bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the lights4violence program: reduction in machismo and acceptance of violence among adolescents in Europe
Authors: Pérez-Martínez Vanesa , Sanz-Barbero Belén , Ferrer-Cascales Rosario , Bowes Nicola , Ayala Alba , Sánchez-SanSegundo Miriam , Albaladejo-Blázquez Natalia , Rosati Nicoletta , Neves Sofia , Vieira Cristina Pereira , Jankowiak Barbara , Jaskulska Sylwia , Waszyńska Katarzyna , Vives-Cases Carmen
Published: March 2022

Background

Machismo and acceptance of violence (AV) against women are part of the social construction of hegemonic masculinity and are related to the risk of dating violence. This study aims to analyze the effectiveness of the Lights4Violence program in reducing machismo and AV in secondary school students from different European cities.

Methods

Quasi-experimental longitudinal study using a convenience sample of 1,146 high school students from different European cities (12–17 years old) including 575 intervention group students (59.1% girls) and 571 control group students (62.7% girls). We performed linear regression models to identify the effect of the intervention, modelling the difference in means in machismo and AV (dependent variables) between wave-2 and wave-1.

Results

An interaction was identified between the group variable and the empathy variable. In wave-2, girls with high empathy at baseline in the intervention group obtained lower mean AV scores (β: -0.131; p = 0.004). However, the boys in the intervention group (reference: control group) with low empathy at baseline registered a significant increase in the mean values of machismo (β: 0.247; p < 0.001).

Conclusion

The importance of empathy is shown in the effectiveness of interventions to reduce machismo and AV in adolescents. While the Lights4Violence program focuses on promoting healthy relationships, there were some controversial results. It is possible that some children, especially those with less empathy, may have felt “challenged” during the intervention and/or assessment. This suggests the need for the development of interventions that also consider psychological processes and integrate the promotion of positive expressions of masculinity.
Dynamic changes in the systemic immune-inflammation index predict the prognosis of EGFR-mutant lung adenocarcinoma patients receiving brain metastasis radiotherapy
Authors: Wang Qi , Tan Xiaojing , Deng Guangchuan , Fu Shuai , Li Jianbin , Li Zhenxiang
Published: March 2022

Background

The systemic immune-inflammation index (SII) has recently emerged as a predictor of survival in non-small cell lung cancer patients. There is also tight correlation between radiotherapy and immune status, and brain metastases (BM) radiotherapy is an important treatment in patients with BM from lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations. Hence, this study aimed to present the prognostic value of SII and its dynamic changes during BM radiotherapy in EGFR-mutant lung adenocarcinoma patients with BM.

Methods

Patients with EGFR-mutant lung adenocarcinoma who received BM radiotherapy between November 2011 and April 2021 were included in this retrospective study. The SII was calculated using data acquired within 1 week before the start of radiation treatment and 1 week before its completion. According to the cutoff value of SII before radiation treatment determined using receiver operating characteristic curve analyses, we divided the patients into a high group and a low group. Patients were further classified into high–high, high–low, low–low, and low–high groups based on dynamic changes in SII. Prognostic values of the SII and other factors were determined using the Kaplan–Meier method, as well as univariate and multivariate Cox analysis.

Results

A total of 202 patients met the inclusion criteria, and the median overall survival (OS) of the entire cohort was 36 months. According to the SII cutoff of 859.79, an SII value below this cutoff was associated with longer OS (hazard ratio 0.6653, 95% confidence interval 0.4708–0.9402, P < 0.05). The patients in the low–low group, whose SII within 1 week before the start and end of BM radiotherapy were below the cutoff, had a median OS of 55.2 months, which was significantly longer than the OS in all other groups (P < 0.05). Univariate and multivariate analyses confirmed that dynamic SII change (P = 0.032), Lung-molGPA (P < 0.001), and thoracic radiation (P = 0.048) were independently correlated with OS.

Conclusions

The SII and its dynamic change may have a prognostic value in patients with EGFR-mutant lung adenocarcinoma treated with BM radiotherapy.
Preliminary report of the outcomes and indications of single approach, double-channel core decompression with structural bone support and bone grafting for osteonecrosis of the femoral head
Authors: Yue Ju’an , Guo Xiaozhong , Wang Randong , Li Bing , Sun Qiang , Liu Wangyan , Chen Jiao
Published: March 2022

Background

To report the outcomes of the single approach to double-channel core decompression and bone grafting with structural bone support (SDBS) for osteonecrosis of the femoral head (ONFH) and define the indications.

Methods

One-hundred-and-thirty-nine hips in 96 patients (79 males, 17 females; mean age 37.53±10.31 years, range 14–58 years; mean body mass index 25.15±3.63 kg/m2) were retrospectively analysed. The Harris hip score (HHS) was used to assess hip function, and radiographs were used to assess the depth of femoral head collapse. Treatment failure was defined as the performance of total hip arthroplasty (THA). The variables assessed as potential risk factors for surgical failure were: aetiology, Japanese Osteonecrosis Investigation Committee (JIC) type, age, and Association Research Circulation Osseous (ARCO) stage. Complications were recorded.

Results

The mean follow-up time was 29.26±10.02 months. The HHS increased from 79.00±13.61 preoperatively to 82.01±17.29 at final follow-up (P=0.041). The average HHS improvement was 3.00±21.86. The combined excellent and good rate at final follow-up (65.6%) was significantly higher than that before surgery (34.5%) (P<0.05). On radiographic evaluation, 103 (74.1%) hips remained stable, while 36 (25.9%) had femoral head collapse or aggravation of ONFH. THA was performed in 18 hips. Thus, the overall femoral head survival rate was 87.05% (121/139). The success rate was adversely affected by JIC type, but not by aetiology, age, or ARCO stage. The only complication was a subtrochanteric fracture in one patient.

Conclusion

The SDBS may be an effective method to delay or even terminate the natural progression of ONFH, especially for patients with JIC types B and C1. The SDBS represents a new option for treating early-stage ONFH.
Somatropin therapy in italian adults with growth hormone deficiency
Authors: Pricci Flavia , Rotondi Daniela , Villa Marika , Valerio Arianna , Agazio Elvira , Roazzi Paolo
Published: March 2022

Background

In adult population, Growth Hormone Deficiency (GHD) is a complex clinical condition with heterogeneity of causes and duration. Growth Hormone (GH) replacement therapy has beneficial effects entailing a chronic and expensive use. Therefore, entity, appropriateness and standardization of GHD treatment need to be accurately analysed.

In Italy, the epidemiological surveillance on somatropin therapy is entrusted to the National Register of Growth Hormone Therapy (Registro Nazionale degli Assuntori dell’Ormone della Crescita-RNAOC) by the Italian Regulation, in accordance of which the RNAOC-database is collecting the notifications of somatropin prescriptions.

Methods

Aim of this study is to analyse data on somatropin-treated adult population communicated to the RNAOC by the specialist centres of 15 Italian regions and 2 autonomous provinces.

Results

From 2011 to 2019, the somatropin-treated adults were 970 with 4061 examinations (1.21 ± 0.33 visits/year).

The diagnoses were: hypopituitarism (n = 579); hypophysectomy (n = 383); and congenital GHD (n = 3). Five subjects were addressed with diagnoses not included in the regulation.

The starting posology of somatropin was 0.320 (± 0.212) mg/day, 0.292 (± 0.167) mg/day in male and 0.360 (± 0.258) in female patients, with 7 administrations/week in 70.31% of the prescriptions. The differences in posology by gender persisted at 10th year of the follow-up. Starting dosage was higher in patients diagnosed with adult GHD before the age of 30 (0.420 ± 0.225 mg/day), with a progressive decrease of the dosage during the follow-up.

Conclusions

This is the first report on adult GH treatment, describing numbers, diagnoses, and pharmaceutical prescriptions associated to somatropin therapy in a large cohort of Italian GHD-adults.
Alterations in the oral microbiome of individuals with a healthy oral environment following COVID-19 vaccination
Authors: Uehara Osamu , Abiko Yoshihiro , Nagasawa Toshiyuki , Morikawa Tetsuro , Hiraki Daichi , Harada Fumiya , Kawano Yutaka , Toraya Seiko , Matsuoka Hirofumi , Paudel Durga , Shimizu Shintaro , Yoshida Koki , Asaka Masahiro , Furuichi Yasushi , Miura Hiroko
Published: March 2022

Background

Several reports suggest that the microbiome of the digestive system affects vaccine efficacy and that the severity of coronavirus disease (COVID-19) is associated with decreased diversity of the oral and/or intestinal microbiome. The present study examined the effects of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine on the oral microbiome.

Methods

Forty healthy Japanese oral healthcare personnel were recruited, and unstimulated saliva was collected before vaccination, after the 1st vaccination, and after the 2nd vaccination. Genomic DNA was extracted from saliva samples, and PCR amplicons of the 16S rRNA gene were analyzed using next-generation sequencing. Microbial diversity and composition were analyzed using Quantitative Insights into Microbial Ecology 2. In addition, alterations in microbial function were assessed using PICRUSt2.

Results

SARS-CoV-2 mRNA vaccination significantly increased oral bacterial diversity and significantly decreased the proportion of the genus Bacteroides.

Conclusions

The SARS-CoV-2 mRNA vaccine alters the oral microbiome; accordingly, vaccination might have beneficial effects on oral health.
Nodular fasciitis of the breast: the report of three cases
Authors: Lin Wanling , Bao Lingyun
Published: March 2022

Background

Nodular Fasciitis is a benign fibroblastic proliferation in soft tissues, which mostly occurs in the upper extremities, trunk, head and neck region. It is rarely reported to occur in the breast.

Case presentation

Herein, we present sonograms of nodular fasciitis in the breast at different durations in three cases. In Case 1, we provided the longest follow-up time in all literatures. In Case 2 and Case 3, we provided the automated breast ultrasound finding of breast nodular fasciitis for the first time.

Conclusion

Nodular Fasciitis shows clinical features and ultrasonography findings are similar to those of breast cancer. For superficially located breast lesions with a single and rapid growth, nodular fasciitis may be considered in the differential diagnosis of benign entities resembling malignant tumors on breast imaging.
A systematic umbrella review of the association of prescription drug insurance and cost-sharing with drug use, health services use, and health
Authors: Guindon G. Emmanuel , Fatima Tooba , Garasia Sophiya , Khoee Kimia
Published: March 2022

Background

Increasing spending and use of prescription drugs pose an important challenge to governments that seek to expand health insurance coverage to improve population health while controlling public expenditures. Patient cost-sharing such as deductibles and coinsurance is widely used with aim to control healthcare expenditures without adversely affecting health.

Methods

We conducted a systematic umbrella review with a quality assessment of included studies to examine the association of prescription drug insurance and cost-sharing with drug use, health services use, and health. We searched five electronic bibliographic databases, hand-searched eight specialty journals and two working paper repositories, and examined references of relevant reviews. At least two reviewers independently screened the articles, extracted the characteristics, methods, and main results, and assessed the quality of each included study.

Results

We identified 38 reviews. We found consistent evidence that having drug insurance and lower cost-sharing among the insured were associated with increased drug use while the lack or loss of drug insurance and higher drug cost-sharing were associated with decreased drug use. We also found consistent evidence that the poor, the chronically ill, seniors and children were similarly responsive to changes in insurance and cost-sharing. We found that drug insurance and lower drug cost-sharing were associated with lower healthcare services utilization including emergency room visits, hospitalizations, and outpatient visits. We did not find consistent evidence of an association between drug insurance or cost-sharing and health. Lastly, we did not find any evidence that the association between drug insurance or cost-sharing and drug use, health services use or health differed by socioeconomic status, health status, age or sex.

Conclusions

Given that the poor or near-poor often report substantially lower drug insurance coverage, universal pharmacare would likely increase drug use among lower-income populations relative to higher-income populations. On net, it is probable that health services use could decrease with universal pharmacare among those who gain drug insurance. Such cross-price effects of extending drug coverage should be included in costing simulations.
Prevalence and health correlates of workplace violence and discrimination against hospital employees – a cross-sectional study in German-speaking Switzerland
Authors: Stahl-Gugger Alenka , Hämmig Oliver
Published: March 2022

Background

Violence and discrimination are common events at work, especially in health care. Moreover, such workplace experiences are considered to have negative impacts and particularly adverse health consequences on health care workers. Nevertheless, the problem is still highly underreported and thus largely ignored and unexplored in Switzerland as comprehensive data and studies on their prevalence and health correlates among hospital staffs and health professionals are widely missing.

Methods

This cross-sectional study was based on secondary data from a company survey among several public hospitals and rehabilitation clinics in German-speaking Switzerland conducted in 2015/16. The study population was limited to a subsample of 1567 health professionals among the surveyed staffs of five participating hospitals and clinics. Relative frequencies of different forms of violence and discrimination at work and the total number of such experiences were calculated for the entire study population and for occupational subgroups. These data were compared with a nationally representative subsample of the Swiss Health Survey 2017 as a reference population. Multiple logistic regression analyses were further computed to investigate the association between the number of different experienced forms of violence and/or discrimination at work and several poor general and mental health outcomes.

Results

23% of the inverviewed hospital employees experienced at least one form of discrimination or violence at work in the past year, compared to 18% of the general working population. Nurses were by far the most affected occupational group regarding all forms of violence. More and particularly the most exposed and affected hospital employees with regard to experiences of violence and/or discrimination at work showed almost consistently increased frequencies and relative risks for the studied poor mental and general health outcomes. Prevalence rates and odds ratios for strong sleep disorders, strong stress feelings and increased burnout symptoms were between 3 and 4 times higher among the most exposed compared to the non-exposed group of hospital employees.

Conclusions

Study findings underline the importance of an active combat against violent and discriminatory behaviors in health care. Prevention strategies should particularly focus on nurses and midwives, which turned out to be the most affected and exposed group of all health professions.
Implementing the WHO Safe Childbirth Checklist modified for preterm birth: lessons learned and experiences from Kenya and Uganda
Authors: Achola Kevin Abidha , Kajjo Darious , Santos Nicole , Butrick Elizabeth , Otare Christopher , Mubiri Paul , Namazzi Gertrude , Merai Rikita , Otieno Phelgona , Waiswa Peter , Walker Dilys
Published: March 2022

Background

The WHO Safe Childbirth Checklist (SCC) contains 29 evidence-based practices (EBPs) across four pause points spanning admission to discharge. It has been shown to increase EBP uptake and has been tailored to specific contexts. However, little research has been conducted in East Africa on use of the SCC to improve intrapartum care, particularly for preterm birth despite its burden. We describe checklist adaptation, user acceptability, implementation and lessons learned.

Methods

The East Africa Preterm Birth Initiative (PTBi EA) modified the SCC for use in 23 facilities in Western Kenya and Eastern Uganda as part of a cluster randomized controlled trial evaluating a package of facility-based interventions to improve preterm birth outcomes. The modified SCC (mSCC) for prematurity included: addition of a triage pause point before admission; focus on gestational age assessment, identification and management of preterm labour; and alignment with national guidelines. Following introduction, implementation lasted 24 and 34 months in Uganda and Kenya respectively and was supported through complementary mentoring and data strengthening at all sites. PRONTO® simulation training and quality improvement (QI) activities further supported mSCC use at intervention facilities only. A mixed methods approach, including checklist monitoring, provider surveys and in-depth interviews, was used in this analysis.

Results

A total of 19,443 and 2229 checklists were assessed in Kenya and Uganda, respectively. In both countries, triage and admission pause points had the highest rates of completion. Kenya’s completion was greater than 70% for all pause points; Uganda ranged from 39 to 75%. Intervention facilities exposed to PRONTO and QI had higher completion rates than control sites. Provider perceptions cited clinical utility of the checklist, particularly when integrated into patient charts. However, some felt it repeated information in other documentation tools. Completion was hindered by workload and staffing issues.

Conclusion

This study highlights the feasibility and importance of adaptation, iterative modification and complementary activities to reinforce SCC use. There are important opportunities to improve its clinical utility by the addition of prompts specific to the needs of different contexts. The trial assessing the PTBi EA intervention package was registered at ClinicalTrials.gov NCT03112018 Registered December 2016, retrospectively registered.
Blood-feeding patterns of Anopheles vectors of human malaria in Malawi: implications for malaria transmission and effectiveness of LLIN interventions
Authors: Mbewe Rex B. , Keven John B. , Mzilahowa Themba , Mathanga Don , Wilson Mark , Cohee Lauren , Laufer Miriam K. , Walker Edward D.
Published: March 2022

Background

Access to human hosts by Anopheles mosquitoes is a key determinant of vectorial capacity for malaria, but it can be limited by use of long-lasting insecticidal nets (LLINs). In Malawi, pyrethroid-treated LLINs with and without the synergist piperonyl butoxide (PBO) were distributed to control malaria. This study investigated the blood-feeding patterns of malaria vectors and whether LLINs containing pyrethroid and PBO led to a reduction of human blood feeding than those containing only pyrethroids.

Methods

Mosquitoes were sampled inside houses from May 2019 through April 2020 by aspiration, pyrethrum spray catch, and light trap methods in two sites. One site (Namanolo, Balaka district) had LLINs containing only pyrethroids whereas the other (Ntaja, Machinga district) had LLINs with both pyrethroids and PBO. Anopheles species, their blood-meal host, and infection with Plasmodium falciparum were determined using PCR methods.

Results

A total of 6585 female Anopheles were sampled in 203 houses. Of these, 633 (9.6%) were blood-fed mosquitoes comprising of 279 (44.1%) Anopheles arabiensis, 103 (16.3%) Anopheles gambiae 212 (33.5), Anopheles funestus, 2 (0.3%), Anopheles parensis and 37 (5.8%) were unidentified Anopheles spp. Blood meal hosts were successfully identified for 85.5% (n = 541) of the blood-fed mosquitoes, of which 436 (81.0%) were human blood meals, 28 (5.2%) were goats, 11 (2.0%) were dogs, 60 (11.1%) were mixed goat-human blood meals, 5 (0.9%) were dog–human, and 1 was a mixed dog-goat. Human blood index (fraction of blood meals that were humans) was significantly higher in Namanolo (0.96) than Ntaja (0.89). Even though human blood index was high, goats were over-selected than humans after accounting for relative abundance of both hosts. The number of infectious Anopheles bites per person-year was 44 in Namanolo and 22 in Ntaja.

Conclusion

Although LLINs with PBO PBO may have reduced human blood feeding, access to humans was extremely high despite high LLIN ownership and usage rates in both sites. This finding could explain persistently high rates of malaria infections in Malawi. However, this study had one village for each net type, thus the observed differences may have been a result of other factors present in each village.
A global cautionary tale: discrimination and violence against trans women worsen despite investments in public resources and improvements in health insurance access and utilization of health care
Authors: Arayasirikul Sean , Turner Caitlin , Trujillo Dillon , Sicro Sofia L. , Scheer Susan , McFarland Willi , Wilson Erin C.
Published: March 2022

Background

To determine if improvements in social determinants of health for trans women and decreases in transphobic discrimination and violence occurred over three study periods during which extensive local programs were implemented to specifically address longstanding inequities suffered by the transgender community.

Methods

Interviewer-administered surveys from repeated cross-sectional Transwomen Empowered to Advance Community Health (TEACH) studies in 2010, 2013 and 2016-2017 in San Francisco collected experiences with transphobia violence and discrimination. Respondent-driven sampling was used to obtain a sample of participants who identified as a trans woman.

Results

Violence due to gender identity was prevalent; in each study period, verbal abuse or harassment was reported by over 83% of participants, and physical abuse or harassment was reported by over 56%. Adverse social determinants of health including homelessness, living below the poverty limit, methamphetamine use, depression, PTSD, and anxiety all significantly increased from 2010 to 2016. When testing for trends, housing discrimination and physical violence were both more likely in 2016-2017 compared to the two earlier study periods. Housing discrimination (aOR 1.41, 95% CI 1.00-1.98) and physical violence due to gender identity/presentation (aOR 1.39, 95% CI 1.00-1.92) both significantly increased from 2010 to 2016.

Conclusion

Our findings are particularly alarming during a period when significant public health resources and community-based initiatives specifically for trans women were implemented and could have reasonably led us to expect improvements. Despite these efforts, physical violence and housing discrimination among trans women worsened during the study periods. To ensure future improvements, research and interventions need to shift the focus and burden from trans people to cisgender people who are the perpetuators of anti-trans sentiment, stigma, discrimination and victimization.
Coenzyme Q10 supplementation improves adipokine profile in dyslipidemic individuals: a randomized controlled trial
Authors: Zhang Peiwen , Chen Ke , He Taiping , Guo Honghui , Chen Xu
Published: March 2022

Background

In previous study, we found that coenzyme Q10 (CoQ10) improved glucolipid profile in dyslipidemic individuals, but the mechanism is not yet clear. Adipokines have been demonstrated to be vital targets of metabolic diseases. The hypothesis that adipokines mediate the association of CoQ10 on glucolipid metabolism needs to be further studied in human.

Methods

In this randomized, double-blinded, placebo-controlled trial, 101 dyslipidemic individuals were administrated to 120 mg CoQ10 or placebo for 24 weeks. Anthropometric parameters, glucolipid profile, serum total adiponectin, leptin, and resistin were evaluated at baseline, week 12 and week 24.

Results

CoQ10 treatment significantly increased serum adiponectin levels at week 12 (165 [0, 362] ng/mL, p < 0.001) and at week 24 (523 [0, 1056] ng/mL, p < 0.001]), which was significant different compared with placebo (p < 0.001). The increase of adiponectin was negative associated with decrease in index of homeostasis model assessment of insulin resistance (HOMA-IR, r = − 0.465, p = 0.001), triglyceride (TG, r = − 0.297, p = 0.047), and low-density lipoprotein cholesterol (LDL-c, r = − 0.440, p = 0.002) at week 24 only in CoQ10-treated group. Resistin was reduced by CoQ10 only at week 24 (− 1.19 [− 4.35, 0.00] ng/mL, p < 0.001), which was significant different compared with placebo (p < 0.001). Reduction of resistin was positively correlated with the change in HOMA-IR (r = 0.343, p = 0.021) and TG (r = 0.323, p = 0.030) at week 24 in CoQ10-treated group but not placebo group. Leptin was not influenced by CoQ10 treatment. Mediation analysis indicated that the improvement of HOMA-IR, TG and LDL-c by CoQ10 was mediated by adiponectin but not resistin.

Conclusions

Our study shows that CoQ10 ameliorates glucolipid profile and adipokines dysfunction in dyslipidemic patients in 24 weeks’ intervention. The beneficial effect of CoQ10 on glucolipid profile was mediated by adiponectin. Trial registration: ClinicalTrials.gov, NCT02407548. Registered on April 3, 2015, https://clinicaltrials.gov/ct2/show/NCT02407548.
SATB2-associated syndrome: characterization of skeletal features and of bone fragility in a prospective cohort of 19 patients
Authors: Mouillé M. , Rio M. , Breton S. , Piketty M. L. , Afenjar A. , Amiel J. , Capri Y. , Goldenberg A. , Francannet C. , Michot C. , Mignot C. , Perrin L. , Quelin C. , Van Gils J. , Barcia G. , Pingault V. , Maruani G. , Koumakis E. , Cormier-Daire V.
Published: March 2022

Background

Individuals with pathogenic variants in SATB2 display intellectual disability, speech and behavioral disorders, dental abnormalities and often features of Pierre Robin sequence. SATB2 encodes a transcription factor thought to play a role in bone remodeling. The primary aim of our study was to systematically review the skeletal manifestations of SATB2-associated syndrome. For this purpose, we performed a non-interventional, multicenter cohort study, from 2017 to 2018. We included 19 patients, 9 females and 10 males ranging in age from 2 to 19 years-old. The following data were collected prospectively for each patient: clinical data, bone markers and calcium and phosphate metabolism parameters, skeletal X-rays and bone mineral density.

Results

Digitiform impressions were present in 8/14 patients (57%). Vertebral compression fractures affected 6/17 patients (35%). Skeletal demineralization (16/17, 94%) and cortical thinning of vertebrae (15/17) were the most frequent radiological features at the spine. Long bones were generally demineralized (18/19). The distal phalanges were short, thick and abnormally shaped. C-telopeptide (CTX) and Alkaline phosphatase levels were in the upper normal values and osteocalcin and serum procollagen type 1 amino-terminal propeptide (P1NP) were both increased. Vitamin D insufficiency was frequent (66.7%).

Conclusion

We conclude that SATB2 pathogenic variants are responsible for skeletal demineralization and osteoporosis. We found increased levels of bone formation markers, supporting the key role of SATB2 in osteoblast differentiation. These results support the need for bone evaluation in children and adult patients with SATB2-associated syndrome (SAS).
Advances in the diagnosis and treatment of sickle cell disease
Authors: Brandow A. M. , Liem R. I.
Published: March 2022

Sickle cell disease (SCD), which affects approximately 100,000 individuals in the USA and more than 3 million worldwide, is caused by mutations in the βb globin gene that result in sickle hemoglobin production. Sickle hemoglobin polymerization leads to red blood cell sickling, chronic hemolysis and vaso-occlusion. Acute and chronic pain as well as end-organ damage occur throughout the lifespan of individuals living with SCD resulting in significant disease morbidity and a median life expectancy of 43 years in the USA. In this review, we discuss advances in the diagnosis and management of four major complications: acute and chronic pain, cardiopulmonary disease, central nervous system disease and kidney disease. We also discuss advances in disease-modifying and curative therapeutic options for SCD. The recent availability ofl-glutamine, crizanlizumab and voxelotor provides an alternative or supplement to hydroxyurea, which remains the mainstay for disease-modifying therapy. Five-year event-free and overall survival rates remain high for individuals with SCD undergoing allogeneic hematopoietic stem cell transplant using matched sibling donors. However, newer approaches to graft-versus-host (GVHD) prophylaxis and the incorporation of post-transplant cyclophosphamide have improved engraftment rates, reduced GVHD and have allowed for alternative donors for individuals without an HLA-matched sibling. Despite progress in the field, additional longitudinal studies, clinical trials as well as dissemination and implementation studies are needed to optimize outcomes in SCD.
FAM167A is a key molecule to induce BCR-ABL-independent TKI resistance in CML via noncanonical NF-κB signaling activation
Authors: Yang Taewoo , Sim Kyu-Young , Ko Gwang-Hoon , Ahn Jae-Sook , Kim Hyeoung-Joon , Park Sung-Gyoo
Published: March 2022

Background

BCR-ABL-independent drug resistance is a barrier to curative treatment of chronic myeloid leukemia (CML). However, the molecular pathways underlying BCR-ABL-independent tyrosine kinase inhibitor (TKI) resistance remain unclear.

Methods

In silico bioinformatic analysis was performed to identify the most active transcription factor and its inducer that contribute to BCR-ABL-independent TKI resistance. Tandem mass spectrometry analysis was performed to identify the receptor for the noncanonical NF-κB activator FAM167A. In vitro and in vivo mouse experiments revealed detailed molecular insights into the functional role of the FAM167A-desmoglein-1 (DSG1) axis in BCL-ABL-independent TKI resistance. CML cells derived from CML patients were analyzed using quantitative reverse transcription PCR and flow cytometry.

Results

We found that NF-κB had the greatest effect on differential gene expression of BCR-ABL-independent TKI-resistant CML cells. Moreover, we found that the previously uncharacterized protein FAM167A activates the noncanonical NF-κB pathway and induces BCR-ABL-independent TKI resistance. Molecular analyses revealed that FAM167A activates the noncanonical NF-κB pathway by binding to the cell adhesion protein DSG1 to upregulate NF-κB-inducing kinase (NIK) by blocking its ubiquitination. Neutralization of FAM167A in a mouse tumor model reduced noncanonical NF-κB activity and restored sensitivity of cells to TKIs. Furthermore, FAM167A and surface DSG1 levels were highly upregulated in CD34+ CML cells from patients with BCR-ABL-independent TKI-resistant disease.

Conclusions

These results reveal that FAM167A acts as an essential factor for BCR-ABL-independent TKI resistance in CML by activating the noncanonical NF-κB pathway. In addition, FAM167A may serve as an important target and biomarker for BCR-ABL-independent TKI resistance.
Tumor bud-derived CCL5 recruits fibroblasts and promotes colorectal cancer progression via CCR5-SLC25A24 signaling
Authors: Gao Ling-Fang , Zhong Yan , Long Ting , Wang Xia , Zhu Jia-Xian , Wang Xiao-Yan , Hu Zhi-Yan , Li Zu-Guo
Published: March 2022

Background

Tumor budding is included in the routine diagnosis of colorectal cancer (CRC) and is considered a tumor prognostic factor independent of TNM staging. This study aimed to identify the fibroblast-mediated effect of tumor bud-derived C–C chemokine ligand 5 (CCL5) on the tumor microenvironment (TME).

Methods

Recruitment assays and a human cytokine array were used to detect the main cytokines that CRC tumor buds secrete to recruit fibroblasts. siRNA transfection and inhibitor treatment were used to investigate the role of fibroblast CCL5 receptors in fibroblast recruitment. Subsequently, transcriptome sequencing was performed to explore the molecular changes occurring in fibroblasts upon stimulation with CCL5. Finally, clinical specimens and orthotopic xenograft mouse models were studied to explore the contribution of CCL5 to angiogenesis and collagen synthesis.

Results

Hematoxylin–eosin staining and immunochemistry revealed a higher number of fibroblasts at the invasive front of CRC tissue showing tumor budding than at sites without tumor budding. In vitro experiments demonstrated that CCL5 derived from tumor buds could recruit fibroblasts by acting on the CCR5 receptors on fibroblasts. Tumor bud-derived CCL5 could also positively regulate solute carrier family 25 member 24 (SLC25A24) expression in fibroblasts, potentially activating pAkt-pmTOR signaling. Moreover, CCL5 could increase the number of α-SMAhigh CD90high FAPlow fibroblasts and thus promote tumor angiogenesis by enhancing VEGFA expression and making fibroblasts transdifferentiate into vascular endothelial cells. Finally, the results also showed that CCL5 could promote collagen synthesis through fibroblasts, thus contributing to tumor progression.

Conclusions

At the invasive front of CRC, tumor bud-derived CCL5 can recruit fibroblasts via CCR5-SLC25A24 signaling, further promoting angiogenesis and collagen synthesis via recruited fibroblasts, and eventually create a tumor-promoting microenvironment. Therefore, CCL5 may serve as a potential diagnostic marker and therapeutic target for tumor budding in CRC.
Towards accurate and reliable resolution of structural variants for clinical diagnosis
Authors: Liu Zhichao , Roberts Ruth , Mercer Timothy R. , Xu Joshua , Sedlazeck Fritz J. , Tong Weida
Published: March 2022

Structural variants (SVs) are a major source of human genetic diversity and have been associated with different diseases and phenotypes. The detection of SVs is difficult, and a diverse range of detection methods and data analysis protocols has been developed. This difficulty and diversity make the detection of SVs for clinical applications challenging and requires a framework to ensure accuracy and reproducibility. Here, we discuss current developments in the diagnosis of SVs and propose a roadmap for the accurate and reproducible detection of SVs that includes case studies provided from the FDA-led SEquencing Quality Control Phase II (SEQC-II) and other consortium efforts.
Effect of first dorsal interosseous strengthening on clinical outcomes in patients with thumb osteoarthritis: a study protocol for a randomized controlled clinical trial
Authors: Tossini Natália Barbosa , Pereira Natália Duarte , de Oliveira Gabriela Sardeli , da Silva Serrão Paula Regina Mendes
Published: March 2022

Background

Thumb carpometacarpal osteoarthritis (CMC OA) is characterized by chronic progressive degeneration of the joint cartilage, with high prevalence. Patients present with pain at the base of the thumb, morning stiffness, and muscle weakness, symptoms that affect hand function and therefore interfere in activities and social participation. Movements that involve grip or lateral pinch are the most affected and directly impact independence, self-care, and leisure activities. In the literature consulted, several protocols with exercises for these patients were found. However, most do not compare the same intervention modality and only provide basic methodological information, with no consistent information on training load and load progression. In addition, most protocols only address the strengthening of the abductor and extensor thumb muscles and pinching or grasping exercises. However, some biomechanical and electromyographic studies have demonstrated the important role of the first dorsal interosseous muscles as stabilizers of the thumb carpometacarpal joint.

Methods

This is a randomized, controlled, double-blind, and parallel clinical trial that will include 56 participants, over 40 years old, with radiographic evidence of thumb base osteoarthritis. Participants will be randomly allocated into two groups: control and intervention. The following evaluations will be conducted: the Australian/Canadian Hand Osteoarthritis Index, Canadian Occupational Performance Measure, Nine-Hole Peg Test, grip and pinch strength associated with muscle activation assessment, and Bilateral Upper Limb Function Test at four different times: baseline, session 13, session 18, and follow-up. Treatment will take place over 6 weeks, with reassessments in the fourth and sixth weeks and 3 months after the end of the intervention (follow-up). Qualitative variables will be expressed as frequency and percentage, and quantitative variables as mean and standard deviation. Intergroup comparison of the intervention will be performed by repeated measures ANOVA, considering the effect of the two groups and four assessments, and interactions between them.

Discussion

This study will demonstrate whether the specific strengthening of the first dorsal interosseous muscle has a superior and positive effect on the clinical picture of patients with CMC OA. Additionally, if specific strengthening of the muscle is not superior to the traditional protocol in the literature, it will also be determined whether the two protocols are equivalent in terms of the best clinical picture.

Trial registration

Brazilian Registry of Clinical Trials (ReBEC) RBR-8kgqk4. Prospectively registered on 15 January 2020
Functional predictors of treatment induced diabetic neuropathy (TIND): a prospective pilot study using clinical and neurophysiological functional tests
Authors: Hoffmann Yvonne , Toyka Klaus V. , Blüher Matthias , Classen Joseph , Baum Petra
Published: March 2022

Background

A treatment-induced drop in HbA1c has been suggested to be a risk factor for TIND.

Methods

From 60 included patients with severe diabetes mellitus (HbA1c over 8.5) only 21 patients adhered to the study protocol over 1 year with a battery of autonomic nervous system tests scheduled before and after starting antidiabetic treatment.

Results

In patients with a drop of HbA1c greater than 2 per cent points only some neurophysiologic tests and lab values tended to deteriorate with a trend to improve at later time points along the study. None of these changes were statistically significant, most likely because the study failed to reach the planned number of patients.

Conclusion

Poor adherence to diabetes treatment and to following the study protocol were the assumed obstacles in our patient cohort selected for very high HbA1c levels. In future studies a multi-center trial and case numbers of up to 500 patients may be needed to account for drop outs in the range observed here. Moreover, the number of tests in each patient at each visit may have to be reduced and special educational group sessions are warranted to cope with the limited adherence.

Trial registration Ethic Committee University of Leipzig 439/15-ek. Registered 22 April 2016
Prevalence and molecular characterization of Vibrio cholerae from fruits and salad vegetables sold in Jakarta, Indonesia, using most probable number and PCR
Authors: Budiman Andrea , Kurnia Kevin , Waturangi Diana E.
Published: March 2022

Objective

Cholera is an intestinal infection caused by Vibrio cholerae, it is usually occurs in developing countries that lack of sanitation. In developing country including Indonesia, awareness importance of sanitation is still low. Unfortunately, research related to the detection of V. cholerae from fruit and vegetables in Indonesia is still rare. In this study, MPN method was used to determine the prevalence of V. cholerae followed by single and multiplex PCR to detect virulence genes, including toxR, ctxA, tcpA, hlyA, ace, ompU, and zot.

Results

We found 3 fruits and 2 vegetables positive for toxR gene. Fruit samples which were showed toxR positive found from East Jakarta while for vegetables, it was recovered from West Jakarta and Central Jakarta. Twenty-three isolates were recovered from toxR positive samples. The result of antibiotic resistance analysis showed that 4.35% of the isolates resistant to gentamicin, streptomycin (17.39%), trimethoprim (52.17%), ciprofloxacin (30.43%), ampicillin (13.04%), nalidixic acid (82.61%), and polymyxin B (91.30%). None of these isolates were resistant to kanamycin. Combination of MPN and Multiplex PCR method can be used to detect the prevalence and characterize the virulence properties of V. cholerae.
Nonsurgical management of Fusobacterium necrophorum sternoclavicular septic arthritis: a case report
Authors: Kim SangMin , Kanwar Ruhi , Marshall M. Blair
Published: March 2022

Background

To date, the gold-standard treatment for sternoclavicular septic arthritis has been surgery due to the high failure and complication rates of medical treatment. In particular, presentation of Fusobacterium sternoclavicular septic arthritis has been rarely reported and very sparsely investigated, and only one other case report of septic arthritis caused by this pathogen exists in literature.

Case presentation

We report a case of an otherwise healthy 38-year-old Caucasian woman who presented with sternoclavicular septic arthritis as a complication of Fusobacterium necrophorum mediastinitis. Our patient underwent successful management through nonstandard, conservative treatment of 7 weeks of intravenous piperacillin + tazobactam followed by 6 weeks of oral amoxicillin + clavulanic acid.

Conclusion

We highlight a case of the rare presentation of Fusobacterium necrophorum sternoclavicular septic arthritis that did not require surgical intervention for successful management. Though infection of the sternoclavicular joint is unusual, it continues to be seen in thoracic surgery, and there are increasing numbers of antibiotic-resistant organisms. This case broadens insight into the clinical course and treatment of such conditions. The success of conservative management in this case aligns with the similar nonsurgical course of the one previous report of Fusobacterium sternoclavicular septic arthritis occurrence. Thus, further discussion and thought for reevaluating the current standard practice of surgery for sternoclavicular joint infection is suggested. Our case supports assessing a patient’s overall health, causative organism, and extent of infection in interventional course and taking the feasibility of conservative management into more weighted consideration.
Combination of stem cell therapy and acupuncture to treat ischemic stroke: a prospective review
Authors: Jia Huidong , He Jia , Zhao Lan , Hsu Chia-Chen , Zhao Xiaofeng , Du Yuzheng , Han Lin , Cui Zhanfeng , Shi Xuemin , Ye Hua
Published: March 2022

Stroke is the second leading cause globally that leads to severe disability and death. Stem cell therapy has been developed over the recent years to treat stroke and diminish the mortality and disability rate of brain injuries. Acupuncture, which can activate endogenous recovery via physical stimuli, has been applied to enhance the recovery and rehabilitation of stroke patients. Attempts have been made to combine stem cell therapy and acupuncture to treat stroke patients and have shown the promising results. This prospective review will look into the possible mechanisms of stem cell therapy and acupuncture and intend to undercover the potential benefit of the combined therapy. It intends to bridge the modern emerging stem cell therapy and traditional acupuncture at cellular and molecular levels and to demonstrate the potential benefit to improve clinical outcomes.
The functional mechanism of bone marrow-derived mesenchymal stem cells in the treatment of animal models with Alzheimer’s disease: crosstalk between autophagy and apoptosis
Authors: Qin Chuan , Bai Lin , Li Yongning , Wang Kewei
Published: March 2022

The transplantation of bone marrow-derived mesenchymal stem cells (BMMSCs) alleviates neuropathology and improves cognitive deficits in animal models with Alzheimer’s disease. However, the underlying mechanism remains undefined. Based on meta-analysis and comprehensive review, high-profile studies support the theory that transplanted BMMSCs activate autophagy, as evidenced by the expression levels of signal molecules such as Beclin-1, Atg5, LC3-II, and mTOR. Functional autophagy mitigates neuronal apoptosis, which is reflected by the alterations of IAPs, Bcl-2, caspase-3, and so forth. Moreover, the transplantation of BMMSCs can decrease aberrant amyloid-beta peptides as well as tau aggregates, inhibit neuroinflammation, and stimulate synaptogenesis. There is a signal crosstalk between autophagy and apoptosis, which may be regulated to produce synergistic effect on the preconditioning of stem cells. Forasmuch, the therapeutic effect of transplanted BMMSCs can be enhanced by autophagy and/or apoptosis modulators.
Design of dynamic resource allocation scheme for real-time traffic in the LTE network
Authors: Mai Yi-Ting , Hu Chih-Chung
Published: March 2022

The 5G wireless technology is recently standardized for meeting intense demand. The Long Term Evolution (LTE) technology provides an easy, time-saving, and low-cost method for deploying a 4G/5G network infrastructure. To support multimedia service and higher bandwidth data delivery, an LTE MAC layer has Quality of Service (QoS) support with several QoS class indicator (QCI) levels. Based on LTE current QCI priority and QoS requirements in UEs, the original Max-Rate scheduler, Proportionally Fair (PF) and Modified Largest Weighted Delay First (M-LWDF) algorithms could not achieve their goal owing to the UE’s dynamic physical capacity with a different Channel Quality Indicator (CQI) at run time. For better QoS service than LTE networks, per UE’s CQI state for each resource block (RB) must be considered simultaneously in LTE MAC layer resource allocation with cross-layer support. As downlink real estimated capacity is dynamic owing to a UE’s periodic CQI reporting, the CQI state in LTE scheduling must be considered. This study proposes a smart and flexible scheme for Enhanced Utilization Resource Allocation (EURA) including three novel mechanisms that can dynamically fit UEs’ CQI states. The simulation results in this study demonstrate that the proposed EURA scheme outperforms the contrast schemes (Max-Rate, EXP/PF and M-LWDF), can save more rare radio capacity, and improve the utilization of radio resource assignment.
Explicit iteration and unbounded solutions for fractional q–difference equations with boundary conditions on an infinite interval
Authors: Boutiara Abdellatif , Benbachir Maamar , Kaabar Mohammed K. A. , Martínez Francisco , Samei Mohammad Esmael , Kaplan Melike
Published: March 2022

In this work, a proposed system of fractional boundary value problems is investigated concerning its unbounded solutions’ existence for a class of nonlinear fractional q-difference equations in the context of the Riemann–Liouville fractional q-derivative on an infinite interval. The system’s solution is formulated with the help of Green’s function. A compactness criterion is established in a special space. All the obtained results of uniqueness and existence are investigated with the help of fixed-point theorems. Some essential examples are illustrated to support our main outcomes.