bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTOR Ser1261 is an AMPK‐dependent phosphosite in mouse and human skeletal muscle not required for mTORC2 activity
Authors: Li Jingwen , Madsen Agnete B. , Knudsen Jonas R. , Henriquez‐Olguin Carlos , Persson Kaspar W. , Li Zhencheng , Raun Steffen H. , Li Tianjiao , Kiens Bente , Wojtaszewski Jørgen F. P. , Richter Erik A. , Nogara Leonardo , Blaauw Bert , Ogasawara Riki , Jensen Thomas E. 
Published: January 2025

AbstractThe kinases AMPK, and mTOR as part of either mTORC1 or mTORC2, are major orchestrators of cellular growth and metabolism. Phosphorylation of mTOR Ser1261 is reportedly stimulated by both insulin and AMPK activation and a regulator of both mTORC1 and mTORC2 activity. Intrigued by the possibilities that Ser1261 might be a convergence point between insulin and AMPK signaling in skeletal muscle, we investigated the regulation and function of this site using a combination of human exercise, transgenic mouse, and cell culture models. Ser1261 phosphorylation on mTOR did not respond to insulin in any of our tested models, but instead responded acutely to contractile activity in human and mouse muscle in an AMPK activity‐dependent manner. Contraction‐stimulated mTOR Ser1261 phosphorylation in mice was decreased by Raptor muscle knockout (mKO) and increased by Raptor muscle overexpression, yet was not affected by Rictor mKO, suggesting most of Ser1261 phosphorylation occurs within mTORC1 in skeletal muscle. In accordance, HEK293 cells mTOR Ser1261Ala mutation strongly impaired phosphorylation of mTORC1 substrates but not mTORC2 substrates. However, neither mTORC1 nor mTORC2‐dependent phosphorylations were affected in muscle‐specific kinase‐dead AMPK mice with no detectable mTOR Ser1261 phosphorylation in skeletal muscle. Thus, mTOR Ser1261 is an exercise but not insulin‐responsive AMPK‐dependent phosphosite in human and murine skeletal muscle, playing an unclear role in mTORC1 regulation but clearly not required for mTORC2 activity.
Clinical Outcome of Endothelium-Outward Preloaded Descemet Membrane Endothelial Keratoplasty in Long-Term Dextran-Containing Transport Medium Preservation
Authors: Rickmann Annekatrin , Wahl Silke , Messias André , Trouvain André M. , Roberts Philipp K. , Boden Karl T. , Szurman Peter 
Published: January 2025

Purpose:
To analyze the clinical outcome of organ-cultured endothelium-outward preloaded DMEK (pDMEK) using the RAPID cartridge.

Methods:
This prospective study included 80 eyes of 80 patients who received a pDMEK. Best-corrected visual acuity (BCVA), endothelial cell count (ECC), and central corneal thickness were measured preoperatively and 4 to 6 weeks, 3 months, 6 months, and 1 year postoperatively. The difficulty of graft preparation and implantation, rebubbling, and re-DMEK frequency were evaluated.

Results:
The graft preparation time was 5.3 ± 1.2 minutes on average. After preparation, the ECC before preloading was 2652 ± 180 cells/mm2 (P = 0.9, endothelial cell loss [ECL] = 0.8%). After pDMEK, the cornea started to clear up after 1.6 ± 1 day. Compared with the preoperative values, BCVA and central corneal thickness significantly improved during the postoperative course (P < 0.0001). At the first follow-up examination, the ECL was 43% (P < 0.0001) and remained stable throughout the follow-up period (all P > 0.5). Rebubbling was necessary in 39/80 patients (48.75%). One patient (1/80, 1.25%) required a re-DMEK after 1 year owing to secondary graft failure with insufficient ECC.

Conclusions:
The clinical results after endothelium-outward pDMEK showed a significant improvement in BCVA and corneal thickness over the 1-year follow-up period, but the relatively high rebubbling rate and ECL should be taken into account. Therefore, we recommend that further comparative clinical studies should be conducted.
EBUS-guided Iodine-125 seed implantation in lymph node as a novel therapy for MCAO: A case report
Authors: Qian Huiwen , Jin Jianqiang , Wang Changguo , Wang Yuting , Ge Juxiang , Huang Jianan , Ji Cheng 
Published: January 2025

Rationale:
We report here a case of using iodine-125 (125I) seed implantation via endobronchial ultrasound (EBUS) in the treatment of malignant central airway obstruction (MCAO) in a patient with lung adenocarcinoma.

Patient concerns:
The patient still experienced MCAO after conventional bronchoscopic interventional therapy.

Diagnoses:
The patient was diagnosed as lung adenocarcinoma stage IV (T4N2M1a).

Interventions:
She received implantation of radioactive 125I seeds in the lesion inside the right middle lobe bronchus and 12R lymph node via bronchoscopy and EBUS, in combination with chemotherapy and immunotherapy.

Outcomes:
The patient’s MCAO has been effectively controlled.

Lessons:
The success of this case suggests that EBUS-guided 125I seed implantation to lymph nodes is a safe and effective therapeutic option for MCAO.
Efficacy and safety of ivermectin–albendazole combination versus ivermectin or albendazole monotherapy in soil-transmitted helminthiasis: A systematic review and meta-analysis
Authors: Malik Hurais , Din Muhammad Fazal Ud , Faizan Muhammad Aqib , Rehman Tooba , Hudaib Muhammad , Shah Syed Muhammad Abdullah , Khan Abdullah Abid , Amir Syeda Fatima , Fraz Musarrat , Khalid Maham , Anjum Muhammad Umair , Larik Muhammad Omar , Bhattarai Pratik 
Published: January 2025

Background:
Soil-transmitted helminthiasis remains a daunting challenge to global health, exerting its greatest toll on resource-limited regions of the world. A dual drug approach using the co-administration of ivermectin and albendazole has shown promising results in comparison to the traditional monotherapy strategy. In light of this, a systematic review and meta-analysis of randomized controlled trials was conducted.

Methods:
Several electronic databases including PubMed, Cochrane Central, Google Scholar, and Embase were explored to search for relevant studies from inception to September 2023. The Cochrane Risk of Bias Tool for Randomized Controlled Studies was utilized to evaluate the quality of studies.

Results:
A total of 8 randomized controlled trials, reporting 10 patient populations, were included. The treatment of trichuriasis significantly favored the dual therapy regimen of ivermectin–albendazole over albendazole-only monotherapy (risk ratio [RR]: 2.86; 95% confidence interval [CI]: 1.66–4.93; P = .0002), with no significant differences observed for ascariasis and hookworm. The treatment of trichuriasis and hookworm significantly favored the dual therapy regimen of ivermectin–albendazole over ivermectin-only monotherapy (RR: 1.86; 95% CI: 1.56–2.21; P < .00001 and RR: 2.31; 95% CI: 1.23–4.31; P = .009, respectively). There were no statistically significant differences between dual therapy and monotherapy in terms of adverse effects.

Conclusion:
These findings highlight the nuanced effectiveness of combined therapy specific to certain helminth types, in addition to their comparable safety profiles, thereby providing pivotal insights that contribute to the evolving landscape of soil-transmitted helminth treatment strategies.
Alkaptonuria presenting as lumbar degenerative disease: A case report and literature review
Authors: Sang Peiming , Ma Yanyan , Yang Jun , He Fan , Chen Jingyan , Zhang Xie , Chen Binhui , Cai Ying , Chen Zhenjing 
Published: January 2025

Rationale:
Alkaptonuria (AKU) is a rare, inherited metabolic disease caused by deficient activity of homogentisic acid oxidase, leading to the accumulation of homogentisic acid and its oxidized product, benzoquinone acetic acid. These compounds cause black discoloration of cartilage, degeneration, inflammation, and calcification of intervertebral disks and large joints, resulting in pain and impaired quality of life. Despite its debilitating effects, there are no curative treatments for AKU, and management remains supportive. This study aims to contribute to the limited literature on AKU-related spinal manifestations by reporting a case of lumbar degenerative disease in an AKU patient and highlighting surgical intervention as an effective treatment approach.

Patient concerns:
A 49-year-old woman presented with chronic lower back pain and the posterior side of right lower limb radiating pain for 1 year, worsening over the past week. Magnetic resonance imaging revealed lumbar spondylolisthesis at the L4/5 level and migrated lumbar disk herniation at the L5/S1 level.

Interventions:
The patient underwent transforaminal lumbar interbody fusion surgery at L4/5 and L5/S1. Intraoperatively, the resected disk material was black, with darkened intervertebral disks and cartilage endplates, distinct from the typical white appearance of degenerative disks. Surgical intervention included disk and cartilage endplate removal, insertion of cages with harvested autografts, and implantation of bilateral pedicle screws and rods.

Diagnosis:
AKU with lumbar degenerative disease.

Outcome:
The patient experienced resolution of pain postoperatively.

Lessons:
This case underscores the importance of recognizing AKU as a potential cause of lumbar degenerative disease and highlights transforaminal lumbar interbody fusion surgery as a viable treatment option for pain relief and improved functionality in affected individuals.
Retroperitoneal cystic mature teratoma in an adult male: A clinical report of one case and review of the literature
Authors: Zhang Zekai , Zhang Ling , Zhang Hua , Huo Xiaoguang , Xu Wenzhe , Zhang Yongting 
Published: January 2025

Rationale:
A case of retroperitoneal cystic mature teratoma in an adult male. Retroperitoneal cystic mature teratoma is a type of teratoma. The disease has occult onset, does not have the typical characteristics of teratoma, and is difficult to distinguish from cystadenoma and other diseases. Cystic mature teratoma is benign, but it has a certain risk of malignant transformation. The purpose of this case report is to highlight the specificity of the case, collect and analyze the imaging features of the disease, and provide assistance for daily clinical diagnosis.

Patient concerns:
Adult extraglandular abdominopelvic teratoma is extremely rare, especially in men. These masses are most commonly found by chance and require surgical resection for diagnostic confirmation after a thorough examination.

Diagnoses:
We report a case of retroperitoneal cystic mature teratoma in an 86-year-old man. Abdominal ultrasound revealed a cystic mass in the abdominal cavity (possibly from the pancreas). Enhanced abdominal computed tomography showed a space-occupying lesion with a lack of blood supply in the hepatogastric space (above the pancreas), and the local boundary with the pancreas was unclear. The tumor was considered first, but pancreatic cystadenoma was not excluded.

Interventions:
Surgical resection is the most important treatment for retroperitoneal cystic teratoma, and the best adjuvant treatment needs further study.

Outcomes:
Postoperative pathological findings showed (retroperitoneal) mature cystic teratoma with lymphoid hyperplasia, lymphoid follicle formation, and mild to moderate atypical hyperplasia of squamous epithelium.

Lessons:
In conclusion, adult retroperitoneal cystic mature teratoma is a rare disease. This disease should be taken into account when we find a retroperitoneal cystic mass on our routine imaging. The shortcomings of this case report are mainly single case, small sample size, need to collect more cases, and long-term follow-up to summarize the characteristics of retroperitoneal cystic mature teratoma, in addition, this case did not undergo magnetic resonance imaging examination, magnetic resonance images cannot be analyzed.
The clinicopathologic features of uterine inflammatory myofibroblastic tumor: A case report
Authors: Pan Xiaoming , Zou Jian , Yang Shizhou , Wang Yuanhe , Luo Jie , Zhu Xiaojun 
Published: January 2025

Rationale:
Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue neoplasm with low malignant potential. These patients present with a certain probability of malignant potential. The management of IMT has not been standardized, especially for the patients with fertility needs.

Patient concerns and Diagnoses:
Thirteen patients with IMT who attended in the Department of Gynecology, Women’s Hospital, Zhejiang University School of Medicine were enrolled between 2019 and 2023. The data of the clinical and pathological features was analyzed.

Interventions and Outcomes:
The mean age of the patients was 45.31 ± 12.80 years. Seven of the 13 cases (53.85%) had abnormal uterine bleeding. Five of them (38.46%) had a rapidly growing mass, and 2 of them (15.38%) had no obvious symptoms. With regard to surgical strategies, 7 patients underwent hysterectomy, and 6 patients underwent mass resection only. All the patients were alive with no evidence of disease at an average of 9.58 months of follow-up. One of them gave birth to a full-term male infant at 40 weeks of gestation after hysteroscopic resection, without recurrence.

Lessons:
Uterine inflammatory myofibroblastic tumor can be diagnosed by the anaplastic lymphoma kinase overexpression. Complete excision under hysteroscopy or laparoscopy seems to be effective and safe. Because there is a certain risk of recurrence and metastasis, conservative surgery should be performed carefully to preserve fertility in patients who can undergo close follow-up.
Low-dose dasatinib-induced chylothorax, pulmonary hypertension, and pericardial effusion in a patient with chronic myeloid leukemia: A case report and literature review
Authors: Pai Ting-Wei , Huang Cheng-Wei 
Published: January 2025

Rationale:
Chylothorax is a rare adverse effect that is associated with dasatinib, a tyrosine kinase inhibitor administered for chronic myeloid leukemia (CML) treatment. Most reported cases have described standard dosing. In this case report, we described a 43-year-old male patient with CML who developed chylothorax after 4 years of low-dose dasatinib therapy. To the best of our understanding, this is the first case to report the simultaneous development of pulmonary hypertension, pericardial effusion, and dasatinib-induced chylothorax.

Patient concerns:
A 43-year-old male patient with CML developed chylothorax after 4 years of low-dose dasatinib.

Diagnoses:
The patient also developed pulmonary hypertension and pericardial effusion at the same time.

Interventions:
Therapeutic interventions included thoracentesis, steroids, diuretics, and sildenafil. Dasatinib was discontinued and replaced with nilotinib, which resolved the chylothorax, pulmonary hypertension, and pericardial effusion.

Outcomes:
Chylothorax occurs with long-term and low-dose dasatinib administration. Concurrent pulmonary hypertension and pericardial effusion, although infrequent, may occur. Prompt recognition, dasatinib discontinuation, and therapeutic interventions are crucial for optimizing outcomes.

Lessons:
Close monitoring for these rare side effects is paramount even in patients on long-term or low-dose dasatinib.
Differences in lasers and laser technologies: what does a clinician need to know?
Authors: Morozov Andrey , Skossyrskiy Vladislav , Babaevskaya Diana , Gauhar Vineet , Enikeev Dmitry 
Published: January 2025

Purpose of review
This review focuses on recent advancements in laser technologies used in urology, particularly in enucleation, vaporization, lithotripsy, and focal laser ablation (FLA). The growing use of the thulium fiber laser (TFL) and the development of pulsed thulium lasers (p-Tm:YAG) highlight the relevance of this review, as these innovations aim to improve precision and outcomes in urological procedures.

Recent findings
Recent studies have shown the advantages of TFL in achieving precise tissue ablation, reduced retropulsion offered by the Moses technology in holmium lasers, and the potential of pulsed thulium lasers for more precise control of the effects on tissues. Additionally, FLA is gaining traction for its ability to treat localized prostate cancer with minimal collateral damage. These technologies not only optimize procedural accuracy but also reduce complications, making them safer for high-risk patients, including those receiving anticoagulants.

Summary
The advancements in laser technology, including TFL, Moses technology, and pulsed thulium lasers, are improving outcomes in urological surgeries by increasing precision, reducing operative time, and minimizing complications. FLA represents a promising alternative for minimally invasive cancer treatments. Ongoing research should focus on optimizing laser parameters and exploring broader clinical applications.
En bloc resection of large bladder tumor: is it feasible and reasonable?
Authors: Babaevskaya Diana , Morozov Andrey , Fridman Eddie , Tsoy Larisa , Shariat Shahrokh F. , Molchanov Yossef , Yakimov Maxim , Compérat Eva , Herrmann Thomas R.W. , Enikeev Dmitry 
Published: January 2025

Purpose of review
Transurethral resection of bladder tumor (TURBT) remains the basis of bladder tumor diagnosis and an effective means of treating nonmuscle invasive bladder cancer (NMIBC). There are several limitations to this procedure: TURBT may cause free floating of malignant cells in the bladder and as a result re-implantation and early recurrence. Also, it does not allow the pathologist to define the correct spatial orientation of the specimen. The development of en bloc resection of bladder tumor (ERBT) has helped overcome the abovementioned key disadvantages of TURBT. However, many urologists doubt whether this approach is feasible for treating larger tumors.

Recent findings
In this review, it is shown that ERBT of large bladder tumor (>3 cm) is in fact a feasible and well tolerated method. Although there is a lack of comparative data proving its advantages over TURBT, en bloc in large tumor seems to result in better local cancer control (due to higher prevalence of detrusor specimen, lower need for re-TURBT), lower rate of relapse outside the resection area (due to lower risk of tumor cells circulation), and higher quality of pathology specimen.

Summary
Despite the skepticism of some surgeons, potential difficulties caused by larger tumor size may be overcome easily, and most agree that tumor size should not limit the implementation of the method in their daily practice.
What Matters Most for Long-Acting Antiretroviral Therapy? A Best-Worst Scaling Discrete Choice Experiment
Authors: Fisk-Hoffman Rebecca J , Liu Yiyang , Somboonwit Charurut , Widmeyer Maya , Bilello Lori A , Cohen Colby , Leeman Robert F , Prosperi Mattia , Salloum Ramzi G , Cook Robert L 
Published: January 2025

Introduction:
Florida remains a high-incidence, high-prevalence setting for HIV. Long-acting (LA) antiretroviral therapies (ART) could improve HIV-related outcomes and reduce transmission. This study identifies preferred LA ART characteristics and classes of preference among people with HIV (PWH) in Florida.

Methods:
The Florida Cohort enrolls adult PWH from six counties. In February 2023, a best-worst scaling discrete choice experiment (BWDCE) was added which included 12 tasks with three alternatives and an opt-out (i.e., their current regimen). Six attributes were included: treatment type (e.g., shot), long-term effects, side effects, location (e.g., at home), effectiveness, and frequency. A Hierarchical Bayes model was used to estimate level utilities, attribute importance was calculated, and a latent class model was run in Sawtooth Software.

Results:
Overall, 208 PWH participated (60% aged 50+, 49% non-Hispanic Black, 54% male). Treatment type had the greatest impact on preference [27.2% (95%CI 25.1-29.3)], followed by frequency [23.4% (95%CI 21.6-25.2)], and long-term effects [19.0% (95%CI 17.8-20.3)]. Within treatment type, LA pills were preferred over other options, including their current regimen. Less frequent administration was preferred, but only yearly administration was preferred over their current regimen. Within long-term effects, participants preferred no increase in risk. Two classes were identified where one class (27% of participants) preferred their current regimen and the other (73% of participants) preferred an alternative, placing greater importance on frequency.

Conclusion:
PWH preferred LA pills and less frequent administration, so future ART development could focus on options with these traits. Further exploration of user preference classes is needed.
Bi-allelic variants in the aminopeptidase XPNPEP3 cause mitochondrial disease with pediatric cardiomyopathy
Authors: Ruijmbeek Claudine W.B. , Ruizenaar Sjoerd , van der Linde Herma C. , Nollet Edgar E. , Doff Wouter A.S. , Bogaard Victoria C.S. , de Pee Marlène , Ferraro Federico , Rodenburg Richard J. , Schipper Henk S. , Hirsch Alexander , van Slegtenhorst Marjon A. , von der Thüsen Jan H. , Demmers Jeroen A.A. , van IJcken Wilfred F.J. , van Ham Tjakko J. , Verhagen Judith M. A. 
Published: January 2025

AbstractBi-allelic variants inXPNPEP3are known to cause nephronophthisis-like nephropathy-1. However, recent findings indicate XPNPEP3 deficiency causes a broader phenotypic spectrum encompassing extra-renal manifestations. XPNPEP3 is suggested to be the human ortholog of ICP55, a mitochondrial protein involved in the processing and maturation of mitochondrial proteins in plants and yeast.Here, we present a family with two children affected by a homozygous splice variant inXPNPEP3. Both children exhibited early-onset renal insufficiency and progressive mixed hypertrophic and dilated cardiomyopathy, requiring cardiac transplantation during childhood. RNA and protein analysis of patient fibroblasts and cardiac tissue revealed loss of XPNPEP3 expression due to the splice variant. Assessment of explanted cardiac tissue confirmed mitochondrial dysfunction, indicated by decreased cytochrome c oxidase activity and changes in mitochondrial morphology.Although the deficiency of Xpnpep3 in zebrafish did not result in noticeable phenotypic abnormalities during early larval stages, transcriptomic and proteomic analyses revealed mitochondrial alterations. Notably, proteomic profiling identified decreased abundance of mitochondrial proteins inxpnpep3Δ7/Δ7mutants as compared to wild-types, including those identified in our study as putative substrates of Xpnpep3. We hypothesize that impaired processing of these proteins plays a critical role in the early developmental molecular changes observed, potentially predisposing to disease and also underlies the clinical manifestations in affected children.In summary, our study underscores that loss of XPNPEP3 causes a mitochondrial disorder with varied phenotypes, including cardiomyopathy, through a molecular mechanism likely involving abnormal processing and stabilization of mitochondrial precursor proteins. AddingXPNPEP3to cardiac and mitochondrial disease gene panels is essential for the accurate diagnosis and management of potential cardiac complications.