bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical presentation, diagnostic findings and outcome of dogs undergoing surgical resection for intracranial meningioma: 101 dogs
Authors: Forward Alexander K. , Volk Holger Andreas , Cherubini Giunio Bruto , Harcourt-Brown Tom , Plessas Ioannis N. , Garosi Laurent , De Decker Steven 
Published: March 2022

AbstractBackgroundMeningioma is the most common primary brain neoplasm in dogs. Further information is required regarding the expected long-term prognosis of dogs following the surgical resection of an intracranial meningioma together with the influence of adjunctive therapies. Whilst there have been several studies reporting the long-term outcome of intracranial meningioma resection following surgery alone, surgery with the use of an ultrasonic aspirator, surgery combined with radiotherapy and surgery combined with the addition of hydroxyurea, it is currently unclear which type of adjunctive therapy is associated with the most favourable outcomes. The objective of this study is to describe the presentation and outcome of dogs undergoing surgery for the resection of an intracranial meningioma and the effect of clinical factors, adjunctive therapies and meningioma histopathological subtype on the long-term outcome.ResultsA hundred and one dogs that had intracranial surgery for meningioma resection were investigated from four referral centres. 94% of dogs survived to hospital discharge with a median survival time of 386 days. Approximately 50% of dogs survived for less than a year, 25% survived between 1 and 2 years, 15% survived between 2 and 3 years and 10% survived for greater than 3 years following discharge from hospital. One or more adjunctive therapies were used in 75 dogs and the analysis of the data did not reveal a clear benefit of a specific type of adjunctive therapy. Those dogs that had a transfrontal approach had a significantly reduced survival time (MST 184 days) compared to those dogs that had a rostrotentorial approach (MST 646 days;p < 0.05). There was no association between meningioma subtype and survival time.ConclusionsThis study did not identify a clear benefit of a specific type of adjunctive therapy on the survival time. Dogs that had a transfrontal approach had a significantly reduced survival time. Intracranial surgery for meningioma resection offers an excellent prognosis for survival to discharge from hospital with a median long term survival time of 386 days.
The role of the M-band myomesin proteins in muscle integrity and cardiac disease
Authors: Lamber Ekaterina P. , Guicheney Pascale , Pinotsis Nikos 
Published: March 2022

AbstractTransversal structural elements in cross-striated muscles, such as the M-band or the Z-disc, anchor and mechanically stabilize the contractile apparatus and its minimal unit—the sarcomere. The ability of proteins to target and interact with these structural sarcomeric elements is an inevitable necessity for the correct assembly and functionality of the myofibrillar apparatus. Specifically, the M-band is a well-recognized mechanical and signaling hub dealing with active forces during contraction, while impairment of its function leads to disease and death. Research on the M-band architecture is focusing on the assembly and interactions of the three major filamentous proteins in the region, mainly the three myomesin proteins including their embryonic heart (EH) isoform, titin and obscurin. These proteins form the basic filamentous network of the M-band, interacting with each other as also with additional proteins in the region that are involved in signaling, energetic or mechanosensitive processes. While myomesin-1, titin and obscurin are found in every muscle, the expression levels of myomesin-2 (also known as M-protein) and myomesin-3 are tissue specific: myomesin-2 is mainly expressed in the cardiac and fast skeletal muscles, while myomesin-3 is mainly expressed in intermediate muscles and specific regions of the cardiac muscle. Furthermore, EH-myomesin apart from its role during embryonic stages, is present in adults with specific cardiac diseases. The current work in structural, molecular, and cellular biology as well as in animal models, provides important details about the assembly of myomesin-1, obscurin and titin, the information however about the myomesin-2 and -3, such as their interactions, localization and structural details remain very limited. Remarkably, an increasing number of reports is linking all three myomesin proteins and particularly myomesin-2 to serious cardiovascular diseases suggesting that this protein family could be more important than originally thought. In this review we will focus on the myomesin protein family, the myomesin interactions and structural differences between isoforms and we will provide the most recent evidence why the structurally and biophysically unexplored myomesin-2 and myomesin-3 are emerging as hot targets for understanding muscle function and disease.
Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis
Authors: Xue Song-tao , Zheng Bin , Cao Shi-qiang , Ding Jian-cheng , Hu Guo-sheng , Liu Wen , Chen Chun 
Published: March 2022

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is a common invasive malignancy worldwide with poor clinical outcomes. Increasing amount of long non-coding RNAs (lncRNAs) have been reported to be involved in cancer development. However, lncRNAs that are functional in ESCC and the underlying molecular mechanisms remain largely unknown.

Methods
Transcriptomic analysis was performed to identify dysregulated lncRNAs in ESCC tissue samples. The high expression of LINC00680 in ESCC was validated by RT-qPCR, and the oncogenic functions of LINC00680 was investigated by cell proliferation, colony formation, migration and invasion assays in ESCC cells in vitro and xenografts derived from ESCC cells in mice. RNA-seq, competitive endogenous RNA (ceRNA) network analysis, and luciferase reporter assays were carried out to identify LINC00680 target genes and the microRNAs (miRNAs) bound to LINC00680. Antisense oligonucleotides (ASOs) were used for in vivo treatment.

Results
Transcriptome profiling revealed that a large number of lncRNAs was dysregulated in ESCC tissues. Notably, LINC00680 was highly expressed, and upregulation of LINC00680 was associated with large tumor size, advanced tumor stage, and poor prognosis. Functionally, knockdown of LINC00680 restrained ESCC cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, LINC00680 was found to act as a ceRNA by sponging miR-423-5p to regulate PAK6 (p21-activated kinase 6) expression in ESCC cells. The cell viability and motility inhibition induced by LINC00680 knockdown was significantly reversed upon PAK6 restoration and miR-423-5p inhibition. Furthermore, ASO targeting LINC00680 substantially suppressed ESCC both in vitro and in vivo.

Conclusions
An oncogenic lncRNA, LINC00680, was identified in ESCC, which functions as a ceRNA by sponging miR-423-5p to promote PAK6 expression and ESCC. LINC00680/miR-423-5p/PAK6 axis may serve as promising diagnostic and prognostic biomarkers and therapeutic targets for ESCC.
Lenvatinib inhibits the growth of gastric cancer patient-derived xenografts generated from a heterogeneous population
Authors: Karalis John D. , Yoon Lynn Y. , Hammer Suntrea T. G. , Hong Changjin , Zhu Min , Nassour Ibrahim , Ju Michelle R. , Xiao Shu , Castro-Dubon Esther C. , Agrawal Deepak , Suarez Jorge , Reznik Scott I. , Mansour John C. , Polanco Patricio M. , Yopp Adam C. , Zeh Herbert J. , Hwang Tae Hyun , Zhu Hao , Porembka Matthew R. , Wang Sam C. 
Published: March 2022

Abstract
Background
Lenvatinib is a multitargeted tyrosine kinase inhibitor that is being tested in combination with immune checkpoint inhibitors to treat advanced gastric cancer; however, little data exists regarding the efficacy of lenvatinib monotherapy. Patient-derived xenografts (PDX) are established by engrafting human tumors into immunodeficient mice. The generation of PDXs may be hampered by growth of lymphomas. In this study, we compared the use of mice with different degrees of immunodeficiency to establish PDXs from a diverse cohort of Western gastric cancer patients. We then tested the efficacy of lenvatinib in this system.

Methods
PDXs were established by implanting gastric cancer tissue into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) or Foxn1nu (nude) mice. Tumors from multiple passages from each PDX line were compared histologically and transcriptomically. PDX-bearing mice were randomized to receive the drug delivery vehicle or lenvatinib. After 21 days, the percent tumor volume change (%Δvtumor) was calculated.

Results
23 PDX models were established from Black, non-Hispanic White, Hispanic, and Asian gastric cancer patients. The engraftment rate was 17% (23/139). Tumors implanted into NSG (16%; 18/115) and nude (21%; 5/24) mice had a similar engraftment rate. The rate of lymphoma formation in nude mice (0%; 0/24) was lower than in NSG mice (20%; 23/115; p < 0.05). PDXs derived using both strains maintained histologic and gene expression profiles across passages. Lenvatinib treatment (mean %Δvtumor: -33%) significantly reduced tumor growth as compared to vehicle treatment (mean %Δvtumor: 190%; p < 0.0001).

Conclusions
Nude mice are a superior platform than NSG mice for generating PDXs from gastric cancer patients. Lenvatinib showed promising antitumor activity in PDXs established from a diverse Western patient population and warrants further investigation in gastric cancer.
Non-linear relationship between the body roundness index and incident type 2 diabetes in Japan: a secondary retrospective analysis
Authors: Wu Liling , Pu Hailu , Zhang Man , Hu Haofei , Wan Qijun 
Published: March 2022

Abstract
Background
Body roundness index (BRI) is one of the obesity-related anthropometric indices. However, studies on the relationship between BRI and diabetes risk is limited. The purpose of this study was to explore the relationship between baseline BRI and incident type 2 diabetes mellitus (T2DM) in the Japanese population.

Methods
A retrospective longitudinal study of 15,310 participants in a physical examination program at Murakami Memorial Hospital in Japan from 2004 to 2015. The association between BRI levels and incident T2DM was analyzed by Cox proportional-hazards regression, smooth curve fitting, subgroup analyses, and a set of sensitivity analyses. Receiver operating characteristic curve analysis was used to assess the ability of BRI to predict diabetes.

Result
Baseline BRI levels were elevated in participants who developed T2DM. Baseline BRI levels were positively associated with incident T2DM after adjusting confounding variables (HR = 1.570, 95% CI 1.360–1.811). Additionally, we did a set of sensitivity analyses to ensure the robustness of the results. There was also a non-linear relationship between BRI and incident diabetes in both genders, and the inflection point of BRI was 4.137 in females and 3.146 in males. We found a strong positive correlation between BRI and the incidence of diabetes on the right of the inflection point (Male: HR = 1.827, 95% CI 1.449–2.303; Female: HR = 4.189, 95% CI 1.862–9.421). What’s more, among the anthropometric indices, BRI showed the optimal capability to predict T2DM (Male: AUC = 0.706, 95% CI 0.674–0.738; Female: AUC = 0.735, 95% CI 0.676–0.795).

Conclusion
An elevated BRI level in baseline was independently associated with incident T2DM. Baseline BRI improves the identification of patients at risk of T2DM and may enable early and optimized therapy to improve their outcomes.
Deconvolution of the epigenetic age discloses distinct inter-personal variability in epigenetic aging patterns
Authors: Shahal Tamar , Segev Elad , Konstantinovsky Thomas , Marcus Yonit , Shefer Gabi , Pasmanik-Chor Metsada , Buch Assaf , Ebenstein Yuval , Zimmet Paul , Stern Naftali 
Published: March 2022

AbstractBackgroundThe epigenetic age can now be extrapolated from one of several epigenetic clocks, which are based on age-related changes in DNA methylation levels at specific multiple CpG sites. Accelerated aging, calculated from the discrepancy between the chronological age and the epigenetic age, has shown to predict morbidity and mortality rate. We assumed that deconvolution of epigenetic age to its components could shed light on the diversity of epigenetic, and by inference, on inter-individual variability in the causes of biological aging.ResultsUsing the Horvath original epigenetic clock, we identified several CpG sites linked to distinct genes that quantitatively explain much of the inter-personal variability in epigenetic aging, with CpG sites related to secretagogin and malin being the most variable. We show that equal epigenetic age in different subjects can result from variable contribution size of the same CpG sites to the total epigenetic age. In a healthy cohort, the most variable CpG sites are responsible for accelerated and decelerated epigenetic aging, relative to chronological age.ConclusionsOf the 353 CpG sites that form the basis for the Horvath epigenetic age, we have found the CpG sites that are responsible for accelerated and decelerated epigenetic aging in healthy subjects. However, the relative contribution of each site to aging varies between individuals, leading to variable personal aging patterns. Our findings pave the way to form personalized aging cards allowing the identification of specific genes related to CpG sites, as aging markers, and perhaps treatment of these targets in order to hinder undesirable age drifting.
Examining the interaction of different factors on pointing precision when using handheld laser pointers
Authors: Tse Choi Yeung Andy , Kong Pui Wah , Poh Jun Jie , Fong Daniel T. P. 
Published: March 2022

Abstract
Objective
Laser pointers are common teaching tools used during lessons. The pointing precision may influence the teaching effectiveness. In this study, we examined the effect of four external factors, namely aiming distance, target size, light condition and colour of the laser beam on the pointing precision.

Results
Thirty participants (15 males and 15 females; age = 23.2 ± 4.3) were asked to aim at the target black circles with different sizes (diameters = 4 mm, 8 mm, 12 mm and 16 mm) from five various distances (2 m, 4 m, 6 m, 8 m and 10 m) at two brightness conditions (i.e., bright and dark) using two different coloured laser pointers (red and green). Three aiming parameters, namely number of hits, duration per hit and pointing precision were measured. Results showed that the aiming parameters were the highest with the aiming distance of 2 m and the use of green laser pointer towards larger target sizes regardless of the environmental brightness. Among all factors, aiming distance was the most important external factor that could influence pointing precision.
Plasma Neuron-Specific Enolase is not a reliable biomarker for staging Trypanosoma brucei rhodesiense sleeping sickness patients
Authors: Kato Charles D. , Twesigye Dorothy , Alibu Vincent P. , Nanteza Ann , Nsubuga Julius , Mugasa Claire M. , Matovu Enock 
Published: March 2022

Abstract
Objective
Currently, the only available staging criterion for T. b. rhodesiense requires a lumber puncture to collect and later examine cerebrospinal fluid (CSF). This study examined the potential of plasma Neuron-Specific Enolase (NSE) in discriminating between early and late-stage patients.

Results
When median NSE levels were compared between early and late-stage patients, results showed a significant (P < 0.02) upregulation among late-stage patients (599.8 ng/mL). No significant differences (P > 0.9) in NSE levels were observed between early-stage patients (300 ng/mL) and controls (454 ng/mL). We used Receiver Operator Characteristic (ROC) curves to explore the likelihood of using plasma NSE as a potential stage biomarker in discriminating between early and late-stage HAT patients. Our results showed that NSE demonstrated an area under the curve (AUC) of 0.702 (95% CI 0.583–0.830). A high staging accuracy for NSE was obtained by using a cutoff of > 346.5 ng/mL with a sensitivity of 68.6% (95% CI 55–79.7%) and a specificity of 93.3% (95% CI 70.2–99.7%). Although our results demonstrate that plasma NSE is upregulated in T. b. rhodesiense sleeping sickness patients, its value in discriminating between late and early-stage patients is limited. However, future studies could consider improving its specificity by combining it with other identified plasma biomarkers.
Levothyroxine dosages during pregnancy among hypothyroid women. An experience from a tertiary care center of Karachi, Pakistan, based on data from Maternal Hypothyroidism on Pregnancy Outcomes Study (MHPO-5)
Authors: Kiran Zareen , Khalid Wardah , Sheikh Aisha , Islam Najmul 
Published: March 2022

Abstract
Objectives
The dosage of levothyroxine (LT4) during pregnancy differs among different ethnic groups worldwide. These differences are due to variations in geographical iodine distribution, autoimmunity, and variations in thyrotropin (TSH) targets for pregnancy. To the best of our knowledge, we report the levothyroxine dosage prescribed during pregnancy in hypothyroid women, for the first time from Pakistan.

Results
Levothyroxine dosage of 280 hypothyroid women during pregnancy were reviewed. The median LT4 dosages prescribed before conception was 85.7 mcg per day which increased by 14.3 mcg per day in the first trimester (P 0.001). A significant difference in dosage was observed between controlled and uncontrolled TSH groups in the first trimester (P 0.05). Lower LT4 dosage was prescribed for subclinical hypothyroid women as compared to overt hypothyroid cases, whereas dosages did not differ according to autoimmune status in the latter part of gestation.
Extrapulmonary tuberculosıs: an old but resurgent problem
Authors: Baykan Ali H. , Sayiner Hakan S. , Aydin Elcin , Koc Mustafa , Inan Ibrahim , Erturk Sukru M. 
Published: March 2022

AbstractTuberculosis (TB) primarily affects the lungs, but some of its most devastating clinical consequences arise because of its ability to spread from the lungs to other organs. Extrapulmonary TB (EPTB) constitutes 15–20% of all TB cases. Imaging findings are not always specific and can mimic many diseases; therefore, EPTB should be considered in the differential diagnosis, particularly in patients with immune system disorders (AIDS, patients receiving chemotherapy, etc.) and those in other high-risk groups including people with diabetes. The bacterium's passage to the regional lymph nodes is essential for developing a protective T-cell-mediated immune response, but the bacterium can spread hematologically and via the lymphatic system, leading to extrapulmonary involvement. Diagnosis of EPTB in high-risk patients is made based on suspected clinical and radiological findings, but further positive culture and histopathological confirmation may be required in some instances. Radiological evaluations are critical for diagnosis and crucial in planning the treatment and follow-up. This paper aims to review the typical and atypical imaging features and the differential diagnosis of EPTB.
Impact of a radiological protection campaign in emergency paediatric radiology: a multicentric observational study in Brazil
Authors: Oliveira Bernardo Mônica , Morgado Flávio , dos Santos Alair Augusto Sarmet Moreira Damas , Foley Shane , Paulo Graciano , de Almeida Fernando Antônio 
Published: March 2022

Abstract
Purpose
To evaluate the impact of a paediatric radiological protection campaign, implemented in the emergency units of a healthcare provider network in Brazil. This campaign aimed to promote awareness among emergency department physicians, regarding justification of paediatric X-ray referrals for paranasal sinus, chest and CT exams, as a strategy to reduce exposure to ionising radiation.

Method
Frequency analysis of common paediatric imaging referrals from 19 emergency departments was performed for a 3-year period (2015–2018) to coincide with before, during and after the implementation of the radiation protection campaign. The campaign was multifaceted and involved dissemination of educational materials and imaging referral guidelines along with quarterly meetings with participating centres' leaderships. Additionally, patient dose cards were distributed to patients/carers. The Chi-Square test was used to examine the association between the type of examination and the patient's age group. Exact-Fisher test was performed to check for an association between participant engagement and the existence of the radiation protection committee.

Results
Referrals reduced by 25% following the campaign with no reports of misdiagnosis. Many referrals in the youngest age groups. In 15 units, a radiological protection committee was created to raise awareness and to create a multi professional team to communicate the risks and benefits of radiological procedure in children.

Conclusion
The campaign resulted in a substantial reduction in radiological referrals while promoting a radiation protection culture. Simple education initiatives can contribute to savings in both finances and radiation doses, particularly important in radiosensitive cohorts.
Genetic correction of concurrent α- and β-thalassemia patient-derived pluripotent stem cells by the CRISPR-Cas9 technology
Authors: Li Lingli , Yi Hongyan , Liu Zheng , Long Ping , Pan Tao , Huang Yuanhua , Li Yongsheng , Li Qi , Ma Yanlin 
Published: March 2022

Abstract
Background
Thalassemia is a genetic blood disorder characterized by decreased hemoglobin production. Severe anemia can damage organs and severe threat to life safety. Allogeneic transplantation of bone marrow-derived hematopoietic stem cell (HSCs) at present represents a promising therapeutic approach for thalassemia. However, immune rejection and lack of HLA-matched donors limited its clinical application. In recent years, human-induced pluripotent stem cells (hiPSCs) technology offers prospects for autologous cell-based therapy since it could avoid the immunological problems mentioned above.

Methods
In the present study, we established a new hiPSCs line derived from amniotic cells of a fetus with a homozygous β41-42 (TCTT) deletion mutation in the HBB gene and a heterozygous Westmead mutation (C > G) in the HBA2 gene. We designed a CRISPR-Cas9 to target these casual mutations and corrected them. Gene-corrected off-target analysis was performed by whole-exome capture sequencing. The corrected hiPSCs were analyzed by teratoma formation and erythroblasts differentiation assays.

Results
These mutations were corrected with linearized donor DNA through CRISPR/Cas9-mediated homology-directed repair. Corrections of hiPSCs were validated by sequences. The corrected hiPSCs retain normal pluripotency. Moreover, they could be differentiated into hematopoietic progenitors, which proves that they maintain the multilineage differentiation potential.

Conclusions
We designed sgRNAs and demonstrated that these sgRNAs facilitating the CRISPR-Cas9 genomic editing system could be applied to correct concurrent α- and β-thalassemia in patient-derived hiPSCs. In the future, these corrected hiPSCs can be applied for autologous transplantation in patients with concurrent α- and β-thalassemia.