that this factor is species dependent.
Efficacy of photobiomodulation therapy on pain perception reduction associated with dental anesthetic infiltration injection: A systematic review and meta‐analysis
Authors: Hakimiha Neda , Amiri Pantea , Sheibani Fatemeh , Razzaghi Zahra
Published: June 2024

Dental anesthetic injections, a common source of patient discomfort, often deter individuals from seeking dental care. Recently, there has been a growing focus on photobiomodulation therapy (PBMT) and its potential role in pain reduction. This systematic review explored the efficacy of PBMT in alleviating pain associated with dental anesthetic infiltration injections. A systematic literature search of different databases was performed up to December, 2023 using specific search strategy to find eligible studies that assessed the impact of PBMT on pain during local anesthesia injections. Data extraction was done based on the inclusion/exclusion criteria. A total of 13 studies, involving 972 patients were included. The studies employed various PBMT parameters, including wavelengths, and energy densities. Meta‐analyses revealed a significant reduction in pain with PBMT compared to controls (MD = −0.90, 95% CI: −1.36 to −0.44, and p = 0.0001), with notable heterogeneity (I2 = 91.79%). Stratified analyses by age demonstrated consistent pain reduction in both adults (MD = −0.59, 95% CI: −1.11 to −0.08, and p < 0.0001) and children (MD = −0.59, 95% CI: −1.11 to −0.08, and p = 0.025). In conclusion, it seems that PBMT using infrared diode lasers can effectively reduce injection pain in both pediatric and adult populations. Further research should focus on optimizing PBMT parameters for enhanced pain management during dental procedures.
How do private and publicly‐traded R&D service firms differ in their innovation performance and strategy? Evidence from the United Kingdom
Authors: Li Xiuqin , Deng Xin
Published: June 2024

R&D service firms (RDSFs) are increasingly recognized as a hidden engine of the UK economy and crucial drivers within the UK’s innovation ecosystem, evolving from mere contractors and intermediaries to genuine innovators. Understanding the drivers of their innovation and growth is crucial for catalyzing economic advancement in the UK. Despite their acknowledged importance, research on RDSFs remains nascent, often relying on interviews and case studies without large‐scale empirical analysis. This study addresses this gap by comparing the innovation outcomes of private versus publicly‐traded RDSFs, reflecting their distinct financial and strategic environments, which influence their innovation trajectories. Using patent and scientific publication data from 2003 to 2019, we provide a robust analysis of the differences in innovation performance, efficiency, and strategic focus between these two categories of RDSFs. Our findings indicate that private RDSFs outperform in patent and publication outputs, exert greater influence on subsequent innovation, and demonstrate superior efficiency and exploration in their innovation process. This study offers critical insights for policymakers and industry leaders to formulate strategies that enhance the innovation impact of RDSFs within the broader UK innovation system.
Sustained remission induced by 2 years of treatment with benralizumab in patients with severe eosinophilic asthma and nasal polyposis
Authors: Pelaia Corrado , Crimi Claudia , Benfante Alida , Caiaffa Maria Filomena , Campisi Raffaele , Candia Claudio , Carpagnano Giovanna Elisiana , Carrieri Isabella , D'Amato Maria , Detoraki Aikaterini , Barbaro Maria Pia Foschino , Lombardo Nicola , Macchia Luigi , Maglio Angelantonio , Minenna Elena , Nolasco Santi , Paglino Giuseppe , Papia Francesco , Ricciardi Luisa , Scichilone Nicola , Scioscia Giulia , Spadaro Giuseppe , Tondo Pasquale , Uletta Lionetti Simona , Valenti Giuseppe , Vatrella Alessandro , Crimi Nunzio , Pelaia Girolamo
Published: June 2024

Background and Objective

Several randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on‐treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on‐treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP).

Methods

Throughout 2 years of treatment with benralizumab, a four‐component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function.

Results

The present study recruited 164 patients suffering from SEA. After 24 months of add‐on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on‐treatment (exacerbation rate = 0, OCS dose = 0, pre‐bronchodilator FEV1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT‐22 < 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post‐bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on‐treatment (OR = 2.32, p < 0.05 and OR = 5.59, p < 0.01, respectively).

Conclusion

Taken together, the results of this real‐life clinical investigation indicate that benralizumab can induce a sustained remission on‐treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation.

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Evidence and uncertainty: An info‐gap analysis of uncertainty‐augmenting evidence
Authors: Ben‐Haim Yakov
Published: June 2024

Decisions in many disciplines are based on understanding and evidence. More evidence is better than less when it enhances the decision‐maker's understanding. This is achieved by reducing uncertainty confronting the decision‐maker and reducing the potential for misunderstanding and failure. However, some evidence may actually augment uncertainty by revealing prior error or ignorance. True evidence that augments uncertainty is important because it identifies inadequacies of current understanding and may suggest directions for rectifying this. True evidence that reduces uncertainty may simply reconfirm or strengthen prior understanding. Uncertainty‐augmenting evidence, when it is true, can support the expansion of one's previously incomplete understanding. A dilemma arises because both reduction and enhancement of uncertainty can be beneficial, and both are not simultaneously possible on the same issue. That is, uncertainty can be either pernicious or propitious. Info‐gap theory provides a response. The info‐gap robustness function enables protection against pernicious uncertainty by inhibiting failure. The info‐gap opportuneness function enables exploitation of propitious uncertainty by facilitating wonderful windfall outcomes. The dilemma of uncertainty‐augmenting evidence is that robustness and opportuneness are in conflict; a decision that enhances one, worsens the other. This antagonism between robustness and opportuneness—between protecting against pernicious uncertainty and exploiting propitious uncertainty—is characterized in a generic proposition and corollary. These results are illustrated in an example of allocation of limited resources.
Improved insomnia is one pathway underlying the anti‐suicidal properties of clozapine
Authors: Vayalapalli Ankita , McCall William V. , McEvoy Joseph P. , Miller Brian J.
Published: June 2024

Background

Insomnia is common in schizophrenia and associated with suicide. Clozapine has anti‐suicidal properties and beneficial effects on sleep. Whether effects on insomnia mediate the anti‐suicidal properties of clozapine remains unclear.

Methods

In n = 76 patients from the Clinical Antipsychotic Trials of intervention effectiveness schizophrenia trial using a within‐subjects design, we investigated whether improvement in terminal insomnia was associated with improvement in suicidal ideation (SI) after treatment with non‐clozapine antipsychotics, and then after treatment with clozapine, using binary logistic regression. Terminal insomnia and SI over the past 2 weeks were assessed before and after both non‐clozapine antipsychotic and clozapine treatment with the Calgary Depression Scale for Schizophrenia.

Results

There was no association between improved terminal insomnia and resolution of SI after treatment with non‐clozapine antipsychotics (OR = 0.2, 95% CI 0.0–9.0, p = 0.41). In the same patients, improved terminal insomnia was associated with resolution of SI after clozapine treatment (OR = 14.6, 95% CI 1.7–129.2, p = 0.02).

Conclusions

Improved terminal insomnia is associated with improved SI following clozapine treatment. Findings warrant replication in a larger sample with standard instruments in the assessment of insomnia and suicide, but suggest beneficial effects on sleep as a mediator of the anti‐suicidal properties of clozapine. Future mechanistic studies are also needed.
Comparison of biosimilar filgrastim and originator filgrastim for peripheral blood stem cell mobilization for allogeneic hematopoietic stem cell transplantation
Authors: Shahzad Moazzam , Amin Muhammad Kashif , Bellman Polina , Al‐Ramahi Joe , Noor Jawad , Vyas Abhinav , Mahmoudjafari Zahra , McGuirk Matthew , DeJarnette Shaun , Ahmed Nausheen , Abdallah Al‐Ola , Shune Leyla , Singh Anurag K. , McGuirk Joseph P. , Abhyankar Sunil , Mushtaq Muhammad Umair
Published: June 2024

Background

Nivestym, a biosimilar granulocyte colony‐stimulating factor (G‐CSF) to the originator filgrastim (Neupogen), is now being used for the mobilization of peripheral blood stem cells (PBSC) in allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We aim to compare the efficacy of Nivestym and Neupogen for PBSC mobilization in healthy allogeneic donors.

Methods

We conducted a retrospective single‐center study including 541 adult allo‐HSCT donors receiving Nivestym (January 2013–July 2020), or Neupogen (July 2020–June 2023) for donor PBSC mobilization. Bivariate analysis was conducted using SPSS version 28. Statistical significance was determined at a p‐value <.05.

Results

Our study included 541 allo‐HSCT donors who received Neupogen (n = 345, 64%) or Nivestym (n = 196, 36%) for PBSC mobilization. The median age was 47 years (range 17–76). The median donor weight was 86 kg (95% confidence interval [CI]: 87–91). Donors receiving Neupogen had similar pre‐G‐CSF white blood cell count, CD34+ percentages, and circulating CD34+ count compared with donors receiving Nivestym. The Neupogen group had similar median PBSC product total neutrophil count, CD34+ percentage, absolute CD34+ count, and infused CD34+ dose compared with the Nivestym group. For donors aged 35 years or younger, the median CD34+ dose was higher in donors who received Neupogen compared with Nivestym (6.9 vs. 6.3 million cells/kg, p = .044).

Conclusions

Nivestym demonstrated similar efficacy for PBSC mobilization compared with Neupogen among allo‐HSCT donors. In donors aged 35 years or younger, a slightly lower PBSC product CD34+ count was noted with Nivestym compared with Neupogen.
Topological recursion for Kadomtsev–Petviashvili tau functions of hypergeometric type
Authors: Bychkov Boris , Dunin‐Barkowski Petr , Kazarian Maxim , Shadrin Sergey
Published: June 2024

We study the ‐point differentials corresponding to Kadomtsev–Petviashvili (KP) tau functions of hypergeometric type (also known as Orlov–Scherbin partition functions), with an emphasis on their ‐deformations and expansions. Under the naturally required analytic assumptions, we prove certain higher loop equations that, in particular, contain the standard linear and quadratic loop equations, and thus imply the blobbed topological recursion. We also distinguish two large families of the Orlov–Scherbin partition functions that do satisfy the natural analytic assumptions, and for these families, we prove in addition the so‐called projection property and thus the full statement of the Chekhov–Eynard–Orantin topological recursion. A particular feature of our argument is that it clarifies completely the role of ‐deformations of the Orlov–Scherbin parameters for the partition functions, whose necessity was known from a variety of earlier obtained results in this direction but never properly understood in the context of topological recursion. As special cases of the results of this paper, one recovers new and uniform proofs of the topological recursion to all previously studied cases of enumerative problems related to weighted double Hurwitz numbers. By virtue of topological recursion and the Grothendieck–Riemann–Roch formula, this, in turn, gives new and uniform proofs of almost all Ekedahl–Lando–Shapiro–Vainshtein (ELSV)‐type formulas discussed in the literature.
Three-dimensional modelling of underwater noise produced by a bulk carrier vessel and estimation of its environmental impact
Authors: Petrov Pavel S. , Tyshchenko Andrey G. , MacGillivray Alexander O.
Published: June 2024

This study presents the results of three-dimensional (3D) propagation modeling of noise from a transiting bulk carrier vessel. In the simulated scenario, the surface vessel is moving past a bottom-mounted hydrophone system. Sound levels are estimated in decidecade frequency bands as the vessel transits past the hydrophone, and the simulation results are compared against real measured data. The modelling is performed using the program AMPLE, which is based on the wide-angle mode parabolic equation theory for simulating 3D broadband acoustic fields in a shallow sea. The model is used to investigate the effect of 3D phenomena on the surface vessel sound propagation. It is shown that an inaccuracy of the noise simulation associated with the use of a two-dimensional model can be as high as 7–10 dB for certain distances and for frequency bands over which a major part of the source energy is distributed. An approach to the selection of data-adjusted media parameters based on the Bayesian optimization is suggested, and the influence of the various parameters on the sound levels is discussed.