bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep histopathology genotype–phenotype analysis of focal cortical dysplasia type II differentiates between the GATOR1-altered autophagocytic subtype IIa and MTOR-altered migration deficient subtype IIb
Authors: Honke Jonas , Hoffmann Lucas , Coras Roland , Kobow Katja , Leu Costin , Pieper Tom , Hartlieb Till , Bien Christian G. , Woermann Friedrich , Cloppenborg Thomas , Kalbhenn Thilo , Gaballa Ahmed , Hamer Hajo , Brandner Sebastian , Rössler Karl , Dörfler Arnd , Rampp Stefan , Lemke Johannes R. , Baldassari Sara , Baulac Stéphanie , Lal Dennis , Nürnberg Peter , Blümcke Ingmar 
Published: November 2023

AbstractFocal cortical dysplasia type II (FCDII) is the most common cause of drug-resistant focal epilepsy in children. Herein, we performed a deep histopathology-based genotype–phenotype analysis to further elucidate the clinico-pathological and genetic presentation of FCDIIa compared to FCDIIb. Seventeen individuals with histopathologically confirmed diagnosis of FCD ILAE Type II and a pathogenic variant detected in brain derived DNA whole-exome sequencing or mTOR gene panel sequencing were included in this study. Clinical data were directly available from each contributing centre. Histopathological analyses were performed from formalin-fixed, paraffin-embedded tissue samples using haematoxylin–eosin and immunohistochemistry for NF-SMI32, NeuN, pS6, p62, and vimentin. Ten individuals carried loss-of-function variants in the GATOR1 complex encoding genes DEPDC5 (n = 7) and NPRL3 (n = 3), or gain-of-function variants in MTOR (n = 7). Whereas individuals with GATOR1 variants only presented with FCDIIa, i.e., lack of balloon cells, individuals with MTOR variants presented with both histopathology subtypes, FCDIIa and FCDIIb. Interestingly, 50% of GATOR1-positive cases showed a unique and predominantly vacuolizing phenotype with p62 immunofluorescent aggregates in autophagosomes. All cases with GATOR1 alterations had neurosurgery in the frontal lobe and the majority was confined to the cortical ribbon not affecting the white matter. This pattern was reflected by subtle or negative MRI findings in seven individuals with GATOR1 variants. Nonetheless, all individuals were seizure-free after surgery except four individuals carrying a DEPDC5 variant. We describe a yet underrecognized genotype–phenotype correlation of GATOR1 variants with FCDIIa in the frontal lobe. These lesions were histopathologically characterized by abnormally vacuolizing cells suggestive of an autophagy-altered phenotype. In contrast, individuals with FCDIIb and brain somatic MTOR variants showed larger lesions on MRI including the white matter, suggesting compromised neural cell migration.
Chitobiose exhibited a lipid-lowering effect in ob/ob−/− mice via butyric acid enrolled liver–gut crosstalk
Authors: Zhuang Xinye , Zhao Mengyao , Ji Xiaoguo , Yang Sihan , Yin Hao , Zhao Liming 
Published: November 2023

AbstractChitobiose (COS2) efficiently lowers lipids in vivo and facilitates butyric acid enrichment during human fecal fermentation. However, whether COS2 can interact with butyric acid to generate a hypolipidemic effect remains unclear. This study examined the hypolipidemic mechanism of COS2 involving butyric acid, which could alleviate non-alcoholic fatty liver disease (NAFLD). The results revealed that COS2 administration modulated the β-oxidation pathway in the liver and restructured the short chain fatty acids in the fecal of ob/ob−/− mice. Moreover, the hypolipidemic effect of COS2 and its specific accumulated metabolite butyric acid was verified in sodium oleate-induced HepG2 cells. Butyric acid was more effective to reverse lipid accumulation and up-regulate β-oxidation pathway at lower concentrations. Furthermore, structural analysis suggested that butyric acid formed hydrogen bonds with key residues in hydrophilic ligand binding domains (LBDs) of PPARα and activated the transcriptional activity of the receptor. Therefore, the potential mechanism behind the lipid-lowering effect of COS2 in vivo involved restoring hepatic lipid disorders via butyric acid accumulation and liver–gut axis signaling.
Graphical Abstract
Intraoperative cardiac arrest caused by unexpected vasospastic angina requiring prolonged resuscitation using extracorporeal membrane oxygenation: a case report
Authors: Sugita Shinji , Obata Masanobu , Hasunuma Fumihiko , Sakamoto Atsuhiro 
Published: November 2023

Abstract
Background
Vasospastic angina (VSA) occurring during surgery is rare but can lead to sudden intraoperative cardiac arrest.

Case presentation
A 77-year-old man with hypertension, and no history of coronary artery disease, displayed an abrupt ST-segment elevation on the electrocardiogram (ECG) during laparoscopic inguinal hernia surgery under general anesthesia. Subsequently, ventricular fibrillation (VF) occurred, with a finding suggesting ischemic myocardial contracture by transesophageal echocardiography. VF was refractory to cardiopulmonary resuscitation (CPR), and veno-arterial extracorporeal membrane oxygenation (VA ECMO) was introduced. Spontaneous circulation resumed 77 min post-cardiac arrest. VSA was confirmed through the patient’s clinical course and coronary angiography. Subsequently, VA ECMO was terminated, and the patient was discharged uneventfully.

Conclusions
Extracorporeal CPR may be a valuable alternative to extended resuscitation for refractory ventricular arrhythmias by VSA.
Recurrent artery of Heubner infarction: a complication after clipping of anterior communicating artery aneurysm
Authors: Atallah Oday , Almealawy Yasser F. , Wawi Omar , Maurya Ved , Rahman Md Moshiur , Agrawal Amit 
Published: November 2023

AbstractRecurrent artery of Heubner (RAH) infarction is a potential complication following the surgical clipping of anterior communicating artery (A-comm) aneurysms. RAH plays a crucial role in supplying blood to the basal ganglia and anterior limb of the internal capsule. Understanding the pathogenesis, prognosis, and surgical result of RAH infarction is critical for providing the best care for patients. The literature study produced case reports and retrospective research on topics including the RAH infarct and A-comm aneurysm clipping. The importance of recognizing and controlling the risk of a RAH infarction in relation to A-comm aneurysm clipping is emphasized in this research. RAH infarction following clipping of an A-comm aneurysm has a complex pathophysiology, and by learning more about its causes, prognosis, and surgical results, medical personnel may better assist their patients. While further study is needed to overcome the obstacles highlighted here, the information presented here lays the groundwork for future research and adds to what is already known about the topic.
Evaluation of adding magnesium sulphate to intrathecal bupivacaine in lower limb orthopedic surgery
Authors: Solanki Nilesh M. , Bhimani Maulik P. , Mistry Nirmal S. , Rajan Diya 
Published: November 2023

Abstract
Background
A subarachnoid block is the cheaper and widely used regional block for lower limb surgery. Postoperative pain occurs after lower limb orthopedic surgery from moderate to severe. We conducted a prospective, randomized, double-blind controlled trial. All patients were assessed for onset and duration of sensory and motor block, total duration of analgesia, and postoperative pain relief.
This study was conducted to evaluate the efficacy of intrathecal bupivacaine with magnesium undergoing lower limb orthopedic surgery.

Results
One hundred patients were randomly divided into two equal groups. Group M: Intrathecal 3 ml (15 mg) of 0.5% bupivacaine + 0.2 ml (50 mg) of preservative-free 25% of magnesium sulphate. Group B: Intrathecal 3 ml (15 mg) of 0.5% bupivacaine + 0.2 ml preservative-free 0.9% normal saline. The mean time that occurred for the sensory blockade at T10 was 2.49 ± 0.49 min in group B, while it was 4.13 ± 0.74 min in group BM (p value < 0.0001). The mean of the total duration of the sensory block in group B was 139.5 ± 32.01 min, while it was 366.4 ± 30.12 min in group BM (p value < 0.0001). The time taken for the onset of motor block in group B was 5.28 ± 1.31 min, while it was 7.86 ± 1.19 min in group BM (p value < 0.0001). The mean total duration of the motor block in group B was 136.3 ± 8.19 min, while it was 336.5 ± 37.08 min in group BM (p value < 0.0001). The total duration of analgesia in group B was 141.4 ± 14.85 min, while it was 365.9 ± 44.91 min in group BM (p value < 0.0001). The mean dose required for rescue analgesia in group B was 2.2 ± 1.14, while in group BM was 1.28 ± 0.96 (p value < 0.0001).

Conclusions
The addition of 50 mg magnesium sulphate in intrathecal hyperbaric bupivacaine significantly prolongs the extended duration of sensory, motor blockade, and total duration of analgesia for patients undergoing lower limb orthopedic surgery.
Clinical efficacy of local infiltration of lidocaine and tranexamic acid application in tonsillar region on postoperative pain and bleeding during tonsillectomy: prospective, randomized, double-blind controlled study
Authors: Aboelsuod Mohamed Abdelgawad Abdelhalim , Abdalla Abdalla Mohamed , Ahmed Ismail Mohamed Abdelgawad , Seyam Sameh Hamdy , Hassan Ahmed Mohamed 
Published: November 2023

Abstract
Background
Anesthetic techniques are designed to minimize intraoperative surgical bed bleeding which is a major problem that may interfere with precision, surgery duration, or postoperative wound healing. The main reason for reoperation and/or mortality in children who have had tonsillectomies is post-tonsillectomy hemorrhage. We evaluate the local application effect of tranexamic acid and lidocaine local infiltration in the tonsillar bed during tonsillectomy surgery on postoperative analgesia and bleeding.

Results
FLACC scores showed a statistically significant reduction in the first 24 h in group T (P < 0.05). Post-tonsillectomy hemorrhage was significantly minimized in group T. No complications were recorded following the local application of tranexamic acid and local lidocaine infiltration inside the tonsil bed.

Conclusions
Local infiltration of lidocaine provides adequate postoperative analgesia, and tranexamic acid application during tonsillectomy surgery minimizes postoperative bleeding and shortens surgery duration.

Trial registration
This study was preregistered with the Clinical Trials Registry (NCT05817474).
Photocatalytic degradation of azithromycin formulation in aqueous solution by doped titanium dioxide/fiberglass-rubberized silicone photocatalytic membrane
Authors: Lupu Giovanina-Iuliana , Orbeci Cristina , Bobirică Constantin , Bobirică Liliana , Lazăr Elena Sorana , Pandele-Cusu Jeanina , Verziu Marian Nicolae , Pîrvu Cristian , Irodia Roberta-Geanina 
Published: November 2023

AbstractThe objective of this work was to develop a novel photocatalytic membrane for the photocatalytic degradation of azithromycin formulation from aqueous solutions which, in addition to a high photocatalytic activity, should have a good mechanical and physico-chemical stability over time. Thus, the Nb-TiO2 and Nb-Fe-TiO2 photocatalysts were prepared by the solution combustion synthesis method, and then they were manually embedded in a fiberglass – rubberized silicone support. The mineralogical, morphological, and structural characterization of the obtained materials showed that both niobium and iron replace titanium in the titanium dioxide network, thus confirming the synthesis of new photocatalysts. The results of the photocatalytic oxidation tests showed a good photocatalytic activity of the developed photocatalytic membranes (degradation efficiency of up to 70% in the first 15 min of irradiation), this being on the one hand attributed to the increase of the specific surface of the photocatalyst by introducing niobium into the photocatalyst structure, and on the other hand due to the triggering of the Fenton photo oxidation mechanism due to the presence of trivalent iron in the photocatalyst structure. Also, the results indicated an excellent mechanical and physico-chemical resistance of the photocatalytic membranes, they are being practically inert to the harsh conditions in the photocatalytic reactor.
The identification, goals and principles of difficult-to-treat inflammatory arthritis: a consensus statement
Authors: El Miedany Yasser , Abu-Zaid Mohammed Hassan , El Gaafary Maha , Mansour Mona , Elwy Mohamed , Palmer Deborah , Fathi Nihal , Hassan Waleed , Mortada Mohamed , Eissa Mervat , Tabra Samar Abdelhamed , Galal Salwa , Fouad Nermeen , Ibrahim Rehab Ali , Medhat Basma , Adel Yasmin , Ghaleb Rasha , Saber Sally , Gadallah Naglaa , Elwakil Walaa 
Published: November 2023

Abstract
Background
Despite the recent advances in the management of inflammatory arthritis, a considerable proportion of arthritis patients remain symptomatic. This cohort has recently been identified as ‘difficult to treat’ (D2T). In view of the limited evidence base, management of these patients has been a challenge particularly in view of its associated significant economic health burden. A better understanding of the D2T may help recognise or develop new therapeutic targets and facilitate earlier intervention in the disease course to prevent the progression of such condition.
The aim of this work is to address the unmet needs in the management of D2T arthritis and develop a comprehensive approach towards the identification and proper assessment of those patients.

Results
At the completion of round 3 Delphi process, a total of 20 items were obtained and divided into 5 domains. From 88.9 to 100% of respondents agreed with the recommendations (ranks 7–9). All 20 of the clinical standards that the scientific committee identified were agreed upon in terms of wording, recommendation grade, and level of evidence (i.e. 75% of respondents strongly agreed or agreed).

Conclusion
D2T inflammatory arthritis remains a relevant clinical challenge, despite the endorsement of the treat-to-target approach and the availability of a broad range of targeted arthritis medications. This study provided a comprehensive definition of the condition to facilitate the identification of this patients’ group. It also highlighted the goals and principles aiming at providing an effective framework for D2T assessment, closely monitor and set up a strategy to intervene in standard clinical practice.
Standardized In Vitro Models of Human Adipose Tissue Reveal Metabolic Flexibility in Brown Adipocyte Thermogenesis
Authors: Cero Cheryl , Shu Weiguo , Reese Amy L , Douglas Diana , Maddox Michael , Singh Ajeet P , Ali Sahara L , Zhu Alexander R , Katz Jacqueline M , Pierce Anne E , Long Kelly T , Nilubol Naris , Cypess Raymond H , Jacobs Jonathan L , Tian Fang , Cypess Aaron M 
Published: November 2023

Abstract
Functional human brown and white adipose tissue (BAT and WAT) are vital for thermoregulation and nutritional homeostasis, while obesity and other stressors lead, respectively, to cold intolerance and metabolic disease. Understanding BAT and WAT physiology and dysfunction necessitates clinical trials complemented by mechanistic experiments at the cellular level. These require standardized in vitro models, currently lacking, that establish references for gene expression and function. We generated and characterized a pair of immortalized, clonal human brown (hBA) and white (hWA) preadipocytes derived from the perirenal and subcutaneous depots, respectively, of a 40-year-old male individual. Cells were immortalized with hTERT and confirmed to be of a mesenchymal, nonhematopoietic lineage based on fluorescence-activated cell sorting and DNA barcoding. Functional assessments showed that the hWA and hBA phenocopied primary adipocytes in terms of adrenergic signaling, lipolysis, and thermogenesis. Compared to hWA, hBA were metabolically distinct, with higher rates of glucose uptake and lactate metabolism, and greater basal, maximal, and nonmitochondrial respiration, providing a mechanistic explanation for the association between obesity and BAT dysfunction. The hBA also responded to the stress of maximal respiration by using both endogenous and exogenous fatty acids. In contrast to certain mouse models, hBA adrenergic thermogenesis was mediated by several mechanisms, not principally via uncoupling protein 1 (UCP1). Transcriptomics via RNA-seq were consistent with the functional studies and established a molecular signature for each cell type before and after differentiation. These standardized cells are anticipated to become a common resource for future physiological, pharmacological, and genetic studies of human adipocytes.
The Big (Genetic) Sort? A Research Note on Migration Patterns and Their Genetic Imprint in the United Kingdom
Authors: Furuya Shiro , Liu Jihua , Sun Zhongxuan , Lu Qiongshi , Fletcher Jason M. 
Published: November 2023

Abstract
This research note reinvestigates Abdellaoui et al.’s (2019) findings that genetically selective migration may lead to persistent and accumulating socioeconomic and health inequalities between types (coal mining or non–coal mining) of places in the United Kingdom. Their migration measure classified migrants who moved to the same type of place (coal mining to coal mining or non–coal mining to non–coal mining) into “stay” categories, preventing them from distinguishing migrants from nonmigrants. We reinvestigate the question of genetically selective migration by examining migration patterns between places rather than place types and find genetic selectivity in whether people migrate and where. For example, we find evidence of positive selection: people with genetic variants correlated with better education moved from non–coal mining to coal mining places with our measure of migration. Such findings were obscured in earlier work that could not distinguish nonmigrants from migrants.
CEO Activism and Firm Value
Authors: Mkrtchyan Anahit , Sandvik Jason , Zhu Vivi Z. 
Published: November 2023

We investigate the increasingly common practice of chief executive officers (CEOs) taking public stances on social and political issues (CEO activism). We find that CEO activism stems from a CEO’s personal ideology and its alignment with investor, employee, and customer ideologies. We show that CEO activism results in positive market reactions. Furthermore, firms with CEO activism realize increased shareholdings from investors with a greater liberal leaning, who rebalance their portfolios toward these firms. Our results suggest that investors’ socio-political preferences are an important channel through which CEO activism affects equity demand and stock prices. Notably, CEOs are less likely to be fired when their activist stances generate positive market responses. This paper was accepted by Victoria Ivashina, finance. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2023.4971 .
A systematic review of the clinical profile of patients with bubonic plague and the outcome measures used in research settings
Authors: Bourner Josephine , Andriamarohasina Lovarivelo , Salam Alex , Kayem Nzelle Delphine , Randremanana Rindra , Olliaro Piero 
Published: November 2023

Background
Plague is a zoonotic disease that, despite affecting humans for more than 5000 years, has historically been the subject of limited drug development activity. Drugs that are currently recommended in treatment guidelines have been approved based on animal studies alone–no pivotal clinical trials in humans have yet been completed. As a result of the sparse clinical research attention received, there are a number of methodological challenges that need to be addressed in order to facilitate the collection of clinical trial data that can meaningfully inform clinicians and policy-makers. One such challenge is the identification of clinically-relevant endpoints, which are informed by understanding the clinical characterisation of the disease–how it presents and evolves over time, and important patient outcomes, and how these can be modified by treatment.

Methodology/Principal findings
This systematic review aims to summarise the clinical profile of 1343 patients with bubonic plague described in 87 publications, identified by searching bibliographic databases for studies that meet pre-defined eligibility criteria. The majority of studies were individual case reports. A diverse group of signs and symptoms were reported at baseline and post-baseline timepoints–the most common of which was presence of a bubo, for which limited descriptive and longitudinal information was available. Death occurred in 15% of patients; although this varied from an average 10% in high-income countries to an average 17% in low- and middle-income countries. The median time to death was 1 day, ranging from 0 to 16 days.

Conclusions/Significance
This systematic review elucidates the restrictions that limited disease characterisation places on clinical trials for infectious diseases such as plague, which not only impacts the definition of trial endpoints but has the knock-on effect of challenging the interpretation of a trial’s results. For this reason and despite interventional trials for plague having taken place, questions around optimal treatment for plague persist.
The practice of defensive medicine among Jordanian physicians: A cross sectional study
Authors: Al-Balas Qosay , Altawalbeh Shoroq , Rinaldi Carmela , Ibrahim Ibtihal 
Published: November 2023

Background
Defensive medicine (DM) is a deviation from medical practice that is induced primarily by a threat of liability. While the DM behavior is well studied in the developed countries, little is known in developing countries and never been evaluated in Jordan.

Objective
To evaluate the prevalence of DM practice in Jordan among physicians and to investigate reasons behind its practice and potential strategies to alleviate this practice.

Methods
In this Cross-sectional study, self-administered questionnaire was distributed to a sample of physicians in both public and private sectors in Jordan. The collection period was from Jan 2021 to June 2021. The prevalence of DM practice was estimated among the study sample. Frequency scores of different DM behaviors, reasons of DM behaviors, and effectiveness of strategies in changing DM behaviors were summarized as average frequency scores with standard deviations. Multivariable linear regression models were conducted to evaluate potential predictors of total assurance and avoidance behavior scores.

Results
A total of 175 Jordanian physicians completed the survey. The prevalence of adopting (or witnessing) DM behaviors among the study sample was 68% (n = 119). Diagnostic laboratory exams followed by prescribed medications were the most practiced behaviors in excessive rate during a typical working week. Unfavorable legislation for the physician was reported as the headmost reason for practicing DM, followed by pressure from the public and mass media opinion. Continuous update of knowledge, abilities, and performance and following specific protocols and/or appropriate clinical evidence and appropriate multidisciplinary and multi-professional communication were the most effective strategies that can mitigate DM behaviors.

Conclusions
Defensive medicine practice is common among Jordanian physicians with concerns about increasing pattern in the future.