bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the Genome: Professional Guidelines in Clinical Genomic Testing and Interpretation
Authors: Lyon Elaine
Published: April 2021

The rapid evolution of genomic testing gives new meaning to the term "high-complexity testing." Variant classification is clearly challenging, but with the aid of American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) professional guidelines for combining evidence used in conjunction with national efforts, laboratories may be better able to standardize and establish quality metrics. Additionally, guidelines for evaluating types of evidence and interpreting sequence variations have been developed. This session will review these guidelines to address expectations of data quality, as well as elements of reporting identified variants and their interpretations. Efforts by the molecular community to address consistency in using these guidelines will also be shown. The objectives of this presentation are to list technical guidelines for genomic sequencing to ensure quality data, to describe evidence used to classify variants, and to identify variability in how evidences are used.

Disclosures

Lyon: Complete Genomics: Consultancy; Korean Society for Medical and Molecular Genetics: Honoraria; Association for Molecular Pathology: Honoraria; American College of Medical Genetics and Genomics: Membership on an entity's Board of Directors or advisory committees.
Beyond Cytosine Methylation: Ten-Eleven Translocation Proteins, Oxidized Methylcytosines, and Cancer
Authors: Rao Anjana
Published: April 2021

We discovered some years ago that enzymes of the TET (Ten-Eleven Translocation) family were a new class of epigenetic regulators that altered the modification status of cytosine bases in DNA. The three mammalian TET enzymes - TET1, TET2 and TET3 - successively oxidize the methyl group of 5-methylcytosine (5mC) to yield 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). These modified cytosine bases (together termed oxidized methylcytosines, oxi-mC) facilitate DNA demethylation and are also novel epigenetic marks. DNA methylation has long been linked to developmental processes and to oncogenesis; similarly TET proteins, which alter DNA modification status, are implicated in numerous biological processes, including cell lineage specification, embryonic development, neuronal function, somatic cell reprogramming and cancer. Loss-of-function mutations in the TET2 gene are frequently associated with lymphoid and myeloid cancers in humans. Using mouse models and biochemical and genome-wude approaches, we have analysed the role of TET proteins and oxi-mC in immune and haematopoietic cells. I will describe the data and discuss possible mechanisms.

Disclosures

Rao: Cambridge Epigenetix: Consultancy, Membership on an entity's Board of Directors or advisory committees.
Zinc-dependent multimerization of mutant calreticulin is required for MPL binding and MPN pathogenesis
Authors: Rivera Jeanne F. , Baral April J. , Nadat Fatima , Boyd Grace , Smyth Rachael , Patel Hershna , Burman Emma L. , Alameer Ghadah , Boxall Sally A. , Jackson Brian R. , Baxter E. Joanna , Laslo Peter , Green Anthony R. , Kent David G. , Mullally Ann , Chen Edwin
Published: April 2021

Calreticulin (CALR) is mutated in the majority of JAK2/MPL-unmutated myeloproliferative neoplasms (MPNs). Mutant CALR (CALRdel52) exerts its effect by binding to the thrombopoietin receptor MPL to cause constitutive activation of JAK-STAT signaling. In this study, we performed an extensive mutagenesis screen of the CALR globular N-domain and revealed 2 motifs critical for CALRdel52 oncogenic activity: (1) the glycan-binding lectin motif and (2) the zinc-binding domain. Further analysis demonstrated that the zinc-binding domain was essential for formation of CALRdel52 multimers, which was a co-requisite for MPL binding. CALRdel52 variants incapable of binding zinc were unable to homomultimerize, form CALRdel52-MPL heteromeric complexes, or stimulate JAK-STAT signaling. Finally, treatment with zinc chelation disrupted CALRdel52-MPL complexes in hematopoietic cells in conjunction with preferential eradication of cells expressing CALRdel52 relative to cells expressing other MPN oncogenes. In addition, zinc chelators exhibited a therapeutic effect in preferentially impairing growth of CALRdel52-mutant erythroblasts relative to unmutated erythroblasts in primary cultures of MPN patients. Together, our data implicate zinc as an essential cofactor for CALRdel52 oncogenic activity by enabling CALRdel52 multimerization and interaction with MPL, and suggests that perturbation of intracellular zinc levels may represent a new approach to abrogate the oncogenic activity of CALRdel52 in the treatment of MPNs.
Short-term earnings mobility in the Canadian and German context: the role of cognitive skills
Authors: Pullman Ashley , Gauly Britta , Lechner Clemens M.
Published: April 2021

It is well-established that human capital contributes to unequal levels of earnings mobility. Individuals with higher levels of human capital, typically measured through education, earn more on average and are privy to greater levels of upward change over time. Nevertheless, other factors may have an incremental effect over education, namely cognitive ability and the skill demands of employment. To deepen insight into whether these aspects contribute to earnings mobility over a four-year period, the present study examines positional change in Canada and Germany—two contexts typified as examples of liberal and coordinated market economies. A series of descriptive indices and relative change models assess how different measures of human capital are associated with earnings mobility. The results indicate that, while individuals with higher cognitive skills experience greater earnings stability and upward mobility in both countries, there is only an incremental effect of skills on mobility in Germany once we account for educational credentials. The results also provide evidence on the role of skill demands for earnings mobility; in both countries, advanced skills at work are associated with greater short-term mobility, even while controlling for cognitive ability and other factors. Together the results showcase how longitudinal data containing detailed measures of human capital allow for deeper insight into what facilitates earnings mobility.
Functional genomics of a Spiroplasma associated with the carmine cochineals Dactylopius coccus and Dactylopius opuntiae
Authors: Vera-Ponce León Arturo , Dominguez-Mirazo Marian , Bustamante-Brito Rafael , Higareda-Alvear Víctor , Rosenblueth Mónica , Martínez-Romero Esperanza
Published: April 2021

Background

Spiroplasma is a widely distributed endosymbiont of insects, arthropods, and plants. In insects, Spiroplasma colonizes the gut, hemolymph, and reproductive organs of the host. Previous metagenomic surveys of the domesticated carmine cochineal Dactylopius coccus and the wild cochineal D. opuntiae reported sequences of Spiroplasma associated with these insects. However, there is no analysis of the genomic capabilities and the interaction of this Spiroplasma with Dactylopius.

Results

Here we present three Spiroplasma genomes independently recovered from metagenomes of adult males and females of D. coccus, from two different populations, as well as from adult females of D. opuntiae. Single-copy gene analysis showed that these genomes were > 92% complete. Phylogenomic analyses classified these genomes as new members of Spiroplasma ixodetis.

Comparative genome analysis indicated that they exhibit fewer genes involved in amino acid and carbon catabolism compared to other spiroplasmas. Moreover, virulence factor-encoding genes (i.e., glpO, spaid and rip2) were found incomplete in these S. ixodetis genomes. We also detected an enrichment of genes encoding the type IV secretion system (T4SS) in S. ixodetis genomes of Dactylopius. A metratranscriptomic analysis of D. coccus showed that some of these T4SS genes (i.e., traG, virB4 and virD4) in addition to the superoxide dismutase sodA of S. ixodetis were overexpressed in the ovaries.

Conclusion

The symbiont S. ixodetis is a new member of the bacterial community of D. coccus and D. opuntiae. The recovery of incomplete virulence factor-encoding genes in S. ixodetis of Dactylopius suggests that this bacterium is a non-pathogenic symbiont. A high number of genes encoding the T4SS, in the S. ixodetis genomes and the overexpression of these genes in the ovary and hemolymph of the host suggest that S. ixodetis use the T4SS to interact with the Dactylopius cells. Moreover, the transcriptional differences of S. ixodetis among the gut, hemolymph and ovary tissues of D. coccus indicate that this bacterium can respond and adapt to the different conditions (e.g., oxidative stress) present within the host. All this evidence proposes that there is a strong interaction and molecular signaling in the symbiosis between S. ixodetis and the carmine cochineal Dactylopius.
Analgesic efficacy of postoperative bilateral, ultrasound-guided, posterior transversus abdominis plane block for laparoscopic colorectal cancer surgery: a randomized, prospective, controlled study
Authors: Zhao Yang , Zhang Han-Ying , Yuan Zong-Yi , Han Yi , Chen Yi-Rong , Liu Qi-lin , Zhu Tao
Published: April 2021

Background

We assessed whether a postoperative bilateral, ultrasound-guided, posterior transversus abdominis plane (TAP) block could reduce 24 h rescue tramadol requirement compared with placebo in patients undergoing elective laparoscopic colorectal cancer surgery.

Methods

Patients scheduled to undergo elective laparoscopic surgery following the diagnosis of colorectal cancer were included in this study and randomized into Group and Group Control. The patients received a postoperative bilateral, ultrasound-guided, posterior TAP block in either 20 mL of 0.5% ropivacaine (Group TAP) per side or an equivalent volume of normal saline (Group Control). The primary outcome was the cumulative consumption of rescue tramadol within 24 h after the surgery. Secondary endpoints included (1) resting and movement numerical rating scale (NRS) pain scores at 2, 4, 6, 12, 24, 48, and 72 h; (2) incidences of related side effects; (3) time to the first request for rescue tramadol; (4) patient satisfaction regarding postoperative analgesia; (5) time to restoration of intestinal function; (6) time to mobilization; and (7) the length of hospital stay.

Results

In total, 92 patients were randomized, and 82 patients completed the analysis. The total rescue tramadol requirement (median [interquartile range]) within the first 24 h was lower in Group TAP (0 [0, 87.5] mg) than in Group Control (100 [100, 200] mg), P < 0.001. The posterior TAP block reduced resting and movement NRS pain scores at 2, 4, 6, 12, and 24 h after surgery (all P < 0.001) but showed similar scores at 48 h or 72 h. A higher level of satisfaction with postoperative analgesia was observed in Group TAP on day 1 (P = 0.002), which was similar on days 2 (P = 0.702) and 3 (P = 0.551), compared with the Group Control. A few incidences of opioid-related side effects (P < 0.001) and a lower percentage of patients requiring rescue tramadol analgesia within 24 h (P < 0.001) were observed in Group TAP. The time to the first request for rescue analgesia was prolonged, and the time to mobilization and flatus was reduced with a shorter hospital stay in Group TAP as compared with Group Control.

Conclusions

A postoperative bilateral, ultrasound-guided, posterior TAP block resulted in better pain management and a faster recovery in patients undergoing laparoscopic colorectal cancer surgery, without adverse effects.

Trial registration

The study was registered at http://www.chictr.org.cn (ChiCTR-IPR-17012650; Sep 12, 2017).
Differential trends of admissions in accident and emergency departments during the COVID-19 pandemic in Germany
Authors: Jaehn Philipp , Holmberg Christine , Uhlenbrock Greta , Pohl Andreas , Finkenzeller Thomas , Pawlik Michael T. , Quack Ivo , Ernstberger Antonio , Rockmann Felix , Schreyer Andreas G.
Published: April 2021

Background

Recent studies have shown a decrease of admissions to accident and emergency (A&E) departments after the local outbreaks of COVID-19. However, differential trends of admission counts, for example according to diagnosis, are less well understood. This information is crucial to inform targeted intervention. Therefore, we aimed to compare admission counts in German A&E departments before and after 12th march in 2020 with 2019 according to demographic factors and diagnosis groups.

Methods

Routine data of all admissions between 02.12.2019–30.06.2020 and 01.12.2018–30.06.2019 was available from six hospitals in five cities from north-western, eastern, south-eastern, and south-western Germany. We defined 10 diagnosis groups using ICD-10 codes: mental disorders due to use of alcohol (MDA), acute myocardial infarction (AMI), stroke or transient ischemic attack (TIA), heart failure, pneumonia, chronic obstructive pulmonary disease (COPD), cholelithiasis or cholecystitis, back pain, fractures of the forearm, and fractures of the femur. We calculated rate ratios comparing different periods in 12.03.2020–30.06.2020 with 12.03.2019–30.06.2019.

Results

Forty-one thousand three hundred fifty-three cases were admitted between 12.03.2020–30.06.2020 and 51,030 cases between 12.03.2019–30.06.2019. Admission counts prior to 12.03. were equal in 2020 and 2019. In the period after 12.03., the decrease of admissions in 2020 compared to 2019 was largest between 26.03. and 08.04. (− 30%, 95% CI − 33% to − 27%). When analysing the entire period 12.03.-30.06., the decrease of admissions was heterogeneous among hospitals, and larger among people aged 0–17 years compared to older age groups. In the first 8 weeks after 12.03., admission counts of all diagnoses except femur fractures and pneumonia declined. Admissions with pneumonia increased in this early period. Between 07.05. and 30.6.2020, we noted that admissions with AMI (+ 13%, 95% CI − 3% to + 32%) and cholelithiasis or cholecystitis (+ 20%, 95% CI + 1% to + 44%) were higher than in 2019.

Conclusions

Our results suggest differential trends of admission counts according to age, location, and diagnosis. An initial decrease of admissions with MDA, AMI, stroke or TIA, heart failure, COPD, cholelithiasis or cholecystitis, and back pain imply delays of emergency care in Germany. Finally, our study suggests a delayed increase of admissions with AMI and cholelithiasis or cholecystitis.
Relationship between mortality and use of sodium bicarbonate at the time of dialysis initiation: a prospective observational study
Authors: Morooka Hikaru , Yamamoto Junichiro , Tanaka Akihito , Inaguma Daijo , Maruyama Shoichi
Published: April 2021

Background

Patients with chronic kidney disease often experience metabolic acidosis. Whether oral sodium bicarbonate can reduce mortality in patients with metabolic acidosis has been debated for years. Hence, this study was conducted to evaluate the utility of sodium bicarbonate in patients who will undergo dialysis therapy. In this study, we investigated the effect of oral sodium bicarbonate therapy on mortality in patients with end-stage kidney disease (ESKD) initiated on dialysis therapy.

Methods

We conducted an observational study of patients when they started dialysis therapy. There were 17 centres participating in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis. Data were available on patients’ sex, age, use of sodium bicarbonate, drug history, medical history, vital data, and laboratory data. We investigated whether patients on oral sodium bicarbonate for more than three months before dialysis initiation had a better prognosis than those without sodium bicarbonate therapy. The primary outcome was defined as all-cause mortality.

Results

The study included 1524 patients with chronic kidney disease who initiated dialysis between October 2011 and September 2013. Among them, 1030 were men and 492 women, with a mean age of 67.5 ± 13.1 years. Of these, 677 used sodium bicarbonate and 845 did not; 13.6% of the patients in the former group and 21.2% of those in the latter group died by March 2015 (p <  0.001). Even after adjusting for various factors, the use of sodium bicarbonate independently reduced mortality (p <  0.001).

Conclusions

The use of oral sodium bicarbonate at the time of dialysis initiation significantly reduced all-cause mortality in patients undergoing dialysis therapy.
An autopsy-proven case of Corticobasal degeneration heralded by Pontine infarction
Authors: Yoo Dallah , Park Sung-Hye , Yu Sungwook , Ahn Tae-Beom
Published: April 2021

Background

Neurodegenerative disorders are characterized by insidious progression with poorly-delineated long latent period. Antecedent clinical insult could rarely unmask latent neurodegenerative disorders. Here, we report an autopsy-proven case of corticobasal degeneration which was preceded by a lacunar infarction.

Case presentation

A 58-year-old man presented with acute ataxia associated with a lacunar infarction in the right paramedian pons. His ataxia persisted with additional progressive gait difficulty and left arm clumsiness. Six months later, a follow-up neurological examination showed asymmetrical bradykinesia, apraxia, dystonic posturing, postural instability, and mild ataxia of the left limbs. Cognitive examination revealed frontal executive dysfunction and visuospatial difficulties. Dopamine transporter imaging scan demonstrated bilateral reduced uptakes in mid-to-posterior putamen, more prominent on the right side. Levodopa-unresponsive parkinsonism, asymmetric limb dystonia, and ideomotor apraxia became more conspicuous, while limb ataxia gradually vanished. The patient became unable to walk without assistance after 1 year, and died 4 years after the symptom onset. Autopsy findings showed frontoparietal cortical atrophy, ballooned neurons, and phosphorylated tau-positive astrocytic plaques and neuropil threads with gliosis and neuronal loss, confirming the corticobasal degeneration.

Conclusions

The case illustrates that precedent clinical events such as stroke might tip a patient with subclinical CBS into overt clinical manifestations.
Psychosocial stratification of antenatal indicators to guide population-based programs in perinatal depression
Authors: Eastwood John , Wang Andy , Khanlari Sarah , Montgomery Alicia , Yang Jean Yee Hwa
Published: April 2021

Background

There is increasing awareness that perinatal psychosocial adversity experienced by mothers, children, and their families, may influence health and well-being across the life course. To maximise the impact of population-based interventions for optimising perinatal wellbeing, health services can utilise empirical methods to identify subgroups at highest risk of poor outcomes relative to the overall population.

Methods

This study sought to identify sub-groups using latent class analysis within a population of mothers in Sydney, Australia, based on their differing experience of self-reported indicators of psychosocial adversity. This study sought to identify sub-groups using latent class analysis within a population of mothers in Sydney, Australia, based on their differing experience of self-reported indicators of psychosocial adversity. Subgroup differences in antenatal and postnatal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale.

Results

Latent class analysis identified four distinct subgroups within the cohort, who were distinguished empirically on the basis of their native language, current smoking status, previous involvement with Family-and-Community Services (FaCS), history of child abuse, presence of a supportive partner, and a history of intimate partner psychological violence. One group consisted of socially supported ‘local’ women who speak English as their primary language (Group L), another of socially supported ‘migrant’ women who speak a language other than English as their primary language (Group M), another of socially stressed ‘local’ women who speak English as their primary language (Group Ls), and socially stressed ‘migrant’ women who speak a language other than English as their primary language (Group Ms.). Compared to local and not socially stressed residents (L group), the odds of antenatal depression were nearly three times higher for the socially stressed groups (Ls OR: 2.87 95%CI 2.10–3.94) and nearly nine times more in the Ms. group (Ms OR: 8.78, 95%CI 5.13–15.03). Antenatal symptoms of depression were also higher in the not socially stressed migrant group (M OR: 1.70 95%CI 1.47–1.97) compared to non-migrants. In the postnatal period, Group M was 1.5 times more likely, while the Ms. group was over five times more likely to experience suboptimal mental health compared to Group L (OR 1.50, 95%CI 1.22–1.84; and OR 5.28, 95%CI 2.63–10.63, for M and Ms. respectively).

Conclusions

The application of empirical subgrouping analysis permits an informed approach to targeted interventions and resource allocation for optimising perinatal maternal wellbeing.
Complex interactions of lovastatin with 10 chemotherapeutic drugs: a rigorous evaluation of synergism and antagonism
Authors: Khandelwal Gilman Kaitlyn A. , Han Seungmin , Won Young-Wook , Putnam Charles W.
Published: April 2021

Background

Evidence bearing on the role of statins in the prevention and treatment of cancer is confounded by the diversity of statins, chemotherapeutic agents and cancer types included in the numerous published studies; consequently, the adjunctive value of statins with chemotherapy remains uncertain.

Methods

We assayed lovastatin in combination with each of ten commonly prescribed chemotherapy drugs in highly reproducible in vitro assays, using a neutral cellular substrate, Saccharomyces cerevisiae. Cell density (OD600) data were analyzed for synergism and antagonism using the Loewe additivity model implemented with the Combenefit software.

Results

Four of the ten chemotherapy drugs – tamoxifen, doxorubicin, methotrexate and rapamycin – exhibited net synergism with lovastatin. The remaining six agents (5-fluorouracil, gemcitabine, epothilone, cisplatin, cyclophosphamide and etoposide) compiled neutral or antagonistic scores. Distinctive patterns of synergism and antagonism, often coexisting within the same concentration space, were documented with the various combinations, including those with net synergism scores. Two drug pairs, lovastatin combined with tamoxifen or cisplatin, were also assayed in human cell lines as proof of principle.

Conclusions

The synergistic interactions of tamoxifen, doxorubicin, methotrexate and rapamycin with lovastatin – because they suggest the possibility of clinical utility - merit further exploration and validation in cell lines and animal models. No less importantly, strong antagonistic interactions between certain agents and lovastatin argue for a cautious, data-driven approach before adding a statin to any chemotherapeutic regimen. We also urge awareness of adventitious statin usage by patients entering cancer treatment protocols.
The effect of depressive symptomatology on the association of vitamin D and sleep
Authors: Mergl Roland , Dogan-Sander Ezgi , Willenberg Anja , Wirkner Kerstin , Kratzsch Jürgen , Riedel-Heller Steffi , Allgaier Antje-Kathrin , Hegerl Ulrich , Sander Christian
Published: April 2021

Background

Sleep disorders and vitamin D deficiency are highly prevalent health problems. Few studies examined the effect of vitamin D concentrations on objectively measured sleep with high methodological quality and temporal proximity. Previous analysis within the LIFE-Adult-Study suggested that a lower concentration of serum vitamin D was associated with both shorter and later night sleep. However, no conclusion about underlying mechanisms could be drawn. We addressed the question whether this relationship is explained by the presence of depressive syndromes, which are linked to both vitamin D deficiency and sleep disturbances.

Methods

It was investigated whether the association of vitamin D concentrations and night sleep parameters is mediated or moderated by depressive symptomatology. We investigated a subset (n = 1252) of the community sample from the LIFE-Adult-Study, in which sleep parameters had been objectively assessed using actigraphy, based on which two sleep parameters were calculated: night sleep duration and midsleep time. Serum 25(OH) D concentrations were measured using an electrochemiluminescence immunoassay. Depressive symptomatology was evaluated with the Centre for Epidemiological Studies Depression Scale. The mediation effect was analyzed by using Hayes’ PROCESS macro tool for SPSS for Windows.

Results

The depressive symptomatology was neither significantly associated with night sleep duration nor midsleep time. The associations between vitamin D concentrations and night sleep duration/midsleep time through mediation by depressive symptomatology were not significant. Corresponding moderator analyses were also non-significant.

Conclusion

The associations between vitamin D concentrations and night sleep parameters (sleep duration and midsleep time) seem to be neither mediated nor moderated by depressive symptomatology.
A comparison of the prevalence of sexually transmitted infections among circumcised and uncircumcised adult males in Rustenburg, South Africa: a cross-sectional study
Authors: Iyemosolo Blanchard Mbay , Chivese Tawanda , Esterhuizen Tonya M.
Published: April 2021

Background

South Africa has a persistent burden of sexually transmitted infections (STIs). Male circumcision has been shown to be effective in preventing HIV and STIs, but data are scarce on the protective effect of circumcision in high-risk populations such as migrant miners. The objective of this study was to assess the effect of medical and traditional circumcision on the prevalence of STIs after adjusting for other risk factors in Rustenburg, a mining town in North West Province, South Africa.

Methods

This cross-sectional study used baseline data collected from a cohort study. Adult males in a mining town were assessed for STIs (gonorrhea, chlamydia, and trichomoniasis) using syndromic assessment. Data on circumcision status and other risk factors for STI syndromes were collected using an interviewer-administered questionnaire. The following symptoms were assessed; penile discharge, painful urination, dyspareunia or penile sores. These symptoms indicate sexually transmitted infection in general since laboratory tests were not performed. Multivariable log binomial regression was used to assess the independent effect of circumcision on STI presence after adjusting for confounders.

Results

A total of 339 participants with a median age of 25 years (IQR 22–29) were included in the study, of whom 116 (34.2%) were circumcised. The overall STIs prevalence was 27.4% (95% CI 22.8 to 32.6%) and was lower in the circumcised participants compared with those who were uncircumcised (15.5% vs 33.6%, respectively, p < 0.001). Both medical (OR 0.57, 95% CI 0.34–0.95, p = 0.030) and traditional circumcision (OR 0.34, 95% CI 0.13–0.86, p = 0.022) were strongly associated with a lower risk of STIs after adjustment for employment and condom use.

Conclusion

In this high-risk population in a mining town in South Africa, with a relatively high prevalence of STIs, and where one third of males are circumcised, both medical and traditional circumcision appear to be protective against STIs.
A bilingual systematic review of South Korean medical tourism: a need to rethink policy and priorities for public health?
Authors: Xu Qing , Purushothaman Vidya , Cuomo Raphael E. , Mackey Tim K.
Published: April 2021

Background

In 2016, the “Act on Support for Overseas Expansion of Healthcare System and Attraction of International Patients” was enacted by the South Korean government in an attempt to accelerate growth of its medical tourism industry. However, only a few years after its implementation, the benefits are not well understood, nor have the positive or negative impacts of expanding Korea’s medical tourism sector been properly evaluated.

Objective

We aimed to systematically review and summarize existing literature describing South Korea’s medical tourism policy and legislative history, while also assessing the impact of this domestic policy approach on the country’s public health systems.

Methods

A bilingual systematic literature review was conducted per PRISMA guidelines for all South Korean medical tourism legislative and policy literature using MeSH terms and other related keywords in two academic databases, PubMed and JSTOR. Published studies were included if they directly addressed South Korean medical tourism policy. To supplement results from the peer-review, the grey literature was also searched using Google search engine for relevant policy documents, information from government websites, and national statistics on medical tourism-related data.

Results

This review included 14 peer-reviewed journal articles and 9 websites. The majority of literature focused on the legislative history of South Korea’s pro-medical tourism policy, economic considerations associated with industry growth, and the specific experiences of medical tourists. There was a lack of studies, analytical or commentary-based, conducting in-depth analysis of the healthcare impact of these policies or comparing benefits and costs compared to other medical tourism destinations. Proponents of medical tourism continue to advocate the government for increased deregulation and investment in the sector.

Conclusion

This systematic review suggests that policy decisions may prioritize economic growth offered by medical tourism over negative effects on the healthcare workforce, access and equity, and its potential to undermine Universal Health Coverage. South Korea continues to examine ways to further amend the Act and grow this sector, but these actions should be taken with caution by critically examining how other countries have adapted their policymaking based on the real-world costs associated with medical tourism.
Pathways to sexual decision making by Pentecostal church youths in Botswana
Authors: Mpofu Elias , Ntinda Kayi , Levers Lisa Lopez , van Rensberg Angelique , Nkomazana Fidelis
Published: April 2021

Background

The ways church youth make sexual decisions are incompletely understood and yet important for public health interventions. This study aimed to examine personal religiosity influences on the sexual decisions by church youth from the country of Botswana, taking into account their sense of personal agency.

Method

Participants were 235 Botswana Pentecostal faith church youth (females = 67.2%, male = 32.8%; age range 12–23 years). They completed measures of personal religiosity, personal agency, sexual abstinence, and contraception use predisposition. We analysed the data applying Structural Equation Modelling to test five paths - personal religiosity to personal agency, personal agency to abstinence, personal religiosity to abstinence, personal agency to contraceptive use, and personal religiosity to contraceptive use.

Results

Results suggest that personal religiosity influences the youth in their sexual abstinence and contraception decisions through personal agency. High personal agency, but not personal religiosity, was associated with pro-sexual abstinence, and contraception use was associated with religiosity. Personal agency augmented the likelihood of both abstinence and contraception use decisions among the older church youth and with church youth with higher levels of formal education.

Conclusion

Church youth likely adopt discretionary sexual behaviours over the developmental period from early to older adolescents, which would make them more receptive to public sexual health messages. Personal agency appears to be an important resource for public health interventions aimed at influencing church youth’s sexual decisions.
Workplace musculoskeletal problems in occupational therapy students
Authors: Morabito Joanne , Penkala Stefania , Coxon Kristy
Published: April 2021

Background

Workplace musculoskeletal disorders are the leading cause of morbidity and disability in the Australian workforce. Over one in five occupational therapists report workplace musculoskeletal disorders, with almost half reporting workplace musculoskeletal symptoms. In other health professions, students and novice clinicians (≤5 years practice) experience greater risk but little is known about occupational therapy students.

Methods

In this cross-sectional study, a survey including the self-reported Standardised Nordic Musculoskeletal Questionnaire was administered to occupational therapy students post work-based training. Musculoskeletal problems were defined as aches, pains, numbness or discomfort. Questions explored body sites affected, prevalence, impact on activity, need for medical assistance, demographic and workplace information. Prevalence was reported using descriptive statistics. Factors associated with workplace musculoskeletal problems over the previous 12 months and last 7 days were examined using logistic regression modelling.

Results

Response rate was 53% (n = 211/397). One-third of respondents (33.6%,n = 71/211) reported a workplace musculoskeletal problem over 12 months. Nearly half (47.9%,n = 34/71) of these students reported a problem over the last 7 days. Neck was the most commonly affected area reported for musculoskeletal problems over the past 12 months (24.2%,n = 51/211) and shoulder areas affected over the past 7 days (10.9%,n = 23/211). Musculoskeletal problems preventing daily activities were reported most commonly from lower back problems over 12 months (23.9%,n = 17/71) and for shoulder problems over the last 7 days (21.9%,n = 7/32). Shoulders and knees were the most common body areas requiring medical attention. Previous musculoskeletal problems and female gender were associated with reported problems over 12 months and last 7 days (p < 0.05). Non-standard joint mobility (OR = 3.82,p = 0.002) and working in psychosocially focused caseloads (including mental health or case management) (OR = 3.04,p = 0.044) were also associated with reporting musculoskeletal problems over the last 7 days.

Conclusions

One in three occupational therapy students already experience workplace musculoskeletal problems impacting daily activities and requiring medical assistance prior to graduation. High prevalence of musculoskeletal problems in this study calls for educators and researchers to find sustainable strategies to address these problems, with particular consideration to the impact of previous disorders and working in psychosocially focused caseloads on musculoskeletal health.
Assessment of operator performance during oocyte retrievals: residents’ learning curve and continuous monitoring of senior physicians
Authors: Verhaeghe C. , El Hachem H. , Inchboard L. , Corroenne R. , Dreux C. , Jeanneteau P. , Legendre G. , Descamps P. , Saulnier P. , May-Panloup P. , Bouet P. E.
Published: April 2021

Background

The learning curve cumulative summation test (LC CUSUM test) allows to define an individualized learning curve and determine the moment when clinical proficiency is attained. After acquisition of the skills, the cumulative summation test (CUSUM test) allows to monitor the maintenance of the required level over time. The LC CUSUM test has been frequently used in the field of Obstetrics and Gynecology (Ob/Gyn) for several procedures, but only once for OR.

Methods

We performed a retrospective study at Angers university hospital between May 2017 and September 2018. Seven Ob/Gyn residents and 5 senior physicians were included, and all OR performed during that time (n = 690) were analyzed. The performance index assessed was the oocyte retrieval rate (ORR), defined as the ratio of oocytes retrieved to follicles aspirated. We used the LC CUSUM test to analyze the learning curves of residents, and the CUSUM test to monitor the performance of senior physicians. An ORR ≥50% in 60% of retrievals was defined as the threshold for clinical proficiency.

Results

Six hundred seventy-four oocyte retrieval (OR) were included: 315 were performed by residents, 220 by senior physicians, and 139 by both residents and physicians (mixed retrievals). Four residents (57%) reached the threshold after aspirating 82, 67, 53 and 46 ovaries, respectively. The mean number of ovaries aspirated in order to reach clinical proficiency was 62, and the mean number of weeks needed was 21. The duration of the learning period varied between 26 and 80 days. Two senior physicians (40%) remained proficient across the duration of the study, while two physicians (40%) had one statistically “suboptimal” OR, and one physician (20%) had two suboptimal retrievals.

Conclusion

There is a large variability in the duration of the learning period and the number of procedures needed for a resident to master OR. Senior physicians maintain an adequate performance.
Adoption of a laboratory EMR system and inappropriate laboratory testing in Ontario: a cross-sectional observational study
Authors: Chami Nadine , Mathew Silvy , Weir Sharada , Wright James G. , Kantarevic Jasmin
Published: April 2021

Background

Electronic medical record (EMR) systems have the potential to facilitate appropriate laboratory testing. We examined three common medical tests in primary care—hemoglobin A1c (HbA1c), lipid, and thyroid stimulating hormone (TSH)— to assess whether adoption of a laboratory EMR system in Ontario had an impact on the rate of inappropriate testing among primary care physicians.

Methods

We used FY2016–17 population-level laboratory data to estimate the association between adoption of a laboratory EMR system and the rate of inappropriate testing. Inappropriate testing was assessed based on recommendations for screening, monitoring, and follow-up that take into account risk factors related to patient age and certain clinical conditions. To overcome the problem of potential endogeneity of physician choice to use the EMR, the EMR penetration rate in the physician’s geographical area of practice was used as an instrumental variable in an ordinary least squares (OLS) regression. We then simulated the change in the rate of inappropriate testing, by physician payment model, as the EMR penetration rate increased from the baseline percentage.

Results

The simulation models showed that an increase in the rate of EMR penetration from a baseline average was associated with a statistically significant decrease in inappropriate hbA1c and lipid testing, but a statistically insignificant increase in inappropriate TSH testing. The impact of EMR penetration also varied by payment model.

Conclusions

This study demonstrated a positive association between availability of an EMR system and appropriate service utilization. Varying impacts of the EMR system availability by primary care payment model may be reflective of different incentives or attributes inherent in payment models. Policies to encourage physicians to increase their use of laboratory EMR systems could improve the quality and continuity of patient care.
Machine learning for subtype definition and risk prediction in heart failure, acute coronary syndromes and atrial fibrillation: systematic review of validity and clinical utility
Authors: Banerjee Amitava , Chen Suliang , Fatemifar Ghazaleh , Zeina Mohamad , Lumbers R. Thomas , Mielke Johanna , Gill Simrat , Kotecha Dipak , Freitag Daniel F. , Denaxas Spiros , Hemingway Harry
Published: April 2021

Background

Machine learning (ML) is increasingly used in research for subtype definition and risk prediction, particularly in cardiovascular diseases. No existing ML models are routinely used for cardiovascular disease management, and their phase of clinical utility is unknown, partly due to a lack of clear criteria. We evaluated ML for subtype definition and risk prediction in heart failure (HF), acute coronary syndromes (ACS) and atrial fibrillation (AF).

Methods

For ML studies of subtype definition and risk prediction, we conducted a systematic review in HF, ACS and AF, using PubMed, MEDLINE and Web of Science from January 2000 until December 2019. By adapting published criteria for diagnostic and prognostic studies, we developed a seven-domain, ML-specific checklist.

Results

Of 5918 studies identified, 97 were included. Across studies for subtype definition (n = 40) and risk prediction (n = 57), there was variation in data source, population size (median 606 and median 6769), clinical setting (outpatient, inpatient, different departments), number of covariates (median 19 and median 48) and ML methods. All studies were single disease, most were North American (n = 61/97) and only 14 studies combined definition and risk prediction. Subtype definition and risk prediction studies respectively had limitations in development (e.g. 15.0% and 78.9% of studies related to patient benefit; 15.0% and 15.8% had low patient selection bias), validation (12.5% and 5.3% externally validated) and impact (32.5% and 91.2% improved outcome prediction; no effectiveness or cost-effectiveness evaluations).

Conclusions

Studies of ML in HF, ACS and AF are limited by number and type of included covariates, ML methods, population size, country, clinical setting and focus on single diseases, not overlap or multimorbidity. Clinical utility and implementation rely on improvements in development, validation and impact, facilitated by simple checklists. We provide clear steps prior to safe implementation of machine learning in clinical practice for cardiovascular diseases and other disease areas.
Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD
Authors: Li Xiuying , Noell Guillaume , Tabib Tracy , Gregory Alyssa D. , Trejo Bittar Humberto E. , Vats Ravi , Kaminski Tomasz W. , Sembrat John , Snyder Mark E. , Chandra Divay , Chen Kong , Zou Chunbin , Zhang Yingze , Sundd Prithu , McDyer John F. , Sciurba Frank , Rojas Mauricio , Lafyatis Robert , Shapiro Steve D. , Faner Rosa , Nyunoya Toru
Published: April 2021

Background

Whole lung tissue transcriptomic profiling studies in chronic obstructive pulmonary disease (COPD) have led to the identification of several genes associated with the severity of airflow limitation and/or the presence of emphysema, however, the cell types driving these gene expression signatures remain unidentified.

Methods

To determine cell specific transcriptomic changes in severe COPD, we conducted single-cell RNA sequencing (scRNA seq) on n = 29,961 cells from the peripheral lung parenchymal tissue of nonsmoking subjects without underlying lung disease (n = 3) and patients with severe COPD (n = 3). The cell type composition and cell specific gene expression signature was assessed. Gene set enrichment analysis (GSEA) was used to identify the specific cell types contributing to the previously reported transcriptomic signatures.

Results

T-distributed stochastic neighbor embedding and clustering of scRNA seq data revealed a total of 17 distinct populations. Among them, the populations with more differentially expressed genes in cases vs. controls (log fold change >|0.4| and FDR = 0.05) were: monocytes (n = 1499); macrophages (n = 868) and ciliated epithelial cells (n = 590), respectively. Using GSEA, we found that only ciliated and cytotoxic T cells manifested a trend towards enrichment of the previously reported 127 regional emphysema gene signatures (normalized enrichment score [NES] = 1.28 and = 1.33, FDR = 0.085 and = 0.092 respectively). Among the significantly altered genes present in ciliated epithelial cells of the COPD lungs, QKI and IGFBP5 protein levels were also found to be altered in the COPD lungs.

Conclusions

scRNA seq is useful for identifying transcriptional changes and possibly individual protein levels that may contribute to the development of emphysema in a cell-type specific manner.
Adhatoda Vasica attenuates inflammatory and hypoxic responses in preclinical mouse models: potential for repurposing in COVID-19-like conditions
Authors: Gheware Atish , Dholakia Dhwani , Kannan Sadasivam , Panda Lipsa , Rani Ritu , Pattnaik Bijay Ranjan , Jain Vaibhav , Parekh Yash , Enayathullah M. Ghalib , Bokara Kiran Kumar , Subramanian Venkatesan , Mukerji Mitali , Agrawal Anurag , Prasher Bhavana
Published: April 2021

Background

COVID-19 pneumonia has been associated with severe acute hypoxia, sepsis-like states, thrombosis and chronic sequelae including persisting hypoxia and fibrosis. The molecular hypoxia response pathway has been associated with such pathologies and our recent observations on anti-hypoxic and anti-inflammatory effects of whole aqueous extract of Adhatoda Vasica (AV) prompted us to explore its effects on relevant preclinical mouse models.

Methods

In this study, we tested the effect of whole aqueous extract of AV, in murine models of bleomycin induced pulmonary fibrosis, Cecum Ligation and Puncture (CLP) induced sepsis, and siRNA induced hypoxia-thrombosis phenotype. The effect on lung of AV treated naïve mice was also studied at transcriptome level. We also determined if the extract may have any effect on SARS-CoV2 replication.

Results

Oral administration AV extract attenuates increased airway inflammation, levels of transforming growth factor-β1 (TGF-β1), IL-6, HIF-1α and improves the overall survival rates of mice in the models of pulmonary fibrosis and sepsis and rescues the siRNA induced inflammation and associated blood coagulation phenotypes in mice. We observed downregulation of hypoxia, inflammation, TGF-β1, and angiogenesis genes and upregulation of adaptive immunity-related genes in the lung transcriptome. AV treatment also reduced the viral load in Vero cells infected with SARS-CoV2.

Conclusion

Our results provide a scientific rationale for this ayurvedic herbal medicine in ameliorating the hypoxia-hyperinflammation features and highlights the repurposing potential of AV in COVID-19-like conditions.
Improving support for breastfeeding mothers: a qualitative study on the experiences of breastfeeding among mothers who reside in a deprived and culturally diverse community
Authors: Cook Erica Jane , Powell Faye , Ali Nasreen , Penn-Jones Catrin , Ochieng Bertha , Randhawa Gurch
Published: April 2021

Background

The United Kingdom has one of the lowest breastfeeding rates in Europe, with the initiation and continuation of breastfeeding shown to be closely related to the mothers’ age, ethnicity and social class. Whilst the barriers that influence a woman’s decision to breastfeed are well documented, less is known how these barriers vary by the UK’s diverse population. As such, this study aimed to explore mothers’ experiences of breastfeeding and accessing breastfeeding services offered locally amongst a deprived and culturally diverse community.

Methods

A qualitative interpretive study comprising of 63 mothers (white Britishn = 8, Pakistanin = 13, Bangladeshin = 10, black Africann = 15 and Polishn = 17) who took part in single-sex focus groups, conducted in local community centres across the most deprived and ethnically diverse wards in Luton, UK. The focus groups were audio-recorded, transcribed and analysed thematically using Framework Analysis.

Results

The most common barriers to breastfeeding irrespective of ethnicity were perceptions surrounding pain and lack of milk. Confidence and motivation were found to be crucial facilitators of breastfeeding; whereby mothers felt that interventions should seek to reassure and support mothers not only during the early stages but throughout the breastfeeding journey. Mothers particularly valued the practical support provided by health care professions particularly surrounding positioning and attachment techniques. However, many mothers felt that the support from health care professionals was not always followed through.

Conclusions

The findings presented inform important recommendations for the design and implementation of future programs and interventions targeted at reducing breastfeeding inequalities. Interventions should focus on providing mothers practical support and reassurance not only during the early stages but throughout their breastfeeding journey. The findings also highlight the need for tailoring services to support diverse communities which acknowledge different traditional and familial practices.