bluuebunny/crossref_metadata_2025 huggingface dataset:
The modules of mental health programs implemented in schools in low- and middle-income countries: findings from a systematic literature review
Authors: Gimba Solomon Musa , Harris Paul , Saito Amornrat , Udah Hyacinth , Martin Averil , Wheeler Amanda J.
Published: October 2020

Background

Secondary schools in low- and middle-income countries (LMICs) provide health promotion, preventive, and early intervention services. Nevertheless, literature indicates that the modules of these services are either adapted or modified from existing mental health programs in developed countries. The literature also highlights the provision of non-comprehensive services (mental health promotion, prevention, and early intervention), in LMICs. These findings inform the need for undertaking this systematic literature review. The aim of this review was thus to identify the modules of school-based mental health programs (SBMHP) that have been implemented in LMICs to guide the development of a culturally sensitive comprehensive mental health program for adolescents in a LMIC country.

Methods

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was used to guide this review. The following databases were searched in September 2018, to identify the relevant literature: PubMed, CINAHL, Scopus, Web of Science, PsycINFO, and ERIC. The search was conducted by the first author and reviewed by the authors.

Results

Following the screening process, a total of 11 papers were identified and reviewed for quality. The systematic review highlighted that the mental health programs provided in schools included: an introduction module, a communication and relationship module, a psychoeducation module, a cognitive skills module, a behavioral skills module, establishing social networks for recovery and help seeking behavioral activities and a summary/conclusion module.

Conclusion

This review sheds light on the characteristics of the programs in LMICs. Two programs were found to be universal in nature. Five programs were directed at key risk factors or at-risk groups, and four were early intervention programs. The review also revealed that only one program out of the 11 programs included modules for parents. The synthesis indicated that all the identified programs were adapted or modified from existing programs. The dearth of comprehensive programs in LMICs was also revealed. Lastly, the review revealed seven modules that can be useful for developing a SBMHP.
Clinical efficacy of enhanced recovery after surgery in percutaneous nephrolithotripsy: a randomized controlled trial
Authors: Li Qing , Wan Li , Liu Shucheng , Li Mingyong , Chen Libo , Hou Zhengwu , Zhang Wang
Published: October 2020

Background

To evaluate the feasibility, safety, applied value and efficacy of enhanced recovery after surgery (ERAS) for PCNL for the treatment of renal calculi. Although the ERAS is applied for many urological diseases, its application in percutaneous nephrolithotripsy (PCNL) is still limited.

Methods

This was a prospective study of patients admitted to hospital January and December 2018 and who were only diagnosed with renal calculi and excepted for serious or uncontrollable basic diseases and patients with multiple operation history and medication history. Patients were randomized 1:1 to the ERAS and traditional operation groups starting on the day before operation and end on the day of discharge. Each group was 118 cases. The stone clearance rate, visual analogue scale (VAS) pain score, the occurrence of perirenal hematoma and effusion, the incidence of extravasation of urine, the incidence of fever, bleeding and blood transfusion, and postoperative hospital stay were observed.

Results

The stone clearance rates were similar between the two groups (ERAS: 93.2% (109/117) vs. traditional: 89.8% (106/118), P = 0.800). The operation time was similar in the two groups (ERAS: 54 ± 12 vs. traditional: 58 ± 11 min, P = 0.656). VAS pain score that was 0.79 ± 0.76 in the ERAS group at 4 h after surgery and was significantly lower than 2.79 ± 0.98 in the traditional group (P < 0.0001). The total complication rate was 15 cases in the ERAS group and 22 cases in the traditional group (P = 0.573). There were no difference in costs (21,348 ± 2404 vs. 21,597 ± 2293 RMB, P = 0.529).

Conclusions

ERAS perioperative management in PCNL was feasible, was without additional complications, and had well economic and social benefits. It is worth of clinical promotion and application.
Tracking personalized functional health in older adults using geriatric assessments
Authors: Mishra Anup K. , Skubic Marjorie , Popescu Mihail , Lane Kari , Rantz Marilyn , Despins Laurel A. , Abbott Carmen , Keller James , Robinson Erin L. , Miller Steve
Published: October 2020

Background

Higher levels of functional health in older adults leads to higher quality of life and improves the ability to age-in-place. Tracking functional health objectively could help clinicians to make decisions for interventions in case of health deterioration. Even though several geriatric assessments capture several aspects of functional health, there is limited research in longitudinally tracking personalized functional health of older adults using a combination of these assessments.

Methods

We used geriatric assessment data collected from 150 older adults to develop and validate a functional health prediction model based on risks associated with falls, hospitalizations, emergency visits, and death. We used mixed effects logistic regression to construct the model. The geriatric assessments included were Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), and Short Form 12 (SF12). Construct validators such as fall risks associated with model predictions, and case studies with functional health trajectories were used to validate the model.

Results

The model is shown to separate samples with and without adverse health event outcomes with an area under the receiver operating characteristic curve (AUC) of > 0.85. The model could predict emergency visit or hospitalization with an AUC of 0.72 (95% CI 0.65–0.79), fall with an AUC of 0.86 (95% CI 0.83–0.89), fall with hospitalization with an AUC of 0.89 (95% CI 0.85–0.92), and mortality with an AUC of 0.93 (95% CI 0.88–0.97). Multiple comparisons of means using Turkey HSD test show that model prediction means for samples with no adverse health events versus samples with fall, hospitalization, and death were statistically significant (p < 0.001). Case studies for individual residents using predicted functional health trajectories show that changes in model predictions over time correspond to critical health changes in older adults.

Conclusions

The personalized functional health tracking may provide clinicians with a longitudinal view of overall functional health in older adults to help address the early detection of deterioration trends and decide appropriate interventions. It can also help older adults and family members take proactive steps to improve functional health.
Mechanisms of ivermectin-induced wound healing
Authors: Sia Daniel Kwesi , Mensah Kwesi Boadu , Opoku-Agyemang Tony , Folitse Raphael D. , Darko David Obiri
Published: October 2020

Background

Wounds cause structural and functional discontinuity of an organ. Wound healing, therefore, seeks to re-establish the normal morphology and functionality through intertwined stages of hemostasis, inflammation, proliferation, and tissue remodelling. Ivermectin, a macrolide, has been used as an endectoparasiticide in human and veterinary medicine practice for decades. Here, we show that ivermectin exhibits wounding healing activity by mechanisms independent of its well-known antiparasitic activity. This study aimed to evaluate the wound healing property of ivermectin cream using histochemistry and enzyme-linked immunosorbent assay techniques.

Results

Non-irritant dose of ivermectin cream (0.03–1%) decreased wound macroscopic indices such as exudation, edge edema, hyperemia, and granulation tissue deposition by day 9 compared to day 13 for the vehicle-treated group. This corresponded with a statistically significant wound contraction rate, hydroxyproline deposition, and a decreased time to heal rate. The levels of growth factors TGF-β1 and VEGF were significantly elevated on day 7 but decreased on day 21. This corresponded with changes in cytokines (IL-1α, IL-4, IL-10, and TNF-α) and eicosanoids (LTB4, PGE2, and PGD2) levels on days 7 and 21.. Interestingly, low doses of ivermectin cream (0.03–0.1%) induced wound healing with minimal scarring compared to higher doses of the cream and the positive control, Silver Sulfadiazine.

Conclusion

Ivermectin promotes wound healing partly through modulation of the inflammatory process and the levels of Transforming Growth Factor-Beta 1 and Vascular Endothelial Growth Factor. Low doses of ivermectin cream have the potential to be used in treating wounds with minimal scar tissue formation.
Serum symmetric dimethylarginine concentration in healthy horses and horses with acute kidney injury
Authors: Siwinska Natalia , Zak Agnieszka , Slowikowska Malwina , Niedzwiedz Artur , Paslawska Urszula
Published: October 2020

Background

There are limited options to diagnose acute kidney injury (AKI) in horses. Symmetric dimethylarginine (SDMA) is routinely used in human and small animal medicine. The aim of this study was to assess serum SDMA concentrations in healthy horses and horses with AKI. The objective of this study was to evaluate the association of: 1) age, 2) sex, 3) body weight and 4) serum creatinine and urea levels on serum SDMA concentrations. Fifty-three healthy horses, including 17 foals (2–6 months of age) and 36 adult horses (3–29 years of age), and 23 horses with AKI were included in the study based on history, physical examination, blood analysis, urinalysis and an ultrasonographic examination of the urinary tract. Serum SDMA concentrations were measured using a non-species specific commercial ELISA test.

Results

In healthy adult horses, the value of SDMA was 0.53 ± 0.14 μmol/L. The value was higher in foals (1.5 ± 0.4 μmol/L, P < 0.001). Horses with AKI had significantly higher concentrations of SDMA compared to healthy horses (1.76 ± 1.05 μmol/L, P < 0.001). In the healthy adult horses, there was no association of sex, age or body weight on SDMA. However, a significant positive relationship was found between serum creatinine and SDMA concentrations.

Conclusions

Healthy adult horses had SDMA values similar to those of other species. Foals had higher SDMA values. Therefore, different reference values should be created for them. The study confirmed an increased SDMA in horses with AKI. This, as well as the low influence of extrarenal factors on the SDMA values, may confirm its usefulness in the diagnosis of kidney dysfunction. Higher SDMA values may also indicate a more advanced degree of kidney dysfunction. Further research is required to determine whether SDMA could be used to detect kidney dysfunction in the asymptomatic stage of AKI.
SNP barcodes provide higher resolution than microsatellite markers to measure Plasmodium vivax population genetics
Authors: Fola Abebe A. , Kattenberg Eline , Razook Zahra , Lautu-Gumal Dulcie , Lee Stuart , Mehra Somya , Bahlo Melanie , Kazura James , Robinson Leanne J. , Laman Moses , Mueller Ivo , Barry Alyssa E.
Published: October 2020

Background

Genomic surveillance of malaria parasite populations has the potential to inform control strategies and to monitor the impact of interventions. Barcodes comprising large numbers of single nucleotide polymorphism (SNP) markers are accurate and efficient genotyping tools, however may need to be tailored to specific malaria transmission settings, since ‘universal’ barcodes can lack resolution at the local scale. A SNP barcode was developed that captures the diversity and structure ofPlasmodium vivaxpopulations of Papua New Guinea (PNG) for research and surveillance.

Methods

Using 20 high-qualityP. vivaxgenome sequences from PNG, a total of 178 evenly spaced neutral SNPs were selected for development of an amplicon sequencing assay combining a series of multiplex PCRs and sequencing on the Illumina MiSeq platform. For initial testing, 20 SNPs were amplified in a small number of mono- and polyclonalP. vivaxinfections. The full barcode was then validated by genotyping and population genetic analyses of 94P. vivaxisolates collected between 2012 and 2014 from four distinct catchment areas on the highly endemic north coast of PNG. Diversity and population structure determined from the SNP barcode data was then benchmarked against that of ten microsatellite markers used in previous population genetics studies.

Results

From a total of 28,934,460 reads generated from the MiSeq Illumina run, 87% mapped to thePvSalIreference genome with deep coverage (median = 563, range 56–7586) per locus across genotyped samples. Of 178 SNPs assayed, 146 produced high-quality genotypes (minimum coverage = 56X) in more than 85% ofP. vivaxisolates. No amplification bias was introduced due to either polyclonal infection or whole genome amplification (WGA) of samples before genotyping. Compared to the microsatellite panels, the SNP barcode revealed greater variability in genetic diversity between populations and geographical population structure. The SNP barcode also enabled assignment of genotypes according to their geographic origins with a significant association between genetic distance and geographic distance at the sub-provincial level.

Conclusions

High-throughput SNP barcoding can be used to map variation of malaria transmission dynamics at sub-national resolution. The low cost per sample and genotyping strategy makes the transfer of this technology to field settings highly feasible.
Acceptable health and ageing: results of a cross-sectional study from Hungary
Authors: Péntek Márta , van Exel Job , Gulácsi László , Brodszky Valentin , Zrubka Zsombor , Baji Petra , Rencz Fanni , Brouwer Werner B. F.
Published: October 2020

Background

We aimed to investigate the acceptability of imperfect health states in relation to age in Hungary and analyse its determinants. Results are contrasted to age-matched actual population health scores and to findings from a previous study in The Netherlands.

Methods

A cross-sectional online survey was performed. The same survey questions were applied as in a previous study in The Netherlands in order to enable inter-country comparisons. The descriptive system of the EQ-5D-3L health status questionnaire was used to assess the acceptability of moderate and severe health problems at ages from 30 to 80 by 10-year age-groups. Descriptive statistics were performed and linear regression analysis was used to investigate the determinants of acceptability.

Results

Altogether 9281 (female 32.8%) were involved with mean age 36.0 years and EQ-5D-3L index score of 0.852 (SD 0.177). Acceptability of health problems increased with age, differed per health domain and with severity of the problems. Except for ‘Self-care’, moderate health problems were acceptable by the majority from age 70 and acceptability scores were lower than EQ-5D-3L population norms from that age. The lowest average acceptability age was found in the ‘Anxiety/depression’ and dimension the highest in the ‘Self-care’ dimension. Respondents’ age, current health, and lifestyle were significant determinants (R2: 0.041–0.130). With a few minor exceptions in some health dimensions, acceptability levels and patterns were strikingly similar to the Dutch findings.

Conclusion

In Hungary, acceptability of health problems increases with age and the majority found severe problems never acceptable. Views on acceptability of health problems seem to be fairly generalizable across European countries with different health and economic indicators.
Are health care assistants part of the long-term solution to the nursing workforce deficit in Kenya?
Authors: Fitzgerald Louise , Gathara David , McKnight Jacob , Nzinga Jacinta , English Mike
Published: October 2020

This commentary article addresses a critical issue facing Kenya and other Low- and Middle-Income Countries (LMIC): how to remedy deficits in hospitals’ nursing workforce. Would employing health care assistants (HCAs) provide a partial solution? This article first gives a brief introduction to the Kenyan context and then explores the development of workforce roles to support nurses in Europe to highlight the diversity of these roles. Our introduction pinpoints that pressures to maintain or restrict costs have led to a wide variety of formal and informal task shifting from nurses to some form of HCA in the EU with differences noted in issues of appropriate skill mix, training, accountability, and regulation of HCA. Next, we draw from a suite of recent studies in hospitals in Kenya which illustrate nursing practices in a highly pressurized context. The studies took place in neo-natal wards in Kenyan hospitals between 2015 and 2018 and in a system with no legal or regulatory basis for task shifting to HCAs. We proffer data on why and how nurses informally delegate tasks to others in the public sector and the decision-making processes of nurses and frame this evidence in the specific contextual conditions. In the conclusion, the paper aims to deepen the debates on developing human resources for health. We argue that despite the urgent pressures to address glaring workforce deficits in Kenya and other LMIC, caution needs to be exercised in implementing changes to nursing practices through the introduction of HCAs. The evidence from EU suggests that the rapid growth in the employment of HCA has created crucial issues which need addressing. These include clearly defining the scope of practice and developing the appropriate skill mix between nurses and HCAs to match the specific health system context. Moreover, we suggest efforts to develop and implement such roles should be carefully designed and rigorously evaluated to inform continuing policy development.
Public target interventions to reduce the inappropriate use of medicines or medical procedures: a systematic review
Authors: Lin Leesa , Alam Prima , Fearon Elizabeth , Hargreaves James R.
Published: October 2020

Background

An epidemic of health disorders can be triggered by a collective manifestation of inappropriate behaviors, usually systematically fueled by non-medical factors at the individual and/or societal levels. This study aimed to (1) landscape and assess the evidence on interventions that reduce inappropriate demand of medical resources (medicines or procedures) by triggering behavioral change among healthcare consumers, (2) map out intervention components that have been tried and tested, and (3) identify the “active ingredients” of behavior change interventions that were proven to be effective in containing epidemics of inappropriate use of medical resources.

Methods

For this systematic review, we searched MEDLINE, EMBASE, the Cochrane Library, and PsychINFO from the databases’ inceptions to May 2019, without language restrictions, for behavioral intervention studies. Interventions had to be empirically evaluated with a control group that demonstrated whether the effects of the campaign extended beyond trends occurring in the absence of the intervention. Outcomes of interest were reductions in inappropriate or non-essential use of medicines and/or medical procedures for clinical conditions that do not require them. Two reviewers independently screened titles, abstracts, and full text for inclusion and extracted data on study characteristics (e.g., study design), intervention development, implementation strategies, and effect size. Data extraction sheets were based on the checklist from the Cochrane Handbook for Systematic Reviews.

Results

Forty-three studies were included. The behavior change technique taxonomy v1 (BCTTv1), which contains 93 behavioral change techniques (BCTs), was used to characterize components of the interventions reported in the included studies. Of the 93 BCTs, 15 (16%) were identified within the descriptions of the selected studies targeting healthcare consumers. Interventions consisting of education messages, recommended behavior alternatives, and a supporting environment that incentivizes or encourages the adoption of a new behavior were more likely to be successful.

Conclusions

There is a continued tendency in research reporting that mainly stresses the effectiveness of interventions rather than the process of identifying and developing key components and the parameters within which they operate. Reporting “negative results” is likely as critical as reporting “active ingredients” and positive findings for implementation science. This review calls for a standardized approach to report intervention studies.

Trial registration

PROSPERO registration number CRD42019139537
Administration of a herbal formulation enhanced blastocyst implantation via IκB activation in mouse endometrium
Authors: Jeon Songhee , Liu Quan Feng , Cai Hua , Jeong Ha Jin , Kim Su-Hyun , Kim Dong-Il , Lee Ju-Hee
Published: October 2020

Background

BaelanChagsangBang (BCB), a herbal formulation consisting of eleven herbs, may be prescribed as a reproductive functional supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Korean Medicine. This study aimed to investigate the effects and action mechanisms of water-extracted BCB on endometrial receptivity and blastocyst implantation under normal conditions and in a mifepristone (RU486)-induced implantation failure murine model.

Methods

In vitro, the antioxidant potentials of BCB were evaluated using DPPH and superoxide anion radical scavenging assays and a DCFH-DA assay, and the cytotoxic and cytoprotective effects of BCB were confirmed using an MTT assay. In vivo, C57BL/6 female mice (n = 6 per group) orally received BCB (300 mg/kg/day), a dose similar to that used clinically, from 7 days before pregnancy until the end of the experiment. On day 4 of pregnancy, RU486 (4 mg/kg) was injected subcutaneously to induce implantation failure. The effect of BCB on embryo implantation was evaluated by implantation rate analysis, histological examination, and western blotting of uterus tissues.

Results

BCB water extract showed strong anti-oxidative and cytoprotective effects in vitro. In vivo administration of BCB water extract increased the number of newborn pups in BCB-treated mice versus sham-treated mice under normal conditions and improved the number of implantation sites in pregnant mice despite RU486 injection. BCB increased the protein levels of cyclooxygenase-2 and inducible nitric oxide synthase through IκB activation. Moreover, the expression levels of matrix metalloproteinases at uterus implantation sites were up-regulated in the BCB-treated group as compared with those in the RU486-treated group.

Conclusion

These results show BCB improved embryo implantation through IκB activation in our mouse model and suggest that BCB has therapeutic potential in the context of poor endometrial receptivity.
English version of the self-administered Fabry Pain Questionnaire for adult patients
Authors: Jovanovic Ana , Klassen Philipp , Heuschmann Peter , Sommer Claudia , Roberts Mark , Üçeyler Nurcan
Published: October 2020

Background

Pain is an early symptom of Fabry disease (FD) and is characterized by a unique phenotype with mainly episodic acral and triggerable burning pain. Recently, we designed and validated the first pain questionnaire for adult FD patients in an interview and a self-administered version in German: the Würzburg Fabry Pain Questionnaire (FPQ). We now report the validation of the English version of the self-administered FPQ (enFPQ).

Methods

After two forward–backward translations of the FPQ by native German and native English speakers, the enFPQ was applied at The Mark Holland Metabolic Unit, Manchester, UK for validation. Consecutive patients with genetically ascertained FD and current or previous FD pain underwent a face-to-face interview using the enFPQ. Two weeks later, patients filled in the self-administered enFPQ at home. The agreement between entries collected by supervised administration and self-administration of the enFPQ was assessed via Gwet’s AC1-statistics (AC1) for nominal-scaled scores and intraclass correlation coefficient (ICC) for interval-scaled elements.

Results

Eighty-three FD patients underwent the face-to-face interview and 54 patients sent back a completed self-administered version of the enFPQ 2 weeks later. We found high agreement with a mean AC1-statistics of 0.725 for 55 items, and very high agreement with a mean ICC of 0.811 for 9 items.

Conclusions

We provide the validated English version of the FPQ for self-administration in adult FD patients. The enFPQ collects detailed information on the individual FD pain phenotype and thus builds a solid basis for better pain classification and treatment in patients with FD.
Researching the delivery of health and nutrition interventions for women and children in the context of armed conflict: lessons on research challenges and strategies from BRANCH Consortium case studies of Somalia, Mali, Pakistan and Afghanistan
Authors: Gaffey Michelle F. , Ataullahjan Anushka , Das Jai K. , Mirzazada Shafiq , Tounkara Moctar , Dalmar Abdirisak A. , Bhutta Zulfiqar A.
Published: October 2020

Background

The BRANCH Consortium recently conducted 10 mixed-methods case studies to investigate the provision of health and nutrition interventions for women and children in conflict-affected countries, aiming to better understand the dominant influences on humanitarian health actors’ programmatic decision-making and how such actors surmount intervention delivery barriers. In this paper, the research challenges encountered and the mitigating strategies employed by the case study investigators in four of the BRANCH case study contexts are discussed: Somalia, Mali, Pakistan and Afghanistan.

Discussion

Many of the encountered research challenges were anticipated, with investigators adopting mitigation strategies in advance or early on, but others were unexpected, with implications for how studies were ultimately conducted and how well the original study aims were met. Insecurity was a fundamental challenge in all study contexts, with restricted geographical access and concerns for personal safety affecting sampling and data collection plans, and requiring reliance on digital communications, remote study management, and off-site team meetings wherever possible. The need to navigate complex local sociopolitical contexts required maximum reliance on local partners’ knowledge, expertise and networks, and this was facilitated by early engagement with a wide range of local study stakeholders. Severe lack of reliable quantitative data on intervention coverage affected the extent to which information from different sources could be triangulated or integrated to inform an understanding of the influences on humanitarian actors’ decision-making.

Conclusion

Strong local partners are essential to the success of any project, contributing not only technical and methodological capacity but also the insight needed to truly understand and interpret local dynamics for the wider study team and to navigate those dynamics to ensure study rigour and relevance. Maintaining realistic expectations of data that are typically available in conflict settings is also essential, while pushing for more resources and further methodological innovation to improve data collection in such settings. Finally, successful health research in the complex, dynamic and unpredictable contexts of conflict settings requires flexibility and adaptability of researchers, as well as sponsors and donors.
Family violence against children in the wake of COVID-19 pandemic: a review of current perspectives and risk factors
Authors: Pereda Noemí , Díaz-Faes Diego A.
Published: October 2020

The situation of crisis produced by the Coronavirus (COVID-19) pandemic poses major challenges to societies all over the world. While efforts to contain the virus are vital to protect global health, these same efforts are exposing children and adolescents to an increased risk of family violence. Various criminological theories explain the causes of this new danger. The social isolation required by the measures taken in the different countries, the impact on jobs, the economic instability, high levels of tension and fear of the virus, and new forms of relationships have all increased levels of stress in the most vulnerable families and, therefore, the risk of violence. In addition, mandatory lockdowns imposed to curb the spread of the disease have trapped children in their homes, isolating them from the people and the resources that could help them. In general, the restrictive measures imposed in many countries have not been accompanied by an analysis of the access to the resources needed to reduce this risk. It is necessary to take urgent measures to intervene in these high-risk contexts so that children and adolescents can develop and prosper in a society which is likely to undergo profound changes, but in which the defense of their rights and protection must remain a major priority.
The specific distribution pattern of IKZF1 mutation in acute myeloid leukemia
Authors: Zhang Xiang , Zhang Xuewu , Li Xia , Lv Yunfei , Zhu Yanan , Wang Jinghan , Jin Jie , Yu Wenjuan
Published: October 2020

IKZF1 belongs to the IKAROS family of transcription factors, and its deletion/mutation frequently affects acute lymphoblastic leukemia. In acute myeloid leukemia, IKZF1 deletion has been demonstrated recurrent, but whether IKZF1 mutation also exists in AML remained largely unknown. Herein, we analyzed the IKZF1 mutation in AML. In our cohort, the frequency of IKZF1 mutation was 2.6% (5/193), and 5 frameshift/nonsense mutations as well as 2 missense mutations were identified in total. Molecularly, IKZF1 mutation was absent in fusion gene-positive AML, but it was demonstrated as the significant concomitant genetic alteration with SF3B1 or bi-alleleCEBPA mutation in AML. Clinically, two IKZF1, PTPN11 and SF3B1-mutated AML patients exhibited one aggressive clinical course and showed primary resistant to chemotherapy. Furthermore, we confirmed the recurrent IKZF1 mutation in AML with cBioPortal tool from OHSU, TCGA and TARGET studies. Interestingly, OHSU study also showed that SF3B1 mutation was the significant concomitant genetic alteration with IKZF1 mutation, indicating their strong synergy in leukemogenesis. In conclusion, IKZF1 mutation recurrently affected AML.
High throughput single-cell detection of multiplex CRISPR-edited gene modifications
Authors: ten Hacken Elisa , Clement Kendell , Li Shuqiang , Hernández-Sánchez María , Redd Robert , Wang Shu , Ruff David , Gruber Michaela , Baranowski Kaitlyn , Jacob Jose , Flynn James , Jones Keith W. , Neuberg Donna , Livak Kenneth J. , Pinello Luca , Wu Catherine J.
Published: October 2020

CRISPR-Cas9 gene editing has transformed our ability to rapidly interrogate the functional impact of somatic mutations in human cancers. Droplet-based technology enables the analysis of Cas9-introduced gene edits in thousands of single cells. Using this technology, we analyze Ba/F3 cells engineered to express single or multiplexed loss-of-function mutations recurrent in chronic lymphocytic leukemia. Our approach reliably quantifies mutational co-occurrences, zygosity status, and the occurrence of Cas9 edits at single-cell resolution.
Effectiveness and safety of tenosynovitis of the long head of the biceps brachii with acupuncture: a protocol for a systematic review and meta-analysis
Authors: Li Rongrong , Jiang Yongliang , Hu Renjie , He Xiaofen , Fang Jianqiao
Published: October 2020

Background

Tenosynovitis of the long head of the biceps (LHB) brachii is a common disease in patients over 40 years old. It can always result in chronic anterior shoulder pain and limited function. Acupuncture is one of most popular conservative treatment methods, and increasing studies indicate that it has remarkable therapeutic effects on the tenosynovitis of LHB brachii. However, the effectiveness and safety of acupuncture for treating tenosynovitis of LHB brachii remain largely uncertain. In our study, we will perform the first systematic review and meta-analysis to explore the effectiveness and safety of acupuncture on the tenosynovitis of LHB brachii.

Methods

We will search the randomized controlled trial (RCT) literatures involving acupuncture for treating tenosynovitis of LHB brachii in eight electric databases, including PubMed, Web of Science, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang Database, and Technology Periodical Database (VIP). We will define the visual analog scale (VAS), the Melle score of shoulder joint functional activity, and the ability assessment of daily living activities (ADL) as the primary outcomes. Besides quality of life, adverse events caused by acupuncture will be regarded as the secondary outcomes. Quality assessment of the included studies will be independently performed according to the Cochrane Risk of Bias tool. Meanwhile, the level of evidence for results will be assessed by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. All analyses will be conducted by using the RevMan software V5.3.

Results

From the study, we will ascertain the effectiveness and safety of acupuncture treatment on tenosynovitis of LHB brachii.

Conclusion

The conclusion of this study will confirm the effectiveness and safety of acupuncture in the treatment of tenosynovitis of LHB brachii, which can provide new evidence to guide appropriate interventions on tenosynovitis of LHB brachii with acupuncture in the future.

Ethics and dissemination

Ethical approval is not required because no individual patient data are collected. This review will be published in a peer-reviewed journal and presented at an international academic conference for dissemination.

Trial registration

PROSPERO registration number CRD42020167434. Registered on April 28, 2020.
Ketamine can be produced by Pochonia chlamydosporia: an old molecule and a new anthelmintic?
Authors: Ferreira Sebastiao Rodrigo , Machado Alan Rodrigues T. , Furtado Luís Fernando , Gomes Jose Hugo de S. , de Almeida Raquel M. , de Oliveira Mendes Thiago , Maciel Valentina N. , Barbosa Fernando Sergio , Carvalho Lorendane M. , Bueno Lilian Lacerda , Bartholomeu Daniella Castanheira , de Araújo Jackson Victor , Rabelo Elida M. L. , de Pádua Rodrigo Maia , Pimenta Lucia Pinheiro Santos , Fujiwara Ricardo Toshio
Published: October 2020

Background

Infection by nematodes is a problem for human health, livestock, and agriculture, as it causes deficits in host health, increases production costs, and incurs a reduced food supply. The control of these parasites is usually done using anthelmintics, which, in most cases, have not been fully effective. Therefore, the search for new molecules with anthelmintic potential is necessary.

Methods

In the present study, we isolated and characterized molecules from the nematophagous fungus Pochonia chlamydosporia and tested these compounds on three nematodes: Caenorhabditis elegans; Ancylostoma ceylanicum; and Ascaris suum.

Results

The ethyl acetate extract showed nematicidal activity on the nematode model C. elegans. We identified the major substance present in two sub-fractions of this extract as ketamine. Then, we tested this compound on C. elegans and the parasites A. ceylanicum and A. suum using hamsters and mice as hosts, respectively. We did not find a difference between the animal groups when considering the number of worms recovered from the intestines of animals treated with ketamine (6 mg) and albendazole (P > 0.05). The parasite burden of larvae recovered from the lungs of mice treated with ketamine was similar to those treated with ivermectin.

Conclusions

The results presented here demonstrate the nematicidal activity of ketamine in vitro and in vivo, thus confirming the nematicidal potential of the molecule present in the fungus P. chlamydosporia may consist of a new method of controlling parasites.
Sequencing of E. coli strain UTI89 on multiple sequencing platforms
Authors: Fenlon Shannon N. , Chee Yuemin Celina , Chee Jacqueline Lai Yuen , Choy Yeen Hui , Khng Alexis Jiaying , Liow Lu Ting , Mehershahi Kurosh S. , Ruan Xiaoan , Turner Stephen W. , Yao Fei , Chen Swaine L.
Published: October 2020

Objectives

The availability of matched sequencing data for the same sample across different sequencing platforms is a necessity for validation and effective comparison of sequencing platforms. A commonly sequenced sample is the lab-adapted MG1655 strain of Escherichia coli; however, this strain is not fully representative of more complex and dynamic genomes of pathogenic E. coli strains.

Data description

We present six new sequencing data sets for another E. coli strain, UTI89, which is an extraintestinal pathogenic strain isolated from a patient suffering from a urinary tract infection. We now provide matched whole genome sequencing data generated using the PacBio RSII, Oxford Nanopore MinION R9.4, Ion Torrent, ABI SOLiD, and Illumina NextSeq sequencers. Together with other publically available datasets, UTI89 has a nearly complete suite of data generated on most second- and third-generation sequencers. These data can be used as an additional validation set for new sequencing technologies and analytical methods. More than being another E. coli strain, however, UTI89 is pathogenic, with a 10% larger genome, additional pathogenicity islands, and a large plasmid, features that are common among other naturally occurring and disease-causing E. coli isolates. These data therefore provide a more medically relevant test set for development of algorithms.
A comparative study of Candida species diversity among patients with oral squamous cell carcinoma and oral potentially malignant disorders
Authors: Sankari Sankar Leena , Mahalakshmi Krishnan , Kumar Venkatesan Naveen
Published: October 2020

Objectives

To determine the prevalence of Candida species by PCR–RFLP method in the saliva of patients with oral squamous cell carcinoma (OSCC), oral potentially malignant disorders (OPMD) and healthy cohorts. Unstimulated saliva was collected from patients with OSCC (n = 97), OPMD (n = 200), and healthy controls (n = 200). Candida species were isolated using the standard protocol. The isolates were identified using phenotypic and genotypic methods. The odds/risk ratio was calculated using Pearson’s Chi-square test. The significance of Candidal carriage was calculated by independent T-test.

Results

Oral Candidal carriage was 72.2%, 58% and 20.5% among patients with OSCC, OPMD, and healthy controls respectively. The oral Candidal carriage in OSCC and OPMD was highly significant (p = 0.0001). Non albicans Candida predominated over Candida albicans. Candida species were diverse among the study groups with a predominance of Candida krusei, Candida tropicalis, and Pichia anomala formerly Candida pelliculosa. P. anomala occurrence outnumbered in health. The odds/risk ratio for OSCC and OPMD were 4.25/11.87 and 3.52/6.99 respectively. A high prevalence of non albicans Candida was observed both in all the three groups (OSCC, OPMD and healthy controls). High odds and risk ratio associates Candida species to OSCC and OPMD. Candida famata may be associated with OSCC and OPMD.
Imbalance of laminar-specific excitatory and inhibitory circuits of the orbitofrontal cortex in autism
Authors: Liu Xuefeng , Bautista Julied , Liu Edward , Zikopoulos Basilis
Published: October 2020

Background

The human orbitofrontal cortex (OFC) is involved in assessing the emotional significance of events and stimuli, emotion-based learning, allocation of attentional resources, and social cognition. Little is known about the structure, connectivity and excitatory/inhibitory circuit interactions underlying these diverse functions in human OFC, as well as how the circuit is disrupted in individuals with autism spectrum disorder (ASD).

Methods

We used post-mortem brain tissue from neurotypical adults and individuals with ASD. We examined the morphology and distribution of myelinated axons across cortical layers in OFC, at the single axon level, as a proxy of excitatory pathways. In the same regions, we also examined the laminar distribution of all neurons and neurochemically- and functionally-distinct inhibitory neurons that express the calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR).

Results

We found that the density of myelinated axons increased consistently towards layer 6, while the average axon diameter did not change significantly across layers in both groups. However, both the density and diameter of myelinated axons were significantly lower in the ASD group compared with the Control group. The distribution pattern and density of the three major types of inhibitory neurons was comparable between groups, but there was a significant reduction in the density of excitatory neurons across OFC layers in ASD.

Limitations

This study is limited by the availability of human post-mortem tissue optimally processed for high-resolution microscopy and immunolabeling, especially from individuals with ASD.

Conclusions

The balance between excitation and inhibition in OFC is at the core of its function, assessing and integrating emotional and social cues with internal states and external inputs. Our preliminary results provide evidence for laminar-specific changes in the ratio of excitation/inhibition in OFC of adults with ASD, with an overall weakening and likely disorganization of excitatory signals and a relative strengthening of local inhibition. These changes likely underlie pathology of major OFC communications with limbic or other cortices and the amygdala in individuals with ASD, and may provide the anatomic basis for disrupted transmission of signals for social interactions and emotions in autism.
On the reasonability of linearized approximation and Hopf bifurcation control for a fractional-order delay Bhalekar–Gejji chaotic system
Authors: Shi Jianping , Ruan Liyuan
Published: October 2020

In this paper, we study the reasonability of linearized approximation and Hopf bifurcation control for a fractional-order delay Bhalekar–Gejji (BG) chaotic system. Since the current study on Hopf bifurcation for fractional-order delay systems is carried out on the basis of analyses for stability of equilibrium of its linearized approximation system, it is necessary to verify the reasonability of linearized approximation. Through Laplace transformation, we first illustrate the equivalence of stability of equilibrium for a fractional-order delay Bhalekar–Gejji chaotic system and its linearized approximation system under an appropriate prior assumption. This semianalytically verifies the reasonability of linearized approximation from the viewpoint of stability. Then we theoretically explore the relationship between the time delay and Hopf bifurcation of such a system. By introducing the delayed feedback controller into the proposed system, the influence of the feedback gain changes on Hopf bifurcation is also investigated. The obtained results indicate that the stability domain can be effectively controlled by the proposed delayed feedback controller. Moreover, numerical simulations are made to verify the validity of the theoretical results.
$L^{p}-L^{q}$-Maximal regularity of the Van Wijngaarden–Eringen equation in a cylindrical domain
Authors: Lizama Carlos , Murillo-Arcila Marina
Published: October 2020

We consider the maximal regularity problem for a PDE of linear acoustics, named the Van Wijngaarden–Eringen equation, that models the propagation of linear acoustic waves in isothermal bubbly liquids, wherein the bubbles are of uniform radius. If the dimensionless bubble radius is greater than one, we prove that the inhomogeneous version of the Van Wijngaarden–Eringen equation, in a cylindrical domain, admits maximal regularity in Lebesgue spaces. Our methods are based on the theory of operator-valued Fourier multipliers.
Composite submental flaps in facial reconstructive surgery involving the zygoma and orbit
Authors: Khan Usman , Haupt Sebastian , Rigby Matthew , Taylor S. Mark , Corsten Martin , Trites Jonathan
Published: October 2020

Background

The submental island flap (SIF) is a reliable option for reconstructing defects in the facial region and offers several advantages when compared to free-flap alternatives. While the reconstructive applications of the SIF have been demonstrated in the lower face, there are limited reports on its utility as a composite flap for reconstructing defects of the upper facial skeleton. To our knowledge, we report the first cases of composite (osteocutaneous) SIFs used for reconstruction of complex facial defects involving the zygoma and lateral orbit respectively.

Case presentations

Three consecutive cases are presented. All were performed following resection of skin cancers with invasion of the upper facial skeleton. The first case was a 68-year-old male with a longstanding history of non-melanoma skin cancers who presented with a 7 cm recurrent basal cell carcinoma (BCC) with bicortical invasion of the left zygoma. The second case was an 88-year-old female with several squamous cell carcinomas (SCC), including a dominant 7.1 cm SCC on the right temple with orbital invasion. A third case was a 75-year-old immunosuppressed male with a 6.5 cm SCC of the right cheek with invasion of the orbit and zygoma following prior resection as well as high dose radiotherapy. The operative management of all cases involved harvesting the SIF on its vascular pedicle alongside the inferior portion of the mandible with rigid fixation to address the bony defects. The first case was robust throughout adjuvant radiotherapy with no flap complications after 2 year follow up. The second patient received adjuvant radiation therapy to an area that was previously radiated. Although the flap remained viable for a year, the patient experienced delayed soft tissue loss over the bony segment and eventual devitalization of the distal flap. The third case achieved a satisfactory result with no complications.

Conclusions

Our case series outlines a unique application of the composite (osteocutaneous) submental island flap (SIF) for reconstruction of complex facial defects involving the upper facial skeleton. The osteocutaneous SIF should be used with caution in patients receiving adjuvant radiotherapy who have a history of previous radiation to the same or overlapping field.

Graphical abstract