bluuebunny/crossref_metadata_2025_split huggingface dataset:
Only cervical vertebrae C0-C2, not C3 are relevant for subgrouping migraine patients according to manual palpation and pain provocation: secondary analysis of a cohort study
Authors: Schwarz Annika , Luedtke Kerstin , Schöttker-Königer Thomas 
Published: April 2022

Abstract
Background
Subgrouping of migraine patients according to the pain response to manual palpation of the upper cervical spine has been recently described. Based on the neuroanatomy and the convergence of spinal and trigeminal nerves in the trigeminocervical complex, the cervical segments C1 to C3 are potentially relevant. To date it has not been investigated whether palpation results of all upper cervical segments are based on one underlying construct which allows combining the results of several tests. Therefore, the aim of this secondary analysis of a cohort study was to determine whether results from all three segments form one construct.

Methods
Seventy-one migraine patients with chronic or frequent episodic migraine diagnosed according to the international headache society classification version 3 were examined by one physiotherapist. Manual palpation using a posterior to anterior pressure was performed on the upper three cervical vertebrae unilaterally left and right. The results of the palpation according to the patients’ responses were combined using factor analysis. In addition, item response theory (IRT) was used to investigate the structure of the response pattern as well as item difficulty and discrimination.

Findings
Factor analysis (principal component) showed that the palpation of C3 loads less onto the underlying construct than the palpation of C1 and C2. Considering a cut-off value > 1.0, the eigenvalues of all three segments do not represent one underlying construct. When excluding the results from C3, remaining items form one construct. The internal consistency of the pain response to palpation of C1 and C2 is acceptable with a Cronbach’s alpha of 0.69. IRT analysis showed that the rating scale model fits best to the pain response pattern. The discrimination value (1.24) was equal for all items. Item difficulty showed a clear hierarchical structure between the palpation of C1 and C2, indicating that people with a higher impairment are more likely to respond with referred pain during palpation of C2.

Conclusion
Statistical analysis confirms that results from the palpation of the cervical segments C1 and C2 in migraine patients can be combined. IRT analysis confirmed the ordinal pattern of the pain response and showed the higher probability of a pain response during palpation of C2. The pain response to C3 palpation is not relevant for unidimensional IRT analysis.

Trial Registration
German registry of clinical trials (DRKS00015995), Registered 20. December 2018, https://www.drks.de/drks_web/setLocale_EN.do
Palliative care in Uganda: quantitative descriptive study of key palliative care indicators 2018-2020
Authors: Kagarmanova Ainur , Mwesiga Mark Donald , Sisk Matthew L. , Kabagambe Cynthia , Nyakaisiki Sheba , Marentette Tom , Ahern Lacey N. 
Published: April 2022

Abstract
Background
The first and most recent nationwide audit of palliative care services in Uganda was conducted in 2009. Since then, Uganda has made great strides in palliative care development, including policy, education, and services implementation. This study provides an overview of the availability of palliative care services in the country and the challenges and gaps in Uganda prior to the global COVID-19 pandemic. This lays the foundation for better understanding the challenges and changes needed to support palliative care development and access in the wake of the pandemic.

Methods
We conducted a descriptive quantitative study of secondary data on nationwide morphine distribution, collated a list of accredited facilities, and analyzed key palliative care indicators collected through the mHealth surveillance project present at a subset of accredited facilities. Descriptive statistical analysis involved non-parametric tests using SPSS, mapping geographical distribution of available palliative care services using Geographic Information Systems software, and identification of challenges from the subset of accredited facilities.

Results
There were 226 accredited palliative care facilities across Uganda’s 135 districts in 2020. Thirty districts lacked any accredited palliative care facility. The estimated population coverage was 88.5%. The majority (68.1%) of accredited facilities were public, and private facilities received slightly more pain-relieving morphine. There was an alternating trend in the volumes of morphine delivered to public and private facilities. More than a third of the patients were diagnosed with non-communicable diseases, highlighting their significance alongside cancer and HIV/AIDS as conditions requiring palliative care. Palliative care accredited facilities offered six types of services: outreach, home visits, psychosocial, legal, bereavement, and spiritual support, but only for an average of 7 months a year due to lack of facilitation and transportation.

Conclusion
Palliative care in Uganda developed in quality, volume, and geographic coverage since 2009. The shift in palliative care patients’ primary diagnosis from HIV/AIDS to non-communicable diseases marks an important epidemiologic transition. Although accredited facilities are present in most administrative districts, more research is needed to evaluate the actual accessibility of these services. The existing services, both private and public, are limited by the amount of pain-relieving morphine, financial and transport resources. More quality data collected on key palliative care indicators is needed into geographical accessibility of palliative care services, morphine availability trends, and patient diagnoses in order to improve the provision of palliative care in Uganda.
Anti-SARS-CoV-2 potential of Cissampelos pareira L. identified by connectivity map-based analysis and in vitro studies
Authors: Haider Madiha , Anand Vivek , Enayathullah M. Ghalib , Parekh Yash , Ram Sushma , Kumari Surekha , Anmol  , Panda Gayatri , Shukla Manjari , Dholakia Dhwani , Ray Arjun , Bhattacharyya Sudipta , Sharma Upendra , Bokara Kiran Kumar , Prasher Bhavana , Mukerji Mitali 
Published: April 2022

AbstractBackgroundViral infections have a history of abrupt and severe eruptions through the years in the form of pandemics. And yet, definitive therapies or preventive measures are not present. Herbal medicines have been a source of various antiviral compounds such as Oseltamivir, extracted using shikimic acid from star anise (Illicium verum) and Acyclovir fromCarissa edulisare FDA (Food and Drug Administration) approved antiviral drugs. In this study, we dissect the anti-coronavirus infection activity ofCissampelos pareiraL (Cipa) extract using an integrative approach.MethodsWe analysed the signature similarities between predicted antiviral agents andCipausing the connectivity map (https://clue.io/). Next, we tested the anti-SARS-COV-2 activity ofCipain vitro. Molecular docking analyses of constituents of with key targets of SARS-CoV2 protein viz. spike protein, RNA‑dependent RNA‑polymerase (RdRp) and 3C‑like proteinase. was also performed. A three-way comparative analysis ofCipatranscriptome, COVID-19 BALF transcriptome and CMAP signatures of small compounds was also performed.ResultsSeveral predicted antivirals showed a high positive connectivity score withCipasuch as apcidin, emetine, homoharringtonine etc. We also observed 98% inhibition of SARS-COV-2 replication in infected Vero cell cultures with the whole extract. Some of its prominent pure constituents e.g. pareirarine, cissamine, magnoflorine exhibited 40–80% inhibition. Comparison of genes between BALF andCipashowed an enrichment of biological processes like transcription regulation and response to lipids, to be downregulated inCipawhile being upregulated in COVID-19. CMAP also showed that Triciribine, torin-1 and VU-0365114–2 had positive connectivity with BALF 1 and 2, and negative connectivity withCipa. Amongst all the tested compounds, Magnoflorine and Salutaridine exhibited the most potent and consistent strong in silico binding profiles with SARS-CoV2 therapeutic targets.
How to implement person-centred care and support for dementia in outpatient and home/community settings: Scoping review
Authors: Marulappa Nidhi , Anderson Natalie N. , Bethell Jennifer , Bourbonnais Anne , Kelly Fiona , McMurray Josephine , Rogers Heather L. , Vedel Isabelle , Gagliardi Anna R. 
Published: April 2022

Abstract
Background
Little prior research focused on person-centred care and support (PCCS) for dementia in home, community or outpatient care. We aimed to describe what constitutes PCCS, how to implement it, and considerations for women who comprise the majority of affected persons (with dementia, carers).

Methods
We conducted a scoping review by searching multiple databases from 2000 inclusive to June 7, 2020. We extracted data on study characteristics and PCCS approaches, evaluation, determinants or the impact of strategies to implement PCCS. We used summary statistics to report data and interpreted findings with an existing person-centred care framework.

Results
We included 22 studies with qualitative (55%) or quantitative/multiple methods design (45%) involving affected persons (50%), or healthcare workers (50%). Studies varied in how PCCS was conceptualized; 59% cited a PCC definition or framework. Affected persons and healthcare workers largely agreed on what constitutes PCCS (e.g. foster partnership, promote autonomy, support carers). In 4 studies that evaluated care, barriers of PCCS were reported at the affected person (e.g. family conflict), healthcare worker (e.g. lack of knowledge) and organizational (e.g. resource constraints) levels. Studies that evaluated strategies to implement PCCS approaches were largely targeted to healthcare workers, and showed that in-person inter-professional educational meetings yielded both perceived (e.g. improved engagement of affected persons) and observed (e.g. use of PCCS approaches) beneficial outcomes. Few studies reported results by gender or other intersectional factors, and none revealed if or how to tailor PCCS for women. This synthesis confirmed and elaborated the PCC framework, resulting in a Framework of PCCS for Dementia.

Conclusion
Despite the paucity of research on PCCS for dementia, synthesis of knowledge from diverse studies into a Framework provides interim guidance for those planning or evaluating dementia services in outpatient, home or community settings. Further research is needed to elaborate the Framework, evaluate PCCS for dementia, explore determinants, and develop strategies to implement and scale-up PCCS approaches. Such studies should explore how to tailor PCCS needs and preferences based on input from persons with dementia, and by sex/gender and other intersectional factors such as ethnicity or culture.
Exploring the contexts, mechanisms and outcomes of a torture, abuse and dental anxiety service in Norway: a realist evaluation
Authors: Bryne Emilie , Hean Sarah Catherine Patricia Duff , Evensen Kjersti Berge , Bull Vibeke Hervik 
Published: April 2022

Abstract
Background
Torture, abuse and dental anxiety (TADA) are often precursors to developing a pathological relationship with dental care due to elevated anxiety. Consequently, patients who suffer from one or more of these tend to avoid dental services. This could leave them with severe tooth decay, which could affect their general and psychosocial health. Norwegian dental services have implemented the TADA service to specifically alleviate dental anxiety and restore oral health for the TADA patient group. However, the service has not been evaluated, and there is a need to understand how and why this service works, for whom, under what circumstances. Therefore, this study aimed to develop theories on how the service’s structure alleviates dental anxiety and restores these patients’ oral health. Although developed in a Norwegian context, these theories may be applicable to other national and international contexts.

Methods
This realist evaluation comprised multiple sequential methods of service and policy documents (n = 13), followed by interviews with service developers (n = 12).

Results
The analysis suggests that, by subsidising the TADA service, the Norwegian state has removed financial barriers for patients. This has improved their access to the service and, hence, their service uptake. National guidelines on service delivery are perceived as open to interpretation, and can hereby meet the needs of a heterogeneous patient group. The services have become tailored according to the available regional resources and heterogeneous needs of the patient population. A perceived lack of explicit national leadership and cooperative practices has resulted in regional service teams becoming self-reliant and insular. While this has led to cohesion within each regional service, it is not conducive to interservice collaborations. Lastly, the complexity of migration processes and poor dissemination practices is presumed to be the cause of the lack of recruitment of torture survivors to the service.

Conclusions
Policy documents and service developers described the TADA service as a hybrid bottom-up/top-down service that allows teams to practise discretion and tailor their approach to meet individual needs. Being free of charge has improved access to the service by vulnerable groups, but the service still struggles to reach torture survivors.
Complications and owner satisfaction associated with limb amputation in cats: 59 cases (2007–2017)
Authors: Wagner John R. , DeSandre-Robinson Dana M. , Moore George E. , Loughin Catherine A. , Simons Micha C. 
Published: April 2022

Abstract
Background
Limb amputation may be recommended in domestic cats following a severe injury or disease. The purpose of the study was to report the signalment, the complications, recovery outcome, owner satisfaction and expectations of domestic cats following limb amputation.

Results
Medical records of 3 specialty hospitals were reviewed for cats that received a single limb amputation in a 10 year period (2007–2017). These cat owners were contacted, and 59 owners completed surveys, comprising the study population. The most common reasons for limb amputation were neoplasia (54.2%, 32/59), traumatic injury (40.7%, 24/59), bone or joint infection (3.4%, 2/59), and thromboembolism (1.7%, 1/59). Thirty-four cats (57.6%) had postoperative complications. Of the fifty-nine surveys, 52.5% reported minor complications and 5.1% reported major complications. There were no differences in postoperative complication rates for thoracic versus pelvic limb amputations. All owners reported either excellent (77.9%, 46/59), good (20.3% 12/59), or fair (1.7%, 1/59) satisfaction with the procedure. Based on their previous experiences, 84.7% (50/59) of owners would elect limb amputation if medically warranted for another pet. The remaining 15.3% of owners who would not elect limb amputation again had experienced death of their pet with a median survival time of 183 days.

Conclusion
Owners reported a positive satisfaction when considering complications, recovery outcome, and expectations. This study can be used by veterinarians to guide cat owners in the decision making process of limb amputation.
Synthetic acid stress-tolerance modules improve growth robustness and lysine productivity of industrial Escherichia coli in fermentation at low pH
Authors: Yao Xurong , Liu Peng , Chen Bo , Wang Xiaoyan , Tao Fei , Lin Zhanglin , Yang Xiaofeng 
Published: April 2022

Abstract
Background
During fermentation, industrial microorganisms encounter multiple stresses that inhibit cell growth and decrease fermentation yields, in particular acid stress, which is due to the accumulation of acidic metabolites in the fermentation medium. Although the addition of a base to the medium can counteract the effect of acid accumulation, the engineering of acid-tolerant strains is considered a more intelligent and cost-effective solution. While synthetic biology theoretically provides a novel approach for devising such tolerance modules, in practice it is difficult to assemble stress-tolerance modules from hundreds of stress-related genes.

Results
In this study, we designed a set of synthetic acid-tolerance modules for fine-tuning the expression of multi-component gene blocks comprising a member of the proton-consuming acid resistance system (gadE), a periplasmic chaperone (hdeB), and reactive oxygen species (ROS) scavengers (sodB and katE). Directed evolution was used to construct an acid-responsive asr promoter library, from which four variants were selected and used in the synthetic modules. The module variants were screened in a stepwise manner under mild acidic conditions (pH 5–6), first by cell growth using the laboratory Escherichia coli strain MG1655 cultured in microplates, and then by lysine production performance using the industrial lysine-producing E. coli strain MG1655 SCEcL3 cultured first in multiple 10-mL micro-bioreactors, and then in 1.3-L parallel bioreactors. The procedure resulted in the identification of a best strain with lysine titer and yield at pH 6.0 comparable to the parent strain at pH 6.8.

Conclusion
Our results demonstrate a promising synthetic-biology strategy to enhance the growth robustness and productivity of E. coli upon the mildly acidic conditions, in both a general lab strain MG1655 and an industrial lysine-producing strain SCEcL3, by using the stress-responsive synthetic acid-tolerance modules comprising a limited number of genes. This study provides a reliable and efficient method for achieving synthetic modules of interest, particularly in improving the robustness and productivity of industrial strains.
A single point mutation in the Plasmodium falciparum 3′–5′ exonuclease does not alter piperaquine susceptibility
Authors: Boonyalai Nonlawat , Kirativanich Kirakarn , Thamnurak Chatchadaporn , Praditpol Chantida , Vesely Brian A. , Wojnarski Mariusz , Griesenbeck John S. , Waters Norman C. 
Published: April 2022

Abstract
Background
The rise in Plasmodium falciparum resistance to dihydroartemisinin–piperaquine (DHA–PPQ) treatment has been documented in the Greater Mekong Subregion with associations with mutations in the P. falciparum chloroquine resistance transporter (pfcrt) and plasmepsin 2 (pfpm2) genes. However, it is unclear whether other genes also play a role with PPQ resistance, such as the E415G mutation in the exonuclease (pfexo) gene. The aim of this study was to investigate the role of this mutation in PPQ resistance by generating transgenic parasites expressing the pfexo-E415G mutant allele.

Methods
Transgenic parasite clones carrying the E415G mutation in PfEXO of the B5 isolate were derived by CRISPR-Cas9 gene editing and verified using PCR and gene sequencing. Polymorphisms of pfkelch-13, pfcrt, and pfexo were examined by PCR while the copy number variations of pfpm2 were examined by both relative quantitative real-time PCR and the duplication breakpoint assay. Drug sensitivity against a panel of antimalarials, the ring-stage survival assay (RSA), the PPQ survival assay (PSA), and bimodal dose-response curves were used to evaluate antimalarial susceptibility.

Results
The transgenic line, B5-rexo-E415G-B8, was successfully generated. The PPQ-IC90, %PPQ survival, and the bimodal dose-response clearly showed that E415G mutation in PfEXO of B5 isolate remained fully susceptible to PPQ. Furthermore, growth assays demonstrated that the engineered parasites grew slightly faster than the unmodified parental isolates whereas P. falciparum isolates harbouring pfkelch-13, pfcrt, and pfexo mutations with multiple copies of pfpm2 grew much more slowly.

Conclusions
Insertion of the E415G mutation in PfEXO did not lead to increased PPQ-IC90 and %PPQ survival, suggesting that this mutation alone may not be associated with PPQ resistance, but could still be an important marker if used in conjunction with other markers for monitoring PPQ-resistant parasites. The results also highlight the importance of monitoring and evaluating suspected genetic mutations with regard to parasite fitness and resistance.
CDK6-PI3K signaling axis is an efficient target for attenuating ABCB1/P-gp mediated multi-drug resistance (MDR) in cancer cells
Authors: Zhang Lei , Li Yidong , Hu Chaohua , Chen Yangmin , Chen Zhuo , Chen Zhe-Sheng , Zhang Jian-Ye , Fang Shuo 
Published: April 2022

Abstract
Background
Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1/P-gp) is a major cause of cancer chemotherapy failure, but the regulation mechanisms are largely unknown.

Methods
Based on single gene knockout, we studied the regulation of CDK6-PI3K axis on ABCB1-mediated MDR in human cancer cells. CRISPR/Cas9 technique was performed in KB-C2 cells to knockout cdk6 or cdk4 gene. Western blot, RT-PCR and transcriptome analysis were performed to investigate target gene deletion and expression of critical signaling factors. The effect of cdk4 or cdk6 deficiency on cell apoptosis and the cell cycle was analyzed using flow cytometry. In vivo studies were performed to study the sensitivity of KB-C2 tumors to doxorubicin, tumor growth and metastasis.

Results
Deficiency of cdk6 led to remarkable downregulation of ABCB1 expression and reversal of ABCB1-mediated MDR. Transcriptomic analysis revealed that CDK6 knockout regulated a series of signaling factors, among them, PI3K 110α and 110β, KRAS and MAPK10 were downregulated, and FOS-promoting cell autophagy and CXCL1-regulating multiple factors were upregulated. Notably, PI3K 110α/110β deficiency in-return downregulated CDK6 and the CDK6-PI3K axis synergizes in regulating ABCB1 expression, which strengthened the regulation of ABCB1 over single regulation by either CDK6 or PI3K 110α/110β. High frequency of alternative splicing (AS) of premature ABCB1 mRNA induced by CDK6, CDK4 or PI3K 110α/110β level change was confirmed to alter the ABCB1 level, among them 10 common skipped exon (SE) events were found. In vivo experiments demonstrated that loss of cdk6 remarkably increased the sensitivity of KB-C2 tumors to doxorubicin by increasing drug accumulation of the tumors, resulting in remarkable inhibition of tumor growth and metastasis, as well as KB-C2 survival in the nude mice.

Conclusions
CDK6-PI3K as a new target signaling axis to reverse ABCB1-mediated MDR is reported for the first time in cancers. Pathways leading to inhibition of cancer cell proliferation were revealed to be accompanied by CDK6 deficiency.