bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of equine herpesvirus 8 in donkey abortion: a case report
Authors: Wang Tongtong , Hu Leyu , Wang Yonghui , Liu Wenqiang , Liu Guiqin , Zhu Mingxia , Zhang Wei , Wang Changfa , Ren Huiying , Li Liangliang 
Published: January 2022

AbstractBackgroundEquine herpesvirus-8 (EHV-8) is one of the most economically significant viruses that infect mammals of the genus Equus worldwide, which cause severe respiratory diseases and abortion in horses. However, there is no report of abortion caused by EHV-8 in donkeys.Case presentationThe present case report is about a 4-year-old donkey having an abortion and showing a serious respiratory issue on the 296th day of pregnancy. Bacteriological and molecular tests were used to screen possible bacterial/viral pathogens to detect the etiological agent.Salmonella abortus equi, EHV-1, EHV-4, and EAV were all negative in the current study. EHV-8, on the other hand, was the only agent that was isolated and identified.ConclusionsThis was for the first time that EHV-8 had been isolated from a donkey in China. EHV-8 infection can cause abortion in donkeys; therefore, veterinarians and breeders should be aware of it.
Association between baseline and changes in high-sensitive C-reactive protein and metabolic syndrome: a nationwide cohort study and meta-analysis
Authors: Xue Qingping , Yang Xue , Huang Yuli , Zhu Dongshan , Wang Yi , Wen Ying , Zhao Jian , Liu Yanjun , Yang Chun-Xia , Pan Jay , Yan Tong , Pan Xiong-Fei 
Published: January 2022

Abstract
Background
We aimed to prospectively evaluate the associations between the baseline and changes in high-density C-reactive protein (hs-CRP) and incident metabolic syndrome (MetS) in China and update the evidence based on a meta-analysis of cohort studies in different populations.

Methods
Data from the China Health and Retirement Longitudinal Study among adults aged 45 years or older were analyzed. Participants who were recruited in the study in 2011–2012 without MetS and successfully followed up to 2015–2016 were included in our final analysis. Logistic regressions were applied to examine the prospective associations of baseline and changes in hs-CRP with incident MetS and estimate corresponding odds ratios (ORs) and 95% confidence intervals (95% CIs). A meta-analysis was conducted to synthesize effect estimates from our findings and other cohort studies on this topic.

Results
Among 4,116 participants, 535 developed MetS after a 4-year follow-up. Compared with the participants with hs-CRP in the lowest quartile, those with hs-CRP in the second, third, and highest quartiles had higher odds of MetS, with multivariable-adjusted ORs (95% CIs) of 1.51 (1.12, 2.06), 1.50 (1.11, 2.04), and 1.83 (1.37, 2.47). For the hs-CRP changes, ORs (95% CIs) were 3.24 (2.51, 4.02), 3.34 (2.56, 4.38), and 3.34 (2.54, 4.40) respectively. One unit (log of 1 mg/L) increase in hs-CRP was associated with 23% higher risk of MetS (OR 1.23; 95% CI 1.10, 1.38). In a meta-analysis of 6 cohort studies, the pooled relative risk for MetS was 1.63 (1.38, 1.93) for the highest versus lowest level of hs-CRP. In addition, the pooled relative risk for MetS was 1.29 (1.05, 1.59) for each unit increase of hs-CRP after log-transformation.

Conclusions
Both higher baseline hs-CRP and longitudinal hs-CRP increases were associated with higher risks of incident MetS. Individuals with high hs-CRP levels may need to be closely monitored for future risk of MetS.
Efficiency of primary spine care as compared to conventional primary care: a retrospective observational study at an Academic Medical Center
Authors: Bezdjian Serena , Whedon James M. , Russell Robb , Goehl Justin M. , Kazal Louis A. 
Published: January 2022

Abstract
Background
Primary Spine Care (PSC) is an innovative model for the primary management of patients with spine-related disorders (SRDs), with a focus on the use of non-pharmacological therapies which now constitute the recommended first-line approach to back pain. PSC clinicians serve as the initial or early point of contact for spine patients and utilize evidence-based spine care pathways to improve outcomes and reduce escalation of care (EoC; e.g., spinal injections, diagnostic imaging, hospitalizations, referrals to a specialist). The present study examined 6-month outcomes to evaluate the efficiency of care for patients who received PSC as compared to conventional primary care. We hypothesized that patients seen by a PSC clinician would have lower rates of EoC compared to patients who received usual care by a primary care (PC) clinician.

Methods
This was a retrospective observational study. We evaluated 6-month outcomes for two groups seen and treated for an SRD between February 01, 2017 and January 31, 2020. Patient groups were comprised of N = 1363 PSC patients (Group A) and N = 1329 PC patients (Group B). We conducted Pearson chi-square and logistic regression (adjusting for patient characteristics that were unbalanced between the two groups) to determine associations between the two groups and 6-month outcomes.

Results
Within six months of an initial visit for an SRD, a statistically significantly smaller proportion of PSC patients utilized healthcare resources for spine care as compared to the PC patients. When adjusting for patient characteristics, those who received care from the PSC clinician were less likely within 6 months of an initial visit to be hospitalized (OR = .47, 95% CI .23–.97), fill a prescription for an opioid analgesic (OR = .43; 95% CI .29–.65), receive a spinal injection (OR = .56, 95% CI .33–.95), or have a visit with a specialist (OR = .48, 95% CI .35–.67) as compared to those who received usual primary care.

Conclusions
Patients who received PSC in an academic primary care clinic experienced significantly less escalation of their spine care within 6 months of their initial visit. The PSC model may offer a more efficient approach to the primary care of spine problems for patients with SRDs, as compared to usual primary care.
A pilot study of machine-learning based automated planning for primary brain tumours
Authors: Tsang Derek S. , Tsui Grace , McIntosh Chris , Purdie Thomas , Bauman Glenn , Dama Hitesh , Laperriere Normand , Millar Barbara-Ann , Shultz David B. , Ahmed Sameera , Khandwala Mohammad , Hodgson David C. 
Published: January 2022

Abstract
Purpose
High-quality radiotherapy (RT) planning for children and young adults with primary brain tumours is essential to minimize the risk of late treatment effects. The feasibility of using automated machine-learning (ML) to aid RT planning in this population has not previously been studied.

Methods and materials
We developed a ML model that identifies learned relationships between image features and expected dose in a training set of 95 patients with a primary brain tumour treated with focal radiotherapy to a dose of 54 Gy in 30 fractions. This ML method was then used to create predicted dose distributions for 15 previously-treated brain tumour patients across two institutions, as a testing set. Dosimetry to target volumes and organs-at-risk (OARs) were compared between the clinically-delivered (human-generated) plans versus the ML plans.

Results
The ML method was able to create deliverable plans in all 15 patients in the testing set. All ML plans were generated within 30 min of initiating planning. Planning target volume coverage with 95% of the prescription dose was attained in all plans. OAR doses were similar across most structures evaluated; mean doses to brain and left temporal lobe were lower in ML plans than manual plans (mean difference to left temporal, – 2.3 Gy, p = 0.006; mean differences to brain, – 1.3 Gy, p = 0.017), whereas mean doses to right cochlea and lenses were higher in ML plans (+ 1.6–2.2 Gy, p < 0.05 for each).

Conclusions
Use of an automated ML method to aid RT planning for children and young adults with primary brain tumours is dosimetrically feasible and can be successfully used to create high-quality 54 Gy RT plans. Further evaluation after clinical implementation is planned.
An algorithm for thoracic re-irradiation using biologically effective dose: a common language on how to treat in a “no-treat zone”
Authors: Brooks Eric D. , Wang Xiaochun , De Brian , Verma Vivek , Williamson Tyler D. , Hunter Rachel , Mohamed Abdallah S. R. , Ning Matthew S. , Zhang Xiaodong , Chang Joe Y. 
Published: January 2022

Abstract
Background
Re-irradiation (re-RT) is a technically challenging task for which few standardized approaches exist. This is in part due to the lack of a common platform to assess dose tolerance in relation to toxicity in the re-RT setting. To better address this knowledge gap and provide new tools for studying and developing thresholds for re-RT, we developed a novel algorithm that allows for anatomically accurate three-dimensional mapping of composite biological effective dose (BED) distributions from nominal doses (Gy).

Methods
The algorithm was designed to automatically convert nominal dose from prior treatment plans to corresponding BED value maps (voxel size 2.5 mm3 and α/β of 3 for normal tissue, BED3). Following the conversion of each plan to a BED3 dose distribution, deformable registration was used to create a summed composite re-irradiation BED3 plan for each patient who received two treatments. A proof-of-principle analysis was performed on 38 re-irradiation cases of initial stereotactic ablative radiotherapy (SABR) followed by either re-SABR or chemoradiation for isolated locoregional recurrence of early-stage non-small cell lung cancer.

Results
Evaluation of the algorithm-generated maps revealed appropriate conversion of physical dose to BED at each voxel. Of 14 patients receiving repeat SABR, there was one case each of grade 3 chest wall pain (7%), pneumonitis (7%), and dyspnea (7%). Of 24 patients undergoing repeat fractionated radiotherapy, grade 3 events were limited to two cases each of pneumonitis and dyspnea (8%). Composite BED3 dosimetry for each patient who experienced grade 2–3 events is provided and may help guide development of precise cumulative dose thresholds for organs at risk in the re-RT setting.

Conclusions
This novel algorithm successfully created a voxel-by-voxel composite treatment plan using BED values. This approach may be used to more precisely examine dosimetric predictors of toxicities and to establish more accurate normal tissue constraints for re-irradiation.
Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) decoction suppresses colorectal cancer via downregulation of Wnt5/β-Catenin signal
Authors: Bian Yong , Wang Gang , Zhou Jing , Yin Gang , Liu Tiantian , Liang Li , Yang Xinyue , Zhang Wen , Ni Kexin , Tang Decai , Yu Yun 
Published: January 2022

Abstract
Background
The decoction of Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) has been reported as a potential antitumor agent for colorectal cancer (CRC) in experimental and clinical studies, but its underlying mechanism is still unclear.

Methods
The current research aims to explore the potential of Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) decoction (AR decoction) in the treatment of CRC and explore the underlying mechanism. SW620 cells were transient transfection to overexpress or knock down wnt 5 or β-Catenin. Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) -containing serum (AR-CS) was used to interfere with SW620 cells. Additional AR-CS, Wnt5 inhibitor (IWP-4), and β-Catenin inhibitor (JW55) were used to intervene in SW620 cells. Furthermore, subcutaneously injection of SW620 cells into the right flank of nude mice replicated xenograft mice, which were treated with AR decoction for 21 days.

Results
AR-CS significantly reduced the mRNA and protein expression levels of Wnt5, β-Catenin, ARF6, and N-Cadherin in SW620 cells, while inhibiting the proliferation and migration of SW620 cells. In cells overexpressing Wnt5 or β-Catenin, these effects of AR-CS were significantly suppressed. On the contrary, the inhibitory effect of AR-CS on the mRNA and protein levels of ARF6 and N-Cadherin and cell proliferation and migration of SW620 was enhanced, when Wnt5 or β-Catenin were knocked down or suppressed by the inhibitors. Moreover, in the mouse model of xenograft tumors, AR decoction not only reduced the tumor volume and inhibited the mRNA levels and protein levels of Wnt5, β-Catenin, ARF6, and N-Cadherin in the tumor, but also inhibit the protein levels of LRP5, LRP6, TCF-4, and LEF1.The histopathology of mice also showed increased apoptosis in tumor tissues, and AR decoction treatment did not cause pathological damage to the kidney and liver.

Conclusions
Our results provide evidence that AR decoction inhibits Wnt5/β-catenin signaling and inhibits the development of CRC, which is a promising traditional medicine in the clinical treatment of CRC.
A retrospective cohort study on European Reference Network for Rare Vascular Diseases 5 outcome measures for Hereditary Haemorrhagic Telangiectasia in Denmark
Authors: Hvelplund Troels , Lange Bibi , Bird Susanne Djernes , Korsholm Malene , Kjeldsen Anette Drøhse 
Published: January 2022

Abstract
Background
Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by several clinical symptoms including epistaxis, arteriovenous malformations (AVM), and telangiectasia. In 2018, European Reference Network for Rare Vascular Diseases (VASCERN) recommended five outcome measures for HHT-patients to guide health care providers, some with limited experience in treating HHT, and thereby maximizing the number of HHT-patients receiving good care. The outcome measures cover the following aspects: (1) 90% of the patients should receive a pulmonary AVM (PAVM) screening; (2) 90% of the patients should receive written advice on nosebleed; (3) 70% should be assessed for iron deficiency; (4) 100% of the patients should receive written advice on antibiotic (AB) prophylaxis prior to dental and surgical procedures, and (5) 100% of relevant patients should receive written advice on pregnancy. We have introduced the outcome measures as Benchmarks in our HHT-centre and wanted to evaluate the extend of implementation we have achieved. We constantly struggle to secure the best possible treatment of our HHT-patients.

Methods
The study was a non-interventional retrospective study. Data was collected manually from patient records and from the Danish HHT-database.

Results
A total of 180 HHT-patients were included, all diagnosed in the period from January 1st, 2016, to December 31st, 2020. All patients were screened for PAVM. We could confirm that 66% of patients who had epistaxis received thoroughly advice. Assessment for iron deficiency was performed in 80% of the adult patients. Thoroughly advice on AB prophylaxis was documented in 75%. Thoroughly advice on pregnancy was documented in 80% of female patients 15–45 years of age. There were no significant differences over time for any of the outcome measures.

Conclusions
The Danish HHT-centre reached the target threshold for outcome measures 1 and 3. It could not be documented that the target thresholds for outcome measures 2, 4, and 5 were achieved. As information and education are a very important part of HHT care, focus on and documentation that all patients receive the relevant advice must be a priority in order to ensure best care.
Molecular and clinical characterization of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) in Iranian non-Jewish patients: report of two novel AIRE gene pathogenic variants
Authors: Setoodeh Aria , Panjeh-Shahi Samareh , Bahmani Fariba , Vand-Rajabpour Fatemeh , Jalilian Nazanin , Sayarifard Fatemeh , Abbasi Farzaneh , Sayarifard Azadeh , Rostami Parastoo , Parvaneh Nima , Akhavan-Niaki Haleh , Ahmadifard Mohamadreza , Tabrizi Mina 
Published: January 2022

Abstract
Objective
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) is a rare autosomal recessive systemic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Incidence of this genetic disorder is estimated at 1/90,000–200,000 worldwide and 1/6500–9000 in genetically isolated populations such as Iran. Here, we investigated AIRE gene mutations in eight independent Iranian non-Jewish families.

Methods
We sequenced the coding regions of the AIRE gene and documented mutations which were further confirmed in respective parents.

Results
In total, 11 cases from 8 independent families were recruited. Mucosal candidiasis, Addison’s disease and hypoparathyroidism were the most common clinical manifestations in these patients. One novel homozygous splice acceptor mutation (c.308-1G>C), and one novel heterozygous stop-gain mutation (c.1496delC) combined with a known heterozygous c.232T>C missense mutation were found. Moreover, we observed previously described splice donor (c.1095+2T>A), frameshift (c.967-979del), stop-gain (c.415C>T), and missense (c.62C>T) mutations among the patients. All results were co-segregated in parents.

Conclusion
Here, we reported two novel mutations in the AIRE gene leading to APECED. Our data could provide insight into the phenotypic and genotypic spectrum of APECED in the non-Jewish Iranian population. These findings, in addition to future functional assays, can elucidate disease-causing mechanisms related to the AIRE gene and assist in genetic counseling and diagnosis.
Potential impact of the COVID-19 pandemic on japanese patients with eating disorders -a cross-sectional study
Authors: Takakura Shu , Toda Kenta , Yamashita Makoto , Kitajima Tomoko , Suematsu Takafumi , Yokoyama Hiroaki , Asou Chie Suzuyama , Hata Tomokazu , Sudo Nobuyuki 
Published: January 2022

Abstract
Background
The COVID-19 pandemic and associated lockdown had a considerable impact on eating disorders (EDs). We evaluated the clinical features of Japanese ED patients before and after the first COVID-19 outbreak-related state of emergency (April 7, 2020).

Methods
We studied 148 patients who were divided into two groups based on when they arrived at our clinic: before (Before group: n = 86) or after (After group: n = 62) the start of the first state of emergency. All patients completed the Japanese versions of the Eating Disorder Inventory (EDI) and Parental Bonding Instrument (PBI).

Results
The After group was substantially younger than the Before group (p = .0187). Regardless of the ED type, patients who developed an ED during the first state of emergency tended to be significantly younger than those who developed one before. Differences in EDI characteristics were observed between the two groups. The PBI care subscale was notably higher (p = .0177) in the After group. The PBI maternal care subscale was the only statistically significant factor associated with age (β = -0.35, p < .0001).

Conclusions
Home confinement associated with the COVID-19 pandemic and the ensuing increase in parent-child closeness may have influenced the decreased age of ED patients at their initial consultation. Treatment interventions should consider the differences in the clinical features of EDs.
Relief of neuropathic pain by cell-specific manipulation of nucleus accumbens dopamine D1- and D2-receptor-expressing neurons
Authors: Sato Daisuke , Narita Michiko , Hamada Yusuke , Mori Tomohisa , Tanaka Kenichi , Tamura Hideki , Yamanaka Akihiro , Matsui Ryosuke , Watanabe Dai , Suda Yukari , Senba Emiko , Watanabe Moe , Navratilova Edita , Porreca Frank , Kuzumaki Naoko , Narita Minoru 
Published: January 2022

AbstractEmerging evidence suggests that the mesolimbic dopaminergic network plays a role in the modulation of pain. As chronic pain conditions are associated with hypodopaminergic tone in the nucleus accumbens (NAc), we evaluated the effects of increasing signaling at dopamine D1/D2-expressing neurons in the NAc neurons in a model of neuropathic pain induced by partial ligation of sciatic nerve. Bilateral microinjection of either the selective D1-receptor (Gs-coupled) agonist Chloro-APB or the selective D2-receptor (Gi-coupled) agonist quinpirole into the NAc partially reversed nerve injury-induced thermal allodynia. Either optical stimulation of D1-receptor-expressing neurons or optical suppression of D2-receptor-expressing neurons in both the inner and outer substructures of the NAc also transiently, but significantly, restored nerve injury-induced allodynia. Under neuropathic pain-like condition, specific facilitation of terminals of D1-receptor-expressing NAc neurons projecting to the VTA revealed a feedforward-like antinociceptive circuit. Additionally, functional suppression of cholinergic interneurons that negatively and positively control the activity of D1- and D2-receptor-expressing neurons, respectively, also transiently elicited anti-allodynic effects in nerve injured animals. These findings suggest that comprehensive activation of D1-receptor-expressing neurons and integrated suppression of D2-receptor-expressing neurons in the NAc may lead to a significant relief of neuropathic pain.
Retrospective analysis of arterial occlusive events in the PACE trial by an independent adjudication committee
Authors: Januzzi James L. , Garasic Joseph M. , Kasner Scott E. , McDonald Vickie , Petrie Mark C. , Seltzer Jonathan , Mauro Michael , Croce Kevin , Berman Ellin , Deininger Michael , Hochhaus Andreas , Pinilla-Ibarz Javier , Nicolini Franck , Kim Dong-Wook , DeAngelo Daniel J. , Kantarjian Hagop , Xu Jing , Hall Tracey , Srivastava Shouryadeep , Naranjo Daniel , Cortes Jorge 
Published: January 2022

Abstract
Background
The phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial of ponatinib showed robust long-term benefit in relapsed Philadelphia chromosome-positive (Ph+) leukemia; arterial occlusive events (AOEs) occurred in ≥ 25% of patients based on investigator reporting. However, AOE rates vary depending on the definitions and reporting approach used.

Methods
To better understand clinically relevant AOEs with ponatinib, an independent cardiovascular adjudication committee reviewed 5-year AOE data from the PACE trial according to a charter-defined process and standardized event definitions.

Results
A total of 449 patients with chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) received ponatinib (median age 59 y; 47% female; 93% ≥ 2 prior tyrosine kinase inhibitors (TKIs); median follow-up, 37.3 months). The adjudicated AOE rate (17%) was lower than the non-adjudicated rate (i.e., rate before adjudication; 25%). The only adjudicated AOE in > 2% of patients was peripheral arterial occlusive disease (4%). Exposure-adjusted incidence of newly occurring adjudicated AOEs decreased over time. Patients with multiple baseline cardiovascular risk factors had higher adjudicated AOE rates than those without risk factors.

Conclusions
This independent adjudication study identified lower AOE rates than previously reported, suggesting earlier overestimation that may inaccurately reflect AOE risk with ponatinib. This trial was registered under ClinicalTrials.gov identifier NCT01207440 on September 23, 2010 (https://clinicaltrials.gov/ct2/show/NCT01207440).