bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three cases of alloimmune mediated pancytopenia in calves resembling bovine neonatal pancytopenia
Authors: Chantillon L. , Devriendt B. , De Jonge B. , Oostvogels J. , Coppens J. , Pas M. L. , Bokma J. , Pardon B. 
Published: January 2022

Abstract
Background
Between 2007 and 2011 several thousands of calves died from bovine neonatal pancytopenia (BNP), a bleeding syndrome triggered by vaccine induced alloantibodies from the dams. Following withdrawal of the involved bovine viral diarrhoea virus (BVDv) vaccine, the incidence of this condition rapidly decreased, with no reported cases in the last 5 years. Here, we report a recent immune-mediated pancytopenia in three calves from two different suckler herds, clinically indistinguishable from BNP.

Case presentation
Three Belgian Blue suckler calves from two different farms, aged around two weeks, showed multiple bleedings disseminated on the skin and petechiae and ecchymoses on the mucosae. Blood examination confirmed anaemia, leukopenia and thrombocytopenia. BVDv infection was excluded. Despite blood transfusion and cortisone therapy, all three animals died. Necropsy and histology confirmed bone marrow depletion. Binding of IgG from the dams on leukocytes of the calves was demonstrated by flow cytometry. Two calves, originating from the same farm, received colostrum from the same dam. None of the calves were given colostrum replacers or colostrum supplements. No link with the BNP causing BVDv vaccine could be evidenced. However, dams had been vaccinated against bovine herpesvirus 1, parainfluenza-3 virus, bovine respiratory syncytial virus and bluetongue virus serotype 8.

Conclusions
Alloimmune mediated pancytopenia was evidenced in three animals, clinically and pathologically indistinguishable from BNP. Whether this disease is again vaccine mediated remains to be determined.
Malignancy prediction of cutaneous and subcutaneous neoplasms in canines using B-mode ultrasonography, Doppler, and ARFI elastography
Authors: da Cruz Igor Cezar Kniphoff , Carneiro Rafael Kretzer , de Nardi Andrigo Barboza , Uscategui Ricardo Andrés Ramirez , Bortoluzzi Eduarda Mazzardo , Feliciano Marcus Antônio Rossi 
Published: January 2022

Abstract
Background
Cutaneous and subcutaneous neoplasms are highly prevalent in dogs, ranging from benign to highly aggressive and metastatic lesions. The diagnosis is obtained through histopathology, however it is an invasive technique that may take a long time to obtain the result, delaying the beginning of the adequate treatment. Thus, there is a need for non-invasive tests that can help in the early diagnosis of this type of cancer. The aim of this study was to verify the accuracy of B-mode ultrasonography, Doppler, and ARFI elastography to predict malignancy in cutaneous and subcutaneous canine neoplasms. In addition, we aim to propose an ultrasonography evaluation protocol and perform the neoplasms characterization using these three proposed techniques.

Results
Twenty-one types of specific neoplasm were diagnosed, and using B-mode, we verified the association between heterogeneous echotexture, invasiveness, presence of hyperechoic spots, and cavity areas with malignancy. An increased pulsatility was verified in malignant neoplasms using Doppler (cut-off value > 0.93). When using the elastography, malignancy was associated with non-deformable tissues and shear wave velocity > 3.52 m/s. Evaluation protocols were proposed associating 4, 5, 6, or 7 malignancy predictive characteristics, and characterization was done for all tumors with at least two cases.

Conclusions
We concluded that ultrasonography methods are promising and effective in predicting malignancy in these types of tumors, and the association of methods can increase the specificity of the results.
Novel deletion of exon 3 in TYR gene causing Oculocutaneous albinism 1B in an Indian family along with intellectual disability associated with chromosomal copy number variations
Authors: Dhangar Somprakash , Panchal Purvi , Ghatanatti Jagdeeshwar , Suralkar Jitendra , Shah Anjali , Vundinti Babu Rao 
Published: January 2022

Abstract
Background
Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by hypo-pigmentation of skin, hair, and eyes. The OCA clinical presentation is due to a deficiency of melanin biosynthesis. Intellectual disability (ID) in OCA cases is a rare clinical presentation and appropriate diagnosis of ID is challenging through clinical examination. We report an Indian family with a rare co-inheritance of OCA1B and ID due to a novel TYR gene variant and chromosomal copy number variations.

Methods
We have done a study on three siblings (2 males and 1 female) of a family where all of them presented with hypopigmented skin, hair and eyes. The male children and their father was affected with ID. Targeted exome sequencing and multiplex ligation-dependent probe amplification analysis were carried out to identify the OCA1B and ID associated genomic changes. Further Array-CGH was performed using SurePrint G3 Human CGH + SNP, 8*60 K array.

Results
A rare homozygous deletion of exon 3 in TYR gene causing OCA1B was identified in all three children. The parents were found to be heterozygous carriers. The Array-CGH analysis revealed paternally inherited heterozygous deletion (1.9 MB) of 15q11.1-> 15q11.2 region in all three children. Additionally, paternally inherited heterozygous deletion (2.6 MB) of 10q23.2-> 10q23.31 region was identified in the first male child; this may be associated with ID as the father and the child both presented with ID. While the 2nd male child had a denovo duplication of 13q31.1-> 13q31.3 chromosomal region.

Conclusion
A rare homozygous TYR gene exon 3 deletion in the present study is the cause of OCA1B in all three children, and the additional copy number variations are associated with the ID. The study highlights the importance of combinational genetic approaches for diagnosing two different co-inherited disorders (OCA and ID). Hence, OCA cases with additional clinical presentation need to be studied in-depth for the appropriate management of the disease.
How do we measure gender discrimination? Proposing a construct of gender discrimination through a systematic scoping review
Authors: de la Torre-Pérez Laura , Oliver-Parra Alba , Torres Xavier , Bertran Maria Jesús 
Published: January 2022

AbstractBackgroundGender discrimination (GD) has been frequently linked to mental health. The heterogeneity of how GD is defined has led to variation around the analysis of GD. This might affect the study of the association between GD and health outcomes. The main goal of this systematic scoping review is to operationalize the definition of the GD construct.MethodsThree search strategies were set in Pubmed, CINAHL and PsycINFO. The first strategy obtained results mainly about women, while the second focused on men. The third strategy focused on the identification of GD questionnaires. The prevalence of GD, factors and consequences associated with GD perception, and forms of discrimination were the principal variables collected. Risk of bias was assessed (PROSPERO:CRD42019120719).ResultsOf the 925 studies obtained, 84 were finally included. 60 GD questionnaires were identified. GD prevalence varied between 3.4 and 67 %. Female gender and a younger age were the factors most frequently related to GD. Poorer mental health was the most frequent consequence. Two components of the GD construct were identified: undervaluation (different recognition, opportunities in access, evaluation standards and expectations) and different treatment (verbal abuse and behaviour).ConclusionsTwo-component GD definition can add order and precision to the measurement, increase response rates and reported GD.
Correlation analysis between preoperative systemic immune inflammation index and prognosis of patients after radical gastric cancer surgery: based on propensity score matching method
Authors: Zhaojun Xu , Xiaobin Chen , Juan An , Jiaqi Yuan , Shuyun Jiang , Tao Liu , Baojia Cai , Cheng Wang , Xiaoming Ma 
Published: January 2022

Abstract
Background
To explore the correlation between the preoperative systemic immune inflammation index (SII) and the prognosis of patients with gastric carcinoma (GC).

Methods
The clinical data of 771 GC patients surgically treated in the Department of Gastrointestinal Surgery, Qinghai University Affiliated Hospital from June 2010 to June 2015 were retrospectively analyzed, and their preoperative SII was calculated. The optimal cut-off value of preoperative SII was determined using the receiver operating characteristic (ROC) curve, the confounding factors between the two groups were eliminated using the propensity score matching (PSM) method, and the correlation between preoperative SII and clinicopathological characteristics was assessed by chi-square test. Moreover, the overall survival was calculated using Kaplan-Meier method, the survival curve was plotted, and log-rank test was performed for the significance analysis between the curves. Univariate and multivariate analyses were also conducted using the Cox proportional hazards model.

Results
It was determined by the ROC curve that the optimal cut-off value of preoperative SII was 489.52, based on which 771 GC patients were divided into high SII (H-SII) group and low SII (L-SII) group, followed by PSM in the two groups. The results of Kaplan-Meier analysis showed that before and after PSM, the postoperative 1-, 3-, and 5-year survival rates in L-SII group were superior to those in H-SII group, and the overall survival rate had a statistically significant difference between the two groups (P < 0.05). Before PSM, preoperative SII [hazard ratio (HR) = 2.707, 95% confidence interval (CI) 2.074-3.533, P < 0.001] was an independent risk factor for the prognosis of GC patients. After 1:1 PSM, preoperative SII (HR = 2.669, 95%CI 1.881–3.788, P < 0.001) was still an independent risk factor for the prognosis of GC patients.

Conclusions
Preoperative SII is an independent risk factor for the prognosis of GC patients. The increase in preoperative SII in peripheral blood indicates a worse prognosis.
Transcriptomics of receptive endometrium in women with sonographic features of adenomyosis
Authors: Prašnikar Erika , Kunej Tanja , Gorenjak Mario , Potočnik Uroš , Kovačič Borut , Knez Jure 
Published: January 2022

Abstract
Background
Women with uterine adenomyosis seeking assisted reproduction have been associated with compromised endometrial receptivity to embryo implantation. To understand the mechanisms involved in this process, we aimed to compare endometrial transcriptome profiles during the window of implantation (WOI) between women with and without adenomyosis.

Methods
We obtained endometrial biopsies LH-timed to the WOI from women with sonographic features of adenomyosis (n=10) and controls (n=10). Isolated RNA samples were subjected to RNA sequencing (RNA-seq) by the Illumina NovaSeq 6000 platform and endometrial receptivity classification with a molecular tool for menstrual cycle phase dating (beREADY®, CCHT). The program language R and Bioconductor packages were applied to analyse RNA-seq data in the setting of the result of accurate endometrial dating. To suggest robust candidate pathways, the identified differentially expressed genes (DEGs) associated with the adenomyosis group in the receptive phase were further integrated with 151, 173 and 42 extracted genes from published studies that were related to endometrial receptivity in healthy uterus, endometriosis and adenomyosis, respectively. Enrichment analyses were performed using Cytoscape ClueGO and CluePedia apps.

Results
Out of 20 endometrial samples, 2 were dated to the early receptive phase, 13 to the receptive phase and 5 to the late receptive phase. Comparison of the transcriptomics data from all 20 samples provided 909 DEGs (p<0.05; nonsignificant after adjusted p value) in the adenomyosis group but only 4 enriched pathways (Bonferroni p value < 0.05). The analysis of 13 samples only dated to the receptive phase provided suggestive 382 DEGs (p<0.05; nonsignificant after adjusted p value) in the adenomyosis group, leading to 33 enriched pathways (Bonferroni p value < 0.05). These included pathways were already associated with endometrial biology, such as “Expression of interferon (IFN)-induced genes” and “Response to IFN-alpha”. Data integration revealed pathways indicating a unique effect of adenomyosis on endometrial molecular organization (e.g., “Expression of IFN-induced genes”) and its interference with endometrial receptivity establishment (e.g., “Extracellular matrix organization” and “Tumour necrosis factor production”).

Conclusions
Accurate endometrial dating and RNA-seq analysis resulted in the identification of altered response to IFN signalling as the most promising candidate of impaired uterine receptivity in adenomyosis.
Elevated SAA1 promotes the development of insulin resistance in ovarian granulosa cells in polycystic ovary syndrome
Authors: Zhu Qinling , Yao Yue , Xu Lizhen , Wu Hasiximuke , Wang Wangsheng , He Yaqiong , Wang Yuan , Lu Yao , Qi Jia , Ding Ying , Li Xinyu , Huang Jiaan , Zhao Hanting , Du Yanzhi , Sun Kang , Sun Yun 
Published: January 2022

Abstract
Background
Insulin resistance (IR) contributes to ovarian dysfunctions in polycystic ovarian syndrome (PCOS) patients. Serum amyloid A1 (SAA1) is an acute phase protein produced primarily by the liver in response to inflammation. In addition to its role in inflammation, SAA1 may participate in IR development in peripheral tissues. Yet, expressional regulation of SAA1 in the ovary and its role in the pathogenesis of ovarian IR in PCOS remain elusive.

Methods
Follicular fluid, granulosa cells and peripheral venous blood were collected from PCOS and non-PCOS patients with and without IR to measure SAA1 abundance for analysis of its correlation with IR status. The effects of SAA1 on its own expression and insulin signaling pathway were investigated in cultured primary granulosa cells.

Results
Ovarian granulosa cells were capable of producing SAA1, which could be induced by SAA1 per se. Moreover, the abundance of SAA1 significantly increased in granulosa cells and follicular fluid in PCOS patients with IR. SAA1 treatment significantly attenuated insulin-stimulated membrane translocation of glucose transporter 4 and glucose uptake in granulosa cells through induction of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression with subsequent inhibition of Akt phosphorylation. These effects of SAA1 could be blocked by inhibitors for toll-like receptors 2/4 (TLR 2/4) and nuclear factor kappa light chain enhancer of activated B (NF-κB).

Conclusions
Human granulosa cells are capable of feedforward production of SAA1, which significantly increased in PCOS patients with IR. Excessive SAA1 reduces insulin sensitivity in granulosa cells via induction of PTEN and subsequent inhibition of Akt phosphorylation upon activation of TLR2/4 and NF-κB pathway. These findings highlight that elevation of SAA1 in the ovary promotes the development of IR in granulosa cells of PCOS patients.
Homozygous mutation in SLO3 leads to severe asthenoteratozoospermia due to acrosome hypoplasia and mitochondrial sheath malformations
Authors: Lv Mingrong , Liu Chunyu , Ma Chunjie , Yu Hui , Shao Zhongmei , Gao Yang , Liu Yiyuan , Wu Huan , Tang Dongdong , Tan Qing , Zhang Junqiang , Li Kuokuo , Xu Chuan , Geng Hao , Zhang Jingjing , Li Hang , Mao Xiaohong , Ge Lei , Fu Feifei , Zhong Kaixin , Xu Yuping , Tao Fangbiao , Zhou Ping , Wei Zhaolian , He Xiaojin , Zhang Feng , Cao Yunxia 
Published: January 2022

Abstract
Background
Potassium channels are important for the structure and function of the spermatozoa. As a potassium transporter, the mSlo3 is essential for male fertility as Slo3 knockout male mice were infertile with the series of functional defects in sperm cells. However, no pathogenic variant has been detected in human SLO3 to date. Here we reported a human case with homozygous SLO3 mutation. The function of SLO3 in human sperm and the corresponding assisted reproductive strategy are also investigated.

Methods
We performed whole-exome sequencing analysis from a large cohort of 105 patients with asthenoteratozoospermia. The effects of the variant were investigated by quantitative RT-PCR, western blotting, and immunofluorescence assays using the patient spermatozoa. Sperm morphological and ultrastructural studies were conducted using haematoxylin and eosin staining, scanning and transmission electron microscopy.

Results
We identified a homozygous missense variant (c.1237A > T: p.Ile413Phe) in the sperm-specific SLO3 in one Chinese patient with male infertility. This SLO3 variant was rare in human control populations and predicted to be deleterious by multiple bioinformatic tools. Sperm from the individual harbouring the homozygous SLO3 variant exhibited severe morphological abnormalities, such as acrosome hypoplasia, disruption of the mitochondrial sheath, coiled tails, and motility defects. The levels of SLO3 mRNA and protein in spermatozoa from the affected individual were reduced. Furthermore, the acrosome reaction, mitochondrial membrane potential, and membrane potential during capacitation were also afflicted. The levels of acrosome marker glycoproteins and PLCζ1 as well as the mitochondrial sheath protein HSP60 and SLO3 auxiliary subunit LRRC52, were significantly reduced in the spermatozoa from the affected individual. The affected man was sterile due to acrosome and mitochondrial dysfunction; however, intra-cytoplasmic sperm injection successfully rescued this infertile condition.

Conclusions
SLO3 deficiency seriously impact acrosome formation, mitochondrial sheath assembly, and the function of K+ channels. Our findings provided clinical implications for the genetic and reproductive counselling of affected families.
Use of research evidence varied in efforts to expand specific pharmacist autonomous prescriptive authority: an evaluation and recommendations to increase research utilization
Authors: Kumar Akshara , Ray Amber Bivins , Blanchard Carrie 
Published: January 2022

Abstract
Background
An expanding body of literature shows that pharmacists’ interventions improve health outcomes and are cost-saving. However, diverse state regulations of pharmacists’ scope of practice create a discrepancy between what pharmacists are trained to do and what they legally can do. This study investigated how stakeholders utilized research evidence when developing expanded scope of practice policies in their respective states.

Methods
Using autonomous pharmacist prescriptive authority as a surrogate for general pharmacist scope of practice, a general policy document analysis was performed to understand the scope of practice landscape for pharmacists across the United States. Next, semi-structured interviews with policy-makers and pharmacy advocates were conducted to explore how the identified states in the policy document analysis utilized evidence during the policy-making process. Investigators analysed findings from the transcribed interviews through application of the SPIRIT Action Framework. Resulting codes were summarized across themes, and recommendations to researchers about increasing utilization of research evidence were crafted.

Results
Sixteen states with 27 autonomous pharmacist prescriptive authority policies were identified. Public health need and safety considerations motivated evidence engagement, while key considerations dictating utilization of research included perceptions of research, access to resources and experts, and the successful implementation of similar policy. Research evidence helped to advocate for and set terms for pharmacist prescribing. Barriers to research utilization include stakeholder opposition to pharmacist prescribing, inability to interpret research, and a lack of relevant evidence. Recommendations for researchers include investigating specific metrics to evaluate scope of practice policy, developing relationships between policy-makers and researchers, and leveraging pharmacy practice stakeholders.

Conclusions
Overall, alignment of researcher goals and legislative priorities, coupled with timely communication, may help to increase research evidence engagement in pharmacist scope of practice policy. By addressing these factors regarding research engagement identified in this study, researchers can increase evidence-based scope of practice, which can help to improve patient outcomes, contain costs, and provide pharmacists with the legal infrastructure to practise at the top of their license.
Health technology assessment-informed pricing negotiation in China: higher negotiated price for more effective targeted anticancer medicines?
Authors: Huang Cong , Ung Carolina Oi Lam , Wushouer Haishaerjiang , Bai Lin , Huang Tao , Li Xinyi , Guan Xiaodong , Shi Luwen 
Published: January 2022

Abstract
Background
In China, health technology assessment (HTA) has recently been adopted in pricing negotiation for medicine listing in the National Reimbursement Drug List. At present, how HTA is applied to inform the decision-making process remains underreported. In order to explore how the adoption of HTA was translated into listing and price negotiation results in light of the confidential nature of the negotiating process, this study aimed to compare the negotiated price and the clinical benefit of selected targeted anticancer medicines (TAMs) involved in the 2019 negotiation.

Main text
Among 16 TAMs successfully negotiated, only four TAMs representing four indication groups had appropriate reference medicines for comparison and were, therefore, included in the analysis. The price and clinical benefit of the four TAMs were compared against one or two reference medicines with the same initial indications. The sales prices for nine TAMs before and after the negotiation were extracted from the centralized medication procurement system. Clinical benefits were evaluated based on evidence from published articles and clinical guidelines. The results suggested that, despite the application of HTA, both rational and irrational decisions had been made about the reimbursement of TAMs in the 2019 negotiation, warranting further investigation.

Conclusion
While the development and adoption of HTA has seen significant progress in China, actions are needed to ensure that the adoption of HTA is effectively applied in decisions on the reimbursement of medicines.