bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association mapping uncovers sex-associated copy number variation markers and female hemizygous regions on the W chromosome in Salix viminalis
Authors: Hallingbäck Henrik R. , Pucholt Pascal , Ingvarsson Pär K. , Rönnberg-Wästljung Ann Christin , Berlin Sofia 
Published: October 2021

Abstract
Background
Sex chromosomes are in some species largely undifferentiated (homomorphic) with restricted sex determination regions. Homomorphic but different sex chromosomes are found in the closely related genera Populus and Salix indicating flexible sex determination systems, ideal for studies of processes involved in sex chromosome evolution. We have performed genome-wide association studies of sex and analysed sex chromosomes in a population of 265 wild collected Salix viminalis accessions and studied the sex determining locus.

Results
A total of 19,592 markers were used in association analyses using both Fisher’s exact tests and a single-marker mixed linear model, which resulted in 48 and 41 sex-associated (SA) markers respectively. Across all 48 SA markers, females were much more often heterozygous than males, which is expected if females were the heterogametic sex. The majority of the SA markers were, based on positions in the S. purpurea genome, located on chromosome 15, previously demonstrated to be the sex chromosome. Interestingly, when mapping the genotyping-by-sequencing sequence tag harbouring the two SA markers with the highest significance to the S. viminalis genomic scaffolds, five regions of very high similarity were found: three on a scaffold that represents a part of chromosome 15, one on a scaffold that represents a part of chromosome 9 and one on a scaffold not anchored to the genome. Based on segregation differences of the alleles at the two marker positions and on differences in PCR amplification between females and males we conclude that females had multiple copies of this DNA fragment (chromosome 9 and 15), whereas males only had one (chromosome 9). We therefore postulate that the female specific sequences have been copied from chromosome 9 and inserted on chromosome 15, subsequently developing into a hemizygous W chromosome linked region.

Conclusions
Our results support that sex determination in S. viminalis is controlled by one locus on chromosome 15. The segregation patterns observed at the SA markers furthermore confirm that S. viminalis females are the heterogametic sex. We also identified a translocation from chromosome 9 to the W chromosome.
Structural heart defects associated with ETB mutation, a cause of Hirschsprung disease
Authors: Chen Ko-Chin , Chen Ko-Chien , Song Zan-Min , Croaker Geoffrey D. 
Published: October 2021

AbstractBackgroundHSCR, a colonic neurocristopathy affecting 1/5000 births, is suggested to associate with cardiac septal defects and conotruncal malformations. However, we question subtle cardiac changes maybe more commonly present due to multi-regulations by HSCR candidate genes, in this instance, ETB. To investigate, we compared the cardiac morphology and quantitative measurements ofsl/slrat to those of the control group.MethodsEleven neonatal rats were generated from heterozygote (ETB+/−) crossbreeding. Age and bodyweight were recorded at time of sacrifice. Diffusion-staining protocols with 1.5% iodine solution was completed prior to micro-CT scanning. All rats were scanned using an in vivo micro-CT scanner, Caliper Quantum FX, followed by two quality-control scans using a custom-built ex vivo micro-CT system. All scans were reviewed for gross cardiac dysmorphology. Micro-CT data were segmented semi-automatically post-NLM filtering for: whole-heart, LV, RV, LA, RA, and aortic arch. Measurements were taken with Drishti. Following image analysis, PCR genotyping of rats was performed: fivesl/slrats, three wildtype, and three heterozygotes. Statistical comparisons on organ volume, growth rate, and organ volume/bodyweight ratios were made betweensl/sland the control group.ResultsCardiac morphology and constituents were preserved. However, significant volumetric reductions were recorded insl/slrats with respect to the control: whole heart (38.70%,p value = 0.02); LV (41.22%,p value = 0.01), RV (46.15%,p value = 0.02), LA (44.93%,p value = 0.06), and RA (39.49%,p value = 0.02). Consistent trend was observed in growth rate (~ 20%) and organ-volume/bodyweight ratios (~ 25%). On the contrary, measurements on aortic arch demonstrated no significant difference among the two groups.ConclusionDespite the presence of normal morphology, significant cardiac growth retardation was detected insl/slrat, supporting the likely association of cardiac anomalies with HSCR, at least in ETB−/−subtype. Structural reduction was likely due to a combination of failure to thrive from enteric dysfunction, alterations to CaNCC colonization, and importantly coronary hypoperfusion from elevated ET-1/ETA-mediated hypervasoconstriction. Little correlation was detected between aortic arch development andsl/slrat, supporting minor ETBrole in large vessels. Although further clinical study is warranted, HSCR patients may likely require cardiac assessment in view of potential congenital cardiac defects.
Building the capacity of community health workers to support health and social care for dependent older people in Latin America: a pilot study in Fortaleza, Brazil
Authors: Neto João Bastos Freire , de Moraes Gerídice Lorna Andrade , de Souza Aredes Janaína , Giacomin Karla Cristina , de Melo Luciane Ponte , Sempe Lucas , Lloyd-Sherlock Peter 
Published: October 2021

Abstract
Background
Brazil is seeing rapid population ageing, which is leading to new demands on primary health care services. There is a need to develop and assess the effectiveness of new interventions to build the capacity of staff, including community health workers, to meet the needs of groups such as care-dependent older people and their care-givers. This study examines the feasibility of a small training intervention piloted in the Brazilian city of Fortaleza.

Methods
The study evaluated participants’ own assessments of key knowledge and skills related to the needs of care-dependent older people, both before and after the training intervention. It also assessed their capacity to implement a simple screening tool of geriatric risk factors.

Results
The participant self-assessments indicate significant improvements in their perceived knowledge and capacity in responding to the health needs of care-dependent older people. Additionally, participants were able to successfully conduct the home visits and screening for risk factors.

Conclusions
The study demonstrates the feasibility of developing interventions to enhance the capacity of community health workers to meet the needs of dependent older people in countries like Brazil. The evidence of effectiveness, though limited and subjective, provides justification for a larger, formally evaluated intervention. The experience of Fortaleza provides valuable lessons for other cities and countries in the region which are facing similar challenges.
Factors shaping the COVID-19 epidemic curve: a multi-country analysis
Authors: Jang Su Yeon , Hussain-Alkhateeb Laith , Rivera Ramirez Tatiana , Al-Aghbari Ahmed Asa’ad , Chackalackal Dhia Joseph , Cardenas-Sanchez Rocio , Carrillo Maria Angelica , Oh In-Hwan , Alfonso-Sierra Eduardo Andrés , Oechsner Pia , Kibiwott Kirui Brian , Anto Martin , Diaz-Monsalve Sonia , Kroeger Axel 
Published: October 2021

Abstract
Background
Lockdown measures are the backbone of containment measures for the COVID-19 pandemic both in high-income countries (HICs) and low- and middle-income countries (LMICs). However, in view of the inevitably-occurring second and third global covid-19 wave, assessing the success and impact of containment measures on the epidemic curve of COVID-19 and people’s compliance with such measures is crucial for more effective policies. To determine the containment measures influencing the COVID-19 epidemic curve in nine targeted countries across high-, middle-, and low-income nations.

Methods
Four HICs (Germany, Sweden, Italy, and South Korea) and five LMICs (Mexico, Colombia, India, Nigeria, and Nepal) were selected to assess the association using interrupted time series analysis of daily case numbers and deaths of COVID-19 considering the following factors: The “stringency index (SI)” indicating how tight the containment measures were implemented in each country; and the level of compliance with the prescribed measures using human mobility data. Additionally, a scoping review was conducted to contextualize the findings.

Results
Most countries implemented quite rigorous lockdown measures, particularly the LMICs (India, Nepal, and Colombia) following the model of HICs (Germany and Italy). Exceptions were Sweden and South Korea, which opted for different strategies. The compliance with the restrictions—measured as mobility related to home office, restraining from leisure activities, non-use of local transport and others—was generally good, except in Sweden and South Korea where the restrictions were limited. The endemic curves and time-series analysis showed that the containment measures were successful in HICs but not in LMICs.

Conclusion
The imposed lockdown measures are alarming, particularly in resource-constrained settings where such measures are independent of the population segment, which drives the virus transmission. Methods for examining people’s movements or hardships that are caused by covid- no work, no food situation are inequitable. Novel and context-adapted approach of dealing with the COVID-19 crisis are therefore crucial.
Viral suppression among HIV-positive patients on antiretroviral therapy in northwestern Nigeria: an eleven-year review of tertiary care centre records, January 2009–December 2019
Authors: Abdullahi Suleiman Bello , Ibrahim Olayinka Rasheed , Okeji Abdulkadir Baba , Yandoma Rabilu Iliyasu , Bashir Ibrahim , Haladu Suleiman , Idris Suleiman Ahmad , Oseni T. I. A. , Suleiman Bello Muhammad , Yahaya Mohammed , Aworh Mabel Kamweli , Sufiyan Mu’awiyyah Babale 
Published: October 2021

Abstract
Background
Human Immuno-Deficiency Virus (HIV) remains one of the world’s significant public health challenges. Viral suppression is the key indicator for treatment success in People living with HIV (PLHIV). We determined the level of viral suppression, and its associated factors among PLHIV attending Federal Medical Centre Katsina (FMC Katsina), Nigeria.

Methods
This retrospective descriptive cross-sectional study was conducted on 913 HIV positive adults enrolled in care between January 2009 and December 2019. Information on socio-demographics, clinical, immunological, Viral load (VL), and other relevant parameters were extracted from the patients’ care records. The primary outcome was the proportion of patients that achieved viral suppression. We also analyzed variables that were associated with VL suppression.

Results
Of 913, records of 831 (91.0%) registered patients were analyzed. During the period, 751 (90.4%) achieved viral suppression, 427 (51.4%) had CD4 counts  ≥ 500 and 477 (57.4%) were on HAART for ≥ 5 years. Majority, 793 (95.4%) were on first-line HAART regimen (Tenofovir-Lamivudine-Dolutegravir or Abacavir-Lamivudine-Dolutegravir), and 809 (97.4%) in the non-advanced stage (WHO stages 1 and 2). The median (interquartile range) of viral load was 20 (20–40) vs 19,989 (3311–110,340) cp/ml in virally suppressed, and unsuppressed respectively. Factors associated with viral suppression included being unemployed (Adjusted OR [AOR] 4.9, 95% CI 2.771, 8.539), educated (AOR 4.2, 95% CI 1.098, 16.223), having a baseline CD4 count ≥ 500 cells/µl (AOR 2.7, 95% CI 1.588, 4.625), and being on first line HAART regimen [AOR 7.0, 95% CI 3.220, 15.648].

Conclusions
Our study demonstrated a good viral suppression among PLHIV on HAART. Variables associated with viral suppression included unemployment, formal education, high baseline CD4 count, and first line HAART regimen.
MRI characteristics of brain edema in preeclampsia/eclampsia patients with posterior reversible encephalopathy syndrome
Authors: Mai Hui , Liang Zhiyu , Chen Zhanhang , Liu Zhaoran , Xu Yaxi , Chen Xuting , Du Xiujian , Peng Yuling , Chen Yonglu , Dong Tianfa 
Published: October 2021

Abstract
Background
The neuroimaging manifestations of eclampsia and preeclampsia often overlap, mainly presenting as posterior reversible encephalopathy syndrome (PRES). The purpose of this retrospective study was to compare the extent and nature of brain edema in eclampsia and preeclampsia patients with PRES based on MRI characteristics.

Methods
One hundred fifty women diagnosed with preeclampsia-eclampsia and undergoing cranial MRI were enrolled; 24 of these were diagnosed as having eclampsia. According to clinicoradiologic diagnosis of PRES, eligible patients were classified as having eclampsia with PRES (group E-PRES) and preeclampsia with PRES (group P-PRES). A scale on T2W FLAIR-SPIR images was established to evaluate the extent of brain edema, and the score of brain edema (SBE) of both groups was compared. In patients of the two groups who also underwent DWI sequence, the presence or absence of hyperintensity on DWI and hypointensity on ADC maps were determined to compare the nature of brain edema. Furthermore, clinical and biochemical data of the two groups were compared.

Results
The incidence of PRES in eclampsia patients was significantly higher than that in preeclampsia patients (87.50% vs. 46.03%, P<0.001). The SBE of all regions and typical regions in group E-PRES patients were significantly higher than those in group P-PRES patients (15.88±8.72 vs. 10.90±10.21, P=0.021; 8.52±3.87 vs. 5.01±4.19, P=0.002; respectively). The presence of hyperintensity on DWI was determined more frequently in group E-PRES patients than group P-PRES patients (71.43% vs. 32.00%, P=0.024). Age, systolic blood pressure, white blood cell count, neutrophil count and percentage of neutrophils were significantly different between the two groups (P<0.05).

Conclusions
Certain MRI characteristics that reflect the extent and nature of brain edema were different between eclampsia and preeclampsia patients with PRES. Additional prospective studies are still required to explore whether these MRI characteristics of brain edema may further become a potential predictor for eclamptic seizures in preeclampsia patients with PRES.
Effect of EPA on Hsp90 and GRα protein expression in multiple myeloma drug-resistant cells
Authors: Wu Shenghao , Chen Yuemiao , Wang Xueshuang , Weng Shanshan , Zhou Wenjin , Liu Zhen 
Published: October 2021

Abstract
Background
Approximately 20% of MM patients harbor glucocorticoid (GC) resistance and are not responsive to therapeutic effect. Chaperoneheat-shock proteins Hsp90 is needed for ligand docking, The imbalance of Hsp90/GRα (glucocorticoid receptor α) may be an important cause of GC resistance. Recent studies have indicated that EPA could repress cancer cell growth by regulating critical influential factors in progression of cancer, consisting of resistance to drugs, chemosensitivity. The aim of the present study was to test the cytotoxic effects of EPA alone or EPA + Dexamethasone in dexamethasone-resistant MM cell (MM.1R) and investigate whether DHA can induce apoptosis and reverse acquired glucocorticoid resistance in dexamethasone-resistant MM cell (MM.1R).

Methods
Cell Counting Kit-8 (CCK-8) was used to detect the proliferation of MM.1R cells after treating with EPA alone and EPA combined with DEX. Mitochondrial membrane potential was measured by flow cytometry and GRα and Hsp90 protein expression were assessed by western blot analysis.

Results
EPA alone was able to inhibit cell proliferation as evidenced by CCK-8 assay and the tumor growth was remarkably suppressed by EPA + Dexamethasone, Cell apoptosis after EPA treatment was obviously observed by Flow cytometry analysis of the mitochondrial membrane potential. Analysis of Hsp90 and GRα proteins in MM.1R cells incubated with EPA revealed down-regulation of Hsp90 and up-regulation of GRα. Accordingly, the Hsp90/GRα ratio was significantly decreased with the increase of EPA concentration.

Conclusions
EPA might be used as a new effective treatment for reversal of glucocorticoid-resistance in multiple myeloma.
Effect of free gingival graft before implant placement on peri-implant health and soft tissue changes: a randomized controlled trial
Authors: Zheng Chaoling , Wang Shimin , Ye Hongqiang , Liu Yunsong , Hu Wenjie , Zhou Yongsheng 
Published: October 2021

Abstract
Background
To evaluate the clinical outcome and changes in posterior buccal soft tissue following implant restoration in groups with and without a free gingival graft (FGG) before implant placement.

Methods
Twenty-six individuals who required implant restoration and displayed lack of keratinized mucosa (KM) were recruited and assigned to the FGG group (with FGG before implant placement) or Control group (without FGG before implant placement) randomly. A screw-retained conventional implant restoration was performed for each patient. Peri-implant soft tissue was captured by an intraoral scanner and analyzed by an image processing software. Clinical parameters (plaque index, gingival index, probing depth, and bleeding on probing) were assessed at baseline and 1, 3, 6, and 12 months. Buccal soft tissue changes (mucosal margin, soft tissue thickness, and width of keratinized mucosa) on the buccal side of implant site were assessed at 1, 3, 6, and 12 months. Two-way ANOVA and Bonferroni test were used to analyze significant difference between groups at each time point (α = 0.05).

Results
The clinical parameters were lower in the FGG group than that in the Control group, although there were no significant differences between the two groups (P > 0.05). Peri-implant soft tissue collapsed and the changes (mucosal margin and soft tissue thickness) were significantly greater in the Control group than the FGG group (P < 0.05). Width of KM was larger in the FGG group than the Control group, although there was no significant difference between the two groups (P > 0.05).

Conclusions
Minimal peri-implant soft tissue changes occurred in two groups. Performing FGG before implant placement is a viable procedure to maintain peri-implant soft tissue but might not affect peri-implant health during 12 months follow-up. However, small sample size must be considered.
Trial registration This study was retrospectively registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000037954; Date of registration: 6 September 2020).
Pharmacogenetic testing for adverse drug reaction prevention: systematic review of economic evaluations and the appraisal of quality matters for clinical practice and implementation
Authors: Turongkaravee Saowalak , Jittikoon Jiraphun , Rochanathimoke Onwipa , Boyd Kathleen , Wu Olivia , Chaikledkaew Usa 
Published: October 2021

Abstract
Background
Genetic testing has potential roles in identifying whether an individual would have risk of adverse drug reactions (ADRs) from a particular medicine. Robust cost-effectiveness results on genetic testing would be useful for clinical practice and policy decision-making on allocating resources effectively. This study aimed to update a systematic review on economic evaluations of pharmacogenetic testing to prevent ADRs and critically appraise the quality of reporting and sources of evidence for model input parameters.

Methods
We searched studies through Medline via PubMed, Scopus and CRD’s NHS Economic Evaluation up to October 2019. Studies investigating polymorphism-based pharmacogenetic testing, which guided drug therapies to prevent ADRs, using economic evaluation methods were included. Two reviewers independently performed data extraction and assessed the quality of reporting using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines and the quality of data sources using the hierarchy of evidence developed by Cooper et al.

Results
Fifty-nine economic evaluations of pharmacogenetic testing to avoid drug-induced ADRs were found between 2002 and 2018. Cost-utility and cost-effectiveness analyses were the most common methods of economic evaluation of pharmacogenetic testing. Most studies complied with the CHEERS checklist, except for single study-based economic evaluations which did not report uncertainty analysis (78%). There was a lack of high-quality evidence not only for estimating the clinical effectiveness of pharmacogenetic testing, but also baseline clinical data. About 14% of the studies obtained clinical effectiveness data of testing from a meta-analysis of case-control studies with direct comparison, which was not listed in the hierarchy of evidence used.

Conclusions
Our review suggested that future single study-based economic evaluations of pharmacogenetic testing should report uncertainty analysis, as this could significantly affect the robustness of economic evaluation results. A specific ranking system for the quality of evidence is needed for the economic evaluation of pharmacogenetic testing of ADRs. Differences in parameters, methods and outcomes across studies, as well as population-level and system-level differences, may lead to the difficulty of comparing cost-effectiveness results across countries.
Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids
Authors: Wang Zhiwei , Guo Yinghao , Jin Yun , Zhang Xiaoxiao , Geng Hao , Xie Guangyuan , Ye Dan , Yu Yuanquan , Liu Daren , Zhou Donger , Li Baizhou , Luo Yan , Peng Shuyou , Li Jiangtao 
Published: October 2021

Abstract
Background
Patient-derived organoids (PDO) have been proposed as a novel in vitro method of drug screening for different types of cancer. However, to date, extrahepatic biliary tract carcinoma (eBTC) PDOs have not yet been fully established.

Methods
We collected six samples of gallbladder carcinoma (GBC) and one sample of extrahepatic cholangiocarcinoma (eCCA) from seven patients to attempt to establish eBTC PDOs for drug screening. We successfully established five GBC and one eCCA PDOs. Histological staining was used to compare structural features between the original tissues and cancer PDOs. Whole exome sequencing (WES) was performed to analyze the genetic profiles of original tissues and cancer PDOs. Drug screening, including gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, infigratinib, and ivosidenib, was measured and verified by clinical effects in certain cases.

Results
Different PDOs exhibited diverse growth rates during in vitro culture. Hematoxylin and eosin staining demonstrated that the structures of most cancer PDOs retained the original structures of adenocarcinoma. Immunohistological and periodic acid-schiff staining revealed that marker expression in cancer PDOs was similar to that of the original specimens. Genetic profiles from the four original specimens, as well as paired cancer PDOs, were analyzed using whole exome sequencing. Three of the four PDOs exhibited a high degree of similarity when compared to the original specimens, except for GBC2 PDO, which only had a concordance of 74% in the proportion of single nucleotide polymorphisms in the coding sequence. In general, gemcitabine was found to be the most efficient drug for eBTC treatment, as it showed moderate or significant inhibitory impact on cancer growth. Results from drug screening were confirmed to a certain extent by three clinical cases.

Conclusions
Our study successfully established a series of eBTC PDOs, which contributed to the field of eBTC PDOs. Additional enhancements should be explored to improve the growth rate of PDOs and to preserve their immune microenvironment.