bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of DHES0815A; a novel HER2-directed antibody-drug conjugate comprised of a reduced potency mono-alkylating agent linked to a domain I binding HER2 antibody
Authors: Lewis Gail , Li Guangmin , Guo Jun , Yu Shang-Fan , Fields Carter , Lee Genee , Zhang Donglu , Dragovich Peter , Pillow Thomas , Wei BinQing , Sadowsky Jack , Wilson Timothy , Mamounas Michael , Lee M Violet , Saad Ola , Choeurng Voleak , Ungewickell Alexander , Monemi Shararah , Crocker Lisa , Kalinsky Kevin , Modi Shanu , Jung Kyung-Hae , Hamilton Erika , LoRusso Patricia , Krop Ian , Schutten Melissa , Commerford Renee , Sliwkowski Mark , Cho Eunpi , leipold Douglas 
Published: December 2022

Abstract
Approved antibody-drug conjugates (ADCs) for HER2-positive breast cancer include trastuzumab emtansine and trastuzumab deruxtecan. To develop a novel HER2 ADC, we selected an antibody that does not compete with trastuzumab or pertuzumab for binding, conjugated to a reduced potency PBD (pyrrolobenzodiazepine) dimer payload. PBDs are potent cytotoxic agents that alkylate and cross-link DNA. We modified the PBD dimer to alkylate, but not cross-link DNA. This HER2 ADC, DHES0815A, demonstrated in vivo efficacy in models of HER2-positive and HER2-low cancers and was well-tolerated in cynomolgus monkey safety studies. Mechanisms of action include induction of DNA damage and apoptosis, activity in non-dividing cells, and bystander activity. A dose-escalation study in patients with HER2-positive metastatic breast cancer showed early signs of anti-tumor activity with limited toxicity. However, delayed dermal, ocular and pulmonary toxicities developed. The delayed onset, as well as non-resolvable nature of the toxicities resulted in termination of the phase 1 trial.
CAMK2D: A Novel Molecular Target for BAP1-Deficient Malignant Mesothelioma
Authors: Karnan Sivasundaram , Ota Akinobu , Murakami Hideki , Rahman Md , Wahiduzzaman Md , Hasan Muhammad , Vu Lam , Hanamura Ichiro , Inoko Akihito , Riku Miho , Ito Hideaki , Kaneko Yoshifumi , Hyodo Toshinori , Konishi Hiroyuki , Tsuzuki Shinobu , Hosokawa Yoshitaka 
Published: December 2022

Abstract
Malignant mesothelioma (MM) is a rare but aggressive malignancy. Although the molecular genetics of MM are known, including BRCA1-associated protein-1 (BAP1) gene alterations, the prognosis of MM patients remains poor. Here we generated BAP1 knockout (BAP1-KO) human mesothelial cell clones to develop molecular-targeted therapeutics based on genetic alterations in MM. cDNA microarray and quantitative RT-PCR (qRT-PCR) analyses revealed high expression of a calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D) gene in the BAP1-KO cells. CAMK2D was highly expressed in 70% of the human MM tissues (56/80) and correlated with the loss of BAP1 expression, making it a potential diagnostic and therapeutic target for BAP1-deficient MM. We screened an anticancer drugs library using BAP1-KO cells and successfully identified a CaMKII inhibitor, KN-93, which displayed a more potent and selective antiproliferative effect against BAP1-deficient cells than cisplatin or pemetrexed. KN-93 significantly suppressed the tumor growth in mice xenografted with BAP1-deficient MM cells. This study is the first to provide a potential molecular-targeted therapeutic approach for BAP1-deficient MM.
Estimation of Glomerular Filtration Rate for diabetic patients by using Simplified Modification of Diet in Renal Disease (MDRD), Southwest Ethiopia
Authors: Derso Mohammed Adem , Woyesa Shiferaw Bekele , Mamo Aklilu Getachew 
Published: December 2022

Abstract
Back ground

Renal complicationisthe leading cause of diabetes mellitus related morbidity and mortality. The pathogenesis of diabetic nephropathy or chronic kidney disease is related to chronic hyperglycemia eventhoughthemechanisms by which it leads to end stage renal disease are not completely elucidated.

Methods

This study was aimed to estimate chronic kidney disease (CKD) by directly measuring serum creatinine level and mathematically transforming the measured valuesinto estimate glomerular filtration rate (eGFR) and to assess risk factors associated to renal impairment indiabeticpatients. A cross-sectional study design and a consecutive sampling technique were used to include a total of 234 diabetic patients. Demographic and clinical data were collectedby using interviewer administered questionnaire. A five mililiter fasting blood specimen was analysed by fully automated Chemistry Analyzer. Renal status was assessed using the Kidney Disease Improving Global Outcomes (KDIGO) classification .Bivariate and multivariate logistic regressions, and Pearson`s correlation wereused to assess the independent predicator variables and their correlation to CKDrespectively.

Results

About 19.2% of the study subjects had a substantially reduced estimated glomerular filtration rate (eGFR). High blood pressure (AOR: 7.77; 95% C.I:2.95–20.46; P: 0.001), poor glycemic control (AOR: 9.52; 95% C.I: 2.23–40.63; P: 0.002), long duration of diabeticity (AOR: 3.87; 95% C.I:1.60–9.34, P: 0.003), advance in age (AOR: 5.0; 95% C.I:1.93–12.37; P: 0.001) and being female (AOR: 5.05; 95% C.I: 1.91–13.37, P: 0.001) were indepident predictor variables for reduced eGFR.

Conclusion

The prevalence of CKD was high among diabetic patients in the study area. Age advancement and the increasing prevalence of many risk factors will result in an increase of CKD prevalence in diabetic patients. Therefore, preventive intervention is very important to reduce renal impairment in diabetic patients.
Effects of projected end-of-century temperature on the muscle development of neonate epaulette sharks, Hemiscyllium ocellatum
Authors: Thomas Peyton Alexandria , Peele Emily E. , Wheeler Carolyn R. , Yopak Kara , Rummer Jodie L , Mandelman John W. , Kinsey Stephen T. 
Published: December 2022

Abstract
Epaulette sharks (Hemiscyllium ocellatum) inhabit shallow tropical habitats with elevated and fluctuating temperatures. Yet, according to global climate change projections, water temperatures in these habitats will rise beyond current cyclical variability, warranting further studies incorporating chronically elevated temperature exposure in this species. This study examined the differences in skeletal muscle morphological and metabolic properties in neonate epaulette sharks exposed to their current-day ambient (27°C) or projected end-of-century (31°C) habitat temperatures throughout embryonic and neonatal development. Metrics of skeletal muscle, such as muscle fiber size and density, nuclear density, and satellite cell density, were used to assess the relative contribution of hypertrophic and hyperplastic growth processes. Capillary density was measured as a proxy for peripheral oxygen supply to muscle tissue. At 31°C, sharks hatched earlier, but were similar in body size 60 days post-hatch. Muscle fiber size, nuclear density, and capillary density were similar between temperature regimes. However, fiber density was lower, satellite cell density was higher, and fibers associated with satellite cells were smaller in sharks reared at 31°C. These results suggest that elevated temperature may impair or slow satellite cell fusion to existing fibers and new fiber formation. To assess potential metabolic and developmental consequences of elevated temperatures, oxidative damage (2,4-DNPH, 8-OHdG, 4-HNE), protein degradation (Ubiquitin, LC3B, Hsp70), and muscle differentiation (Myf5, Myogenin) markers were measured. Protein carbonylation was higher at elevated temperatures, suggesting that warmer incubation temperatures at early life stages may result in oxidative damage accrual. However, protein degradation and muscle differentiation markers did not differ. These results suggest that projected end-of-century temperatures may alter muscle growth and metabolism in tropical shark species with potential consequences to shark growth and fitness.
Multiple Primary Pulmonary Meningiomas. Case report and literature review.
Authors: Rusu Stefan , Wellemans Isabelle , Remmelink Myriam , Foucart Annick , Compère Christophe 
Published: December 2022

AbstractBackgroundPrimary pulmonary meningioma (PPM) is a very rare tumor, while multiple PPMs are even more exceptional and herein, we report the sixth case, focusing on the clinicopathological and radiological features of the tumor.Case presentationHerein, we report a case of an asymptomatic 51-year-old female, who presented three solid nodules in both lungs who underwent video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper lobe. The third lesion was followed-up and resected three years later due to its slow but significant growth, alongside two new lesions. All lesions revealed morphological and immunohistochemical profile of meningioma. Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging scans.ConclusionsPPM is mostly benign and slow-growing tumor with an excellent prognosis, it does not present specific radiological characteristics and it is difficult to differentiate it from other lung tumors, surgical resection with subsequent histopathological examination being essential. A causal connection between sex hormones and meningiomas has long been debated and we hypothesize a causal connection between the PPM and her hormonal therapy with progesterone analogue.
Design, synthesis and biological evaluation of aminopyrimidine derivatives bearing dihydroquinoxalinone as novel EGFRL858R/T790M kinase inhibitors against non-small-cell lung cancer
Authors: Fu Liping , Cao Yu , Chen Jingbai , He Ruoyu , Zhao Yanmei , Zhao Yaping , Xi Jianjun , Zhuang Rangxiao , Tian Chongmei 
Published: December 2022

Abstract
The clinical responses to the EGFR kinase inhibitors in non-small cell lung cancer (NSCLC) patients are always followed by drug-resistance mutations, including the gatekeeper T790M mutation. Strategies targeting EGFRT790M are also limited by the toxicity due to the concurrent inhibition of wide-type (WT) EGFR. Here we employed splicing principle to design and synthesize a series of aminopyrimidine derivatives bearing dihydroquinoxalinone (8-15) as novel thirdgeneration inhibitors against double mutant L858R/T790M in EGFR. It’s worth noting that compound 10 presented remarkable inhibitory activity against EGFRL858R/T790M (IC50 = 15 ± 1.8 nM) and anti-proliferative effect against H1975 cells (IC50 = 166.43 ± 14.45 nM). Moreover, the obvious down-regulation effect of EGFR-mediated signaling pathways and the promotion of apoptosis in H1975 cells confirmed its potent efficacy. These results demonstrated that compound 10 deserves the further exploration.
Lumbar Lordosis Curve and Psoas Major Muscle Angle in Magnetic Resonance Imaging Analysis
Authors: Ko Sangbong , Kim Hee-Chan 
Published: December 2022

Abstract
Background
Using axial MRI image, the psoas major muscle is known to work as an anatomical femoral head stabilizer and increases lumbar lordosis keeping the iliopsoas muscle in place at the lumbosacral region. The purpose of this study is to investigate psoas major muscle correlation with lumbar lordosis by analyzing the psoas major angle, which represents the psoas major muscle’s effect on pelvic alignment using sagittal MRI imaging.
Methods
A total of 1064 patients were included in this study. On lateral standing radiography, three pelvic parameters (sacral slope, pelvic tilt, pelvic incidence) can be measured. In the sagittal MRI imaging, the point where the psoas major muscle direction changes (the top of superior pubic ramus) was marked and the angle between the line connecting the two points and the proximal part of the psoas major muscle (Psoas major angle: PMA) was measured.
Results
The average age was 63.88 ± 13.52 (20–89) years old in total; 62.52 ± 15.24 in 426 male patients and 66.12 ± 11.72 in 638 female patients. The average age was older in female patients (p < 0.05). Using the structural equation, the correlation coefficient between PMA and SS was 0.237 (p < 0.001), between PMA and PT was 0.339 (p < 0.001), and between PMA and PI was 0.749 (p < 0.001). PMA has a statistically significant correlation in relation to PI, PT, and SS (p < 0.001).
Conclusion
PMA has a higher correlation with PT, which is related to pelvic compensation, than SS which is closely related to lumbar lordosis. It means that the psoas major muscle’s role of influencing spinopelvic alignment in the supine position is to maintain spinopelvic alignment by adjusting the pelvic tilt rather than by lumbar lordosis using the upper and lower muscle attachments.
Normal Infant Feeding Characteristics Throughout the First Month of Life
Authors: McGrattan Katlyn , Hammel Abbey , Zoeller Morgan , Klein Kristina , Delaware Elise , McCormick Jennie , Weikle Ellen , Broderick Erin , Ramel Sara , Mohr Alicia Hofelich 
Published: December 2022

Abstract
Objective

Elucidate normal characteristics of infant feeding performance throughout the first month of life.

Study Design

Feeding was monitored in 61 healthy infants by caregiver report for 48 hours a week from birth to four weeks old. Outcomes included feeding modality, how much they consumed, how long the feed lasted, and how many coughing episodes the infant exhibited. Data were analyzed with descriptive and non-parametric statistics.

Result

The majority of infants (68%) exhibited at least one problematic feeding behavior. Infants consumed 68 mL/feed over 20 minutes, though the milk volumes and feed durations were highly variable. Coughing occurred an average of 2 feeds per day. No significant change in coughing was observed throughout the first month of life (p = 0.64). Infants coughed significantly less during breast feeds than bottle feeds (p = 0.02).

Conclusion

Healthy term infants exhibit normal developmental imperfections in feeding performance throughout the first month of life.
Declines and pronounced state level disparities in prescription opioid distribution in the United States
Authors: Madera Joshua D. , Ruffino Amanda E. , Feliz Adriana , McCall Kenneth L. , Davis Corey S. , Piper Brian J. 
Published: December 2022

Abstract
The United States (US) opioid epidemic is a persistent and pervasive public health emergency that now claims the lives of over 100,000 Americans per year. There have been sustained efforts to reverse this crisis over the past decade, including a number of measures designed to decrease the use of prescription opioids for the treatment of pain. This study analyzed the changes in federal production quotas for prescription opioids and the distribution of prescription opioids for pain, and identified state-level differences between 2010 and 2019.
Data on opioid production quotas and distribution of ten prescription opioids (codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, and tapentadol) for 2010 to 2019 were obtained from the Drug Enforcement Administration. Total opioid production quotas increased substantially from 2010 to 2013 before decreasing 41.5% from 2013 (87.6 morphine mg equivalent metric tons) to 2019 (51.3). The peak year for distribution of all ten prescription opioids was between 2010 and 2013, except for codeine (2015). The largest quantities of opioid distribution were observed in Tennessee (520.70 morphine mg equivalent or MME per person) and Delaware (251.45) in 2011 and 2019. There was a 52.0% overall decrease in opioid distribution per capita from 2010 to 2019, with the largest decrease in Florida (-61.6%) and smallest in Texas (-18.6%). Southern states had the highest per capita distribution for eight of the ten opioids in 2019. The highest to lowest state ratio of total opioid distribution, corrected for population, decreased from 5.25 in 2011 to 2.78 in 2019. The mean 95 th /5 th ratio was relatively consistent in 2011 (4.78 +0.70) compared to 2019 (5.64+0.98).
In conclusion, this study found a sustained decline in distribution of ten prescription opioids during the last half-decade. Distribution was non-homogeneous at the state level. Analysis of state-level differences revealed a threefold difference in the 95 th :5 th percentile ratio between states which was unchanged over the past decade. Production quotas did not correspond with the distribution, particularly in the 2010-2016 period. Future research focused on identifying factors contributing to the observed regional variability in opioid distribution could prove valuable to understanding, and potentially remediating, the pronounced disparities in prescription opioid-related harm in the US.
Intravenous Busulfan, Dimethylacetamide and neurotoxicity after high-dose pretransplant conditioning chemotherapy
Authors: Ramdial Jeremy , Nieto Yago , Andersson Borje , Chan Kok Hoe , Petitto Gabriela Sanchez , Valdez Benigno 
Published: December 2022

Abstract
Intravenous Busulfan-based (IV Bu-) conditioning regimens are widely used in stem cell transplant and have been demonstrated as more effective and safer than cyclophosphamide and total body irradiation. Despite its superiority concerns remain regarding toxicities, specifically, veno-occlusive disease/sinusoidal obstructive syndrome, reproductive toxicity and neurotoxicity. Some of these concerns do not relate to busulfan itself, but to its composite solvent vehicle including N,N‑dimethylacetamide (DMA). Herein, we report a case series of six patients who received high-dose IV Bu-based conditioning regimens, and who developed neurotoxicity with various neurological manifestations and outcomes, ranging from mild to fatal. This case series highlights the need for further studies to investigate the safety of IV Bu, especially in patients with an underlying organic brain disorder, who have been treated with immunoconjugates with a potential for central neurotoxicity, or who have received therapeutic brain irradiation.
Leveraging primate-specific genomic information for genetic studies of complex diseases
Authors: Wei Wenhua , Guo Hui 
Published: December 2022

Abstract
Genomic changes specific to higher primates are regarded as primate-specific genomic information (PSI). Using PSI to inform genetic studies is highly desirable but hampered by three factors: heterogeneity among PSI studies, lack of integrated profiles of the identified PSI elements and dearth of relevant functional information. We report a database of 19,767 PSI elements collated from nine types of brain-related studies, which form 19,473 non-overlapping PSI regions that distribute unevenly but jointly cover only 0.81% of the genome. About 2.5% of the PSI regions colocalized with variants identified in genome-wide association studies, with disease loci more likely colocalized than quantitative trait loci (p = 1.6⋅10− 5), particularly in regions without obvious regulatory roles. We further showed an LRP4 exemplar region with PSI elements orchestrated with common and rare disease variants and other functional elements. Our results render PSI elements as a valuable source to inform genetic studies of complex diseases.
Nursing students’ simulated home-visit learning experiences-A Qualitative research
Authors: Um Youn-Joo 
Published: December 2022

Abstract
Object

The aim of this study was to explore the learning experiences of student nurses’ simulation-based community visit and understand these experiences in detail.

Method

This study followed Colazzi’s phenomenological research method. Nineteen participants were divided into three teams and participated in focus group interviews. The research question was as follows: “How was your experience with the simulated home-visit nursing?”

Results

The study results uncovered four essential themes: “burden of community nursing simulation-based learning,” “solving the problems faced by patients with dementia through teamwork,” “home-visiting nursing skills learned through physical practice,” and “community nursing competency growth.”

Conclusion

The study results provide a basis for developing a community nursing curriculum with effective evaluation and management of community home-visiting nursing education using simulation.
Investigation of the acoustic emission and fractal characteristics of coal with varying water contents during uniaxial compression failure
Authors: Ali Muhammad , Wang Enyuan , Li Zhonghui , Khan Naseer Muhammad , Sabri Moanad Muayad Sabri , Ullah Barkat 
Published: December 2022

Abstract
To investigate the effect of water on the mechanical properties and acoustic emission (AE) characteristics of coal in the failure and deformation processes. A uniaxial compressive test with the aid AE monitoring was conducted on coal samples. The characteristics of the AE signals were further analyzed using fractal analysis. The results show that saturated coal samples have substantially reduced mechanical properties such as uniaxial compressive strength (UCS), dissipation energy, peak stress, and elastic modulus. The stress-strain curve demonstrated distinct stage characteristics under loading, and also the response AE signals of natural and saturated coal samples were consistent throughout. A novel Grassberger Procaccia (GP) algorithm was utilized for the first time to find the AE fractal characteristics of coal samples in different stages using phase-space theory. The results indicate that AE energy's first and second phases have no fractal properties. In contrast, the third stage has evident fractal characteristics. In the fourth stage, there is a rapid decline in the fractal dimension, followed by a gradual decrease or increase in the fifth stage. In stable crack propagation stages, the AE shows evident fractal characteristics, indicating that coal is stable. During the accelerated crack propagation stage, the correlation dimension decreases rapidly, continues to decline further, and begins to increase again in the fifth stage. Consequently, the coal begins to collapse, potentially resulting in a coal disaster and dynamic failure. It is, therefore, possible to accurately predict coal and rock dynamic failures by observing the subsequent change in the fractal dimension of the AE signals in response to different stages of loading.