bluuebunny/crossref_metadata_2025 huggingface dataset:
Moral challenges and understanding of clinical ethics in Tanzanian hospitals: Perspectives of healthcare professionals
Authors: Kuhumba Shija Kevin , (A.C) Molewijk Bert , Solbakk Jan Helge , Mhando Nandera Ernest , Sævareid Trygve Johannes Lereim
Published: October 2024

Healthcare professionals encounter many moral challenges in their daily clinical practice. However, there have been few studies on the subject matter in Tanzania. This study aims to provide an account of moral challenges faced by healthcare professionals in Tanzanian hospitals, their understanding of clinical ethics, and the ethics education they have received. Many participants reported receiving some kind of ethics training through formal education and on‐the‐job training. Some participants understood ethics in healthcare settings as adherence to established laws, regulations, guidelines, procedures, norms, and rules essential in clinical practice. Analysis of the data identified four themes of moral challenges. These challenges are related to 1) decision‐making and communication in clinical practice, 2) scarcity of medical resources and prioritization in clinical practice, 3) withdrawal of curative treatment, and 4) conflicts between professional judgment, religious convictions and adherence to alternative treatments. Based on the findings, we suggest a context‐sensitive form of clinical ethics training to prepare healthcare professionals to recognize and address these moral challenges.
Neuropromotion in the neonatal intensive care unit: A step up from neuroprotection and a new norm
Authors: Badawi Nadia , Crowle Cathryn
Published: October 2024

This commentary is on the original article by Miller et al. on pages 357–364 of this issue.
Assessment of the Right Ventricle Function in Patients With Significant Tricuspid Regurgitation: A Review
Authors: Bourg Corentin , Raoult Tristan , Istratoaie Sabina , Beaumont Jérémy , Donal Erwan
Published: October 2024

Tricuspid regurgitation (TR) is an increasingly prevalent condition, especially in older populations, and presents significant challenges due to its association with right heart failure, hospital admissions, and high mortality rates. The management of TR has evolved, with new percutaneous valve repair and replacement techniques emerging alongside traditional surgical approaches. However, accurately assessing right ventricular (RV) function–a key prognostic factor in TR–remains difficult due to the RV's unique anatomy and sensitivity to loading conditions. Current echocardiographic methods, such as Tricuspid Annular Plane Systolic Excursion (TAPSE), S' wave analysis, and RV fractional area change (FAC), offer valuable insights but have limitations, particularly regarding load dependence and incomplete assessment of RV function. Advances in 3D echocardiography and myocardial strain imaging provide more comprehensive evaluations, yet challenges persist in integrating these measures in routine clinical practice. The review highlights the importance of a multimodal approach to RV assessment in TR patients, considering both the right atrium and pulmonary artery interactions, and explores potential future tools such as myocardial work and dynamic testing to improve prognostic accuracy and patient outcomes.
Evolution and Prognostic Impact of Left Ventricular Myocardial Work Indices After Transcatheter Aortic Valve Replacement in Patients With Severe Aortic Stenosis
Authors: Wu Hoi W. , Fortuni Federico , Muzafarova Tamilla , Sarrazyn Camille , Lopez Santi Pilar , Chua Aileen P. A. , Butcher Steele C. , van der Kley Frank , de Weger Arend , Jukema J. Wouter , Bax Jeroen J. , Ajmone Marsan Nina
Published: October 2024

Purpose

Left ventricular myocardial work (LVMW) has been shown to better characterize LV function in patients with severe aortic stenosis by correcting LV afterload. The aim of this study was to evaluate the evolution in LVMW indices after transcatheter aortic valve replacement (TAVR) and their prognostic value.

Methods

The following LVMW indices were calculated before and immediately after TAVR in 255 patients (median age 82 years, 51% male): global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). The study endpoint was all‐cause mortality.

Results

After TAVR, LV ejection fraction and LV global longitudinal strain (GLS) did not change significantly (from 56% to 55%, p = 0.470 and from 13.6% to 13.2%, p = 0.068). Concerning LVMW indices, while LV GWW remained unchanged after TAVR (from 247 to 258 mmHg%, p = 0.080), LV GWI, LV GCW, and LV GWE significantly decreased (from 1882 to 1291 mmHg%, p < 0.001, from 2248 to 1671 mmHg%, p < 0.001, and from 89% to 85%, p < 0.001, respectively). During a median follow‐up of 59 [40–72] months, 129 patients died. After correcting for potential confounders (sex, diabetes, renal function, atrial fibrillation, Charlson comorbidity index, and pacemaker implantation post‐TAVR), post‐TAVR LV GLS, GWI, and GCW remained independently associated with all‐cause mortality. However, post‐TAVR LV GWI demonstrated the highest increase in model predictivity.

Conclusion

In patients undergoing TAVR, LVMW parameters significantly change after intervention. LV GWI after TAVR showed the strongest association with all‐cause mortality among both conventional and advanced parameters of LV systolic function both pre‐ and post‐TAVR and might enable better risk stratification of these patients after intervention.
INTERSECCIONALIDADE E ORGANIZAÇÕES: UMA ANÁLISE DAS PUBLICAÇÕES DOS ENCONTROS DA ASSOCIAÇÃO BRASILEIRA DE PÓS‐GRADUAÇÃO E PESQUISA EM ADMINISTRAÇÃO
Authors: Elias Maria Ligia Ganacim Granado Rodrigues , Machado Hilka Pelizza Vier
Published: October 2024

The aim of this research is to understand whether gender issues and their intersections have been incorporated into the production of knowledge coming from the meetings of the National Association of Graduate Studies and Research in Administration in Brazil (ANPAD) over the years. A literature review of papers published in the proceedings of ANPAD Meetings (EnANPAD) between 1997 and 2021 was conducted to identify the presence of the thematic axes: gender, sexuality, class, and race. Titles and abstracts of 21,057 papers were analyzed. Were classified 682 papers, in at least one of the axes. The analysis presents quantitative data that shows the volume of scientific work per thematic axis. In addition, the qualitative analysis of the texts identified as intersectional was carried out. The results showed that intersectionality is still not very present in the research presented at EnANPAD, evidencing a weak connection with the social and economic structural context of the country. However, a growing movement, albeit slow, was noted from 2005. The theoretical contribution of this study consists in highlighting an overview of intersectionality in the field of studies in Administration in Brazil. This study can guide future research agendas and Graduation Policies.
Towards decolonial IS: Insights from applying pluriverse and conviviality to analyse a co‐production intervention in Peru
Authors: Jimenez Andrea , Hoefsloot Fenna Imara , Miranda Sara Liliana
Published: October 2024

While there is a growing interest in applying decolonial approaches within the field of information systems (IS), effective avenues for engagement remain largely unexplored. To this end, our paper introduces a framework focused on decolonial IS research informed by the notions of the pluriverse and conviviality. These concepts emphasise a focus on ontological, epistemological and methodological dimensions, with a strong orientation to justice. We illustrate the application of the framework through a re‐analysis of our own research project, the co‐production of the Metropolitan Water Observatory (MWO) in Lima, Peru. Applying the framework to learn new insights about the MWO, this paper contributes to the IS field by providing a framework from which to examine IS interventions from a decolonial perspective. In addition to advancing theoretical understanding, our framework serves as a valuable resource for scholars navigating the complex landscape of decolonial approaches in IS.
Secukinumab efficacy in patients with hidradenitis suppurativa assessed by the International Hidradenitis Suppurativa Severity Score System (IHS4): A post hoc analysis of the SUNSHINE and SUNRISE trials
Authors: Zouboulis Christos C. , Kyrgidis Athanassios , Alavi Afsaneh , Jemec Gregor B. E. , Martorell Antonio , Marzano Angelo V. , van der Zee Hessel H. , Wozniak Magdalena B. , Martinez Angela Llobet , Kasparek Torben , Bachhuber Teresa , Ortmann Christine‐Elke , Lobach Iryna , Thomas Nicolas , Ravichandran Shoba , Tzellos Thrasyvoulos
Published: October 2024

Introduction

The International Hidradenitis Suppurativa Severity Score System (IHS4) is a validated tool that measures inflammatory lesions, including draining tunnels, in hidradenitis suppurativa (HS).

Objective

To evaluate secukinumab efficacy using IHS4 in patients with moderate to severe HS.

Methods

Data from the SUNSHINE and SUNRISE trials, which assessed subcutaneous secukinumab 300 mg every 2 (SECQ2W) and 4 (SECQ4W) weeks in adults with moderate to severe HS, were analyzed. Assessments included changes from baseline in IHS4 and severity classification up to Week 52; IHS4‐55, IHS4‐75, IHS4‐90 responses (55%, 75% and 90% reduction in IHS4) and concordance between IHS4‐55 and HS clinical response (HiSCR), at Weeks 16 and 52.

Results

In total, 1084 patients (SECQ2W = 361; SECQ4W = 360; placebo = 363) were analyzed. At Week 16, SECQ2W and SECQ4W demonstrated a numerically higher reduction in IHS4 from baseline versus placebo (adjusted mean [95% CI]: −10.80 [−12.30 to −9.30] and −9.46 [−10.96 to −7.96] vs. −4.92 [−6.43 to −3.41]); the reduction was maintained until Week 52 in both dose regimens. A greater proportion of patients achieved IHS4‐55 with SECQ2W (43.4%) and SECQ4W (39.5%) versus placebo (31.5%) at Week 16, with further improvement at Week 52. Similar trends were observed for IHS4‐75 and IHS4‐90 responses. While no patients had mild disease based on IHS4 (80.7% had severe and 19.3% had moderate HS) at baseline, a greater proportion of patients were categorized as having mild disease at Week 16 in the SECQ2W (25.9%) and SECQ4W (24.0%) groups versus placebo (16.4%); this trend continued up to Week 52 in both dose regimens. Strong concordance (>85%) was observed between IHS4‐55 and HiSCR.

Conclusions

Both SECQ2W and SECQ4W demonstrated efficacy in improving treatment response as measured by IHS4 and reducing disease severity versus placebo at Week 16 and these improvements were sustained through Week 52. These findings support that the dynamic and dichotomous IHS4 can efficiently detect treatment response changes in clinical trial settings.
Soft Tissue Contours at Pontic Sites With or Without Soft Tissue Grafting—A 15‐Year Follow‐Up of a Controlled Clinical Study
Authors: Bienz Stefan P. , Ruales‐Carrera Edwin , Mancini Leonardo , Balmer Marc , Jung Ronald E. , Thoma Daniel S.
Published: October 2024

Objectives

To report on soft tissue contour changes at pontic sites with or without soft tissue grafting over an observation period of 15 years.

Methods

Fourteen patients received a fixed dental prosthesis (FDP) in the posterior zone in a controlled clinical study and were available at the 15‐year follow‐up. Eight patients received a subepithelial connective tissue graft in the pontic area (test) while six received the FDP without soft tissue grafting (control). Impressions were taken after FDP cementation and at 15 years. Casts were digitized and a profilometric analysis was performed (mean distance) and the pontic height (PH) and ridge width (RW) were analyzed at the mid‐buccal area. A descriptive analysis and Wilcoxon‐Mann–Whitney test was performed (level of significance: 5%).

Results

Profilometric changes (mean distance) from baseline to 15 years amounted to −0.68 mm (test) and to −0.33 mm (control) (p = 0.208), 95% CI for group difference (0.290; −0.750). PH measured −0.47 mm (test) and 0.0 mm (control) (p = 0.079) and RW amounted to −1.05 mm (test) and −0.38 mm (control) (p = 0.138).

Conclusion

Remodeling of the soft tissue contour at pontic sites of FDPs was evident in both groups, but slightly more accentuated following soft tissue grafting.

Clinical Significance

This study is the first to report on soft tissue changes at pontic sites over more than 10 years. It investigates whether tissue contour changes with and without soft tissue grafting before the insertion of FDPs. Remodeling of the soft tissue contour at pontic sites was observed over 15 years, with more pronounced changes when soft tissues were augmented with SCTGs before FDP insertion. The volume loss at the augmented site must be considered in relation to the overall tissue changes over long periods. Connective tissue grafts reliably improve shape and esthetics around the pontic unit. Further long‐term studies with more patients are needed to evaluate the initial gains and long‐term performance of these augmentations.
Use of Advanced Platelet‐Rich Fibrin for the Treatment of Multiple Adjacent Mucogingival Recessions: A Technical Report of the Fibrin‐Assisted Soft‐Tissue Promotion Protocol
Authors: Aalam Alexandre‐Amir , Krivitsky Aalam Alina , Yermian Nader , Choukroun Joseph
Published: October 2024

Objectives

Platelet‐rich fibrin (PRF) has had a marked impact on regenerative medicine due to its widespread ability to promote angiogenesis to defective tissues. Particularly in the dental field, evidence from randomized clinical trials has further shown that PRF facilitates greater soft‐tissue regeneration when compared with hard tissues.

Clinical Considerations

Recently, the fibrin‐assisted soft‐tissue promotion (FASTP) technique has been developed as a means to promote soft‐tissue regeneration of mucogingival recessions utilizing PRF. Within the present case report, a 28‐year‐old male presented with multiple adjacent mucogingival recessions in the maxilla ranging in probing depths (1–3 mm) and gingival recessions (1–5 mm). For optimal regenerative outcomes, the use of advanced PRF (A‐PRF; 1300 RPM for 8 min) has been utilized to enhance regenerative outcomes by fully taking advantage of the low‐speed centrifugation concept (LSCC).

Conclusions

This case report highlights the latest surgical concepts, centrifugation protocols, and use of the LSCC to regenerate multiple adjacent mucogingival recessions in the esthetic zone.
Dimensions of Posterior Implant Restorations Related to Intra‐Coronal Cantilever and Occlusal Forces: An In Vitro Study
Authors: Tzanetou Panagoula , Kourtis Stefanos , Papalexopoulos Dimokritos , Sykaras Nikitas
Published: October 2024

Objective

The aim of the present study was to investigate the relation of the implant position to the implant crown and analyze the location and magnitude of bite force.

Materials and Methods

The dimensions of 49 posterior implant‐supported restorations were recorded in terms of: 1. implant diameter, 2. crown length, 3. crown width, 4. crown height, 5. occlusal surface of the restoration. The crown/implant height was measured and the distance between the implant center and the restoration center revealed the size of intra‐coronal cantilevers. The occlusal force analysis determined the point and magnitude of loading. Correlation coefficient r was used for the statistical process and statistical control was carried out with the aid of t‐test with minimum level of significance p < 0.05.

Results

The mean crown‐to‐implant ratio was 0.9 and in short implants (< 10mm) the ratio was 1.28.

Intra‐coronal cantilever extensions ranged from 2.1 mm to 6.35 mm depending on crown size.

Occlusal loading was identified in cantilever areas of the crown.

Conclusions

Implant center deviates from crown center in 71%–82% of the cases depending on site location.

Implants with non‐ideal position may support a functionally occluding crown.

Clinical Significance

Intra‐coronal cantilevers are a critical factor to avoid clinical complications and should be taken under consideration both in the planning and fabrication phase of implant restorations.
Is sexual size dimorphism in walleye, Sander vitreus, a driver of seasonal movements in Lake Erie?
Authors: Bihun Christian J. , Faust Matthew D. , Kraus Richard T. , MacDougall Thomas M. , Robinson Jason M. , Vandergoot Christopher S. , Raby Graham D.
Published: October 2024

Walleye (Sander vitreus) are a sexually dimorphic species in which females are larger than males in adulthood. Walleye can also exhibit sex‐ and population‐based differences in migration behavior. In Lake Erie, we used acoustic telemetry to test the prediction that female walleye exhibit larger broad‐scale movements than males during the summer and autumn. This prediction was based on the hypothesis that greater foraging in females would be needed to satisfy their higher energy requirements. We quantified movements of males and females from distinct spawning populations from Lake Erie's west and east basins using a lake‐wide grid of acoustic receivers in 2017 and 2018. We found no differences between male and female home range sizes, core range sizes, or distances travelled in either population. Fish length‐at‐tagging was unrelated to the size of a fish's home range or to its distance travelled, contrary to previous predictions about body size as a driver of migration distance in the Lake Erie population. We found that west basin walleye occupied large and indiscrete portions of the lake, but the core range of females extended into the central basin, whereas males were concentrated in the west basin. Walleye originating from the east basin confined their movements primarily to the east basin and showed stronger home range overlap among members of their population than did walleye from the west basin population. Within either population, walleye had more home range overlap with members of the same sex, which likely reflects differences in the migratory tendencies of males and females.
The value of assessing deep disease healing by probe‐based confocal laser endomicroscopy and histology for long‐term prognosis of ulcerative colitis
Authors: Zheng Yue , Zhang Jixin , Wang Jinwei , Li Junxia , Wang Huahong , Tian Yu
Published: October 2024

Background and Aim

The benefits of deep disease healing need evaluation by long‐term clinical research in different populations. Confocal laser endomicroscopy (CLE) is a superior method for evaluating deep disease healing.

Methods

This prospective study enrolled ulcerative colitis (UC) patients in clinical remission who underwent colonoscopy, CLE, and histological assessment. Patients were monitored for relapse by patient‐reported outcomes and colonoscopy evaluation of mucosal healing. The ability of different methods of mucosal healing to predict long‐term disease recurrence was assessed using Kaplan–Meier estimation and Cox proportional hazard regression.

Results

Forty‐two patients in clinical remission were assessed by colonoscopy. Those with Mayo endoscopic subscores (MES) ≤ 1 were enrolled. The 48‐month recurrence rates in present healing group, assessed by CLE (colonic barrier assessment and ENHANCE index) and by histological examination (Geboes scale), were 20.0%, 26.7%, and 11.1%, respectively, and were significantly lower than absent healing group (P < 0.05). Univariate Cox proportional risk regression analysis in absent of healing disease, determined by the ENHANCE index and Geboes scale, indicated an increased risk of recurrent events, with hazard ratios (HR) of 3.87 (95% CI: 1.18, 12.62) and 8.20 (95% CI: 1.06, 63.30), respectively. Multivariate Cox proportional hazard regression analysis adjusted for the extent of inflammation (E3 or not) showed a significant difference only for the ENHANCE index, with an HR of 3.53 (95% CI: 1.03, 12.10), P = 0.045.

Conclusions

Deep disease healing has a lower recurrence rate. The colonic barrier healing assessment, ENHANCE index, and histological Geboes scale have superior long‐term prognostic value for UC patients.
The isoflavone puerarin promotes generation of human iPSC‐derived pre‐oligodendrocytes and enhances endogenous remyelination in rodent models
Authors: Xu Hao , Zhang Huiyuan , Pop Nona , Hall Joe , Shazlee Ibrahim , Wagner‐Tsukamoto Moritz , Chen Zhiguo , Gu Yuchun , Zhao Chao , Ma Dan
Published: October 2024

Puerarin, a natural isoflavone, is commonly used as a Chinese herbal medicine for the treatment of various cardiovascular and neurological disorders. It has been found to be neuroprotective via TrK‐PI3K/Akt pathway, which is associated with anti‐inflammatory and antioxidant effects. Myelin damage in diseases such as multiple sclerosis (MS) and ischemia induces activation of endogenous oligodendrocyte progenitor cells (OPC) and subsequent remyelination by newly formed oligodendrocytes. It has been shown that human‐induced pluripotent stem cells (hiPSC)‐derived OPCs promote remyelination when transplanted to the brains of disease models. Here, we ask whether and how puerarin is beneficial to the generation of hiPSC‐derived OPCs and oligodendrocytes, and to the endogenous remyelination in mouse demyelination model. Our results show that puerarin increases the proportion of O4+ pre‐oligodendrocytes differentiated from iPSC‐derived neural stem cells. In vitro, puerarin increases proliferation of rat OPCs and enhances mitochondrial activity. Treatment of puerarin at progenitor stage increases the yielding of differentiated oligodendrocytes. In rat organotypic brain slice culture, puerarin promotes both myelination and remyelination. In vivo, puerarin increases oligodendrocyte repopulation during remyelination in mouse spinal cord following lysolethicin‐induced demyelination. Our findings suggest that puerarin promotes oligodendrocyte lineage progression and myelin repair, with a potential to be developed into therapeutic agent for neurological diseases associated with myelin damage.

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Neuralgic amyotrophy presentation of acute intermittent porphyria: A case report
Authors: Theuriet Julian , Gerfaud‐Valentin Mathieu , Durel Cécile‐Audrey , Gouya Laurent , Pegat Antoine
Published: October 2024

Background and Aims

Porphyrias are inherited metabolic disorders caused by mutations in genes encoding enzymes involved in the heme biosynthetic pathway, leading to the accumulation of heme precursors. Acute hepatic porphyrias (AHP), including acute intermittent porphyria (AIP), can present with predominant peripheral neurological manifestations, often leading to a misdiagnosis as Guillain‐Barré syndrome.

Methods

We report a case of AIP initially presenting as a peripheral neuropathy mimicking Parsonage‐Turner syndrome (neuralgic amyotrophy, NA). Clinical and electrophysiological evaluations were conducted, including nerve conduction studies and needle electromyography (EMG).

Results

A 41‐year‐old woman presented with burning pain and electric shock‐like sensations in the shoulders and trunk, alongside asymmetrical motor weakness in the upper limbs affecting arm abduction and finger extension. Electrophysiological evaluation revealed involvement of the superior trunk of the brachial plexus and the posterior interosseous nerve. Initially diagnosed with NA, she showed significant improvement in proximal strength over nine months but relapsed at fourteen months with severe finger extension weakness. Concurrent severe abdominal pain with constipation led to the identification of elevated urinary porphobilinogen (PBG) and delta‐aminolevulinic acid (ALA) levels, confirming AHP and specifically AIP via genetic and biochemical testing. The patient received hemin and givosiran infusions, resulting in decreased ALA levels, improvement of motor weakness, and no further attacks.

Interpretation

This case underscores the need to consider AIP in the differential diagnosis of acute neuropathies like NA, especially when accompanied by abdominal pain and severe constipation. Early recognition and appropriate testing for PBG and ALA can prevent misdiagnosis and enable targeted treatment.
Unpacking leader critical thinking in employee voice quality and silence frequency
Authors: Jiang Jing , Gong Yaping , Dong Yanan , Han Yi , Qin Yu
Published: October 2024

Previous research has predominantly examined either voice quantity or quality. We know little about the potential tradeoff between voice quantity and quality and the role of leaders in this tradeoff. This study focused on the dual aspects of voice, examining how and when the same leader attribute facilitates (inhibits) one aspect of voice, but does not facilitate (inhibit) or even hamper (facilitate) the other aspect. Specifically, we proposed that leader critical thinking stimulates the formation of employees' implicit voice theory of the need for solid data or solutions (IVT‐SDS) before one speaks up. This belief boosts the quality of employee voice especially when voice efficacy is high, but increases the frequency of employee silence especially when voice efficacy is low. In Study 1a, we experimentally tested the relationship between leader critical thinking and employees' IVT‐SDS. In Study 1b, we experimentally examined the interactive effect of employees' IVT‐SDS and their voice efficacy on both their voice quality and silence frequency. In Study 2, a multilevel, multi‐wave and multi‐source field study, we tested the entire research model. The results supported our hypotheses. We extend the research on leadership and voice by revealing a potential tradeoff between voice quality and quantity.
Community Pop‐Up Clinic: Cascade of Care and HCV Treatment of Vancouver's Inner‐City PWID Populations
Authors: Yi Shana , Wiesmann Christina , Truong David , Sharma Shawn , Conway Brian
Published: October 2024

Elimination of HCV infection as a public health concern by the end of this decade will require a concerted effort in all target populations, including drug‐users in the inner‐city. Several strategies have been proposed to identify, engage and provide HCV‐infected residents with antiviral therapy and maximise treatment and cure achievement. This study aims to assess the effectiveness of a multidisciplinary approach in delivering HCV treatment to people who inject drugs (PWID) within Vancouver's inner city. We have evaluated a novel approach, the Community Pop‐Up Clinic, for its ability to promote access to care and uptake of HCV therapy, with additional analyses of HCV reinfection and opioid‐related mortality. From January 2021 to August 2023, we evaluated 1968 individuals. 620 (31.5%) were found to carry HCV antibodies and of these, 474 (76.5%) were found to be viremic. Treatment engagement has been secured in 387 (81.6%). 326 (84.2%) have started treatment, 60 in the pre‐treatment phase and 1 died of an overdose in pre‐treatment. Of 326, 302 completed treatments, 18 are currently on treatment and 1 died of an overdose. Of 302 who completed treatment, 286 confirmed as cured (SVR 12), 16 are awaiting SVR 4, 2 had documented virologic relapse and 1 was reinfected. Three patients withdrew from treatment. By mITT, the cure rate is 286/288 (99.3%). We documented 2 overdose deaths over 326 PY. The data presented validates multidisciplinary programs such as ours aimed at treating HCV in inner‐cities and highlights societal benefits that could be achieved including lower overdose death rates.
Interpreting elevated liver blood test results through a genetic lens: A genome‐wide association study
Authors: Innes Hamish , Buch Stephan , Kendall Timothy J. , Fallowfield Jonathan A. , Guha Indra Neil
Published: October 2024

Background and Aims

Individuals with genetic polymorphisms in UGT1A1 exhibit bilirubin levels that belie their risk of liver disease (Gilbert's syndrome) but it is not known if this phenomenon extends to other common liver blood tests (LBTs).

Methods

A genome‐wide association analysis of 10 LBTs was conducted using the UK biobank. Polygenic scores (PGS) were created from discordant loci (e.g. loci associated with the LBT but not associated with cirrhosis morbidity risk). Participants were assigned to a low, intermediate or high PGS for each LBT. A high PGS approximates Gilbert's syndrome (i.e. elevated LBT without an analogous increase in disease risk). The prognostic significance of an ‘elevated’ LBT—and how this differs by PGS—was assessed through competing risk survival analysis.

Results

This study included 157 005 and 166 871 participants for the discovery and validation phases, respectively. Elevated LBTs were more prevalent in the high versus low PGS group, yet the 10‐year risk of cirrhosis morbidity was comparable. For example, in the low PGS group, 4.3% had an elevated gamma‐glutamyltransferase (GGT) and the 10‐year risk of cirrhosis morbidity was .45%. Conversely, in the high PGS group, 21.2% had an elevated GGT and the 10‐year risk was .38%. Accordingly, the 10‐year risk of cirrhosis morbidity for individuals with an elevated GGT was markedly different in the low vs. high group (4.2% vs. 1.2%; p < .001). Similar results were apparent for Fibrosis‐4 index, total bilirubin, and platelet count.

Conclusion

Variability in LBTs is influenced by genetic polymorphisms that have a neutral effect on disease risk. These findings have implications for interpreting elevated LBTs in clinical practice.
Humes definitions of virtue
Authors: Qu Hsueh
Published: October 2024

Hume offers not one, but two definitions of virtue: a more famous one in terms of usefulness or agreeability to the self or to others, and a second in terms of eliciting approbation or disapprobation from spectators. Some scholars endorse the former definition as the more fundamental one; others endorse the latter as more fundamental. This paper argues that neither definition is more fundamental than the other. The two definitions are distinct but complementary, in that they have to rely on each other in various ways.
Biomolecular condensation programs floral transition to orchestrate flowering time and inflorescence architecture
Authors: Huang Xiaozhen , Yang Yongfang , Xu Cao
Published: October 2024

Biomolecular condensation involves the concentration of biomolecules (DNA, RNA, proteins) into compartments to form membraneless organelles or condensates with unique properties and functions. This ubiquitous phenomenon has garnered considerable attention in recent years owing to its multifaceted roles in developmental processes and responses to environmental cues in living systems. Recent studies have revealed that biomolecular condensation plays essential roles in regulating the transition of plants from vegetative to reproductive growth, a programmed process known as floral transition that determines flowering time and inflorescence architecture in flowering plants. In this Tansley insight, we review advances in how biomolecular condensation integrates developmental and environmental signals to program and reprogram the floral transition thus diversifies flowering time and inflorescence architecture.
Nonphototrophic hypocotyl 3 domain proteins: traffic directors, hitchhikers, or both?
Authors: Verslues Paul E. , Upadhyay‐Tiwari Neha
Published: October 2024

The nonphototrophic hypocotyl 3 (NPH3) domain is plant specific and of unknown function. It is nearly always attached to an N‐terminal BTB domain and a largely unstructured C‐terminal region. Recent reports revealed NPH3‐domain GTPase activity and connection to intracellular trafficking, condensate formation, membrane attachment of the C‐terminal region for some NPH3‐domain proteins and, at the physiological level, drought‐related function for at least one NPH3‐domain protein. We integrate these new ideas of NPH3‐domain protein function into two, nonexclusive, working models: the ‘traffic director’ model, whereby NPH3‐domain proteins regulate intracellular trafficking and, the ‘hitchhiker’ model whereby NPH3‐domain proteins ride the trafficking system to find ubiquitination targets. Determining which model best applies to uncharacterized NPH3‐domain proteins will contribute to understanding intracellular trafficking and environmental responses.
Variable clinical presentation of hypomorphic DCLRE1C deficiency from childhood to adulthood
Authors: Hazar Esra , Karaselek Mehmet Ali , Kapakli Hasan , Dogar Oznur , Kuccukturk Serkan , Uygun Vedat , Artac Hasibe , Fındık Sıdıka , Sahin Ali , Arslan Sevket , Guner Sukru , Reisli Ismail , Keles Sevgi
Published: October 2024

Background

In this study, we aimed to report long‐term follow‐up of our pediatric and adult patients with DCLRE1C (DNA cross‐link repair 1C) hypomorphic mutation who were diagnosed leaky severe combined immunodeficiency (SCID).

Methods

Eighteen patients (13 children and five adults), aged between 6 and 29 years were included. Clinical and immunological features, including immunoglobulin levels, T and B cells, natural killer cell subsets, regulator T (Treg) cell ratios/markers, and cytokines, were assessed before and after hematopoietic stem cell transplantation (HSCT) and compared with healthy controls.

Results

Recurrent infections (78%) and skin manifestations (61%) such as granulomatous skin lesions, warts, and vitiligo were the most common clinical findings. Autoimmune diseases were observed in 33% and malignancy in 17%. Most patients had low serum IgA and B‐ and T‐cell lymphopenia at the first admission. Recent thymic emigrants (RTE), Tnaive, Bnaive, CD56dimCD16+ cell ratios were significantly lower in the patients than in control; however, follicular helper T TFH and Th1 [interferon gamma (IFN‐γ)] cell ratios were significantly higher than the control. Although, Treg ratio and its functional receptors tend to be high but not significant. Eleven patients (61.1%) were treated with HSCT. Median follow‐up times of transplant patients was 56 (9–67) months.

Conclusion

Patients with hypomorphic DCLRE1C mutations may present with variable clinical and laboratory findings at different ages. Our study showed a helper T (Th)1‐dominant immune response before and after HSCT. Increased IFN‐γ and TFH cells ratio could be a reason of chronic inflammation and autoimmunity developing before and after HSCT. Long‐term follow‐up of these patients after HSCT will help to better understand the disease and its pathophysiology.
AST‐001 versus placebo for social communication in children with autism spectrum disorder: A randomized clinical trial
Authors: Kim Hyo‐Won , Kim Ji‐Hoon , Chung Un Sun , Kim Johanna Inhyang , Shim Se‐hoon , Park Tae Won , Lee Moon‐Soo , Hwang Jun‐Won , Park Eun‐Jin , Hwang Su‐Kyeong , Joung Yoo‐Sook
Published: October 2024

Aim

This study examined the efficacy of AST‐001 for the core symptoms of autism spectrum disorder (ASD) in children.

Methods

This phase 2 clinical trial consisted of a 12‐week placebo‐controlled main study, a 12‐week extension, and a 12‐week follow‐up in children aged 2 to 11 years with ASD. The participants were randomized in a 1:1:1 ratio to a high‐dose, low‐dose, or placebo‐to‐high‐dose control group during the main study. The placebo‐to‐high‐dose control group received placebo during the main study and high‐dose AST‐001 during the extension. The a priori primary outcome was the mean change in the Adaptive Behavior Composite (ABC) score of the Korean Vineland Adaptive Behavior Scales II (K‐VABS‐II) from baseline to week 12.

Results

Among 151 enrolled participants, 144 completed the main study, 140 completed the extension, and 135 completed the follow‐up. The mean K‐VABS‐II ABC score at the 12th week compared with baseline was significantly increased in the high‐dose group (P = 0.042) compared with the placebo‐to‐high‐dose control group. The mean CGI‐S scores were significantly decreased at the 12th week in the high‐dose (P = 0.046) and low‐dose (P = 0.017) groups compared with the placebo‐to‐high‐dose control group. During the extension, the K‐VABS‐II ABC and CGI‐S scores of the placebo‐to‐high‐dose control group changed rapidly after administration of high‐dose AST‐001 and caught up with those of the high‐dose group at the 24th week. AST‐001 was well tolerated with no safety concern. The most common adverse drug reaction was diarrhea.

Conclusions

Our results provide preliminary evidence for the efficacy of AST‐001 for the core symptoms of ASD.
Thin‐film iridescence in the eggshell of a stick insect (Myronides glaucus)
Authors: Debruyn Gerben , Büscher Thies H. , Nicolaï Michaël P. J. , Dobson Jessica L. , Xie Wanjie , De Clerck Karen , D'Alba Liliana , Shawkey Matthew D.
Published: October 2024

Colours in nature can be pigmentary, structural or a combination of both. The prevalence, function and nanostructural origin of structural coloration in eggs is largely unknown. Stick and leaf insect eggs display a wide variety of colours, most of which are produced by pigments. The eggs of Myronides glaucus (Phasmida: Lonchodidae; Hennemann, 2021), however, show a clear purple to green iridescence. Here, we use micro‐spectrophotometry, Fourier‐transform infrared reflectance, transmission‐ and scanning electron microscopy, atomic force microscopy, finite‐difference time‐domain optical simulations and experimental approaches to elucidate the mechanism for iridescence in M. glaucus eggshells, which together reveal that iridescence is caused by thin‐film interference by a 200‐ to 450‐nm‐thick outermost layer. These results highlight the diversity of phasmid eggs and the need to study the different mechanisms and functions of structural coloration.
Suicidal thinking and behavior in young people at Clinical High Risk for Psychosis: Psychopathological considerations and treatment response across a 2‐year follow‐up study
Authors: Pelizza Lorenzo , Di Lisi Alessandro , Leuci Emanuela , Quattrone Emanuela , Palmisano Derna , Pellegrini Clara , Pellegrini Pietro , Paulillo Giuseppina , Pupo Simona , Menchetti Marco
Published: October 2024

Introduction

Suicidal ideation has high rates among individuals at Clinical High Risk for Psychosis (CHR‐P). CHR‐P mental states are currently defined as attenuated psychotic symptoms, brief intermittent psychotic symptoms, or genetic risk and functioning deterioration syndrome. However, the relationship between psychotic experiences and suicidality in CHR‐P subjects is still not fully understood. Research emphasizes the need to address suicidality in CHR‐P individuals due to its incidence and severe socio‐economic impact. This study aimed to assess the baseline prevalence and 2‐year incidence rates of suicidal thinking and behaviors in an Italian CHR‐P sample, investigate the stability of suicidal ideation over 2 years, and examine its associations with treatment outcomes, sociodemographic characteristics, and clinical factors.

Methods

CHR‐P participants were treated in an “Early Intervention in Psychosis” program and completed the PANSS and the GAF scale at baseline and every 12 months.

Results

180 CHR‐P individuals were enrolled (92 with suicidal ideation [SI+]). SI+ subjects had a higher baseline prevalence of past suicide attempts. Over 2 years, a decrease in suicidal ideation severity was observed in the total group. Longitudinal improvement in disorganized symptoms was a key predictor of the decrease in suicidal ideation. Participants with a history of suicide attempts were more likely to attempt again.

Conclusion

Addressing disorganization is crucial for suicide prevention in the CHR‐P population. Continuous risk monitoring and preventive actions are needed for those with past suicide attempts.
The elephant in the room? Considerations of politics among older adult daters
Authors: Cotton Cassandra , Zamora Castro Analicia
Published: October 2024

A sharply polarized political climate may increase the importance single adults place on politics in partner selection. While the importance of politics in dating decisions is not surprising in light of homophily, less is known about how older adults consider political differences in partnering. We answer two questions about older daters and politics: (1) How do older adult daters consider potential partners' political views? and (2) How do perceptions of rising political polarization shape these preferences? We use interview data with 67 adults (aged 55–92) from the Romance and Dating in Later Life study, conducted in Phoenix, AZ, in 2022–2023. Findings show politics are highly salient in partner selection across gender, class, and ideology, suggesting older singles place substantial importance on political views when choosing partners. Many older singles prioritize shared beliefs, while others practice open‐mindedness. Extremist politics, particularly right‐leaning, are viewed as a significant barrier to dating. This study demonstrates how older daters consider political beliefs in dating decisions, particularly considering perceptions of rising polarization. This contributes to research highlighting the role of political ideology in shaping dating decisions by extending the research to include explicit study of mid‐ and late‐life adults, whose dating experiences differ from young adult singles.
Can(‘t) have it all? Parents in the Swiss Parliament
Authors: Frech Elena , Bailer Stefanie , Bütikofer Sarah
Published: October 2024

Although a large share of parliamentarians are parents, we know little about how parenthood affects legislative activities and careers of parliamentarians. Children cost time and energy and thus may impact legislative behavior and the possibilities to excel in the legislature, e.g. by obtaining higher positions. Moreover, children may have a different impact on the parliamentary careers of mothers than fathers due to asymmetrical care responsibilities. We investigate whether parliamentarians have fewer children than their voters and show the impact of children on parliamentary careers and activities using a new dataset on Swiss national parliamentarians between 2011 and 2020. Our results reveal that there are many parents of minor children in parliament, even more mothers than fathers. In contrast to fathers, mothers are less likely to be successful when it comes to higher positions. Moreover, mothers have a lower average output in individual legislative activities than their male colleagues with or without children.
Origin of Helium and Associated Fluid in Fault‐Related Hydrothermal Systems of the Eastern Pyrenees
Authors: Milesi Gaétan , Cardoso Carolina Dantas , Pik Raphaël , Moreira Manuel , Charpentier Delphine , Mercadier Julien
Published: October 2024

Intense hydrothermal activity hosted by regional tectonic structures occurs in the Eastern part of the Pyrenees. Helium isotope ratios (3He/4He) in hot springs along the Têt (0.033–0.099 Ra) and the Tech (0.171–0.375 Ra) faults indicate different signatures from purely crustal to slightly contaminated by magmatic helium. 3He/4He ratio increased towards the East, consistently with the observed thinning of the continental crust. These results suggest localised and not interconnected hydrothermal systems at fault scale. The origin of magmatic helium contamination is discussed in the light of the Gulf of Lion geodynamic evolution and data from comparable orogenic hydrothermal systems in the Alps.
Henri Lefebvre and the spatial revolution that never ends: Towards the reconciliation of anarchist and Marxist approaches in geography?
Authors: Kallin Hamish
Published: October 2024

It is widely accepted that Henri Lefebvre's Marxism had anarchistic traits, but few have tried to specify what these traits are, or what they mean. This paper argues that Lefebvre's work should be seen as first and foremost an anti‐authoritarian theory that uses space, rather than a spatial theory. Written from a position that refuses to be either just ‘Marxist’ or just ‘anarchist’, this paper makes a claim to the possibility of a radical geography that can engage with and beyond both.
Association of biofilm and microbial metrics with healing rate in older adults with chronic venous leg ulcers
Authors: Stewart Philip S. , Kim Junglyun , James Garth , Yi Fan , Stechmiller Joyce , Weaver Michael , Kelly Debra L. , Fisher Steve , Schultz Gregory , Lyon Debra
Published: October 2024

The presence of microbial biofilms in many human chronic wounds led to the hypothesis that biofilms delay healing of these wounds. We tested this hypothesis in a population of 117 older individuals with venous leg ulcers who were receiving standardised therapy, including frequent debridement. Debridement specimens were analysed for the amount of bacterial biomass by two independent methods: a microscopic approach that scored the relative size and number of bacterial aggregates, interpreted as a biofilm metric, and conventional enumeration by agar plating for viable bacteria. The plating protocol yielded three distinct values: the total viable bacterial count, bleach‐tolerant bacteria, and the log reduction in viable bacteria upon bleach treatment. Wound healing rates over an 8‐week observation period were calculated as the rate of decrease of the equivalent diameter of the wound. There was no statistically significant association between wound healing and the biofilm metric in any of the three analyses performed (p ≥0.15). In all three statistical tests, wound healing was associated with the log reduction caused by bleach treatment (p ≤0.004); wounds that harboured bacteria that were more bleach‐susceptible healed more slowly. A refinement of the model of chronic wound infection pathogenesis is proposed in which dormant bacteria constitute a persistent nidus and outgrowth of metabolically active cells impairs healing. This model constitutes a new hypothesis as metabolic activity was not directly measured in this investigation.
DEVELOPMENT OF A CORRELATION MODEL FOR TORSIONAL SHEAR MODULUS PROPERTIES BETWEEN STRUCTURAL SIZE SPECIMENS BASED ON EN 384:2016 AND SMALL CLEAR SPECIMENS (MS544: PART 2)
Authors: Mohd Puaad Muhammad Bazli Faliq , Ahmad Zakiah , Mohamad Bhkari Norshariza , Mohamed Ibrahim Mohd Johan , Noh Narita , Mohammad Shahrul Nizam , Ismail Herda Balqis
Published: October 2024

In timber design, the shear modulus of beams is crucial for ensuring torsional stability and minimizing vibrational issues. Traditionally, the ratio of modulus of elasticity (E) to shear modulus (G) is assumed to be 16:1. However, bending tests often combine flexural and shear stresses, making it difficult to assess pure shear properties. The British Standard BS EN 408:2012 now recommends the torsion test as the preferred method for determining the shear modulus of structural-size timber and timber composites. This method has received limited attention in Malaysia. This study investigates the torsional shear modulus of Malaysian tropical timber species across different strength groups (SG), including Balau (SG1), Kempas (SG2), Kelat (SG3), Kapur (SG4), Resak (SG4), Keruing (SG5), Mengkulang (SG5), Light Red Meranti (SG6), and Geronggang (SG7). Torsion tests were conducted in line with BS EN 408, and the results were compared with modulus of elasticity values from MS554: Part 2. The findings showed that the E to G ratio for these species ranged from 17:1 to 29:1, with an average of 21:1—exceeding the conventional 16:1 ratio. This indicates that torsional shear modulus must be experimentally tested rather than inferred from the traditional ratio.