bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel Mcl-1 inhibitor synergizes with venetoclax to induce apoptosis in cancer cells
Authors: Zhao Tianming , He Qiang , Xie Shurong , Zhan Huien , Jiang Cheng , Lin Shengbin , Liu Fangshu , Wang Cong , Chen Guo , Zeng Hui 
Published: January 2023

Abstract
Background
Evading apoptosis by overexpression of anti-apoptotic Bcl-2 family proteins is a hallmark of cancer cells and the Bcl-2 selective inhibitor venetoclax is widely used in the treatment of hematologic malignancies. Mcl-1, another anti-apoptotic Bcl-2 family member, is recognized as the primary cause of resistance to venetoclax treatment. However, there is currently no Mcl-1 inhibitor approved for clinical use.

Methods
Paired parental and Mcl-1 knockout H1299 cells were used to screen and identify a small molecule named MI-238. Immunoprecipitation (IP) and flow cytometry assay were performed to analyze the activation of pro-apoptotic protein Bak. Annexin V staining and western blot analysis of cleaved caspase 3 were employed to measure the cell apoptosis. Mouse xenograft AML model using luciferase-expressing Molm13 cells was employed to evaluate in vivo therapeutic efficacy. Bone marrow samples from newly diagnosed AML patients were collected to evaluate the therapeutic potency.

Results
Here, we show that MI-238, a novel and specific Mcl-1 inhibitor, can disrupt the association of Mcl-1 with BH3-only pro-apoptotic proteins, selectively leading to apoptosis in Mcl-1 proficient cells. Moreover, MI-238 treatment also potently induces apoptosis in acute myeloid leukemia (AML) cells. Notably, the combined treatment of MI-238 with venetoclax exhibited strong synergistic anti-cancer effects in AML cells in vitro, MOLM-13 xenografts mouse model and AML patient samples.

Conclusions
This study identified a novel and selective Mcl-1 inhibitor MI-238 and demonstrated that the development of MI-238 provides a novel strategy to improve the outcome of venetoclax therapy in AML.
Sustainable development goal 13 and switching priorities: addressing climate change in the context of pandemic recovery efforts
Authors: Filho Walter Leal , Minhas Aprajita , Schmook Birgit , Mardero Sofia , Sharifi Ayyoob , Paz Shlomit , Kovaleva Marina , Albertini Maria Cristina , Skouloudis Antonis 
Published: January 2023

AbstractThe COVID-19 pandemic has had many deep social and economic impacts that go beyond health issues. One consequence is that the pandemic has made it even harder to mobilize the financial resources needed to pursue SDG 13 (Climate Action) as a whole and to fund climate change mitigation and adaptation efforts in particular. This is especially acute in respect of the efforts to achieve the targets set by the Paris Agreement and by the recent decisions in Glasgow. This paper looks at how the COVID-19 pandemic has accelerated poverty and undermined climate change mitigation and adaptation efforts, as a result of the switches in priorities and funding. Using a review of the recent literature, an analysis of international trends, and a survey among climate scientists, it identifies some of the impacts of the pandemic on climate change mitigation and adaptation efforts and discusses their implications. The findings indicate a decrease in funding to climate change research since the pandemic crisis. The bibliometric analysis reveals that a greater emphasis has been placed on the relationship between COVID-19 and poverty when compared to the interrelations between COVID-19 and climate change. Addressing climate change is as urgent now as it was before the pandemic crisis started, and efforts need to be made to upkeep the levels of funding needed to support research in this field.
Estimation of genotype by temperature-humidity index interactions on milk production and udder health traits in Montbeliarde cows
Authors: Vinet Aurélie , Mattalia Sophie , Vallée Roxane , Bertrand Christine , Cuyabano Beatriz C. D. , Boichard Didier 
Published: January 2023

Abstract
Background
Heat stress negatively influences cattle welfare, health and productivity. To cope with the forecasted increases in temperature and heat waves frequency, identifying high-producing animals that are tolerant to heat is of capital importance to maintain milk production. This study, based on the joint analysis of on-farm performance and weather data, had two objectives: (1) to determine the response in production performances (milk, fat and protein yields, fat and protein contents) and udder health (somatic cell score) to temperature-humidity index (THI) variations in Montbeliarde cows, and (2) to estimate the interactions between genotype and THI, to enable the identification of the most adapted animals for facing the expected increases in temperature.

Results
Test-day records from first and second lactations from 2016 to 2020 were associated with the average THI during the three days before the test-day record. In total, 446,717 test-day records from 55,650 cows in first lactation and 457,516 test-day records from 58,229 cows in second lactation were analysed. The optimal THI was below 55 (i.e. ~ 12–13 °C) for all traits. Individual responses to THI were estimated by random regression models, which also included individual responses to days in milk. Regardless of the stage of lactation, genetic correlations along the THI gradient were above 0.80, which suggests that genotype-by-THI interactions were weak for production and udder health traits. Nevertheless, a variability in the individual slope of decay could be highlighted at high THI. The genetic correlation between production level at moderate THI and the slope at high THI was negative, while for somatic cell score, it was positive, indicating that heat stress amplifies the susceptibility to mastitis.

Conclusions
The optimal THI for French Montbeliarde cows is below 55 for production and udder health traits. Genetic-by-THI interactions are weak in French Montbeliarde cows for production and udder health traits, but not all animals react in the same way to high temperatures. Even if there is little room for improvement, using a heat tolerance index in cattle selection would be relevant to anticipate the expected increases in temperature. Further investigations are needed to interpret this variability on production traits. However, the current selection for mastitis resistance seems appropriate to adapt cattle to rising temperatures.
Selection signatures for local and regional adaptation in Chinese Mongolian horse breeds reveal candidate genes for hoof health
Authors: Han Haige , Randhawa Imtiaz A. S. , MacHugh David E. , McGivney Beatrice A. , Katz Lisa M. , Dugarjaviin Manglai , Hill Emmeline W. 
Published: January 2023

AbstractBackgroundThousands of years of natural and artificial selection since the domestication of the horse has shaped the distinctive genomes of Chinese Mongolian horse populations. Consequently, genomic signatures of selection can provide insights into the human-mediated selection history of specific traits and evolutionary adaptation to diverse environments. Here, we used genome-wide SNPs from five distinct Chinese Mongolian horse populations to identify genomic regions under selection for the population-specific traits, gait, black coat colour, and hoof quality. Other global breeds were used to identify regional-specific signatures of selection.ResultsWe first identified the most significant selection peak for the Wushen horse in the region on ECA23 harbouring DMRT3, the major gene for gait. We detected selection signatures encompassing several genes in the Baicha Iron Hoof horse that represent good biological candidates for hoof health, including theCSPG4,PEAK1,EXPH5,WWP2andHAS3genes. In addition, an analysis of regional subgroups (Asian compared to European) identified a single locus on ECA3 containing theZFPM1gene that is a marker of selection for the major domestication event leading to the DOM2 horse clade.ConclusionsGenomic variation at these loci in the Baicha Iron Hoof may be leveraged in other horse populations to identify animals with superior hoof health or those at risk of hoof-related pathologies. The overlap between the selection signature in Asian horses with the DOM2 selection peak raises questions about the nature of horse domestication events, which may have involved a prehistoric clade other than DOM2 that has not yet been identified.
Effects of diets with different amino acid release characteristics on the gut microbiota and barrier function of weaned pigs
Authors: Mi Mengmeng , Shen Zhiwen , Hu Nianzhi , Zhang Qiyu , Wang Bin , Pan Li , Qin Guixin , Bao Nan , Zhao Yuan 
Published: January 2023

Abstract
Background
The absorption and utilization of proteins by animals is affected by the amino acid (AA) release characteristics of their diets. In the present study, we aimed to determine the effects of diets with various amino acid release characteristics on the intestinal barrier function and diversity of gut microbiota of weaned pigs.

Results
Forty-eight pigs (7.45 ± 0.58 kg) were fed with diets having different amino acid release characteristics during a period of 28 days. We used a 2 × 3 full-factor (two protein levels and three protein sources with differing amino acid release characteristics) experimental design, with normal (standard terminal ileal digestibility of 17.5%) or low (standard terminal ileal digestibility of 14.9%) protein levels as the first factor. Casein (CAS), corn gluten meal (CGM) and a MIX diet were used as protein sources. Due to the more balanced release of amino acids, the diamine oxidase (DAO) concentrations in the CAS and MIX groups were significantly lower than those in the CGM group (P < 0.05); Reducing the dietary protein content from 17.5% to 14.9% had no significant effects on the levels of serum DAO or D-lactic acid. By contrast, it increased the microbial diversity (chao1 and ACE values) and the number of Lactobacillus in the jejunum (P < 0.05). The CAS-containing diet and the MIX diet resulted in significantly higher microbial diversity (Simpson and Shannon) than the CGM-containing diet in the jejunum.

Conclusion
The balanced release of amino acids in CAS and MIX diets maintained intestinal barrier function and increased gut microbiota diversity. These findings could potentially provide a scientific reference for the rational preparation of piglet feed.
The cost of illness analysis of inflammatory bowel disease
Authors: Pakdin Majid , Zarei Leila , Bagheri Lankarani Kamran , Ghahramani Sulmaz 
Published: January 2023

Abstract
Background
Inflammatory bowel disease (IBD) is a chronic inflammatory condition involving individuals across all age groups. Recent data suggests the increase in the prevalence of IBD and the surge in applying the biologic drugs in which both change the cost of IBD in recent years. Comprehensive assessment of direct and indirect cost profiles associated with IBD in our area is scarce. This study aimed to determine the economic burden of IBD in Iran from a societal perspective, using cost diaries.

Methods
Patients available on clinic registry and hospital information system (HIS), who were diagnosed with IBD, were invited to take part in this study. Demographic and clinical data, the healthcare resource utilization or cost items, absenteeism for the patients and their caregivers were obtained. The cost of the used resources were derived from national tariffs. The data regarding premature mortality in IBD patients was extracted from HIS. Productivity loss was estimated based on the human capital method. Then, cost date were calculated as mean annual costs per patient.

Results
The cost diaries were obtained from 240 subjects (Ulcerative colitis: n = 168, Crohn’s disease, n = 72). The mean annual costs per patient were 1077 US$ (95% CI 900–1253), and 1608 (95% CI 1256, 1960) for the patients with ulcerative colitis and Crohn’s disease, respectively. Of the total costs, 58% and 63% were in terms of the indirect costs for the patients with ulcerative colitis and Crohn’s disease, respectively. The cost of illness for country was found to be 22,331,079 US$ and 15,183,678 US$ for patients with ulcerative colitis and Crohn’s disease, respectively. Highest nationwide economic burden of IBD was found for patients older than 40 years were estimated to be 8,198,519 US$ and 7,120,891 US$, for ulcerative colitis and Crohn’s disease, respectively.

Conclusion
The medication was found to be the greatest contributor of direct medical costs. Productivity loss in terms of long-term disability and premature mortality were major components of IBD’s economic burden in Iran.
What predicts large vessel occlusion in mild stroke patients?
Authors: Lu Zhengzhao , Xiong Yunyun , Yang Kaixuan , Gu Hongqiu , Duan Chunmiao , Zhao Xingquan , Meng Xia , Wang Yongjun 
Published: January 2023

Abstract
Background and purpose
Mild acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) may benefit from thrombolysis or thrombectomy therapy. However, the predictors for LVO in mild AIS patients have not been extensively explored. We aimed to investigate the predictors for LVO in mild AIS patients.

Methods
We collected the data of consecutive AIS patients with a National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 from The Third China National Stroke Registry - a prospective nationwide registry of AIS or transient ischemic attack (TIA) patients in China from August 2015 to March 2018. Patients were divided into LVO and non-LVO group based on the vascular imaging during the hospitalization. Multivariable regression analyses involving clinical characteristics and NIHSS subitems was performed to detect the predictors for LVO.

Result
A total of 7653 mild AIS patients from The Third China National Stroke Registry were included in this study. Among them, 620 patients (8.1%) had LVO. The level of consciousness (adjusted odds ratio, 1.87; 95% confidence interval, 1.08 to 3.23), visual field (adjusted odds ratio, 2.10; 95% confidence interval, 1.43 to 3.06) and sensory (adjusted odds ratio, 0.75; 95% confidence interval, 0.60 to 0.94) were predictors for mild AIS patients with LVO.

Conclusions
Impaired LOC, visual field and sensory were independently predictors for LVO in mild stroke patients. Further studies are warranted to test these predictors in prehospital setting and in other population.
Patterns of staging, treatment, and mortality in gastric, colorectal, and lung cancer among older adults with and without preexisting dementia: a Japanese multicentre cohort study
Authors: Morishima Toshitaka , Kuwabara Yoshihiro , Saito Mari Kajiwara , Odani Satomi , Kudo Haruka , Kato Mizuki , Nakata Kayo , Miyashiro Isao 
Published: January 2023

Abstract
Background
Little is known about dementia’s impact on patterns of diagnosis, treatment, and outcomes in cancer patients. This study aimed to elucidate the differences in cancer staging, treatment, and mortality in older cancer patients with and without preexisting dementia.

Methods
Using cancer registry data and administrative data from 30 hospitals in Japan, this multicentre retrospective cohort study examined patients aged 65–99 years who were newly diagnosed with gastric, colorectal, or lung cancer in 2014–2015. Dementia status (none, mild, and moderate-to-severe) at the time of cancer diagnosis was extracted from clinical summaries in administrative data, and set as the exposure of interest. We constructed multivariable logistic regression models to analyse cancer staging and treatment, and multivariable Cox regression models to analyse three-year survival.

Results
Among gastric (n = 6016), colorectal (n = 7257), and lung (n = 4502) cancer patients, 5.1%, 5.8%, and 6.4% had dementia, respectively. Patients with dementia were more likely to receive unstaged and advanced-stage cancer diagnoses; less likely to undergo tumour resection for stage I, II, and III gastric cancer and for stage I and II lung cancer; less likely to receive pharmacotherapy for stage III and IV lung cancer; more likely to undergo tumour resection for all-stage colorectal cancer; and more likely to die within three years of cancer diagnosis. The effects of moderate-to-severe dementia were greater than those of mild dementia, with the exception of tumour resection for colorectal cancer.

Conclusion
Older cancer patients with preexisting dementia are less likely to receive standard cancer treatment and more likely to experience poorer outcomes. Clinicians should be aware of these risks, and would benefit from standardised guidelines to aid their decision-making in diagnosing and treating these patients.
Implementation of an integrated care strategy for child contacts of tuberculosis patients: a quasi-experimental study protocol
Authors: Benjumea-Bedoya Dione , Villegas Arbeláez Esteban , Martínez-Peñaloza Daniela , Beltrán-Arroyave Claudia Patricia , Restrepo Gouzy Andrea Victoria , Marín Diana , Cadavid Álvarez Lina Marcela , Molinares Beatriz , Montes Zuluaga Fernando Nicolás , Pulido Duarte Henry , Suárez Parra Pedro Mauricio , Alzate Ángel Juan Carlos , Vélez-Parra Guillermo , Realpe Teresa , Vásquez Villa Marisol , Ríos Buitrago Stefani Yamile , Puerta Zapata Jenifer , Arango García Lisandra María , Perea Torres Yesenia , Pérez Doncel Natalia , Arbeláez Montoya María Patricia , Robledo Jaime 
Published: January 2023

Abstract
Background
Childhood tuberculosis continues to be a major public health problem. Although the visibility of the epidemic in this population group has increased, further research is needed.

Objective
To design, implement and evaluate an integrated care strategy for children under five years old who are household contacts of bacteriologically confirmed pulmonary tuberculosis patients in Medellín and the Metropolitan Area.

Methods
A quasi-experimental study in which approximately 300 children who are household contacts of bacteriologically confirmed pulmonary tuberculosis patients from Medellín and the Metropolitan Area will be evaluated and recruited over one year. A subgroup of these children, estimated at 85, who require treatment for latent tuberculosis, will receive an integrated care strategy that includes: some modifications of the current standardized scheme in Colombia, with rifampicin treatment daily for four months, follow-up under the project scheme with nursing personnel, general practitioners, specialists, professionals from other disciplines such as social work, psychology, and nutritionist. Additionally, transportation and food assistance will be provided to encourage treatment compliance. This strategy will be compared with isoniazid treatment received by a cohort of children between 2015 and 2018 following the standardized scheme in the country. The study was approved by the CIB Research Ethics Committee and UPB. ClinicalTrials.gov identifier NCT04331262.

Discussion
This study is expected to contribute to the development of integrated care strategies for the treatment of latent tuberculosis in children. The results will have a direct impact on the management of childhood tuberculosis contributing to achieving the goals proposed by the World Health Organization's End TB Strategy.

Trial registration
ClinicalTrials.gov identifier NCT04331262. Implementation of an Integrated Care Strategy for Children Contacts of Patients with Tuberculosis. Registered 2 April 2020.
The provision of the baby box was associated with safe sleep practices in a low-resource community: a randomized control trial in Ecuador
Authors: Feld Hartley , Osorio Janeth Ceballos , Bahamonde Marisol , Young Thomas , Boada Pablo , Rayens Mary Kay 
Published: January 2023

Abstract
Background
Sudden Unexpected Infant Deaths (SUID) can occur between 1 month and 1 year of age and are inequitably distributed with a greater burden in populations with numerous health disparities. Modifying the infant sleep environment to promote safe sleep is the most effective risk reduction strategy to reduce SUID. The provision of baby boxes with a mattress and infant supplies has been part of a larger anti-poverty social justice maternity package for decades in Finland. While infant mortality rates have generally improved after the maternity package was introduced, little is known about whether the provision of the baby box increased safe sleep practices. The purpose of the study was to evaluate whether the provision of a Finnish-style baby box reinforced safe infant sleep practice in the home in a low-resource community in Ecuador.

Methods
In this longitudinal randomized controlled trial all participants received the same safe sleep education in their third trimester of pregnancy (n = 100). This was followed by randomization into two groups; the control received a diaper bag and newborn gifts, and the intervention group received a baby box and the same gifts at each timepoint. Four infant sleep practices (room sharing, bed sharing/co-sleeping, position, and soft items in the sleep environment) were assessed at 1 month and 1 months post-delivery during a home visit where safe sleep education was also reinforced with both groups.

Results
Those in the baby box group were 2.5 times more likely to report safe sleep practices compared with mothers in the diaper bag group at 1 month (odds ratio [OR] = 2.45 and 95% confidence interval [CI]: 1.03–5.86; χ2 = 4.1, p = .043). The group difference was also present at 6-months post-birth: those in the baby box group were 2.9 times more likely to report safe sleep practices compared with those in the diaper bag group (OR = 2.86 and 95% CI: 1.16–7.05; χ2 = 5.2, p = .022).

Conclusions
While not all participants used the box regularly, the mothers who received the box were more likely to practice safe sleep at 1 month and 6 months. This suggests the baby box may have served as an important prompt towards safer infant sleep practice.

Trial registration
(Clinical Trial Registry, per clinicaltrials.gov: not applicable under 42 CFR 11.22(b) as the study Facility Location was not in the United States (took place in Ecuador), does not involve FDA IND or IDE, and does not involve a drug, biological or device product that is manufactured in and exported from the US for study in another country. The University of San Francisco Quito, Research Ethics Committee in Human Beings approved the study, #2017- 127 M. The University of Kentucky Office of Research Integrity also approved the study, IRB # 42965).