bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical characteristics and outcomes of patients with chondroblastoma undergoing surgery with various adjuvant procedures: a retrospective study of 59 cases
Authors: Hirozane Toru , Sekita Tetsuya , Kobayashi Eisuke , Mori Tomoaki , Asano Naofumi , Udaka Toru , Tajima Takashi , Nakagawa Rumi , Kikuta Kazutaka , Yoshiyama Akira , Morioka Hideo , Watanabe Itsuo , Anazawa Ukei , Susa Michiro , Horiuchi Keisuke , Suzuki Yoshihisa , Morii Takeshi , Nakayama Robert
Published: January 2025

Background

Chondroblastoma is classified as a benign bone tumor. However, postoperative local recurrence remains a concern. We analyzed the factors contributing to chondroblastoma local recurrence and the clinical challenges associated with treating these patients.

Methods

This retrospective study examined 59 patients followed up at our hospitals for ≥ 1 year after surgery during 1990–2020. The most common lesion site was the epiphyses of long bones (42 cases, 71%), including the femur, tibia, and humerus. Curettage was performed in 57 cases; 2 cases with an iliac lesion underwent resection. The median postoperative follow-up period was 47 months. Clinical features of chondroblastoma were retrospectively investigated, and local recurrence and postoperative functional outcomes were assessed.

Results

Local recurrence occurred in 9% (5/57) of patients after curettage but not in the resected cases. The median time to local recurrence was 14 months. The local recurrence-free survival (LRFS) rate for all patients was 92.7% at 2 years and 88.3% at 5 years. All patients with local recurrence were aged < 17 years at the time of surgery. Local recurrence was observed in the proximal humerus in two cases and the calcaneus, acetabulum, and distal femur in one case each. None of the adjuvant procedures (high-speed burr, ablation, bone replacement materials, and preoperative denosumab) helped reduce local recurrence risk (P > 0.05). Trends toward fewer local recurrences were observed in the group treated using the high-speed burr and in the group not treated using bone replacement materials. Among the groups treated with bone replacement materials, artificial bone achieved the best LRFS rate, followed by allograft and autograft. At the final follow-up, the mean Musculoskeletal Tumor Society score was 29.8 (range: 25–30), indicating excellent postoperative functional outcomes. Joint degeneration was observed in five patients. Patients with local recurrence had a high degree of disability and joint deformity (P < 0.05). Two patients received preoperative denosumab and neither experienced local recurrence nor functional impairments.

Conclusions

Good oncological and functional outcomes were achieved. Age < 17 years was associated with a high risk of local recurrence after curettage (P = 0.0198). Patients with local recurrence exhibited poorer functional outcomes. High-speed burr may help reduce the recurrence risk. If bone grafts are necessary, materials with low biocompatibility, including artificial bone, may be optimal. Managing patients with chondroblastoma should encompass curative and functional aspects.
Health economics assessment of statin therapy initiation thresholds for atherosclerosis prevention in China: a cost-effectiveness analysis
Authors: Feng Tianyu , Zhang Xiaolin , Xu Jiaying , Gao Shang , Yu Xihe
Published: January 2025

Background

Recent updates to the Chinese guidelines for dyslipidemia management have reduced the 10-year risk threshold for starting statins in the primary prevention of atherosclerotic heart disease. This study aims to evaluate the potential negative effects of different statin initiation thresholds on diabetes risk in the Chinese population, while also analyzing their health economic implications.

Methods

I We developed a microsimulation model based on event probabilities to assess the cost-effectiveness of statin therapy. The model utilized the China-PAR prediction tool for ASCVD risk and incorporated data from a nationally representative survey and published meta-analyses of middle-aged and elderly Chinese populations. Four strategies were evaluated: a 7.5% 10-year risk threshold, the current guideline strategy, and a 15% threshold. For each strategy, we calculated the incremental cost per quality-adjusted life year (QALY) to gain insights into the economic impact of each approach.

Result

The incremental cost per QALY for the 10% 10-year risk threshold strategy, compared to the untreated, was $52,218.75. The incremental cost per QALY for the guideline strategy, compared to the 7.5% 10-year risk threshold strategy, was $464,614.36. These results were robust in most sensitivity analyses.

Conclusion

Maintaining the recommended thresholds outlined in the current guidelines for the management of dyslipidemia may represent a cost-effective option for China at present. Variations in statin prices and the risk of statin-induced diabetes have significant impacts on the cost-effectiveness outcomes.
Performance analysis of Leica Biosystems p16 monoclonal antibody in oropharyngeal squamous cell carcinoma
Authors: Thavaraj Selvam , Robinson Max , Dayal Shubham , Bowen Claire
Published: January 2025

Background

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer death globally, with newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) cases rising to 54,000 in the US alone in the year 2022. Recently, human papilloma virus (HPV) infection was more prevalent in OPSCC patients than the traditionally known carcinogens such as tobacco or alcohol. HPV 16 is the most common causative HPV strain, which is found in 5–10% of HNSCC patients. HPV 16’s E6 and E7 oncoproteins bind and inactivate p53 and retinoblastoma (Rb) tumor-suppressing genes. This causes aberrant over-expression of the cell cycle inhibitor gene, p16, leading to tumorigenesis. Leica Biosystems (LBS) has developed a p16 antibody (6H12 clone) for qualitatively identifying the p16 protein in formalin-fixed paraffin-embedded (FFPE) tissue by immunohistochemical staining. This method comparison study tested the concordance rates between ready-to-use (RTU) LBS p16/LBS RTU p16 antibody and Roche Tissue Diagnostics (RTD) CINtec p16 Histology immunohistochemical (IHC) assays by measuring overall agreement (OA), average positive agreement (APA), and average negative agreement (ANA) rates in 170 OPSCC FFPE cases. Interobserver agreement of the 2 assays and LBS RTU p16 comparison with the standard HPV molecular assays (DNA ISH and PCR) were also assessed.

Methods

One hundred and seventy (170) unique oropharyngeal cancer cases were stained for qualitative analysis by the LBS p16 antibody on BOND III. This assay was compared to Ventana’s RTD E6H4 (CINtec) clone on Benchmark XT. A stained core was considered p16 positive if the Histoscore (H score) was ≥ 140 and negative if H < 140.

Results

Across the pathologists, the agreement rate between the 2 assays ranged from OA, 98.7 – 98.8%, ANA, 98.8 -98.9%, and APA, 98.6%. For LBS RTU p16, the interobserver agreement was OA, 98.7%, ANA, 98.8%, and APA, 98.6%; while for RTD CINtec p16 assay, the concordance was OA, 98.7%, ANA, 98.8% and APA, 98.6%. In comparison to the HPV molecular testing, DNA ISH, and PCR, across pathologists, LBS p16 clone (LBS RTU p16) showed a concordance rate of 85.8-86.9% and 87.6-88.8%, respectively.

Conclusion

LBS p16 monoclonal antibody demonstrated high concordance with CINtec p16 IHC assay across all the endpoints, suggesting a potential use of LBS RTU p16 clone in detecting p16 protein in oropharyngeal cancer cases.
Surgery impairs glymphatic activity and cognitive function in aged mice
Authors: Chen Kai , Du Xingyu , Chao Melissa A. , Xie Zhongcong , Yang Guang
Published: January 2025

Delirium is a common complication in elderly surgical patients and is associated with an increased risk of dementia. Although advanced age is a major risk factor, the mechanisms underlying postoperative delirium remain poorly understood. The glymphatic system, a brain-wide network of perivascular pathways, facilitates cerebrospinal fluid (CSF) flow and supports the clearance of metabolic waste. Impairments in glymphatic function have been observed in aging brains and various neurodegenerative conditions. Using in vivo two-photon imaging, we examined the effects of surgery (laparotomy) on glymphatic function in adult (6 months) and aged (18 months) mice 24 h post-surgery. In adult mice, CSF tracer entry into the brain parenchyma along periarteriolar spaces occurred rapidly following intracisternal tracer injection, with no significant differences between sham and surgery groups. In contrast, aged mice exhibited delayed tracer influx, with further impairments observed in the surgery group compared to sham controls. This glymphatic dysfunction correlated with poorer T-maze performance in aged mice. These findings suggest that surgery exacerbates glymphatic impairment in aging brains, potentially hindering brain waste clearance and contributing to postoperative delirium.
GPR137-RAB8A activation promotes ovarian cancer development via the Hedgehog pathway
Authors: Tang Chao , Li Lin , Zhu Chongying , Xu Qiang , An Zihao , Xu Shouying , Lin Chao
Published: January 2025

Background

Ovarian cancer (OC) progression is one of the commonest cause of female cancer death. While treatments in clinic includes primary surgery and targeted chemotherapy, curative and survival trends in OC have not significantly improved. Thus, further investigation of the mechanisms regarding OC carcinogenesis and discovery of novel targets is of great importance.

Methods

Human ovarian tissue specimens, RNA sequencing, GEPIA database and bioinformatics analyses were used to analyze the gene correlation, and to identify and validate potential downstream candidates. The biological effects of GPR137-RAB8A-Hedgehog(HH) were investigated using in vitro and in vivo models and methods including qRT-PCR, RNA stability assay, RNA immunoprecipitation assay, GLI-luciferase reporter assay, nucleo-cytoplasmic separation assay, membrane-cytoplasmic separation assay, western blot, co-immunoprecipitation, immunofluorescence staining, cell counting kit-8 assay, wound healing assay, matrigel invasion assay, colony formation assay, xenografts assay, in situ transplantation tumor model of ovarian cancer in nude mice, and immunohistochemistry staining.

Results

GPR137 expression was significantly higher in collected clinical OC tissues, compared with the adjacent normal tissues. Consistently, suppression of GPR137 inhibited human SK-OV-3 and A2780 OC cell proliferation, migration, invasion, and colony formation, whereas overexpression of GPR137 in human OC HO8910 cell exerted the opposite effects on cell biological behaviors. Mechanistically, RAB8A was identified as a downstream target of GPR137, and GPR137 promotes RAB8A expression by promoting RAB8A mRNA stability. By RNA-sequencing and experiments in vitro using multiple ovarian cancer cell models as well as in vivo using subcutaneous xenografts assay and in situ transplantation ovarian cancer model in nude mice, we further demonstrated that RAB8A positively mediated OC progression through activating HH signaling pathway by disassociating the protein–protein complex formation of GLI and SuFu (Suppressor of Fused), which reciprocally enhanced GPR137 activity, forming a regulation loop between HH signaling and GPR137.

Conclusions

Collectively, this study depicts the role of GPR137-RAB8A-HH cascade in the development of OC, deepening our understanding of tumor biomechanics regarding OC progression and providing novel targets for OC therapy in future.
Prediction of pathological complete response after neoadjuvant chemotherapy for HER2-negative breast cancer patients with routine immunohistochemical markers
Authors: Häberle Lothar , Erber Ramona , Gass Paul , Hein Alexander , Niklos Melitta , Volz Bernhard , Hack Carolin C. , Schulz-Wendtland Rüdiger , Huebner Hanna , Goossens Chloë , Christgen Matthias , Dörk Thilo , Park-Simon Tjoung-Won , Schneeweiss Andreas , Untch Michael , Nekljudova Valentina , Loibl Sibylle , Hartmann Arndt , Beckmann Matthias W. , Fasching Peter A.
Published: January 2025

Background

Pathological complete response (pCR) is an established surrogate marker for prognosis in patients with breast cancer (BC) after neoadjuvant chemotherapy. Individualized pCR prediction based on clinical information available at biopsy, particularly immunohistochemical (IHC) markers, may help identify patients who could benefit from preoperative chemotherapy.

Methods

Data from patients with HER2-negative BC who underwent neoadjuvant chemotherapy from 2002 to 2020 (n = 1166) were used to develop multivariable prediction models to estimate the probability of pCR (pCR-prob). The most precise model identified using cross-validation was implemented in an online calculator and a nomogram. Associations among pCR-prob, prognostic IHC3 distant recurrence and disease-free survival were studied using Cox regression and Kaplan–Meier analyses. The model’s utility was further evaluated in independent external validation cohorts.

Results

273 patients (23.4%) achieved a pCR. The most precise model had across-validated area under the curve (AUC) of 0.84, sensitivity of 0.82, and specificity of 0.71. External validation yielded AUCs between 0.75 (95% CI, 0.70–0.81) and 0.83 (95% CI, 0.78–0.87). The higher the pCR-prob, the greater the prognostic impact of pCR status (presence/absence): hazard ratios decreased from 0.55 (95% central range, 0.07–1.77) at 0% to 0.20 (0.11–0.31) at 50% pCR-prob. Combining pCR-prob and IHC3 score further improved the precision of disease-free survival prognosis.

Conclusions

A pCR prediction model for neoadjuvant therapy decision-making was established. Combining pCR and recurrence prediction allows identification of not only patients who benefit most from neoadjuvant chemotherapy, but also patients with a very unfavorable prognosis for whom alternative treatment strategies should be considered.
Prevalence and drivers of malaria infection among asymptomatic and symptomatic community members in five regions with varying transmission intensity in mainland Tanzania
Authors: Chacha Gervas A. , Francis Filbert , Mandai Salehe S. , Seth Misago D. , Madebe Rashid A. , Challe Daniel P. , Petro Daniel A. , Pereus Dativa , Moshi Ramadhani , Budodo Rule , Kisambale Angelina J. , Mbwambo Ruth B. , Bakari Catherine , Aaron Sijenunu , Mbwambo Daniel , Kajange Stella , Lazaro Samuel , Kapologwe Ntuli , Mandara Celine I. , Ishengoma Deus S.
Published: January 2025

Background

Despite implementation of effective interventions in the past two decades, malaria is still a major public health problem in Tanzania. This study assessed the prevalence and drivers of malaria infections among symptomatic and asymptomatic members of selected communities from five regions with varying endemicity in mainland Tanzania.

Methods

A cross-sectional community survey was conducted in five districts, including one district/region in Kagera, Kigoma, Njombe, Ruvuma and Tanga from July to August 2023. Participants aged ≥ 6 months were recruited and tested using rapid diagnostic tests (RDTs). Demographic, anthropometric, clinical, parasitological, type of house, and socio-economic status (SES) data were captured using structured questionnaires. Associations between parasite prevalence and potential drivers were determined by logistic regression, and the results were presented as crude (cOR) and adjusted odds ratios (aOR), with 95% confidence intervals (CIs).

Results

Among 10,228 individuals tested, 3515 (34.4%) had positive results by RDTs. The prevalence of malaria varied from 21.6% in Tanga to 44.4% in Kagera, and from 14.4% to 68.5% among the different villages (P < 0.001). The odds of malaria infections were higher in males (aOR = 1.32, 95% CI 1.19–1.48, P < 0.001), under-fives (aOR = 2.02, 95% CI 1.74–2.40, P < 0.001), schoolchildren [aged 5–9 years (aOR = 3.23, 95% CI 1.19–1.48, P < 0.001) and 10–14 years (aOR = 3.53, 95% CI 3.03–4.11, P < 0.001)], and non-bednet users (aOR = 1.49, 95% CI 1.29–1.72, P < 0.001). Individuals from households with low SES (aOR = 1.40, 95% CI 1.16–1.69, P < 0.001), or living in houses with open windows (aOR = 1.24, 95% CI 1.06–1.45, P < 0.001) and/or holes on the walls (aOR = 1.43, 95% CI 1.14–1.81, P < 0.001) also had higher odds.

Conclusions

Malaria prevalence varied widely across regions and villages, and the odds of infections were higher in males, schoolchildren, non-bednet users, and individuals with low SES or living in houses with open windows and/or holes on the walls. The identified vulnerable groups and hotspots should be targeted with specific interventions to reduce the disease burden and support the ongoing malaria elimination efforts in Tanzania.

Graphical Abstract
Stability of a delayed prey–predator model with fear, stochastic effects and Beddington–DeAngelis functional response
Authors: Zhao Jinxing , Shao Yuanfu
Published: January 2025

In view of the importance of predator-dependent functional response and fear of prey induced by powerful predators, we construct a delayed prey–predator model with fear and Beddington–DeAngelis functional response. The existence, uniqueness, and global asymptotic stability of equilibrium points are investigated and some criteria are established. Next, Hopf bifurcation analysis is executed, and the critical values of such bifurcation parameters as fear and delay for the determinate system are obtained. Then we extend it to a random environment and study the boundedness of expectation of solutions and the global asymptotic stability. Finally, the main findings are validated by numerical examples. It is worth noting that the specific influences of fear by predator, time delay, and white noise are explored numerically. Simulation figures intuitively exhibit that fear, delay, and white noise bring serious influences on the stability of the system. Fear from predator leads to a lower equilibrium state of prey and predator, and it can change the system stability from unstable to stable after exceeding a certain critical value. The time delay has a significant impact on the system stability by producing Hopf bifurcations accompanied by limit cycles, and even lead to multiple stabilities. Larger white noise can change the system stability from stable to unstable.
Up-flow anaerobic sludge blanket bioreactor for the production of carboxylates: effect of inocula on process performance and microbial communities
Authors: Lago Adrián , Greses Silvia , Moreno Inés , González-Fernández Cristina
Published: January 2025

This research investigated the acidogenic fermentation (AF) of sugar cane molasses in an up-flow anaerobic sludge blanket (UASB) reactor for the production of carboxylates. The first step was to assess the optimum process temperature (25, 35 or 55 ºC) using two different granular inocula, one from a brewery company (BGS) and other from a paper plant company (PGS). These experiments determined that the most suitable temperature for carboxylates production was 25 ºC, obtaining higher bioconversions (27.3 ± 0.3% using PGS and 39.2 ± 0.2% using BGS), despite the low pH value recorded (4.0-4.2). Then, both inocula were tested in UASB reactors. As a consequence of the operational conditions (25 ºC, pH = 5.5-6, organic loading rate (OLR) = 3 gCOD·L-1·d-1 and hydraulic retention time (HRT) = 10 d), the microbial communities changed from those typical for biogas production to those specialised in the production of volatile fatty acids (VFAs). Indeed, the highest bioconversion efficiency (70.1%) was obtained with BGS, where uncultured Eubacteriaceae family microorganisms (56.0%) prevailed, enhancing the production of butyric acid (59.5 ± 2.4%w/w). Consequently, this inoculum was used to further identify the OLR threshold that should not be exceeded to attain optimal carboxylates production. OLR of 6 gCOD·L-1·d-1 resulted in a decrease in bioconversion efficiency (59.5%). The VFAs pool was dominated by butyric acid (63.0 ± 1.4%w/w at an OLR of 4.5 gCOD·L-1·d-1 and 52.8 ± 2.2%w/w at 6 gCOD·L-1·d-1). The microbial community became even more specialised, increasing the presence of Firmicutes and Actinobacteriota phyla, proving that the imposed conditions favoured the production of VFAs when operating semicontinuously fed UASB reactors.
An animal model of severe acute respiratory distress syndrome for translational research
Authors: Chu Kuo-An , Lai Chia-Yu , Chen Yu-Hui , Kuo Fu-Hsien , Chen I.-Yuan , Jiang You-Cheng , Liu Ya-Ling , Ko Tsui-Ling , Fu Yu-Show
Published: January 2025

Background

Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine. Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of transplanted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.

Results

In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within seven days after the injury, we found that arterial blood oxygen saturation (SpO2) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2) amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A histological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.

Conclusions

This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
Extracorporeal membrane therapy in a case of ruptured abscess on the mitroaortic intervalvular fibrosa associated to multisystem inflammatory syndrome: a case report
Authors: Montaña-Jimenez Lina P. , Aristizabal Ana M. , Guzmán-Serrano Carlos A. , Reyes Cesar Cely , Vélez Moreno Juan Fernando , Castillo Gastón
Published: January 2025

Background

The mitroaortic intervalvular fibrosa is an avascular structure near the left ventricular outflow tract, between the mitral and aortic valves. Mitroaortic intervalvular fibrosa complications, such as tamponade, hemopericardium, and abscesses, are rare and often diagnosed postmortem. On the other hand, the COVID-19 pandemic notably impacted pediatric patients with congenital heart diseases, who frequently presented cardiac complications including arrhythmias, elevated troponins, myocarditis, and heart failure. However, the rupture of the mitroaortic intervalvular fibrosa kept being unusual, making this case a rare presentation of a COVID-19 complication. The objective of this text is to present an infrequent presentation of COVDI-19 complications, and the approach given at our institution which proved to be effective, and further supports the positive findings described in the literature regarding the utility of extracorporeal hemofiltration membranes.

Case presentation

A case of 15-year-old female, without any prior risk factors or cardiac comorbilities, who developed acute myocarditis, linked to COVID-19 Multisystem Inflammatory Syndrome is presented. She deteriorated despite adequate treatment, presenting mitroaortic intervalvular fibrosa rupture, leading to urgent surgical repair and requiring extracorporeal membrane hemofiltration for cytokine removal, therapeutic approach that proved to be effective. Postoperatively, she received intensive care and antibiotics, showing significant cardiac improvement. Noteworthy, hemofiltration was crucial in managing the cytokine storm, contributing to her recovery and subsequent discharge for continued medical management.

Conclusion

An abscess of the mitroaortic intervalvular fibrosa, though rare, represents a significant challenge to clinicians to diagnose. In patients with a history of COVID-19, especially when multisystem inflammatory syndrome is suspected, thorough evaluation is warranted to rule out cardiovascular complications, even in the absence of pre-existing cardiac conditions. This case contributes to our evolving understanding of the cardiovascular implications of COVID-19 and underscores the potential utility of various approaches, including the use of filtration membrane technologies.
Effective management of nonconvulsive status epilepticus following cardiac surgery: a case report
Authors: Yanagino Yusuke , Yamasumi Taro , Miyauchi Takayuki , Inoue Koichi , Kondoh Haruhiko
Published: January 2025

Background

Epileptic seizures following adult cardiovascular surgery occur in 0.9–3% of patients, with the condition in 3–12% of these patients progressing to status epilepticus (SE). SE is a severe condition that significantly impacts prognosis and necessitates early diagnosis and treatment. However, the diagnosis of nonconvulsive status epilepticus (NCSE) is challenging due to its subtle clinical symptoms. Herein, we report a case of NCSE that was diagnosed early by aggressive electroencephalogram (EEG) and treated effectively following cardiac surgery, resulting in discharge without sequelae.

Case presentation

A 44-year-old man with a history of meningitis-induced intellectual disability since childhood underwent aortic valve replacement and grafting of the ascending aorta for a bicuspid aortic valve, severe aortic regurgitation, and ascending aortic dilatation. We observed repeated tonic–clonic seizures on the day of surgery and the following day when the sedation was reduced. On the first postoperative day, an EEG revealed sharp, high-amplitude waves during the tonic–clonic seizure and 2-Hz rhythmic delta activity after motor symptoms disappeared. Based on these findings, the patient was diagnosed with NCSE. Under EEG monitoring, we initially used propofol at 4 mg/kg/h, but owing to a decrease in blood pressure, we achieved deep sedation and burst suppression by combining propofol at 1.5 mg/kg/h with midazolam at 0.18 mg/kg/h. We also administered levetiracetam and fosphenytoin as antiseizure medications. Levetiracetam was administered at 1000 mg/day and fosphenytoin at 20.5 mg/kg, followed by maintenance at 7.2 mg/kg/day. The patient’s consciousness improved upon cessation of sedation on postoperative day 6. Postoperative magnetic resonance imaging revealed no abnormalities. Fosphenytoin was discontinued, and the patient was discharged on postoperative day 32 without any sequelae. The patient continues to take levetiracetam orally at a dose of 1000 mg/day and has been followed up in the outpatient clinic for 4 years without any seizure recurrence.

Conclusion

Postoperative seizures following cardiac surgery may occur with NCSE, even after visible seizures have ceased. This case highlights the importance of thorough EEG monitoring in cases of prolonged disturbance of consciousness, indicating that early diagnosis and treatment of NCSE can improve the prognosis.
A Story Where Something Turns Out All Right: Remembering Utopia in Mohsin Hamid's Exit West
Authors: Wegner Phillip E.
Published: January 2025

In the current interregnum, there has, not surprisingly, been a great deal of interest in the literary dystopia. However, far less attention has been directed to the dystopia's precursor, the practice Tom Moylan identifies as the critical utopia. The author argues that we see a brilliant realization of the form in Mohsin Hamid's Exit West (2017). Exit West exemplifies Fredric Jameson's generic discontinuity, moving as it does from a realist mode through a science fictional dystopia and the fantastic, arriving finally at the critical utopia. The last transition occurs through the narration of an unexpected event—one in which nothing is happening. The world that emerges is one where new possibilities appear in what Alain Badiou identifies as the conditions of science, art, politics, and “minimal communism,” or love. Such a world—“not a heaven but not a hell”—is one wherein not knowing what is to come allows an authentic future again to become possible. This is in stark contrast to the ideologies of capitalist realism, which teach us that there are no alternatives, that the current interregnum is permanent, and that there is no future that is not a repetition of the past.
Crumpling the Timeline
Authors: Brandolino Gina , Fitzgibbons Moira
Published: January 2025

This introduction defines crumpling the timeline as a classroom practice in which instructors and students explore medieval texts alongside twentieth- and twenty-first-century works. In this special issue, some contributors describe teaching strategies that pair premodern literature with overtly “medievalist” contemporary works. Other contributors engage students in analyzing themes, questions, and rhetorical strategies found both in medieval texts and in more recent works that do not explicitly invoke the Middle Ages. Developments within medieval studies as a field necessitate new ways of conceptualizing the relationship between the present and the past. Often surprised by the common ground between medieval preoccupations and our own, students embrace the opportunity to incorporate their own cultural expertise into classroom conversations.
Crumpling the Timeline, Online
Authors: Morreale Laura
Published: January 2025

Although the collected essays in this special issue were not expressly intended to address the impact of the digital environment on current pedagogies, all the contributions demonstrate in one way or another how computer-based communication modifies the work of teachers and students. Using the key concepts of hybridity, spatiality, connectivity, and user response, this essay describes how the internet, as the dominant twenty-first-century medium for knowledge exchange, has become the filter through which medieval ideas are presented and received. Hybridity refers to a teaching approach that combines face-to-face with virtual, computer-mediated (and often asynchronous) methods, whereas an awareness of spatiality emerges from the advanced geo-location tools now used unthinkingly. Connectivity allows for the creation of virtual communities and communications among their members, while user response refers to the many ways that the digital world supports and even encourages input about computer-based ideas. Since the medieval and digital eras share many characteristics not found in cultures of print communication, making such connections, and thereby crumpling the timeline, can often be automatic and perhaps even unintentional for instructors. The methods described in all the contributions demonstrate the validity of medieval themes for the modern world, which in turn can be effective tools to reach learners beyond traditional academic settings.
Two cGMP-dependent protein kinases have opposing effects on molt-inhibiting hormone regulation of Y-organ ecdysteroidogenesis
Authors: Head Talia B. , Pérez-Moreno Jorge L. , Ventura Tomer , Durica David S. , Mykles Donald L.
Published: January 2025

Decapod crustaceans regulate molting through steroid molting hormones, ecdysteroids, synthesized by the molting gland (Y-organ, YO). Molt-inhibiting hormone (MIH), a neuropeptide synthesized and secreted by the eyestalk ganglia, negatively regulates YO ecdysteroidogenesis. MIH signaling is mediated by cyclic nucleotide second messengers. cGMP-dependent protein kinase (PKG) is the presumed effector of MIH signaling by inhibiting mechanistic Target of Rapamycin Complex 1 (mTORC1)-dependent ecdysteroidogenesis. Phylogenetic analysis of PKG contiguous sequences in CrusTome as well as 35 additional species in NCBI RefSeq, identified 206 PKG1 sequences in 108 species and 59 PKG2 sequences in 53 species. These included four PKG1α splice variants in the N-terminal region that were unique to decapods, as well as PKG1β and PKG2 homologs. In vitro assays using YOs from the blackback land crab (Gecarcinus lateralis) and green shore crab (Carcinus maenas) determined the effects of MIH±PKG inhibitors on ecdysteroid secretion. A general PKG inhibitor, Rp-8-Br-PET-cGMPS, countered the effects of MIH, as ecdysteroid secretion increased in PKG-inhibited YOs compared to C. maenas YOs incubated with MIH alone. By contrast, a PKG2-specific inhibitor, AP-C5 (4-[4-(1H-Imidazol-1-yl)phenyl]-N-2-propyn-1-yl-2-pyrimidinamine), enhanced the effects of MIH, as ecdysteroid secretion decreased in G. lateralis and C. maenas YOs incubated with AP-C5 and MIH compared to YOs incubated with MIH alone. These data suggest that both PKG1 and PKG2 are activated by MIH, but have opposing effects on mTORC1-dependent ecdysteroidogenesis. A model is proposed in which the dominant role of PKG1 is countered by PKG2, resulting in low ecdysteroid production by the basal YO during intermolt.
Contraception Chronicles: The Gamified Approach to Postgraduate Education in Family Medicine
Authors: Syeda Ariba Hashmi  , Marzia Muhammad Hanif  , Ayesha Khan
Published: January 2025

Gamification involves using gaming elements in education to capture learners’ attention and motivate participation, offering innovative solutions to traditional teaching challenges. In various fields gamification enhances learning by fostering competition, collaboration and peer learning. In the realm of medical education, innovation is key to foster knowledge acquisition, critical thinking and skill development. Family physicians, dealing with comprehensive care, emphasize preventive measures like family planning and contraception. Effective contraceptive education is crucial not only for providing patient-centered reproductive healthcare but also to address the unique needs and preferences of a diverse patient population.
To make learning more engaging we incorporated the board game “Snakes and Ladders” into a didactic session for family medicine trainees. Divided into teams, they solved case-based questions linked to game progression. Feedback indicated the session was more engaging and enjoyable compared to traditional lectures and they wish to see similar teaching methods in future academic sessions. doi: https://doi.org/10.12669/pjms.41.2.10239How to cite this: Hashmi SA, Hanif MM, Khan A. Contraception Chronicles: The Gamified Approach to Postgraduate Education in Family Medicin. Pak J Med Sci. 2025;41(2):637-639.   doi: https://doi.org/10.12669/pjms.41.2.10239This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Predictive value of prenatal screening markers combined with serum placental growth factor in early pregnancy for preeclampsia
Authors: Shu Zitan , Wang Weiwei
Published: January 2025

Objective: To observe the predictive value of prenatal screening markers combined with serum placental growth factor(PLGF) in early pregnancy for preeclampsia(PE).
Methods: This was a prospective study. A total of 369 pregnant women undergoing early pregnancy examinations were selected at Jingmen Central Hospital from August 2024 to January 2025 and divided into the PE group(n=43) and the normal group(n=326) according to the presence of PE during the follow-up. The levels of prenatal screening markers alpha-fetoprotein(AFP), serum PLGF, β-human chorionic gonadotropin(β-hCG) and pregnancy-associated plasma protein-A(PAPP-A) were compared between the two groups.
Results: There were 43 patients experiencing PE, with an incidence of 11.65%. The levels of PLGF, β-hCG and PAPP-A were significantly decreased in the PE group compared with those in the normal group, and the differences between the groups were statistically significant (all P<0.05). Logistic regression analysis showed that increased prenatal screening markers AFP, serum PLGF, HCG and PAPP-A were independent risk factors for PE, with statistically significant differences between the groups (all P<0.05). Finally, the results of ROC curve analysis showed that the AUCs of AFP, PLGF, β-hCG and PAPP-A were 0.618, 0.645, 0.690, and 0.645, respectively, and the AUC of combined prediction was 0.825, which was significantly increased compared with that of each marker alone, with statistically significant differences(P<0.05).
Conclusion: The development of PE in pregnancy is closely related to the levels of AFP, PLGF, β-hCG and PAPP-A. The predictive efficiency of combined detection of AFP, PLGF, β-hCG and PAPP-A for PE in pregnancy significantly increases.
Project Title: sFlt-1/PlGF based combined early pregnancy prenatal screening marker Nursing Strategies and Application in Preeclampsia Risk Assessment, Project Number: 2024YFYB111, Year: 2024.
doi: https://doi.org/10.12669/pjms.41.2.9794
How to cite this: Shu Z, Wang W. Predictive value of prenatal screening markers combined with serum placental growth factor in early pregnancy for preeclampsia. Pak J Med Sci. 2025;41(2)598-602. doi: https://doi.org/10.12669/pjms.41.2.9794
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The clinical outcome of treating elderly distal radius fractures by long volar locking plate with the elimination of irreducible metaphyseal comminuted volar cortical fragments: a retrospective case series
Authors: Cha Soo Min
Published: January 2025

Background: In severe comminuted metaphyseal distal radius fracture (DRF) of elderly patients, after maintaining only radiological parameters of the radius using long volar locking plates (VLPs), we inevitably eliminated a few volar cortical fragments of metaphysis. Here, we report the final radiological and clinical outcomes of our method. Methods: For the patients who were treated between 2014 and 2018, the demographic factors, the preoperative radiologic factors, area of the eliminated volar cortical fragment, and final radiologic parameter, were evaluated. Clinical outcomes and ranges of active motion were evaluated. Results: In total, 31 patients were included. The mean patient age was 77.3 years and the mean eliminated cortical area was 3.30 cm2. At the final follow-up, the mean volar tilt, radial inclination, articular step-off, and ulnar variance were 10.35°, 20.00°, 0.58 mm, and 0.71 mm, respectively. There were no definitive correlations between bone mineral density, fragment area, the largest cortical fragment diameter ratio and differences in final and immediate postoperative measurements of these radiological parameters, respectively. Visual analog scale and disabilities of the arm, shoulder, and hand (DASH) scores were satisfactory, and the mean arcs of flexion-extension and pronation-supination were 124.35° and 133.23°. Clinical outcomes were not significantly different according to the AO system category. Conclusions: For maintenance of radiological parameters of the radius, long VLPs are useful in older patients with DRFs who exhibit volar metaphyseal comminution, despite concurrent ulnar fractures. Inevitable elimination of irreducible free comminuted cortical fragments when filling the defect does not affect final radiological and clinical outcomes. Level of evidence: Level IV, case series.
Interpositional tricortical iliac bone graft in nonunion of midshaft clavicular fractures
Authors: Son Eun-Seok , Park Bum-Soon , Yon Chang-Jin , Cho Chul-Hyun
Published: January 2025

Background: The purpose of this study was to investigate the radiological and clinical outcomes after interpositional tricortical iliac bone graft with plate fixation for the nonunion of clavicle midshaft fractures. Methods: Between 2007 and 2020, 17 cases who were treated by interpositional tricortical iliac bone graft with plate fixation for the clavicle midshaft nonunion combined with bone defect were investigated. The mean age was 53 years (range, 22–70 years). The mean follow-up period was 102.2 months (range, 18–193 months). Serial plain radiographs were used to evaluate radiological outcomes. The University of California, Los Angeles (UCLA) score, American Shoulder and Elbow Surgeons (ASES) score, and Quick-disabilities of the arm, shoulder, and hand (DASH) score were used to evaluate clinical outcomes. Complications were also evaluated. Results: All cases achieved complete bony union with mean healing time of 17.6 weeks (range, 14–22 weeks). The mean clavicle length difference was significantly decreased from 9.1 mm preoperatively to 2.6 mm postoperatively (P<0.001). The mean UCLA and ASES scores were significantly improved from 18.1 and 52.2 before surgery to 30.6 and 88.6 after surgery (both P<0.001), respectively. The mean final Quick-DASH score was 18.0. Three cases (17.6%) developed postoperative complications including two cases of shoulder stiffness and one case of screw irritation. Conclusions: Interpositional tricortical iliac bone graft with plate fixation for the clavicle midshaft nonunion demonstrated excellent radiological and clinical outcomes. In cases of atrophic nonunion combined with bone defect, this technique is an effective option that can provide structural support and restore clavicle length. Level of evidence: Level IV, case series.
Outcomes of open reduction and internal fixation using 2.0/2.4 mm locking compression plate in isolated greater tuberosity fractures of humerus
Authors: Choi Sung , Shin Dongju , Kim Sangwoo , Kwack Byung Hoon
Published: January 2025

Background: The purpose of this study was to retrospectively evaluate the radiographic and clinical results of a small single or double low-profile plate fixation of 2.0/2.4 mm locking compression plate (LCP) in treating isolated greater tuberosity (GT) fractures of the humerus. Methods: From June 2015 to October 2022, patients who underwent LCP in treating isolated GT fractures of the humerus were included in this study. The radiological and clinical results were analyzed in 15 patients who underwent open reduction and internal fixation used 2.0/2.4 mm LCP. Results: Bone union was achieved in 14 patients (93.3%) and one failed case was treated with a 2.4 mm single LCP fixation. Radiological union was achieved within 10–20 weeks. Complications occurred in two patients (13.3%), including the reduction failure and shoulder stiffness. At the final follow-up, the average clinical scores were as follows: a visual analog scale for pain of 2.1 (range, 0–5) and a University of California, Los Angeles score of 27.2 (range, 18–31). Regarding range of motion (ROM), the average active ROMs were 142° for forward flexion (range, 120°–150°), 147.1° for abduction (range, 120°– 180°), and 59.3° for external rotation (range, 45°–80°). For internal rotation, the average was observed to reach the 10th thoracic vertebra (range, 1st lumbar vertebra–7th thoracic vertebra). Conclusions: The clinical and radiologic outcomes of treating isolated GT fracture using 2.0/2.4 mm LCP were favorable, and double low-profile plate fixation may be beneficial for sufficient fracture stability if possible. Level of evidence: Level IV, case series.
A guide to selecting high-performing antibodies for S1PR1 (UniProt ID: P21453) for use in western blot, immunoprecipitation, and immunofluorescence
Authors: Ayoubi Riham , Fotouhi Maryam , Alende Charles , González Bolívar Sara , Southern Kathleen , Laflamme Carl ,   NeuroSGC/YCharOS/EDDU collaborative group,   ABIF consortium
Published: January 2025

Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-coupled protein receptor that induces crucial biological processes when bound by sphingosine 1-phosphate. Here, we have characterized nine S1PR1 commercial antibodies for western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.
Expediency of Dynamic Pricing Application (Part 1)
Authors: Boldycheva A. , Saharova N.
Published: January 2025

In the conditions of digitalization and high competition dynamic pricing turns from a tool of choice into a necessary element of successful business strategy. Its implementation allows not only to adapt to market changes, but also to use them in its favor, providing a sustainable competitive advantage. Dynamic pricing allows companies to adapt prices depending on changing factors such as demand, competition or seasonality. This article analyzes the conditions and feasibility of dynamic pricing in different industries. To avoid technical, ethical and legal problems, companies should take into account the quality of data, its origin and use, as well as respect the rights and interests of customers. This approach not only minimizes risks but also helps to build brand trust.
James Brindley: Eighteenth Century Canal Pioneer
Authors: Smith Nick
Published: January 2025

An icon of the industrial revolution era of canal construction, James Brindley’s enduring contribution to engineering was his development of the puddling technique.
Global and International Introduction: Chinese Beauty Influencers and Authenticity
Authors: Li Xinghua , Knight Christina Noble , Thomas Kevin D.
Published: January 2025

Abstract: The Global and International Perspective Section’s contributing editors introduce the article they curated for this issue: Competitive Authenticity: Chinese Beauty Influencers Leverage the Hashtag #ReconcileWithPlainFace to Intensify Their Rivalries .
The Disability Reference Collection at the Smithsonian’s National Museum of American History’s Archives Center
Authors: Timke Edward
Published: January 2025

Abstract: This Advertising in the Archives article shares materials from the Disability Reference Collection at the Smithsonian’s National Museum of American History’s (NMAH) Archives Center. It highlights the Collection’s wealth of archival materials documenting the history of disability rights, advocacy, and representation in media and advertising. Through selected items, including a 1981 conference pamphlet on representations of disability in media, a 1993 article on models with disabilities in Mainstream magazine, and advertisements commemorating the twenty-fifth anniversary of the Americans with Disabilities Act (ADA), this article stresses the need to recognize the long-standing assessment of disability representation in commercial messaging. Additionally, material artifacts, such as Justin Dart, Jr.’s iconic cowboy hat and boots and a tactile model of a Wizard of Oz character from a Comcast ad, reveal the depth of the NMAH’s collection of disability materials. This piece aims to inspire further scholarly engagement with disability perspectives in the archives, which can hopefully foster a more inclusive understanding of the cultural and social history of advertising and its place in society.