bluuebunny/crossref_metadata_2025_split huggingface dataset:
IOA-244 is a Non–ATP-competitive, Highly Selective, Tolerable PI3K Delta Inhibitor That Targets Solid Tumors and Breaks Immune Tolerance
Authors: Johnson Zoë , Tarantelli Chiara , Civanelli Elisa , Cascione Luciano , Spriano Filippo , Fraser Amy , Shah Pritom , Nomanbhoy Tyzoon , Napoli Sara , Rinaldi Andrea , Niewola-Staszkowska Karolina , Lahn Michael , Perrin Dominique , Wenes Mathias , Migliorini Denis , Bertoni Francesco , van der Veen Lars , Di Conza Giusy 
Published: March 2023

PI3K delta (PI3Kδ) inhibitors are used to treat lymphomas but safety concerns and limited target selectivity curbed their clinical usefulness. PI3Kδ inhibition in solid tumors has recently emerged as a potential novel anticancer therapy through the modulation of T-cell responses and direct antitumor activity. Here we report the exploration of IOA-244/MSC2360844, a first-in-class non–ATP-competitive PI3Kδ inhibitor, for the treatment of solid tumors. We confirm IOA-244’s selectivity as tested against a large set of kinases, enzymes, and receptors. IOA-244 inhibits the in vitro growth of lymphoma cells and its activity correlates with the expression levels of PIK3CD, suggesting cancer cell–intrinsic effects of IOA-244. Importantly, IOA-244 inhibits regulatory T cell proliferation while having limited antiproliferative effects on conventional CD4+ T cells and no effect on CD8+ T cells. Instead, treatment of CD8 T cells with IOA-244 during activation, favors the differentiation of memory-like, long-lived CD8, known to have increased antitumor capacity. These data highlight immune-modulatory properties that can be exploited in solid tumors. In CT26 colorectal and Lewis lung carcinoma lung cancer models, IOA-244 sensitized the tumors to anti-PD-1 (programmed cell death protein 1) treatment, with similar activity in the Pan-02 pancreatic and A20 lymphoma syngeneic mouse models. IOA-244 reshaped the balance of tumor-infiltrating cells, favoring infiltration of CD8 and natural killer cells, while decreasing suppressive immune cells. IOA-244 presented no detectable safety concerns in animal studies and is currently in clinical phase Ib/II investigation in solid and hematologic tumors.Significance:IOA-244 is a first-in-class non–ATP-competitive, PI3Kδ inhibitor with direct antitumor in vitro activity correlated with PI3Kδ expression. The ability to modulate T cells, in vivo antitumor activity in various models with limited toxicity in animal studies provides the rationale for the ongoing trials in patients with solid tumors and hematologic cancers.
IL11 (Interleukin-11) Causes Emphysematous Lung Disease in a Mouse Model of Marfan Syndrome
Authors: Ng Benjamin , Xie Chen , Su Liping , Kuthubudeen Fathima F. , Kwek Xiu-Yi , Yeong Daryl , Pua Chee Jian , Cook Stuart A. , Lim Wei-Wen 
Published: March 2023

Background:
Marfan Syndrome (MFS) is an inherited connective tissue disorder caused by mutations in the FBN1 (fibrillin-1) gene. Lung abnormalities are common in MFS, but their pathogenesis is poorly understood. IL11 (interleukin-11) causes aortic disease in a mouse model of MFS and was studied here in the lung.

Methods:

We examined histological and molecular phenotypes in the lungs of
Fbn1
C1041G/+
mice (mouse model of Marfan Syndrome [mMFS]), an established mouse model of MFS. To identify IL11-expressing cells, we used immunohistochemistry on lungs of 4- and 16-week-old
Fbn1
C1041G/+
:
Il11
EGFP/+
reporter mice. We studied the effects of IL11 inhibition by RT-qPCR, immunoblots and histopathology in lungs from genetic or pharmacologic models: (1) 16-week-old IL11 receptor (IL11RA) knockout mMFS mice (
Fbn1
C1041G/+
:
Il11ra1
−/−
mice) and (2) in mMFS mice administered IgG control or interleukin-11 receptor antibodies twice weekly from 4 to 24 weeks of age.

Results:

mMFS lungs showed progressive loss and enlargement of distal airspaces associated with increased proinflammatory and profibrotic gene expression as well as matrix metalloproteinases 2, 9, and 12. IL11 was increased in mMFS lungs and localized to smooth muscle and endothelial cells in young mMFS mice in the
Fbn1
C1041G/+
:
Il11
EGFP/+
reporter strain and in fibroblasts, in older mice. In mMFS mice, genetic (
Fbn1
C1041G/+
:
Il11ra1
−/−
) or pharmacologic (anti-interleukin-11 receptor) inhibition of IL11 signaling reduced lung emphysema, fibrosis, and inflammation. This protective effect was associated with reduced pathogenic ERK1/2 signaling and lower metalloproteinase 2, 9, and 12 expression.

Conclusions:
IL11 causes lung disease in mMFS. This reveals a shared IL11-driven disease mechanism in lung and aorta in MFS and suggests inhibition of IL11 signaling as a holistic approach for treating multiorgan morbidity in MFS.
Intracardiac Echocardiography–Guided Implantation for Proximal Left Bundle Branch Pacing
Authors: Kuang XiaoHui , Zhang Xi , Cui YanJu , Wei FeiYu , Wu Peng , Gao XiaoLong , Xiang Hong , Wu HaiYan , Wang Li-Lin , Zhou Xiaohong , Huang Weijian , Fan Jie 
Published: March 2023

Background:
Multiple screw-in attempts under fluoroscopy are often needed to place the pacing lead tip near or at the left bundle branch (LBB). This study was conducted to evaluate the feasibility of implanting an LBB pacing lead in the proximal LBB (PLBB) guided by intracardiac echocardiography (ICE).

Methods:
The distribution of the LBB was initially determined by ICE anatomic imaging and 3-dimensional electrical mapping of His and LBB potentials in 20 patients in the first parts of the study. In the second part, 101 consecutive pacemaker-indicated patients were randomized into the ICE-guided and non-ICE groups for LBB pacing implantation. The procedural details and electrophysiological characteristics of the 2 groups were compared.

Results:

In the first part of the study, PLBB was identified at 10 to 20 mm from the tricuspid annulus toward the apex with an area of 4.5±1.1 cm
2
. In the second part, the number of lead screw-in attempts in the septum was fewer in the ICE group than in the non-ICE group (1.43±0.62 versus 1.98±0.75,
P
=0.0002). The duration of the procedure (26±8 versus 43±9 minutes,
P
<0.001) and fluoroscopy for LBB pacing implantation (7.4±1.8 versus 10.7±2.4 minutes,
P
<0.001) in the ICE group was significantly shorter than those in the non-ICE group. LBB pacing in the ICE group generated a lesser QRS duration with more cases of LBB trunk pacing (46.8% versus 25%,
P
=0.031) and PLBB (91.5% versus 72.7%,
P
=0.0267) pacing compared with that in the non-ICE group.

Conclusions:
The basal left ventricular septum can be better visualized using ICE. ICE-guided PLBB pacing is feasible and safe, with a shorter duration required for the procedure and fluoroscopy, and generates greater LBB trunk pacing and PLBB pacing.
Safety and Efficacy of MCA‐M2 Thrombectomy in Delayed Time Window: A Propensity Score Analysis From the STAR Registry
Authors: Limaye Kaustubh , Koo Andrew B. , Havenon Adam de , Kasab Sami Al , Bohnstedt Bradley , Maier Ilko L. , Psychogios Marios‐Nikos , Wolfe Stacey , Arthur Adam , Kan Peter , Kim Joon‐Tae , Leacy Reade De , Osbun Joshua , Rai Ansaar , Jabbour Pascal , Park Min , Crosa Roberto , Mascitelli Justin , Levitt Michael R. , Polifka Adam , Casagrande Walter , Yoshimura Shinichi , Williamson Richard W. , Gory Benjamin , Mokin Maxim , Fragata Isabel , Romano Daniele G. , Chowdry Shakeel , Shaban Amir , Moss Mark , Behme Daniel , Spiotta Alejandro M. , Matouk Charles ,   For the Stroke Thrombectomy and Aneurysm Registry (STAR) Collaborators
Published: March 2023

Background
Mechanical thrombectomy of middle cerebral artery M2 segment occlusion of the middle cerebral artery has reported safety and efficacy in recent post‐hoc and observational studies. However, there is no known benefit of mechanical thrombectomy for patients with M2 segment occlusions in the delayed time window (>6 hours).

Methods
The Stroke Thrombectomy and Aneurysm Registry (STAR) is a prospective, multicenter, nonrandomized observational study registry for acute ischemic stroke thrombectomy and aneurysm treatment. We analyzed all patients who underwent mechanical thrombectomy within the late time window (>6 hours from symptom onset) involving isolated M2 occlusions. We used propensity score matching to select a comparison group of patients who underwent mechanical thrombectomy for M1 occlusion in the same time window.

Results

Of 1083 consecutive patients analyzed, propensity matching yielded 180 well matched M1 and M2 pairs. Baseline demographics were well balanced between the groups (M1 and M2). Alberta stroke program early CT score (7.6±1.7 versus 8.3±1.5;
P
<0.001) was higher in the M2 group. There was a trend towards less complete recanalization (Thrombolysis in Cerebral Infarction 3) 46.1% versus 39.9% (
P
=0.053) in the middle cerebral artery M2 segment cohort. However, successful recanalization (Thrombolysis in Cerebral Infarction 2b‐3) was better in middle cerebral artery M2 segment cohort (85% versus 90.5%;
P
=0.053). Postprocedural asymptomatic hemorrhage rates were similar (29.4% versus 27.8%;
P
=0.816), but symptomatic hemorrhage rates were higher in the M1 group (7.2% versus 2.2%;
P
=0.047). Rates of good clinical outcome (modified Rankin scale 0–2) were similar at final follow‐up (43.9% versus 46.7%;
P
=0.672). The overall mortality was also similar between the cohorts (12.8% versus 13.9%;
P
=0.877).

Conclusion
In our analysis of the Stroke Thrombectomy and Aneurysm Registry, M2 occlusions not only achieved similar rates of recanalization and good functional outcome compared with M1 occlusions in a delayed time window (6–24 hours from last normal) but also had less symptomatic intracranial hemorrhage.
مسميات الحرس الملكي في النصوص المصرية
Authors: عباس محمد رأفت 
Published: March 2023

The state in Ancient Egypt depended on the central domination of the king in the political, administrative, military and economic affairs. Therefore, the importance of the Royal Guards appeared as they were responsible for the safety and protection of the king, who was the axis of domination in the Egyptian civilization. The great importance of the Royal Guards appeared clearly in the Egyptian texts; for example, we found it in the famous instructions of King Kheti to his son "Meri-ka-re" from the Tenth Dynasty of the First Intermediate Period. Also, it was found in the various texts of the New Kingdom, as in the famous epic text of King Ramesses II on the battle of Kadesh from the Nineteenth Dynasty, where the guards of the king succeed in saving the King's life in the harsh moments of fighting. Hence, I aimed in my research to browse the various names and titles of the Royal Guards, mentioned in the Egyptian texts and titles, from the beginning of the Old Kingdom to the end of the New Kingdom.
I divided my research paper into four parts, the first one discussed the principal name of the Royal Guards in the Egyptian texts Smsw, meaning retainers, followers or servants, besides referring to the principal name of the royal guards in the Egyptian texts, ranging from the beginning of the First Intermediate Period and the Middle Kingdom to the various periods of the New Kingdom. In the other three parts of my research paper, I discussed the various names and tides of the Royal Guards in the Old Kingdom, Middle Kingdom and New Kingdom in the different texts and titles of these respective historical periods.
استخدام النقوش الكتابية كمصدر لتاريخ مدن غرب الأندلس في العصر الإسلامي
Authors: سالم سحر السيد عبد العزيز 
Published: March 2023

Inscriptions are considered to be the most important source of information in Islamic history. Historians depend on inscriptions and original documents when dating events, because those inscriptions are neutral and non-biased. They are also contemporary witnesses to those events that they record.
This research is dealing with some inscriptions of 5 cities in the West of Andalusia; Badajoz, Merida, Caceres, Trujillo, and Reina. One of those inscriptions has corrected a title of a very distinguished person; others has filled in the gaps of some historical events, which we r e not mentioned in the sources. In addition, they mentioned some people who played a major role, whether politically or scientifically, in the society of this part of Andalusia.
كتابات المسند وكتابات الزبور في اليمن القديم
Authors: الصلوي إبراهيم محمد 
Published: March 2023

The Classical Arabian sources, such as (kitab Al-Iklìl, viii), mentioned that Himyar had two types of pre-Islamic texts. One type was called (Masānid), written in (Musnad script). The other type was called (Zubur), and was written in (Zabûr script). But those sources did not mention the differences between the two types of texts. A first reply of such queries appeared in modern period, after the deciphering of more than thousands of monumental inscriptions and number of texts written on wood.
Through comparing the script, writing-materials, language, and contents of the two types of inscriptions, this study aimed to answer the question: Why did the ancient Yemeni used two types of texts?
الأخطاء الكتابية علا الكتابات الشاهدية في اليمن
Authors: الحداد عبد الله عبد السلام 
Published: March 2023

Sadah is located in the western north of San' a, the capital of Yemen, and is considered to be the country's first city as regards number of tomb stones scattered in the northern Cemetery known as El 'Arar and in its Southern Cemetery known as El Qaredeen. These 2 Cemeteries contain thousands of tombstones. In addition, there are some 60 tombstones inside Al-Emam Al-Hady Mosque.
This research studies 85 tombstones of Sadah Cemetery and Al Emam Al Hady Mosque. Many previous studies have been concerned more about the context, type of calligraphies and its decorative styl es , names and titles of the deceased, its Quranic verses and religious sentences. However, none of those studies were concerned with the grammatical mistakes in the inscription of these tombstones.
Evaluation of Phytochemical Contents, Antimicrobial, and antioxidant Potential of Haloxylon Griffithii Collected From Northern Region of Balochistan, Pakistan
Authors: Asif Rizwan , Ali Muhammad , Mazhar Modasrah , Mustafa Madiha , Yasmin Riffat 
Published: March 2023

Background The therapeutic potential of Haloxylon griffithii found in northern region of Balochistan, so far has been neglected. Purpose The current study was aimed to assess the phytochemicals and pharmacological potential of fractions isolated from H griffithii. Research Design During phytochemicals analysis of H griffithii using GC/MS showed various bioactive compounds like alkaloids, flavonoids, terpenoids, tannins, saponins, and carboxylic acids. In vitro antioxidant activity of H griffithii was determined by 2, 2’- diphenyl-1-picrylhydrazyl (DPPH) assay. Disc diffusion method was used to evaluate the antimicrobial activity. Results The quantitative analysis of ethyl acetate showed highest total flavonoid contents (1.19 ± .05) while ethanol with lowest value (.52 ± .01). The total phenolic contents in ethyle acetate was 1.50 ± .42, whereas ethanol showed lowest value (.77 ± .02). Ethanol exhibited excellent (88.68 ± 3.0) free radical scavenging potential measured by 1,1-diphenyl-2-picryl-hydrazyl radical scavenging assay. For antimicrobial activity, different bacterial and fungal strains like B subtilis, S aureus, E coli, S typhi, C albicans, and A. niger were selected . The essential oil showed maximum % inhibition diameter (9 mm) against B. Subtillus and (5 mm) against C albicans, respectively . The ethyl acetate presented % inhibition diameter (9 mm) against S aureus and (6 mm) against A niger. Anti-urease activity also showed positive response. Conclusions The presence of high (%) bioactive compounds with great therapeutic potential suggest that H griffithii can be used as natural alternative of synthetic drugs without side effects.
Quantitative evaluation of metamictisation of columbite-(Mn) from rare-element pegmatites using Raman spectroscopy
Authors: Hao Yuanyuan , Feng Yonggang , Liang Ting , Brzozowski Matthew , Ju Minghui , Zhou Ruili , Wang Yan 
Published: March 2023

AbstractRaman spectroscopic analysis was performed on columbite-(Mn) samples from a variety of previously studied rare-element pegmatites in Xinjiang, China, including the Jing'erquan No. 1 spodumene-subtype, Dakalasu No. 1 beryl–columbite-subtype and Kalu'an spodumene-subtype pegmatites, to quantify the relationship between the degree of metamictisation of columbite and Raman spectra. For all of the analysed columbites-(Mn), the position (p) and the full width at half maximum (FWHM) of the strongest band, A1g vibration mode related to the Nb/Ta–O bond, in the Raman spectra have a negative correlation. Combined with previously determined U–Pb isotopic data and major–minor-element data for the columbites-(Mn), the degree of metamictisation was quantified using the alpha-decay dose (D) and displacement per atom (dpa), both of which were corrected for effects caused by annealing. The results demonstrate that the columbite-(Mn) from Jing'erquan and Kalu'an are very crystalline, whereas those from Dakalasu are transitional between crystalline and amorphous stages. The main factor influencing the key parameters, i.e. band position and FWHM, of the strongest Raman band of columbite-(Mn) is metamictisation caused by radiation damage, whereas composition and crystal orientation have limited influence. A set of equations are established to quantify the degree of metamictisation of columbite using the band position and the full width at half maximum: FWHM = 8.309 × ln(aD) + 30.11 (R2 = 0.9861); p = –5.187 × ln(aD) + 867.09 (R2 = 0.966); FWHM = 8.1453 × ln(adpa) + 48.425 (R2 = 0.9822); and p = –5.078 × ln(adpa) + 855.67 (R2 = 0.9594).
Grpel2 maintains cardiomyocyte survival in diabetic cardiomyopathy through DLST-mediated mitochondrial dysfunction: a proof-of-concept study
Authors: Yang Rongjin , Zhang Xiaomeng , Zhang Yunyun , Wang Yingfan , Li Man , Meng Yuancui , Wang Jianbang , Wen Xue , Yu Jun , Chang Pan 
Published: March 2023

AbstractBackgroundDiabetic cardiomyopathy (DCM) has been considered as a major threat to health in individuals with diabetes. GrpE-like 2 (Grpel2), a nucleotide exchange factor, has been shown to regulate mitochondrial import process to maintain mitochondrial homeostasis. However, the effect and mechanism of Grpel2 in DCM remain unknown.MethodsThe streptozotocin (STZ)-induced DCM mice model and high glucose (HG)-treated cardiomyocytes were established. Overexpression of cardiac-specific Grpel2 was performed by intramyocardial injection of adeno-associated virus serotype 9 (AAV9). Bioinformatics analysis, co-immunoprecipitation (co-IP), transcriptomics profiling and functional experiments were used to explore molecular mechanism of Grpel2 in DCM.ResultsHere, we found that Grpel2 was decreased in DCM induced by STZ. Overexpression of cardiac-specific Grpel2 alleviated cardiac dysfunction and structural remodeling in DCM. In both diabetic hearts and HG-treated cardiomyocytes, Grpel2 overexpression attenuated apoptosis and mitochondrial dysfunction, including decreased mitochondrial ROS production, increased mitochondrial respiratory capacities and increased mitochondrial membrane potential. Mechanistically, Grpel2 interacted with dihydrolipoyl succinyltransferase (DLST), which positively mediated the import process of DLST into mitochondria under HG conditions. Furthermore, the protective effects of Grpel2 overexpression on mitochondrial function and cell survival were blocked by siRNA knockdown of DLST. Moreover, Nr2f6 bond to the Grpel2 promoter region and positively regulated its transcription.ConclusionOur study provides for the first time evidence that Grpel2 overexpression exerts a protective effect against mitochondrial dysfunction and apoptosis in DCM by maintaining the import of DLST into mitochondria. These findings suggest that targeting Grpel2 might be a promising therapeutic strategy for the treatment of patients with DCM.
Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications
Authors: Gonzalez-Ortiz Fernando , Kac Przemysław R. , Brum Wagner S. , Zetterberg Henrik , Blennow Kaj , Karikari Thomas K. 
Published: March 2023

AbstractAs the leading cause of dementia, Alzheimer's disease (AD) is a major burden on affected individuals, their families and caregivers, and healthcare systems. Although AD can be identified and diagnosed by cerebrospinal fluid or neuroimaging biomarkers that concord with neuropathological evidence and clinical symptoms, challenges regarding practicality and accessibility hinder their widespread availability and implementation. Consequently, many people with suspected cognitive impairment due to AD do not receive a biomarker-supported diagnosis. Blood biomarkers have the capacity to help expand access to AD diagnostics worldwide. One such promising biomarker is plasma phosphorylated tau (p-tau), which has demonstrated specificity to AD versus non-AD neurodegenerative diseases, and will be extremely important to inform on clinical diagnosis and eligibility for therapies that have recently been approved. This review provides an update on the diagnostic and prognostic performances of plasma p-tau181, p-tau217 and p-tau231, and their associations with in vivo and autopsy-verified diagnosis and pathological hallmarks. Additionally, we discuss potential applications and unanswered questions of plasma p-tau for therapeutic trials, given their recent addition to the biomarker toolbox for participant screening, recruitment and during-trial monitoring. Outstanding questions include assay standardization, threshold generation and biomarker verification in diverse cohorts reflective of the wider community attending memory clinics and included in clinical trials.
Multiorgan failure and death from a mixed Dettol and Clorox poisoning: a case report
Authors: Alao David Olukolade , Moin Kinza , Abraham Snaha 
Published: March 2023

Abstract
Background
Dettol and sodium hypochlorite have wide use as household disinfectants and cleaners. Intentional and nonintentional ingestion are widespread, mainly causing mild symptoms that require no specific treatment. However, severe complications can occur when large volumes are ingested. Both products affect the same organ systems in the body, which can result in fatalities when ingested together.

Case presentation
We present the case of a 26-year-old Asian man who died from multiorgan failure after deliberately ingesting a presumed large volume of Dettol and sodium hypochlorite. The case illustrates the severe complications that can occur with mixed ingestion of these commonly used household products.

Conclusion
Clinicians must be aware of the increased risk of death caused by the combined ingestion of chloroxylenol and sodium hypochlorite.