bluuebunny/crossref_metadata_2025_split huggingface dataset:
Midterm results after allogeneic simple limbal epithelial transplantation from deceased‐donor eyes in patients with persistent corneal epithelial defects due to limbal stem cell deficiency
Authors: Riedl Jana C. , Wasielica‐Poslednik Joanna , Giers Bert C. , Buonfiglio Francesco , Pfeiffer Norbert , Musayeva Aytan , Gericke Adrian 
Published: September 2024

AbstractBackgroundThis study aims to characterize the clinical outcomes after allogeneic simple limbal epithelial transplantation (alloSLET) utilizing tissue from cadaveric donor eyes to address persistent corneal epithelial defects caused by limbal stem cell deficiency.MethodsWe conducted a retrospective analysis of medical records from 20 patients, encompassing 24 eyes, who underwent alloSLET at least 2 years prior. The primary endpoint was the achievement of complete epithelialization of the corneal surface by corneal epithelium. Secondary endpoints included corrected distance visual acuity (CDVA) and postoperative adverse events.ResultsThe median postoperative follow‐up period was 36 months (range, 24–74 months). At 1, 3 and 6 months post‐surgery, 96% of eyes demonstrated epithelialized corneal surfaces, which declined to 71% at 12 months, to 54% at 24 and 36 months after surgery, and to 50% thereafter. There were no significant differences in graft survival between alloSLET performed alone versus in combination with penetrating keratoplasty. However, instances of graft failure were associated with postoperative elevated intraocular pressure (IOP) and a history of multiple amniotic membrane and corneal graft transplants.ConclusionsAlloSLET emerges as a viable mid‐term intervention for limbal stem cell deficiency‐associated non‐healing corneal epithelial defects in the absence of autologous limbal tissue. Our findings underscore the increased risk of graft failure in patients with elevated IOP and a background of multiple previous amniotic membrane and corneal graft procedures.
GLP‐1 receptor agonists: A new frontier in combating metabolic liver disease complications
Authors: Fatima Ayesha , Maryam Ayesha , Nadeem Muhammad Salman , Asmat Kashaf Noor 
Published: September 2024

LINKED CONTENTThis article is linked to Elsaid et al paper. To view this article, visit https://doi.org/10.1111/apt.17925
Letter: Prospective evaluation of patients with non‐cirrhotic portal hypertension—A single‐centre study
Authors: Ucdal Mete , Simsek Cem , Durak Bahaddin , Balaban Hatice Yasemin 
Published: September 2024

LINKED CONTENTThis article is linked to Mironova et al papers. To view these articles, visit https://doi.org/10.1111/apt.17987 and https://doi.org/10.1111/apt.18292
Eight‐year efficacy and safety of tenofovir alafenamide for treatment of chronic hepatitis B virus infection: Final results from two randomised phase 3 trials
Authors: Buti Maria , Lim Young‐Suk , Chan Henry Lik Yuen , Agarwal Kosh , Marcellin Patrick , Brunetto Maurizia R. , Chuang Wan‐Long , Janssen Harry L. A. , Fung Scott K. , Izumi Namiki , Jablkowski Maciej S. , Abdurakhmanov Dzhamal , Abramov Frida , Wang Hongyuan , Botros Irina , Yee Leland J. , Mateo Roberto , Flaherty John F. , Osinusi Anu , Pan Calvin Q. , Shalimar X. , Seto Wai‐Kay , Gane Edward J. 
Published: September 2024

SummaryBackgroundIn two phase 3 studies, tenofovir alafenamide (TAF) showed non‐inferior efficacy versus tenofovir disoproxil fumarate (TDF), with more favourable renal and bone safety in patients with chronic hepatitis B (CHB).AimsHere, we report the studies' final 8‐year results.MethodsCHB patients (hepatitis B e antigen [HBeAg]‐negative and HBeAg‐positive) were randomised (2:1) to double‐blind TAF 25 mg/day or TDF 300 mg/day for up to 3 years, followed by open‐label (OL) TAF through year 8. Virological, biochemical, serological and fibrosis responses, and safety, including bone and renal parameters, were evaluated. Resistance to TAF was assessed annually by deep sequencing of polymerase/reverse transcriptase and by phenotyping.ResultsAmong 1298 patients randomised to double‐blind TAF (n = 866) or double‐blind TDF (n = 432), 775 in the TAF group and 382 in the TDF group received OL TAF, including 180 and 202 who switched from TDF to TAF at year 2 (TDF2y → TAF6y) or year 3 (TDF3y → TAF5y), respectively. At year 8, among patients in the TAF8y, TDF2y → TAF6y and TDF3y → TAF5y groups, 69%, 66% and 73% (missing‐equals‐failure analysis) and 95%, 94% and 97% (missing‐equals‐excluded) of patients, respectively, achieved HBV DNA <29 IU/mL. Estimated glomerular filtration rate (Cockcroft‐Gault method; eGFRCG) and hip/spine bone mineral density (BMD) remained stable in patients receiving double‐blind/OL TAF, with only small declines at year 8. Decreases in eGFRCG and hip/spine BMD observed during double‐blind TDF improved after switching to OL TAF. No patients developed resistance to TAF.ConclusionLong‐term TAF treatment exhibited favourable safety and tolerability with high rates of viral suppression and no development of resistance.ClinicalTrials.gov numbers NCT01940341 and NCT01940471.
Letter: Prospective evaluation of patients with non‐cirrhotic portal hypertension—A single centre study. Authors' reply
Authors: Mironova Maria , Gopalakrishna Harish , Heller Theo 
Published: September 2024

LINKED CONTENTThis article is linked to Mironova et al papers. To view these articles, visit https://doi.org/10.1111/apt.17987 and https://doi.org/10.1111/apt.18255
Population pharmacokinetic and dose–response models of nepadutant, a selective antagonist of the NK2 receptors, in infants with colic
Authors: Jönsson Siv , Bouchene Salim , Mazzei Paolo , Borella Elisa , Piana Chiara , Tagliavini Alessia , Koletzko Sibylle , Werkstetter Katharina , Capriati Angela , Pellacani Andrea , Karlsson Mats O. , Jonsson E. Niclas 
Published: September 2024

AimsThe aim of the current analyses was to develop a population pharmacokinetic model for nepadutant in infants with colic, and a pharmacokinetic‐pharmacodynamic model based on observations of duration of crying and fussing following oral nepadutant administration in infants (3–25 weeks) with colic.MethodsThe models were developed based on data obtained at baseline and following treatment with placebo, nepadutant 0.1 mg/kg or nepadutant 0.5 mg/kg administered for 7 days. A continuous response variable, duration of crying and fussing in minutes within 2 h interval, was assembled based on records from “baby's day” diary.ResultsThe pharmacokinetics of nepadutant was described by a one‐compartment model with first‐order absorption and elimination with body weight as a structural covariate incorporated allometrically. For an infant weighing 5.3 kg, the estimated apparent clearance was 68.6 L/h (12% relative standard error) and exhibited large variability (78% coefficient of variation). The pharmacokinetic‐pharmacodynamic model described (i) a circadian rhythm in the response with lowest and highest observations at 4 a.m. and 9 p.m., respectively, (ii) a placebo effect increasing and flattening out with time in an exponential manner, and (iii) a statistically significant (P < .01) linearly increasing response with dose. The observed and model predicted relative change in response from baseline was −35% and −28% (95% prediction interval −36%; −19%) following placebo, and −44% and −36% (−46%; −27%) after 0.5 mg/kg.ConclusionsPopulation pharmacokinetic and dose–response models were successfully developed characterizing the available nepadutant pharmacokinetics and duration of crying and fussing data in infants.
Activation of Piezo1 by intracranial hypertension induced neuronal apoptosis via activating hippo pathway
Authors: Zeng Jia , Fang Zhen , Duan Jiajia , Zhang Zichen , Wang Yunzhi , Wang Yiping , Chen Lei , Wang Jikai , Liu Fei 
Published: September 2024

AbstractAimMost of the subarachnoid hemorrhage (SAH) patients experienced the symptom of severe headache caused by intracranial hypertension. Piezo1 is a mechanosensitive ion channel protein. This study aimed to investigate the effect of Piezo1 on neurons in response to intracranial hypertension.MethodsThe SAH rat model was performed by the modified endovascular perforation method. Piezo1 inhibitor GsMTx4 was administered intraperitoneally after SAH induction. To investigate the underlying mechanism, the selective Piezo1 agonist Yoda1, Piezo1 shRNA, and MY‐875 were administered via intracerebroventricular injection before SAH induction. In vitro, we designed a pressurizing device to exclusively explore the effect of Piezo1 activation on primary neurons. Neurons were pretreated with Piezo1 inhibition followed by intracranial hypertension treatment, and then apoptosis‐related proteins were detected.ResultsPiezo1 inhibition significantly attenuated neuronal apoptosis and improved the outcome of neurological deficits in rats after SAH. The Hippo pathway agonist MY‐875 reversed the anti‐apoptotic effects of Piezo1 knockdown. In vitro, intracranial hypertension mimicked by the pressurizing device induced Piezo1 expression, resulting in Hippo pathway activation and neuronal apoptosis. The Hippo pathway inhibitor Xmu‐mp‐1 attenuated Yoda1‐induced neuronal apoptosis. In addition, the combination of hypertension and oxyhemoglobin treatment exacerbated neuronal apoptosis.ConclusionsIntracranial hypertension induced Piezo1 expression, neuronal apoptosis, and the Hippo pathway activation; the Hippo signaling pathway is involved in Piezo1 activation‐induced neuronal apoptosis in respond to intracranial hypertension. Primary neurons treated with intracranial hypertension and oxyhemoglobin together can better characterize the circumstance of SAH in vivo, which is contributed to construct an ideal in vitro SAH model.
Vitamin D3 Attenuates Neuropathic Pain via Suppression of Mitochondria‐Associated Ferroptosis by Inhibiting PKCα/NOX4 Signaling Pathway
Authors: Zhang Wencui , Yu Shangchen , Jiao Bo , Zhang Caixia , Zhang Kaiwen , Liu Baowen , Zhang Xianwei 
Published: September 2024

ABSTRACTAimsNeuropathic pain remains a significant unmet medical challenge due to its elusive mechanisms. Recent clinical observations suggest that vitamin D (VitD) holds promise in pain relief, yet its precise mechanism of action is still unclear. This study explores the therapeutical role and potential mechanism of VitD3 in spared nerve injury (SNI)‐induced neuropathic pain rat model.MethodsThe analgesic effects and underlying mechanisms of VitD3 were evaluated in SNI and naïve rat models. Mechanical allodynia was assessed using the Von Frey test. Western blotting, immunofluorescence, biochemical assay, and transmission electron microscope (TEM) were employed to investigate the molecular and cellular effects of VitD3.ResultsFerroptosis was observed in the spinal cord following SNI. Intrathecal administration of VitD3, the active form of VitD, activated the vitamin D receptor (VDR), suppressed ferroptosis, and alleviated mechanical nociceptive behaviors. VitD3 treatment preserved spinal GABAergic interneurons, and its neuroprotective effects were eliminated by the ferroptosis inducer RSL3. Additionally, VitD3 mitigated aberrant mitochondrial morphology and oxidative metabolism in the spinal cord. Mechanistically, VitD3 inhibited SNI‐induced activation of spinal PKCα/NOX4 signaling. Inhibition of PKCα/NOX4 signaling alleviated mechanical pain hypersensitivity, accompanied by reduced ferroptosis and mitochondrial dysfunction in SNI rats. Conversely, activation of PKCα/NOX4 signaling in naïve rats induced hyperalgesia, ferroptosis, loss of GABAergic interneurons, and mitochondrial dysfunction in the spinal cord, all of which were reversed by VitD3 treatment.ConclusionsOur findings provide evidence that VitD3 attenuates neuropathic pain by preserving spinal GABAergic interneurons through the suppression of mitochondria‐associated ferroptosis mediated by PKCα/NOX4 signaling, probably via VDR activation. VitD, alone or in combination with existing analgesics, presents an innovative therapeutic avenue for neuropathic pain.
Dynamic transcriptomic and regulatory networks underpinning the transition from fetal primordial germ cells to spermatogonia in mice
Authors: Zhao Jiexiang , Tang Kang , Jiang Gurong , Yang Xinyan , Cui Manman , Wan Cong , Ouyang Zhaoxiang , Zheng Yi , Liu Zhaoting , Wang Mei , Zhao Xiao‐Yang , Chang Gang 
Published: September 2024

AbstractThe transition from fetal primordial germ cells (PGCs) to spermatogonia (SPG) is critical for male germ cell development; however, the detailed transcriptomic dynamics and regulation underlying this transition remain poorly understood. Here by interrogating the comprehensive transcriptome atlas dataset of mouse male germ cells and gonadal cells development, we elucidated the regulatory networks underlying this transition. Our single‐cell transcriptome analysis revealed that the transition from PGCs to SPG was characterized by global hypertranscription. A total of 315 highly active regulators were identified to be potentially involved in this transition, among which a non‐transcription factor (TF) regulator TAGLN2 was validated to be essential for spermatogonial stem cells (SSCs) maintenance and differentiation. Metabolism profiling analysis also revealed dynamic changes in metabolism‐related gene expression during PGC to SPG transition. Furthermore, we uncovered that intricate cell–cell communication exerted potential functions in the regulation of hypertranscription in germ cells by collaborating with stage‐specific active regulators. Collectively, our work extends the understanding of molecular mechanisms underlying male germ cell development, offering insights into the recapitulation of germ cell generation in vitro.
ChatGPT Solving Complex Kidney Transplant Cases: A Comparative Study With Human Respondents
Authors: Mankowski Michal A. , Jaffe Ian S. , Xu Jingzhi , Bae Sunjae , Oermann Eric K. , Aphinyanaphongs Yindalon , McAdams‐DeMarco Mara A. , Lonze Bonnie E. , Orandi Babak J. , Stewart Darren , Levan Macey , Massie Allan , Gentry Sommer , Segev Dorry L. 
Published: September 2024

ABSTRACTIntroductionChatGPT has shown the ability to answer clinical questions in general medicine but may be constrained by the specialized nature of kidney transplantation. Thus, it is important to explore how ChatGPT can be used in kidney transplantation and how its knowledge compares to human respondents.MethodsWe prompted ChatGPT versions 3.5, 4, and 4 Visual (4 V) with 12 multiple‐choice questions related to six kidney transplant cases from 2013 to 2015 American Society of Nephrology (ASN) fellowship program quizzes. We compared the performance of ChatGPT with US nephrology fellowship program directors, nephrology fellows, and the audience of the ASN's annual Kidney Week meeting.ResultsOverall, ChatGPT 4 V correctly answered 10 out of 12 questions, showing a performance level comparable to nephrology fellows (group majority correctly answered 9 of 12 questions) and training program directors (11 of 12). This surpassed ChatGPT 4 (7 of 12 correct) and 3.5 (5 of 12). All three ChatGPT versions failed to correctly answer questions where the consensus among human respondents was low.ConclusionEach iterative version of ChatGPT performed better than the prior version, with version 4 V achieving performance on par with nephrology fellows and training program directors. While it shows promise in understanding and answering kidney transplantation questions, ChatGPT should be seen as a complementary tool to human expertise rather than a replacement.
Seeing Gray in a World of Black and White: Children Appreciate Reasoners Who Approach Moral Dilemmas With Humility
Authors: Li Pearl Han , Kushnir Tamar 
Published: September 2024

ABSTRACTMoral decisions often involve dilemmas: cases of conflict between competing obligations. In two studies (N = 204), we ask whether children appreciate that reasoning through dilemmas involves acknowledging that there is no single, simple solution. In Study 1, 5‐ to 8‐year‐old US children were randomly assigned to a Moral Dilemma condition, in which story characters face dilemmas between two prosocial actions, or a Personal Cost control, in which story characters face decisions between a matched prosocial action and a self‐interested action. Children were then presented with two reasoners who made the same judgment, but one confidently endorsed one moral action, and the other hesitantly acknowledged both actions. As they aged, children became more likely to prefer the uncertain reasoner's “way of thinking” in the Moral Dilemma compared to the Personal Cost condition. They also inferred that the uncertain reasoner was nicer and more trustworthy than the confident one. In Study 2, when both reasoners acknowledged the dilemma and differed only in their level of uncertainty, 5‐year‐olds preferred the acknowledgment to be accompanied by a confident decision, 6‐ and 7‐year‐olds preferred it be accompanied by uncertainty, and 8‐year‐olds showed no preference. These results show that, before the age at which children can resolve dilemmas successfully on their own, they recognize and value others who approach dilemmas with appropriate humility.
No Self‐Reference, No Ownership?
Authors: Ritter Bernhard 
Published: September 2024

AbstractA ‘no‐ownership’ or ‘no‐self theory’ holds that there is no proper subject of experience; the ownership of experience can only be accounted for by invoking a sub‐personal entity. In the recent self‐versus‐no‐self debate, it is widely assumed that the no‐ referent view of ‘I’, which is closely associated with Wittgenstein and G. E. M. Anscombe, implies a no‐ownership theory of experience. I spell out this assumption with regard to both non‐reflective and reflective consciousness and show that it is false. If the so‐called ‘self’ is an individual, the person, nothing more is required for the ownership of sensations than the non‐reflective experiencing, undergoing, or suffering of them, whereas the sense of ‘ownership’ of reflective consciousness varies according to the type of ‘I’‐thought in question. Ownership of ‘I’‐thoughts about one’s own actions, for one thing, is a matter of being able to fit future actions to them or answer questions as to why one is doing what one does.
Reflections on statutory cohabitation law reform in Ireland: Past, present & future post‐O'Meara? 1024 (October 2024/nonmarriage roundtable)
Authors: O'Sullivan Kathryn 
Published: September 2024

AbstractPart 15 of the Civil Partnership and Certain Rights and Obligations of Cohabitants Act 2010 governs the breakdown of cohabiting relationships in the Republic of Ireland. However, although the introduction of the statutory redress scheme under the 2010 Act was considered an important response to the growing need for the protection of vulnerable cohabitants, the extent to which it has provided such protection has remained somewhat obscure. This contribution reflects on what we know about the operation of the scheme as currently framed and questions what scope might exist for it to be gently reformed going forward.
Childhood, Migration and the Pursuit of Happiness in MIDDLE‐CLASS EAST ASIA
Authors: Beck Fanni , Nyíri Pál , Gaspar Sofia 
Published: September 2024

ABSTRACTThis special issue explores the shifting landscape of global middle‐class migration within and from East Asia by taking the relationship between mobility, parenting ideals and changing educational desires as its focus. Contributions explore how East Asian middle‐class families balance the emergent emphasis on their children's well‐being with the demands of global competitiveness as these often‐antagonistic desires are projected onto old and new migration destinations against the background of global geopolitical and economic power shifts. Instead of reifying the simplistic binary of hierarchical, achievement‐oriented East Asian ‘Confucian educational norms’ versus democratic, well‐being‐focussed Western ideals, the contributions offer a nuanced understanding of how these educational ideals coexist within the social, cultural, political and economic contexts of families. By carefully assessing the dialectically entwined intimate experiences of parents and children, the articles collected here set out to broaden our understanding of how middle‐class families in Singapore, South Korea, Japan and China attempt to negotiate the tension between prioritizing children's happiness and maintaining global competitiveness result in a variety of strategies from migrating to less obvious international destinations to crafting domestic alternatives. Taken together, the articles reveal consistent patterns of middle‐class migration and child‐rearing decisions that contest and reshape conventional notions of success, attesting to a shift in global middle‐class migration trends and to the importance of child‐rearing in migratory decisions.
MTAP protein status is highly concordant with CDKN2A fluorescent in situ hybridization and allows stratification of the luminal subtype in muscle‐invasive bladder cancer
Authors: Olkhov‐Mitsel Ekaterina , Oberc Alexander , Craddock Kenneth J , Sherman Christopher , Slodkowska Elzbieta , Downes Michelle R 
Published: September 2024

AimsLoss of heterozygosity in chromosome 9p21, common in urothelial carcinoma (UC), typically involves deletion of CDKN2A and MTAP genes. MTAP loss is emerging as a promising therapeutic target and predictive biomarker in UC. This single‐centrre retrospective study examined the incidence of CDKN2A deletions and MTAP loss in muscle‐invasive bladder cancer (MIBC) and metastatic urothelial carcinoma (mUC), investigating their correlations with clinical, pathological, and genomic features, as well as patient outcomes.MethodsFluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed on 302 MIBC specimens and 63 biopsy‐proven metachronous urothelial metastases to assess CDKN2A deletions and MTAP protein expression.ResultsCDKN2A homozygous deletion (HD), identified in 30.3% of MIBCs, and MTAP loss, found in 28.8% of MIBCs, were both significantly associated with the luminal‐URO subtype, FGFR3 mutations, and normal/wildtype p53 IHC (P < 0.05). Loss of MTAP expression was significantly correlated with CDKN2A HD, with 84.0% sensitivity, 92.3% negative predictive value (NPV), 96.3% specificity, and 91.9% positive predictive value (PPV). MTAP expression was 100% concordant between primary tumours and nodal metastases. Patients with MTAP loss had a higher incidence of visceral metastases (50%) compared to bone/soft tissue (35.7%) and nodes (14.3%). Mean progression‐free survival and overall survival were shorter for patients with MTAP loss, although not statistically significant.ConclusionOur findings highlight CDKN2A HD and MTAP loss as prevalent genetic alterations in MIBC and mUC, particularly within the luminal‐URO subtype and FGFR3‐mutated, p53‐normal/wildtype tumours. MTAP IHC can serve as a surrogate marker for 9p21.3 HD, highlighting its clinical relevance and potential as a therapeutic target and predictive biomarker in MIBC.