bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Great Masquerader’: a history of diagnosing pheochromocytoma
Authors: Parikh Roneil , Diab Jason , Guevara Ronald , Russell Hamish , Campbell Peter
Published: October 2024

Introduction

Pheochromocytoma is a unique tumour with a variety of clinical presentations. Coined as ‘the great masquerader’, it can present with the classical triad of headache, sweating and tachycardia and sometimes in an acute hypertensive crisis. This paper describes the evolutionary history of the diagnosis of this condition.

Methods

A literature review was conducted using Medline Database from 1900 to 2023 outlining the methods of diagnosis for pheochromocytoma.

Results

There have been diagnostic dilemmas and localization challenges of pheochromocytoma over the last century. From the first description of pheochromocytoma in 1886 to the first successful resection in 1926, there was poor recognition of its atypical symptoms and lack of reliable diagnostic tests. Over the next few decades, there were significant advances in screening and biochemical tests. Further understanding of catecholamine release and metabolic pathways led to the development of tests to identify end products of catecholamine metabolism in plasma and urine. Computed imaging however heralded significant improvement in surgical planning and management. The evolution of histopathological diagnosis with the use of immunostains and genetic testing has further contributed to the identification of malignant pheochromocytomas and an understanding of their behaviours.

Conclusion

Significant advances in the biochemical and imaging have shaped our understanding of pathophysiology and management. These diagnostic advances have enabled early and accurate detection and localization of pheochromocytomas to enable prompt surgical management.
Barriers and hurdles delaying governance approval for an ethically approved nationwide clinical trial in pancreatic cancer
Authors: Recasens Ariadna , Li Lin , Ioannou Liane , Greenhill Elysia , Attwood David , Cheek Bruce Ross , Lesage Jacqueline , Madgwick Helen , Walker Tracy , Zalcberg John , Pilgrim Charles
Published: October 2024

Backgrounds

Streamlined, expedited clinical research is fundamental to rapidly test, translate and implement novel treatments into routine care to improve patient outcomes. The National Mutual Acceptance (NMA) scheme was designed to expedite the ethics approval process, however, growing concerns exist about the fragmented time‐consuming governance process needed to actually commence clinical research in Australia. This study reports hurdles and barriers encountered while seeking governance approval for the SCANPatient trial.

Methods

SCANPatient is a nationwide multi‐centre trial comparing standard narrative radiological reporting of CT scans for suspected pancreatic ductal adenocarcinoma. with an alternative structured approach. SCANPatient was approved by a national Human Research Ethics Committee under the NMA. The documents, time, costs and platforms required to obtain governance approval and open the trial at 30 participating hospitals were analysed.

Results

Wide variation exists in research governance office (RGO) requirements for local approval, resulting in extra costs (>$117 000), delays of up to 4 months in commencing the trial at some participating sites, unplanned adjustment of the study design, and ultimately the loss of several potential sites. There were inconsistencies among RGOs minimum requirements and processes across jurisdictions and sites, with delays in obtaining approval signatures, time‐consuming processes, differing platforms used to submit governance reviews and inflexibility of RGO processes all contributing to delays in progressing the trial and obtaining governance approval.

Conclusion

The current governance process is time‐ and cost‐consuming and undermines the NMA scheme's efforts to streamline the clinical trials review process.
Myopia control with orthokeratology lenses. A 3‐year follow‐up study including a cross‐over design: Clinical study Of Near‐sightedness; TReatment with Orthokeratology Lenses 2 (CONTROL2 study)
Authors: Jakobsen T. M. , Høeg K. B. , Møller F.
Published: October 2024

Purpose

The purpose of this study is to investigate 3‐year efficacy of orthokeratology lenses (OKL) in controlling axial length progression in myopic Scandinavian children. Through a cross‐over design of the control group to compare the treatment efficacy in younger versus older children, with the latter having higher cycloplegic spherical refractive error (cSEQ) at treatment initiation. Further, the study aimed to evaluate the safety of the treatment.

Methods

This was a continuation of the randomized controlled study Clinical study Of Near‐sightedness; TReatment with Orthokeratology Lenses (CONTROL study) in which the follow‐up period of the original intervention group, that received OKL, was extended from 18 months to 36 months. Meanwhile, the original control group was crossed‐over to OKL after the 18‐month follow‐up visit and treated for 18 months. Biometry was measured using Lenstar LS900, and contact lens complications were graded according to Efron Grading Scale for Contact Lens Complications (Efron score). Mixed models were used for statistical analysis.

Results

Nineteen subjects in the OKL group and 28 in the control group completed the CONTROL study. Hereof, 17 and 24 subjects from the OKL group and control group, respectively, agreed to participate in the CONTROL2 study. In the OKL continue group, the treatment efficacy did not decline during the 3‐year study period (p‐values for follow‐up visits were all ≥0.82). There was no statistically significant difference between treatment efficacy when OKL treatment was initiated in younger versus older children (p‐value ≥0.14 for all follow‐up visits). Low‐grade corneal staining was seen in several subjects at some point during the study, but here were no treatment‐requiring or sight‐threatening adverse events during the study period.

Conclusion

The efficacy of myopia control by OKL was stable during 3 years of treatment. Similar treatment efficacies were found regardless of the age at treatment initiation. No severe adverse events occurred during the study period.
Percutaneous endoscopic gastrostomy helped to normalise feeding problems and gastrointestinal symptoms in Silver‐Russell syndrome
Authors: Muz Nataliia , Petersson Miriam , Saalman Robert , Dahlgren Jovanna
Published: October 2024

Aim

This study evaluated feeding problems and gastrointestinal symptoms in children with Silver‐Russell syndrome (SRS), which is a rare epigenetic disorder. It also compared the symptoms experienced during different feeding methods, including percutaneous endoscopic gastrostomy (PEG).

Methods

The national expert team for children with SRS at Queen Silvia Children's Hospital, Gothenburg, studied 46 referrals (63% male) who were born with SRS in Sweden from 1984 to 2018. Patient data were extracted from the Paediatric National Growth Hormone Registry.

Results

The medical records covered a median of 68% of the time of the patients' childhood, with a median follow‐up of 9 years. Their symptoms were most prevalent during infancy and decreased when they were toddlers. Feeding problems and gastrointestinal symptoms were reported in 91% of the 46 patients, with vomiting in 57% and constipation in 46%. There were 19 children who relied on enteral feeding for their nutrition and 13 of those received PEG. Their body mass index (BMI) increased significantly 2 years after PEG started (p = 0.005).

Conclusion

Feeding problems and gastrointestinal symptoms were very common in children with SRS, but partly disappeared during childhood. Providing treatment, such as PEG, normalised the BMIs of children with SRS and reduced their symptoms.
Calcineurin inhibitors and the renin–angiotensin–aldosterone system
Authors: Berber Mesut , Penton David
Published: October 2024

Calcineurin inhibitors (CnIs) are effective immunosuppressants with decades of accumulated experience in treating immune disorders and, most notably, solid organ transplantation. While CnIs have significantly increased graft survival and transformed the patient standard of care, their use has been overshadowed by a number of undesired side effects. For instance, CnI‐associated nephrotoxicity has been reported since early studies and remains a major therapeutic concern. The occurrence of several ion imbalances alongside hypertension was also noted early on, indicating the involvement of the renin–angiotensin–aldosterone system (RAAS) in CnI‐mediated toxicity. However, the literature in this field is crowded with conflicting reports from clinical trials as well as studies using animal and invitro models. With this review, we aim to provide a structured and updated overview of the physiological and pathophysiological evidence supporting the involvement of the classical RAAS in CnI‐associated toxicity.
aCCI‐HBV‐ACLF: A Novel Predictive Model for Hepatitis B Virus‐Related Acute‐On‐Chronic Liver Failure
Authors: Chen Xinyi , Gao Feiqiong , Pan Qiaoling , Huang Chenjie , Luo Rui , Lu Xiaoqing , Chen Xiaoxiao , Li Tan , Huang Haijun , Wu Jian , Yu Jiong , Li Lanjuan , Cao Hongcui
Published: October 2024

Background

Early identification of hepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF) holds crucial importance in guiding clinical management and reducing mortality. However, existing scoring systems often overlook patient's underlying clinical condition, which significantly impacts prognosis.

Aims

Use the age‐adjusted Charlson comorbidity index (aCCI) to evaluate the patient's complications to develop a more precise model for predicting transplant‐free mortality in HBV‐ACLF patients.

Methods

Nine hundred and six patients were included for investigation and were segregated into a training cohort and a temporal validation cohort according to the chronological order of admission in a ratio of 7:3. In the training cohort, univariate analysis, logistic regression analysis and LASSO regression analysis were used to construct a prognostic model and it was subsequently validated in a temporal validation cohort and an external validation cohort.

Results

We found total bilirubin, neutrophils, international normalised ratio and aCCI exhibited significant associations with 28‐day transplant‐free mortality and established a novel prognostic model, named aCCI‐HBV‐ACLF. The model demonstrated strong predictive performance, with area under the receiver operating characteristic curve (ROC) values of 0.859 for 28‐day mortality, 0.822 for 90‐day mortality. In the temporal validation cohort, aCCI‐HBV‐ACLF achieved area under the ROC values of 0.869 for 28‐day mortality and 0.850 for 90‐day mortality. In the external validation cohort, aCCI‐HBV‐ACLF had area under the ROC values of 0.868 for 28‐day mortality and 0.888 for 90‐day mortality.

Conclusions

This study proposes a new prognostic model, which achieved excellent predictive ability for 28−/90‐day transplant‐free mortality rates among patients with HBV‐ACLF.
Evidence of renal tubular injury in canine patients after elective desexing
Authors: Male Francesca G , Quinn Christopher T
Published: October 2024

Objective

To investigate the frequency of perioperative acute kidney injury (AKI) in American Society of Anesthesiologists (SA) Grade I canine patients undergoing elective desexing using urine microscopy techniques and assess if pre‐ and intraoperative factors affect risk of developing AKI.

Design

Prospective observational clinical study conducted between September 2020 and October 2020.

Setting

University teaching hospital.

Animals

Thirty‐two female and four male dogs between 5 months and 5 years of age classified as ASA I undergoing elective desexing surgery.

Methods

Urinalysis was performed preoperatively and 20–24 h postoperatively to identify markers of renal tubular injury (RTI), particularly the presence of granular and renal tubular epithelial cell (RTEC) casts on sediment analysis. Dogs underwent a full physical examination and a preoperative assessment including measurement of urine specific gravity (USG), packed cell volume (PCV), total plasma protein and serum creatinine (sCr) was conducted as a part of the desexing programme. Anaesthetic records were examined for any evidence of intraoperative hypotension, defined as a mean arterial pressure (MAP) of <60 mmHg for any duration of time. MAP was measured using an indirect oscillometric technique. For analysis, animals were subdivided into affected and nonaffected groups, with affected animals those that had postoperative increases in granular and RTEC casts. Categorical and comparative analyses were then performed between groups to identify associations of increased casts with pre‐, intra‐ and postoperative variables.

Results

A frequency of RTI of 5.6% was identified. This was accompanied by a significant association between increases in casts with total duration (p = 0.027) and number (p = 0.016) of hypotensive episodes.

Conclusions

RTI is an anaesthetic consideration in ASA I veterinary patients undergoing elective desexing surgery. The identification of an association between the total duration and number of hypotensive episodes and the frequency of RTI highlights the importance of early detection of hypotension along with prompt and effective intervention in veterinary patients.
Attrition in a large‐scale habituation task administered at home
Authors: Seitz Maximilian , Möwisch Dave , Attig Manja
Published: October 2024

Infant research often struggles with selective samples, especially when focusing on behavioural measures, such as those drawn from habituation tasks. However, selectivity may threaten the generalizability and interpretation of results, which is why the current study investigates attrition in a habituation task administered in a household setting in 7‐month‐old infants. We used a large‐scale German dataset, focusing on the children's socioeconomic background, and investigated two aspects of attrition, namely, participation and task completion. The findings suggest significant effects of the children's socioeconomic background on attrition: Maternal education, parental occupation, household income and household language (German vs. other) were positively related to participation and task completion. The analyses indicate that multiple barriers may prevent parents from lower socioeconomic backgrounds from letting their children participate. The study concludes with a critical discussion of possible mechanisms of selectivity in behavioural measures as well as the household setting, in which the data were collected.
Do help options facilitate computer‐based L2 listening comprehension? Evidence from an activity theory perspective
Authors: Li Rui
Published: October 2024

Despite the proliferation of help options for computer‐based second language (L2) listening comprehension, little attention has been given to a comprehensive understanding of the pedagogical effects. To gain a thorough understanding of the overall and moderator effects, drawing on the activity theory (AT), this study conducted a meta‐analysis of 33 valid independent studies on help options for computer‐based L2 listening comprehension with 3697 participants involved. Results demonstrated that (a) compared with those traditional methods, help options are found to be more facilitative for L2 listening comprehension with a small‐to‐moderate effect of g = 0.449, 95% CI [0.303, 0.596]; and (b) the effects of help options for computer‐based L2 listening comprehension are moderated by option types, feedback types, language distance types, intervention durations and learning activity types. Motivated by the results obtained, this study also discussed pedagogical implications for future studies.

Practitioner notes

What is already known about this topic

The improved pedagogical effects of help options for computer‐based second language (L2) listening comprehension have been well‐documented.

A large number of studies on the use of help options for computer‐based L2 listening comprehension have been published.

There has been no research aggregating the overall effects of help options for computer‐based L2 listening comprehension.

Some potential factors that may moderate the effects of help options for computer‐based L2 listening comprehension remain underexplored.

What this paper adds

This paper aims to aggregate the overall and moderator effects from the existing publications of help options for computer‐based L2 listening comprehension.

Compared with those traditional methods, help options are found to be more facilitative for L2 listening comprehension with a small‐to‐moderate effect of g = 0.449.

The effects of help options for computer‐based L2 listening are moderated by option types, feedback types, language distance types, intervention durations and learning activity types.

Implications for practice and/or policy

Help options have been confirmed to facilitate computer‐based L2 listening comprehension, especially among learners of primary and secondary levels.

Call for more empirical studies investigating how different types of options, feedback, language distance and intervention durations along with learning activity moderate the effectiveness.

Further attempts should investigate help options for computer‐based L2 listening comprehension with the integration of generative AI, large language model (LLM) and natural language processing (NLP) techniques.
Inter‐brain synchrony is associated with greater shared identity within naturalistic conversational pairs
Authors: Hinvest Neal S. , Ashwin Chris , Hijazy Muhammad , Carter Felix , Scarampi Chiara , Stothart George , Smith Laura G. E.
Published: October 2024

Inter‐brain synchrony occurs between individuals who feel connected socially, but how synchrony relates to felt connectedness under naturalistic social interaction has remained enigmatic. We hypothesized that inter‐brain synchrony between naturally interacting individuals might be associated with the internalization of a social identity, a link between an individual's personal identity and the social group to which the individual belongs. A convenience sample of sixty participants were split into dyads and interacted naturalistically on a social task. Through mapping EEG oscillatory waveforms onto a conceptual model categorizing the formation of a social identity within a naturalistic conversation, greater inter‐brain synchrony was observed in the emergent stage within the formation of a social identity compared to earlier stages, where a social identity was not present. We provide evidence for greater neural synchrony related to higher socio‐psychological connectedness during the development of social identity under naturalistic social interaction.
Insurance remains a major source of disparity for patients with testicular cancer: call for advocacy
Authors: Starr Savannah , Zhang Jj , Lin Lin , Shen Jolie , Gamalong Giovanni , Litwin Mark S. , Drakaki Alexandra , Chamie Karim
Published: October 2024

Objective

To evaluate the effects of socioeconomic factors, including insurance status, on treatment and survival for patients with testicular cancer.

Patients and Methods

We extracted a retrospective cohort from the National Cancer Database that included patients diagnosed with testicular cancer 2004–2020. Competing‐risks and Cox regression multivariate models including demographic, pathological, and socioeconomic covariates were constructed to evaluate receipt of treatment and death, respectively.

Results

A total of 95 955 patients with testicular cancer were identified. Compared with private insurance, Medicaid (sub‐distribution hazard ratio [SHR] 0.70, P < 0.001), Medicare (SHR 0.73, P < 0.001), and uninsured (SHR 0.72, P < 0.001) patients were associated with decreased likelihood of receiving chemotherapy. Compared with private insurance, Medicaid (SHR 0.55, P < 0.001), Medicare (SHR 0.76, P‐value <0.001), uninsured (SHR 0.63, P‐value < 0.001), and other government insurance (SHR 0.71, P = 0.010) was associated with decreased likelihood of receiving radiation. Medicaid insurance status (reference private, HR 2.60, P < 0.001) conferred the second largest hazard of death, behind having Stage III disease (reference Stage 0). Compared with private insurance, Medicare (HR 2.20, P < 0.001), no insurance (HR 2.32, P < 0.001), and other government insurance (HR 1.53, P = 0.027) statuses had higher risk of death. Patients diagnosed in Medicaid‐expansion states had lower all‐cause mortality (11.4% vs 13.6%, P < 0.001).

Conclusions

Testicular cancer care relies on early diagnosis and treatment. It is critically important to have a healthcare system where individuals have access to insurance and are served equitably.
Analysing the influence of digital strategy and innovation on MSMEs' performance in emerging countries
Authors: Díaz‐Pelaez Alejandro , Chura‐Quispe Gilber , Clemente‐Almendros José Antonio , Velarde‐Molina Jehovanni Fabricio
Published: October 2024

Drawing on the technology–organization–environment (TOE) framework, the diffusion of innovation (DOI) theory and the technology acceptance model (TAM), this research analyses how digital strategic orientation has a direct influence on the performance of micro, small and medium‐sized enterprises (MSMEs) in emerging markets and an indirect influence mediated by innovation. Using a representative sample of Peruvian MSMEs, we shed light on the sometimes inconclusive evidence on why small business struggle to benefit from digitalization, a particularly key issue in emerging economies. The structural equation model used shows that the impact of digitalization on firm performance is significant, as is the mediating effect of innovation. Our results imply that the total effect of digitalization on performance will be greater if the MSMEs develop innovative activities. Furthermore, we show that the performance effect requires not only digital technology but also the involvement of the entire organization.
The Dopamine Transporter Is a New Target for Ischemic Stroke
Authors: Cheng Yan‐Qiong , Zhang Ruo‐Xi , Li Xing‐Yuan , Zhou Xiao‐Ting , Chen Ming , Liu Ai‐Jun
Published: October 2024

Aims

Dopamine transporter (DAT) can regulate DA homeostasis and has been implicated in many nervous system diseases. Whether DAT is involved in the protection against ischemic stroke is unclear.

Methods

In vivo microdialysis measurements of DA were recorded in the ischemic penumbral area of mice with middle cerebral artery occlusion (MCAO). DAT coding gene, Slc6a3 mutation, and DAT overexpression animals were performed MCAO. Madopar (compound formulation of levodopa) and nomifensine (DA reuptake inhibitor) were administered in MCAO animals. Brain slices were prepared in Slc6a3 mutation or wild‐type (WT) animals with MCAO to record miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs). The effects of DA and its dopamine‐1 receptor (D1R) antagonists (SCH‐23390) on mEPSCs, mIPSCs, and neurons protection were recorded.

Results

MCAO caused a prominent increase in DA. Slc6a3 mutation significantly attenuated the ischemic injury, whereas DAT overexpression aggravated this injury. Both nomifensine and madopar protected against brain injury. Slc6a3 mutation and DA restored the disturbance of mEPSCs and mIPSC, and protected against neuron death, which was abolished by SCH‐23390.

Conclusion

DAT inhibition might be explored as a strategy for ischemic stroke prevention. DA and D1R involve in the restoration of synaptic dysfunction and neuron protection.
Neural Influences on Tumor Progression Within the Central Nervous System
Authors: Lv Wenhao , Wang Yongjie
Published: October 2024

For decades, researchers have studied how brain tumors, the immune system, and drugs interact. With the advances in cancer neuroscience, which centers on defining and therapeutically targeting nervous system‐cancer interactions, both within the local tumor microenvironment (TME) and on a systemic level, the subtle relationship between neurons and tumors in the central nervous system (CNS) has been deeply studied. Neurons, as the executors of brain functional activities, have been shown to significantly influence the emergence and development of brain tumors, including both primary and metastatic tumors. They engage with tumor cells via chemical or electrical synapses, directly regulating tumors or via intricate coupling networks, and also contribute to the TME through paracrine signaling, secreting proteins that exert regulatory effects. For instance, in a study involving a mouse model of glioblastoma, the authors observed a 42% increase in tumor volume when neuronal activity was stimulated, compared to controls (p < 0.01), indicating a direct correlation between neural activity and tumor growth. These thought‐provoking results offer promising new strategies for brain tumor therapies, highlighting the potential of neuronal modulation to curb tumor progression. Future strategies may focus on developing drugs to inhibit or neutralize proteins and other bioactive substances secreted by neurons, break synaptic connections and interactions between infiltrating cells and tumor cells, as well as disrupt electrical coupling within glioma cell networks. By harnessing the insights gained from this research, we aspire to usher in a new era of brain tumor therapies that are both more potent and precise.
Association of Intraoperative Hypotension With Delayed Graft Function Following Kidney Transplant: A Single Centre Retrospective Cohort Study
Authors: Sicova Marc , McGinn Ryan , Emerson Sophia , Perez Paula , Gonzalez Roberto , Li Yanhong , Famure Olusegum , Randall Ian , Mina Daniel Santa , Santema Michael , Wijeysundera Duminda N. , Van Klei Wilton , Kim S. Joseph , McCluskey Stuart A.
Published: October 2024

Background

Intraoperative hypotension is associated with acute kidney injury after surgery. However, the definition (duration and magnitude) of hypotension during kidney transplantation (KT) surgery on early graft function remains unclear.

Methods

We conducted a retrospective cohort study of KT recipients from December 1, 2009, to December 31, 2019. Exposure to intraoperative hypotension was characterized as the duration (minutes) of mean arterial pressure (MAP) <55, <65, <75, and <85 mmHg. Our co‐primary outcomes were DGF‐creatinine reduction ratio (DGF‐CRR, <30% creatinine reduction, postoperative days 1 and 2), and DGF‐dialysis (DGF‐D, required dialysis within the week of KT for deceased donor recipients). Logistic regression models were fitted to assess this relationship between MAP and DGF.

Results

We included 1602 KT (939 deceased donors, 663 living donors) and 23 were excluded. DGF‐CRR occurred in 33% of patients. DGF‐CRR was associated with MAP < 65 (>5 min: OR 1.77, 95% confidence interval [CI]: 1.39–2.30; 6–10 min: OR 1.67, 95% CI: 0.97–2.86; 11–20 min: OR 2.18, 95% CI: 1.31–3.63) in unadjusted and <55 mmHg (5 min: OR 1.85, 95% CI: 1.47–2.32; 5–10 min: OR 2.41, 95% CI: 1.65–3.53; 11–20 min: OR 2.36, 95% CI: 1.60, 3.48) in adjusted models. There was also a signal for increased risk of DGF‐CRR at MAP < 75 (>5 min: OR 1.69, 95% CI: 1.02–2.80). DGF‐D (incidence 35%) in deceased donor KT was not associated with hypotension.

Conclusions

We found an association between intraoperative hypotension and DGF‐CRR at a threshold MAP of 55 mmHg, with a consistent signal toward increased risk at both 65 and 75 mmHg, as indicated by unadjusted models.
Lack of oral involvement in a large cohort of women with vulvar lichen sclerosus – a multicenter prospective study
Authors: Corazza Monica , Salvini Camilla , Gaspari Valeria , Simonetti Oriana , Schettini Natale , de Magnis Angelina , Rapparini Luca , Rizzetto Giulio , Misciali Cosimo , Marzola Elisa , Borghi Alessandro
Published: October 2024

Background and Objectives: We assessed the prevalence of oral lichen sclerosus in a cohort of women affected with vulvar lichen sclerosus (VLS).

Patients and Methods: This prospective, observational study included adult female patients with a histologically proven VLS who attended the Vulva Clinics of three Dermatology Units from January 2020 to July 2023. During this period, all VLS patients were asked to be examined in their oral cavities in order to detect any possible sign of oral diseases, which were then biopsied.

Results: Three hundred women (mean age 64.5 ± 13.0 years) were included, of whom 21 (7%) had a concurrent extragenital LS. In six (2%) patients, white, non‐removable lesions were found at oral inspection and biopsied. All cases were histologically lichen planus. No other clinically relevant oral lesions were found. The six women with histologically proven oral lichen planus had more frequent periodontal and autoimmune diseases than the other included subjects.

Conclusions: Our findings confirm the absolute rarity of oral involvement in patients with VLS. They suggest that the oral mucosa, unlike the genitals, is a setting which weakly leads to development of LS, also in predisposed subjects.
Lessons from long‐term research: Diptera species turnover and dominance shifts with respect to climate‐driven changes
Authors: Radošević Marta , Perović Marija , Dorić Valentina , Pozojević Ivana , Baranov Viktor , Kvifte Gunnar Mikalsen , Kolcsár Levente‐Péter , Rumišek Mario , Pont Adrian C. , Ivković Marija
Published: October 2024

The diverse pressures of climate change have influenced many habitats, especially freshwater ones, due to their greater sensitivity to stressors. Aquatic Diptera make up more than 50% off all aquatic insect species described, which makes them an ideal group to monitor changing climate as their diverse assemblages can reflect functions within the entire community.

The aim of this research was to identify variations in the aquatic dipteran community during a 15‐year period at a tufa barrier in a karst barrage lake system and to determine the environmental factors that have the highest influence on this community. We analysed monthly data collected between 2007 and 2021, when we collected adult specimens using 6 pyramid‐type emergence traps.

In total, 167 taxa from 13 different families were gathered. NMDS based on Bray–Curtis similarity analysis amongst assemblages revealed the segregation of samples based on different current velocities and substrates, indicating the importance of microhabitats in dipteran community structuring.

Dipteran taxa indicative of specific 5‐year time periods within the research were identified and were associated with changes in environmental conditions especially discharge. The threshold indicator taxa analysis revealed specific species' responses to changing discharge rates.

The study shows that discharge rate, not water temperature, is the critical factor shaping dipteran composition, whether by removing or adding taxa to the community. Species turnover showed an overall decrease in species numbers, that is, species richness, throughout the research period.

We conclude that changes in the dipteran community, because of the vast functional traits, niches, adaptations and species diversity of the group, are not visible when analysing just the diversity indices. When determining environmental influence on the community in long‐term research, they should be combined with other data such as the overall abundance, the total number of species, as well as the species turnover.
Central nervous system crystal‐storing histiocytosis: A case report and literature review
Authors: Nathoo Nabeela , Larson Daniel P. , Guo Yong , Giannini Caterina , Lucchinetti Claudia F. , Micallef Ivana N. , Rech Karen L. , Jevremovic Dragan , Lachance Daniel H. , Abeykoon Jithma P. , Go Ronald S. , Tobin W. Oliver
Published: October 2024

Background

Crystal‐storing histiocytosis (CSH) is a rare form of histiocytosis with intralysosomal accumulations of immunoglobulins or paraproteins that aggregate as crystals. Central nervous system (CNS) involvement of CSH is uncommon but should be considered in cases of persistent parenchymal enhancement on neuroimaging.

Methods

We describe one local case of CNS CSH and 10 additional cases identified by literature review.

Results

Among 11 CSH patients, lesions involved either the dura (2/11) or brain parenchyma (9/11). Two cases had leptomeningeal enhancement. One case had spinal cord involvement. Two cases were associated with marginal zone lymphoma; one case was associated with an immunoglobulin A‐plasma cell dyscrasia. Eight of 11 cases had outcome data available: 7/8 cases had clinical and/or radiological improvement and 1/8 had radiological stability.

Conclusions

Central nervous system involvement of CSH is rare. Potential cases should be comprehensively evaluated for lymphoma or myeloma with positron emission tomography/computed tomography (CT) of the body or alternatively, CT of the chest, abdomen, pelvis and nuclear bone scan, bone marrow biopsy, serum protein electrophoresis, and cerebrospinal fluid protein electrophoresis. Treatment is targeted toward the underlying malignancy.
Long‐term safety and efficacy of adjunctive lacosamide in the treatment of generalized onset tonic–clonic seizures: An open‐label extension trial
Authors: Vossler David G. , Farkas Mark Kristof , Poverennova Irina , Watanabe Masako , Conrath Peter , Dimova Svetlana , McClung Carrie , Roebling Robert , Williams Paulette , O'Brien Terence J. ,   the EP0012 Study Group
Published: October 2024

Objective

This study was undertaken to assess long‐term safety, tolerability, and efficacy of lacosamide (LCM) as adjunctive therapy for generalized onset tonic–clonic seizures (GTCS) in patients aged ≥4 years with idiopathic generalized epilepsy (IGE).

Methods

EP0012 (NCT02408549) was a phase 3, multicenter, open‐label extension (OLE) trial. Patients were enrolled from SP0982 (NCT02408523). Trial duration was ≥2 years (adults) and ≤5 years (children). The trial consisted of a treatment period, ≤4‐week taper period, and 30‐day safety follow‐up. Safety (primary) variables were incidence of treatment‐emergent adverse events (TEAEs), discontinuations due to TEAEs, incidence of onset of absence or myoclonic seizures, and increase in days with absence or myoclonic seizures per 28 days. Efficacy (secondary) variable was percent change in GTCS frequency per 28 days. Kaplan–Meier estimated retention rates and analyses by number of lifetime antiseizure medications (ASMs) were performed post hoc.

Results

Overall, 239 patients (mean age = 27.9 years, 56.1% female, 18.4% children) were enrolled and received ≥1 dose of LCM in this OLE (median treatment duration = 3.2 years); 157 (65.7%) completed the trial, and 82 (34.3%) discontinued. The most common reason for discontinuation (≥10%) was withdrawn consent (30 [12.6%]). Kaplan–Meier estimated retention rate was 87%, 72%, and 60% at 1, 3, and 5 years, respectively. Overall, 222 (92.9%) patients reported TEAEs; 19 (7.9%) discontinued due to TEAEs. Few patients had an increase in number of days with absence or myoclonic seizures, or incidence of new absence or myoclonic seizures. Median percent change in GTCS frequency per 28 days from the combined baseline was −88.6% (range = −100.0 to 465.4, n = 238). Post hoc analyses demonstrated small numerical differences between patients with 1, 2, and ≥3 lifetime ASMs.

Significance

The results support the use of long‐term adjunctive LCM for GTCS in patients with IGE. Long‐term adjunctive LCM was efficacious and well tolerated independent of the number of ASMs used before LCM initiation.

Clinical trial registration: ClinicalTrials.gov: NCT02408549.
Mouse models of Slc35a2 brain mosaicism reveal mechanisms of mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy
Authors: Yoon Hyojung , Ringland Amanda , Anderson James J. , Sran Sahibjot , Elziny Soad , Huynh Cindy , Shinagawa Noriyuki , Badertscher Samantha , Corrigan Rachel R. , Mashburn‐Warren Lauren , Amari Foued , Chen Min , Coppola Vincenzo , Crino Peter B. , Bedrosian Tracy A.
Published: October 2024

Objective

Brain somatic variants in SLC35A2 were recently identified as a genetic marker for mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). The role of SLC35A2 in cortical development and the contributions of abnormal neurons and oligodendrocytes to seizure activity in MOGHE remain largely unexplored.

Methods

Here, we generated a novel Slc35a2 floxed allele, which we used to develop two Slc35a2 conditional knockout mouse lines targeting (1) the Emx1 dorsal telencephalic lineage (excitatory neurons and glia) and (2) the Olig2 lineage (oligodendrocytes). We examined brain structure, behavior, and seizure activity.

Results

Knockout of Slc35a2 from the Emx1 lineage, which targets both cortical neurons and oligodendrocytes, resulted in early lethality and caused abnormal cortical development, increased oligodendroglial cell density, early onset seizures, and developmental delays akin to what is observed in patients with MOGHE. By tracing neuronal development with 5‐Ethynyl‐2'‐deoxyuridine (EdU) birthdating experiments, we found that Slc35a2 deficiency disrupts corticogenesis by delaying radial migration of neurons from the subventricular zone. To discern the contributions of oligodendrocytes to these phenotypes, we knocked out Slc35a2 from the Olig2 lineage. This recapitulated the increased oligodendroglial cell density and resulted in abnormal electroencephalographic activity, but without a clear seizure phenotype, suggesting Slc35a2 deficiency in neurons is required for epileptogenesis.

Significance

This study presents two novel Slc35a2 conditional knockout mouse models and characterizes the effects on brain development, behavior, and epileptogenesis. Together, these results demonstrate a direct causal role for SLC35A2 in MOGHE‐like phenotypes, including a critical role in neuronal migration during brain development, and identify neurons as key contributors to SLC35A2‐related epileptogenesis.
Leveraging Unsupervised Task Adaptation and Semi‐Supervised Learning With Semantic‐Enriched Representations for Online Sexism Detection
Authors: Rodríguez‐Sánchez Francisco , Carrillo‐de‐Albornoz Jorge , Plaza Laura
Published: October 2024

Over the past decade, the proliferation of hateful and sexist content targeting women on social media has become a concerning issue, adversely affecting women's lives and freedom of expression. Previous efforts to detect online sexism have utilized monolingual ensemble transformers combined with data augmentation techniques that incorporate related‐domain data, such as hate speech. However, these approaches often struggle to capture the full diversity and complexity of sexism due to limitations in the size and quality of training data. In this study, we introduce a novel sexism detection system that employs in‐domain unlabeled data through unsupervised task‐adaptation techniques and semi‐supervised learning, using an efficient single multilingual transformer model. Additionally, we incorporate a Sentence‐BERT layer to enhance our system with semantically meaningful sentence embeddings. Our proposed system outperforms existing state‐of‐the‐art methods across all tasks and datasets, demonstrating its effectiveness in detecting and addressing sexism in social media text. These results underscore the potential of our approach, providing a foundation for further research and practical applications.
“You and me”: Parental perceptions on asymmetry in twins' development and their dominance relationship dynamics
Authors: Segal Hila , Rum Yonat , Barkan Adi , Knafo‐Noam Ariel
Published: October 2024

Objective

This study investigated the role of nontypical development in the relative dominance in twins' relationships throughout childhood.

Background

Dominance dynamics, affecting siblings' well‐being, are different in twins than in singletons for whom age and development often dictate sibling hierarchy. These dynamics in twins, who share similar ages and developmental contexts, remain underexplored and demand further understanding.

Method

A longitudinal study surveyed 1,547 mothers and 536 fathers of 322 monozygotic (sharing nearly 100% genes) and 1,199 dizygotic (sharing 50% genetic variance) twin pairs, aged 3 to 8–9. Both parents reported on the twins' relationships. Mothers reported whether either twin had a developmental condition.

Results

No dominance difference was found in similar developmental conditions dyads, whether both twins had typical or nontypical development. However, in dyads where twins differed in the developmental condition, nontypically developing twins were less dominant than their typically developing cotwins. This dominance imbalance persisted throughout childhood, even if initial developmental issues were resolved.

Conclusion

From parents' perspectives, nontypical development does not, in itself, prevent children from demonstrating dominance behaviors in twinship, but it is more likely that the asymmetry in developmental conditions is associated with the relationship between the twins.

Implications and Recommendations

According to parents' perceptions, twins with nontypical development might experience imbalances in their relationship throughout childhood when their co‐twin is a typically developing child. However, demonstrating dominance might be possible for them in other contexts. Understanding these dominance dynamics is vital for caregivers, informing tailored parenting strategies and interventions to support the well‐being of children.
Integration of plant and microbial oil processing at oilcane biorefineries for more sustainable biofuel production
Authors: Cortés‐Peña Yoel R. , Woodruff William , Banerjee Shivali , Li Yalin , Singh Vijay , Rao Christopher V. , Guest Jeremy S.
Published: October 2024

Oilcane—an oil‐accumulating crop engineered from sugarcane—and microbial oil have the potential to improve renewable oil production and help meet the expected demand for bioderived oleochemicals and fuels. To assess the potential synergies of processing both plant and microbial oils, the economic and environmental implications of integrating microbial oil production at oilcane and sugarcane biorefineries were characterized. Due to decreased crop yields that lead to higher simulated feedstock prices and lower biorefinery capacities, current oilcane prototypes result in higher costs and carbon intensities than microbial oil from sugarcane. To inform oilcane feedstock development, we calculated the required biomass yields (as a function of oil content) for oilcane to achieve financial parity with sugarcane. At 10 dw% oil, oilcane can sustain up to 30% less yield than sugarcane and still be more profitable in all simulated scenarios. Assuming continued improvements in microbial oil production from cane juice, achieving this target results in a minimum biodiesel selling price of 1.34 [0.90, 1.85] USD∙L−1 (presented as median [5th, 95th] percentiles), a carbon intensity of 0.51 [0.47, 0.55] kg CO2e L−1, and a total biodiesel yield of 2140 [1870, 2410] L ha−1 year−1. Compared to biofuel production from soybean, this outcome is equivalent to 3.0–3.9 as much biofuel per hectare of land and a 57%–63% reduction in carbon intensity. While only 20% of simulated scenarios fell within the market price range of biodiesel (0.45–1.11 USD∙L−1), if the oilcane biomass yield would improve to 25.6 DMT∙ha−1∙y−1 (an equivalent yield to sugarcane) 87% of evaluated scenarios would have a minimum biodiesel selling price within or below the market price range.
“Das Problem des Stilwandels”: Stylistic Transformation in the Work of Emil Staiger
Authors: Ronzheimer Elisa
Published: October 2024

This article reconstructs a theoretical and methodological problem in the work of German literary scholar Emil Staiger, a representative of the postwar school of Werkimmanenz, which called for a renewal of form‐sensitive practices of reading. It analyzes Staiger's notion of style and traces its application in his monumental Goethe monograph and his essay collection Stilwandel, highlighting the difficulties that arise from Staiger's attempt to operationalize style in the sense of an artwork's inner unity (“Einstimmigkeit”) for his study of dynamic and changing forms. These difficulties led him to reframe his notion of style in a 1968 paper that, however, ultimately left the problem of how to write a history of literary styles unresolved.
Factors associated with low hepatitis B surface antigen levels in chronic hepatitis B patients treated with nucleot(s)ide analogs
Authors: Suzuki Takanori , Matsuura Kentaro , Inoue Takako , Kawamura Hayato , Fujiwara Kei , Kataoka Hiromi , Tanaka Yasuhito
Published: October 2024

Objectives

Several studies have reported that chronic hepatitis B (CHB) patients with low hepatitis B surface antigen (HBsAg) levels (100 or 10 IU/mL) at the cessation of nucleot(s)ide analogs (NA) have a favorable prognosis. In this retrospective study, we evaluated the duration of NA treatment and the factors associated with achieving these low HBsAg levels. We also examined the relationship between HBsAg and hepatitis B core‐related antigen (HBcrAg) levels at the time of NA discontinuation and subsequent clinical outcomes.

Methods

This study included 153 CHB patients who initiated NA therapy at our hospital, received treatment, and were followed up for over 1 year.

Results

The cumulative incidence rates of achieving low HBsAg levels at 5 and 10 years post‐NA administration were as follows: 19.0% and 29.2% for HBsAg <100 IU/mL, 13.8% and 17.6% for HBsAg <10 IU/mL, and 9.5% and 13.5% for HBsAg <0.05 IU/mL, respectively. Hepatitis B virus genotypes other than genotype C (hazard ratio [HR] 3.47; p < 0.001) and an HBsAg level <1000 IU/mL at the start of NA therapy (HR 2.49; p = 0.008) were significantly associated with achieving HBsAg levels <100 IU/mL. Among 27 patients who discontinued NA therapy, 5 patients with HBsAg levels <100 IU/mL and HBcrAg levels <3 log U/mL at the time of discontinuation did not experience virological relapse.

Conclusions

The cumulative rates of achieving HBsAg levels <100 IU/mL were relatively high. Discontinuation of NA may be considered based on HBsAg and HBcrAg levels during the course of NA therapy.
Mechanical loading‐induced alveolar bone remodeling is suppressed in the diabetic state via the impairment of the specificity protein 1/vascular endothelial growth factor (SP1/VEGF) axis
Authors: Hoshino Rina , Nakamura Nobuhisa , Yamauchi Taisuke , Aoki Yuki , Miyabe Megumi , Sasajima Sachiko , Ozaki Reina , Sekiya Takeo , Sato Takuma , Tabuchi Masako , Miyazawa Ken , Naruse Keiko
Published: October 2024

Aims/Introduction

Orthodontic treatment involves alveolar bone remodeling in response to mechanical loading, resulting in tooth movement through traction‐side bone formation and compression‐side bone resorption. However, there are conflicting reports regarding alveolar bone resorption during the orthodontic treatment of patients with diabetes.

Materials and Methods

Diabetes was induced in 8‐week‐old C56BL/6J mice using streptozotocin (STZ). Four weeks after the injection of STZ, a mechanical load was applied between the first and second molars on the right side of the upper jaw using the Waldo method with orthodontic elastics in diabetic (DM) and normal (N) mice tooth movement, gene expression, osteoclast counts, alveolar bone residual volume, and bone beam structure were evaluated.

Results

The duration until spontaneous elastic loss was significantly longer in the DM group, suggesting that tooth movement may be inhibited in the diabetic state. The number of osteoclasts at 7 days after mechanical loading and the alveolar bone resorption were both significantly lower in the DM group. The gene expression levels of vascular endothelial growth factor (VEGF), a protein related to alveolar bone remodeling, and specificity protein 1 (SP1), a transcription factor of the VEGF gene, were significantly lower in the DM group than in the N group on the compression side of mechanical loading.

Conclusions

Mechanical loading‐induced alveolar bone remodeling is suppressed in the diabetic state. Our results suggest that VEGF is a key molecule involved in impaired bone remodeling under mechanical loading in the diabetic state.