bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness and cost of an incentive-based intervention on food safety and income in “dibiteries” in Dakar, Senegal
Authors: Orou Seko Malik , Ossebi Walter , Houngbedji Clarisse A. , Kreppel Katharina , Dao Daouda , Bonfoh Bassirou
Published: March 2022

Background

Rapid urbanisation in Sub-Saharan African cities such as Dakar, Senegal, leads to proliferation of informal braised meat restaurants known as “dibiteries”. Dibiteries do not often comply with minimal hygiene and food safety standards. The primary objective of this study was to assess the effectiveness and cost of a good hygiene practice intervention, identify factors that incentivize hygiene improvement and how that impacts on dibiteries’ income.

Methods

A randomized controlled trial was carried out in Dakar dibiteries. The 120 random samples of braised meat were collected in three phases: (i) one-month pre-intervention, (ii) 2 months post-intervention, (iii) 10 months post-intervention. The trial comprised four groups of 10 dibiteries each: (a) (control) received no intervention, (b) a standardized training module, (c) a hygiene kit, (d) a training module and hygiene kit. Laboratory analysis of samples determined the total aerobic mesophilic flora (TAMF), thermotolerant coliforms (TC) and Staphylococcus aureus (SA). A questionnaire-based survey and focus group discussion were used to identify pre-intervention hygiene practices, and socioeconomic determinants of hygiene management in dibiteries post-intervention, respectively.

Results

Samples were found to be contaminated with TAMF, TC and SA. In phase 1, 27 and 13% of the samples contained TC and SA, respectively. In phase 2, no significant improvement of contamination rates was seen. In phase 3, microbiological quality of samples was significantly improved, with only 11.5% showing contamination with any of the bacterial species analysed (p < 0.1). Compared to the control group, only samples from dibiteries in group (b) had significantly reduced bacterial load in phase 3. The cost of intervention and hygiene improvement was estimated at 67 FCFA ($ 0.12) and 41 FCFA ($ 0.07) / day respectively and did not significantly impact on dibiterie profitability. Incentives to sustainably implement good hygiene practices were mainly linked to access to secure long-term workspaces.

Conclusion

This intervention may have worked, but globally the results are mixed and not quite significant. However, continuous training in good hygiene practice and access to secure and sustainable infrastructure for dibiterie restaurants are the incentives necessary to achieve sustainable investments and behavioural change. We recommend further intervention refinement and testing other factors for promoting the adoption of good hygiene practices in the dibiteries in relation to consumers health risk.
Development of information dissemination methods that contribute to improving maternal and child healthcare using social networking sites: a community-based cross-sectional study in Japan
Authors: Ikeda Sayaka , Ueda Yutaka , Yagi Asami , Taniguchi Mariko , Matsuzaki Satoko , Takiuchi Tsuyoshi , Miyoshi Ai , Arahori Hitomi , Hirai Kei , Kimura Tadashi
Published: March 2022

Background

In recent years, feelings of isolation among mothers caring for small children has become a significant social issue in Japan. The purpose of this study is to develop a message to alleviate their loneliness, to evaluate the impact of social networking sites (SNS) for delivering such messages, and to propose means of more effective information transmission to promote health for mothers raising small children.

Methods

Our study was conducted in two stages, first an interview and then a cross-sectional study of the mothers involving a questionnaire survey. The interview was targeted two public-health nurses caring for mothers. Based on these interviews, we developed six messages intended to alleviate the mothers’ sense of loneliness, which were vetted by seven mothers. The second stage was to conduct a questionnaire survey of mothers both before and after our selected message as advertisement on Instagram and analyzed the effect. The surveys were collected during routine child health check-ups in the City of Takatsuki, Japan.

Results

From the six draft messages created based on interviews with public health nurses, we selected the message that most relieves the feeling of loneliness of the mothers who are raising small children.

The survey questionnaire was taken by 494 mothers prior to our posting of Instagram advertisements (ads), and afterwards by 419 mothers. The percentage of mothers feeling loneliness tended to decrease after reading the messages (before ads.:8.1%, after ads.:5.8%). 8.6% of the mothers (36/419) remembered seeing the Instagram ads. Mothers with financial anxiety were significantly more likely to have remembered seeing the Instagram ads (p < 0.01).

Conclusions

Our results indicate that usefulness of SNS messaging for mothers raising small children may reduce their feeling of loneliness. Among the SNS, disseminating child-rearing information on Instagram may be more effective for people with financial instability.
Anterior debridement, bone grafting and fixation for cervical spine tuberculosis: an iliac bone graft versus a structural manubrium graft
Authors: Xu Shuang , Wang Gaoju , Yang Jin , Zhang Shuai , Song Yueming , Wang Qing
Published: March 2022

Background

Anterior debridement, decompression, bone grafting, and instrumentation are safe and effective techniques for patients with lower cervical spine tuberculosis. However, there is no consensus regarding the methods for using autogenous bone grafts. The purpose of this retrospective study was to compare the clinical outcomes of anterior surgical management for cervical spine tuberculosis by using an iliac bone graft versus a structural manubrium graft.

Methods

From January 2009 to September 2018, 23 patients with cervical spine tuberculosis were treated with anterior debridement, autogenous structural bone grafting and fixation at our spinal department. The patients were divided into 2 groups according to the different graft materials, namely, iliac crest bone grafts (Group A) and structural manubrium grafts (Group B). The clinical and radiographic results of the 2 groups were analyzed and compared.

Results

The mean duration of follow-up was 24 months. Bony fusion was achieved in all patients without failure of internal fixation. There were no significant differences between the two groups with respect to the operation time, blood loss, fusion time, neurological outcomes, or postoperative local Cobb angle (P > .05). However, the donor site complication rate in Group A was greater than that in Group B. The postoperative ambulation time in Group A was later than that in Group B. The mean visual analog scale (VAS) score for donor site pain in Group A was higher than that in Group B at 1 week after surgery (P < 0.05). However, there was no significant difference between the 2 groups at the last visit (P > .05).

Conclusion

Both iliac bone grafts and sternal manubrium grafts can effectively reconstruct anterior column defects in anterior surgery. However, structural sternal manubrium autografts cause fewer complications associated with donor site morbidities than iliac bone grafts.
Contribution of health information system to child immunization services in Ethiopia: baseline study of 33 woredas
Authors: Worku Abebaw , Alemu Hibret , Belay Hiwot , Mohammedsanni Afrah , Denboba Wubshet , Mulugeta Frehiwot , Omer Shemsedin , Abate Biruk , Mohammed Mesoud , Ahmed Mohammed , Wondarad Yakob , Abebaw Meskerem
Published: March 2022

Background

Monitoring progress using appropriate data, with a functional health information system (HIS), believed to be very crucial for success of immunization program. Baseline study was conducted to assess, immunization service coverage, HIS performance status, and their relationships.

Methods

A linked facility and population-based survey was conducted concurrently from September 21 to October 15, 2020. A total of 3016 households were reached to interview mothers having children aged 12–23 months in the 33 woredas. Overall 81 health posts, 71 health centers, and 15 hospitals were selected for the facility survey. The study used modified Performance of Routine Information System Management (PRISM) tools for the facility survey and a structured questionnaire for the household survey. Using STATA 14.0 software, mixed effect modeling was employed to control the effect of clustering and potential confounders.

Results

The proportion of fully immunized children was 58%. Coverages of measles (at least one dose) and penta3 immunization (received all 3 doses of DPT-HepB-Hib vaccine) were 86%, and 85% respectively. About 27% of mothers had missed their child immunization card mainly due to misplacing or lost. Except ‘source document completeness’ (85%) and ‘use of data for planning and target setting’ (84%), other data quality and use indicators like ‘data accuracy’ (63%), ‘data use for performance review and evidence-based decision making’ (50%), and ‘data use to produce analytical reports’ (31%) show low performance. The odds of fully immunized children is 37% lower in Muslims compared with Orthodox Christians (AOR, 0.63; 95%CI: 0.46, 0.88), higher by 42% with father’s secondary education compared with no education (AOR, 1.42; 95%CI: 1.05, 1.92), and highest wealth quintile compared with lowest quintile (AOR, 2.49; 95%CI: 1.54, 4.03). For each additional score of HIS infrastructure availability, the odds of fully immunized children increased by 22% (AOR:1.22; 95% CI: 1.03, 1.44).

Conclusions

Child immunization coverages are promising However, the current HIS performance is suboptimal. Both service user and HIS related factors are important for immunization service uptake. Documenting required information and advising mothers to keep immunization cards by health workers, and working to have functional HIS are recommended.
Nigeria bee honey-enhanced adherence, neovascularisation and epithelisation of full-thickness skin autografts on distal extremities of dogs
Authors: Kodie Dorcas Oyueley , Oyetayo Noah Segun , Aina Oluwasanmi Olayinka , Eyarefe Oghenemega David
Published: March 2022

Background

Full thickness skin grafts (FTSGs), although ideal for resurfacing large defects of the distal extremities in veterinary patients, have a high failure rate due to issues of adherence, infection and inadequate revascularisation because of its thickness and high nutritional demand. This study investigated the effect of Nigeria bee honey on FTSG take at the distal extremities of dogs. The study was conducted on 6 adult male Nigerian indigenous dogs using 3 of the 4 limbs of each dog randomly divided into 3 treatment groups: Nigerian bee honey (HON group), platelet-rich plasma (PRP group) and normal saline (CON group). Full‐thickness skin wounds (3 cm × 1.5 cm) were created on the lateral aspect of the radioulnar or metatarsal areas and dressed till adequate granulation tissues formed. Donor skins harvested from the lateral thorax of each dog were sutured to the recipient bed following application of the assigned treatment, and evaluated grossly and histologically on days 0, 4, 7, 10, 14, 17, and 21.

Results

A higher percentage (4/6 representing 66.7%) of complete graft take was observed in the HON and PRP groups as compared to 3/6 (50%) in the CON group. The HON group had a greater percentage (5/6 representing 83.3%) of adhered grafts as compared to the PRP (4/6 representing 66.7%) and CON (3/6 representing 50%) groups at day 4. There was a significant decrease (p = 0.022) in percentage necrosis between the CON and HON/PRP groups on day 10, 14 and 17. The percentage open mesh area for the HON group was significantly lesser at day 4, 7 and 10 when compared with CON (p < 0.001) and at day 4 when compared with PRP (p = 0.001). At histology, graft neovascularisation score was highest in the HON group on days 4, 14 and 21.

Conclusion

Nigeria bee honey enhanced take of meshed full-thickness skin autografts by promoting adherence to the recipient bed, enhancing fibroblast proliferation and collagen laydown, and accelerating the rate of neovascularisation suggesting promising application as an alternative modality to enhance FTSG take.
Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: mortality and its prediction model
Authors: Hozumi Hironao , Kono Masato , Hasegawa Hirotsugu , Kato Shinpei , Inoue Yusuke , Suzuki Yuzo , Karayama Masato , Furuhashi Kazuki , Enomoto Noriyuki , Fujisawa Tomoyuki , Inui Naoki , Nakamura Yutaro , Yokomura Koshi , Nakamura Hidenori , Suda Takafumi
Published: March 2022

Background

Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD), like those with idiopathic pulmonary fibrosis (IPF), might develop an unexpected acute exacerbation (AE)—a rapidly progressing and deadly respiratory decline. Although AE incidence and risk factors in RA-ILD patients are known, their post-AE clinical course remains unknown owing to the rarity of AE-RA-ILD. This multicentre retrospective study evaluated post-AE mortality and prognostic variables in AE-RA-ILD patients and created a mortality prediction model for AE-RA-ILD.

Methods

This research comprised 58 patients with AE-RA-ILD and 96 with AE-IPF (a control disease). Multivariate Cox regression analysis was performed to identify prognostic variables. A prediction model was created with recursive partitioning (decision tree).

Results

The post-AE 90-day mortality rate in the overall AE-RA-ILD group was 48.3%; percent predicted forced vital capacity within 12 months before AE onset (baseline %FVC) and PaO2/FiO2 ratio at AE onset (P/F at AE) were independent predictors of mortality. Post-AE 90-day mortality rates were 40.6% and 43.8%, respectively, in AE-RA-ILD and AE-IPF patients propensity score-matched for age, sex, baseline %FVC and P/F at AE (P = 1.0000). In AE-RA-ILD patients, C-indices of baseline %FVC and P/F at AE to predict post-AE 90-day mortality were 0.604 and 0.623, respectively. A decision tree model based on these prognostic factors classified AE-RA-ILD patients into mild, moderate and severe groups (post-AE 90-day mortality rates: 20.8%, 64.0% and 88.9%, respectively; P = 0.0002); the C-index improved to 0.775.

Conclusions

Post-AE mortality was high in AE-RA-ILD patients similar to AE-IPF patients. The discovered prognostic factors and our mortality prediction model may aid in the management of AE-RA-ILD patients.
Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma
Authors: Liu Weiwei , zheng Lu , Zhang Rongguiyi , Hou Ping , Wang Jiakun , Wu Linquan , Li Jing
Published: March 2022

Background

Although the prognostic outcomes of liver cancer (LC) cases have improved with the advancement in diagnostic technology and treatment methods, the transferability and recurrence of HCC and the 5-year and 10-year survival rates of patients have remained unsatisfactory. As a result, there is a need for more accurate diagnostic indicators that can detect liver cancer early, effectively improving the prognosis of patients. Whole-genome sequencing (WGS) revealed that circ-ZEB1 and PIK3CA are highly expressed in HCC tissues, whereas miR-199a-3p is significantly downregulated in HCC. Multiple databases search and biological analysis revealed that elevated expression of circ-ZEB1 and PIK3CA was related to poor prognosis of HCC. In vitro and in vivo studies revealed that upregulated levels of PIK3CA and circ-ZEB1 were closely associated with HCC proliferation and apoptosis. Based on these results, we believe that circ-ZEB1 and PIK3CA could be used as biomarkers to diagnose and treat patients with HCC. More importantly, circ-ZEB1 can promotes the expression of PIK3CA by silencing miR-199a-3p and affecting the progression of HCC.

Methods and results

Postoperative specimens from 56 patients with HCC who had not undergone chemotherapy from 2015 to 2018 were collected from the Department of Hepatobiliary Surgery, Second Affiliated Hospital of Nanchang University. WGS revealed differential expression of genes in HCC. Furthermore, RT-qPCR detected the expression of circ-ZEB1, miR-199a-3p, and PIK3CA in HCC tissues. MTT, EdU, and plate cloning experiments were conducted to detect cell proliferation, whereas flow cytometry analysis was used to detect apoptosis. FISH was used to co-localize circ-ZEB1 and miR-199a-3p, and biotin-coupled probe pull-down assay was used to detect the specific binding of circ-ZEB1 and miR-199a-3p. The dual-luciferase report assay detected the association of miR-199a-3p with PIK3CA. Western blotting was used to study the expression of PIK3CA protein. Circ-ZEB1 and PIK3CA were upregulated in HCC and predicted a poor prognosis. MiR-199a-3p showed low expression in HCC, whereas downregulation of circ-ZEB1 reduced HCC cell proliferation and promoted cell apoptosis. MiR-199a-3p blocked the effect of circ-ZEB1 on HCC. Circ-ZEB1 served as a biomarker of HCC. Circ-ZEB1 promoted the expression of PIK3CA by silencing miR-199a-3p to affect the progress of HCC.

Conclusions

Circ-ZEB1 promoted the expression of PIK3CA by depleting miR-199a-3p, thereby affecting HCC proliferation and apoptosis.
G6PC indicated poor prognosis in cervical cancer and promoted cervical carcinogenesis in vitro and in vivo
Authors: Zhu Kun , Deng Chunling , Du Pan , Liu Taorui , Piao Junjie , Piao Yingshi , Yang Meng , Chen Liyan
Published: March 2022

Background

The glucose-6-phosphatase catalytic subunit (G6PC) is a key enzyme that is involved in gluconeogenesis and glycogen decomposition during glycometabolism. Studies have shown that G6PC is abnormally expressed in various cancers and participates in the proliferation and metastasis of tumors. However, the role of G6PC in cervical cancer remains poorly established.

Methods

To analyze the expression of G6PC in cervical cancer tissues in patients by immunohistochemistry. Effects of G6PC deregulation on cervical cancer phenotype were determined using MTT, colony formation, transwell, and wound-healing assays. And constructed a nude mouse xenograft tumor model and CAM assay in vivo. The effect of G6PC on glycolysis in cervical cancer was also evaluated. Effect of G6PC on PI3K/AKT/mTOR pathway was detected by Western blot assay.

Results

In this study, G6PC expression was found to be upregulated in cervical cancer tissues, and this upregulated expression was associated with LN metastasis, clinical stage, recurrence, and disease-free survival and overall survival rates, indicating that G6PC could serve as a novel marker of early diagnosis in cervical cancer. G6PC promoted proliferation, invasion, epithelial mesenchymal transition (EMT) progression, and angiogenesis of cervical cancer cells. Mechanistically, G6PC activated PI3K/AKT/mTOR pathways. The PI3K/AKT pathway inhibitor, LY294002 could partially attenuate the effect.

Conclusions

G6PC plays a key role in the progression of cervical cancer, and overexpressed G6PC is closely related to patient LN metastasis, clinical stage, recurrence and shortened survival. G6PC promoted cervical cancer proliferation, invasion, migration, EMT progression, and angiogenesis, partially through activating the PI3K/AKT pathway. G6PC, as a metabolic gene, not only plays a role in metabolism, but also participates in the development of cervical cancer. Its complex metabolic and non metabolic effects may be a potential therapeutic target and worthy of further study.
Absence of the lectin-like domain of thrombomodulin reduces HSV-1 lethality of mice with increased microglia responses
Authors: Tsai Meng-Shan , Wang Li-Chiu , Wu Hua-Lin , Tzeng Shun-Fen , Conway Edward M. , Hsu Sheng-Min , Chen Shun-Hua
Published: March 2022

Background

Herpes simplex virus 1 (HSV-1) can induce fatal encephalitis. Cellular factors regulate the host immunity to affect the severity of HSV-1 encephalitis. Recent reports focus on the significance of thrombomodulin (TM), especially the domain 1, lectin-like domain (TM-LeD), which modulates the immune responses to bacterial infections and toxins and various diseases in murine models. Few studies have investigated the importance of TM-LeD in viral infections, which are also regulated by the host immunity.

Methods

In vivo studies comparing wild-type and TM-LeD knockout mice were performed to determine the role of TM-LeD on HSV-1 lethality. In vitro studies using brain microglia cultured from mice or a human microglia cell line to investigate whether and how TM-LeD affects microglia to reduce HSV-1 replication in brain neurons cultured from mice or in a human neuronal cell line.

Results

Absence of TM-LeD decreased the mortality, tissue viral loads, and brain neuron apoptosis of HSV-1-infected mice with increases in the number, proliferation, and phagocytic activity of brain microglia. Moreover, TM-LeD deficiency enhanced the phagocytic activity of brain microglia cultured from mice or of a human microglia cell line. Co-culture of mouse primary brain microglia and neurons or human microglia and neuronal cell lines revealed that TM-LeD deficiency augmented the capacity of microglia to reduce HSV-1 replication in neurons.

Conclusions

Overall, TM-LeD suppresses microglia responses to enhance HSV-1 infection.
Lifestyle changes, mental health, and health-related quality of life in children aged 6–7 years before and during the COVID-19 pandemic in South Germany
Authors: Kurz Deborah , Braig Stefanie , Genuneit Jon , Rothenbacher Dietrich
Published: March 2022

Background

The measures against the COVID-19 pandemic are challenging for children and parents, and detrimental effects on child health are suggested especially from lock-down measures and school closings.

Methods

We conducted a cross-sectional analysis using a population based longitudinal (birth-) cohort study (SPATZ study) conducted in the South of Germany. Data included all 6 or 7 year old children for whom a questionnaire was completed during first grade of school. Consequently, we were able to analyze children being in first grade before the first lockdown in Germany (≤ 15th March 2020), as well as children being in first grade during the pandemic (> 15th March 2020). We conducted descriptive statistics and estimated the associations between the two time periods, before and during the pandemic, and various outcomes of child health using multivariable adjusted linear or logistic regression modeling. The analysis was stratified by gender.

Results

Results among n = 362 children aged six or seven years showed substantially lower mean scores of health-related quality of life (difference in means: − 5.5, 95% confidence interval (CI) − 9.0, − 2.0), and higher mean scores in total emotional and behavioral difficulties (difference in means: 2.0, 95% CI 0.2, 3.8) in girls during vs. before the COVID-19 pandemic using multivariable linear regression modeling. In addition, weekly screen-time was increased in boys by 3.5 h (95% CI 0.6, 6.4). We did not find substantial differences in sleep quality, physical activity, and time spent with books, neither in boys nor in girls, however, the limited sample size has to be considered.

Conclusion

Child health (and behavior) of first grade school children is possibly impacted by the COVID-19 pandemic with adverse consequences possibly differing by gender.
Intravenous immunoglobulins improve live birth rate among women with underlying immune conditions and recurrent pregnancy loss: a systematic review and meta-analysis
Authors: Habets Denise H. J. , Pelzner Kim , Wieten Lotte , Spaanderman Marc E. A. , Villamor Eduardo , Al-Nasiry Salwan
Published: March 2022

Intravenous immunoglobulin (IVIG) is increasingly used as a treatment for recurrent pregnancy loss (RPL) despite lack of clear evidence on efficacy. Recent data suggest IVIG might be more effective in a subgroup of women with an aberrant immunological profile. Therefore, a systematic review and meta-analysis of studies on the effectiveness of IVIG treatment on pregnancy outcome among women with RPL and underlying immunological conditions (e.g., elevated NK cell percentage, elevated Th1/Th2 ratio, diagnosis with autoimmune disorders) was conducted. Eight non-randomized controlled trials, including 478 women (intervention: 284; control: 194), met eligibility criteria. Meta-analysis showed that treatment with IVIG was associated with a two-fold increase in live birth rate (RR 1.98, 95% CI 1.44–2.73, P < 0.0001). The effect of IVIG was particularly marked in the subgroup of studies including patients based on presence of elevated (> 12%) NK-cell percentage (RR 2.32, 95% CI 1.77–3.02, P < 0.0001) and when starting intervention prior to or during cycle of conception (RR 4.47, 95% CI 1.53–13.05, P = 0.006). In conclusion, treatment with IVIG may improve live birth rate in women with RPL and underlying immune conditions. However, these results should be interpreted with caution as studies are limited by low number of participants and the non-randomized design, which represent seriously biases. Future randomized controlled trials in women with RPL and underlying immune conditions are needed before using IVIG in a clinical setting.
Glycyrrhiza uralensis attenuates TNF-α-induced muscle atrophy in myoblast cells through the Nrf2 and MAFbx signaling cascades
Authors: Choi Ji-Won , Choi Sang Yoon , Lee Hyun Hee L. , Yoo Guijae , Lee Sang-Hoon , Choi In-Wook , Cho Chi Heung , Hur Jinyoung
Published: March 2022

Muscle atrophy is associated with chronic diseases, such as heart failure diabetes, and aging-related diseases. Glycyrrhiza uralensis (GU) extract is widely used in traditional medicine. However, no studies have evaluated the effects of GU on muscle atrophy. Thus, in this study, we assessed the effects of GU on prevention of muscle atrophy. GU reduced the levels of the TNF-α-induced muscle atrophy markers, muscle RING-finger protein-1(Murf-1) and muscle atrophy F-box (MAFbx), and upregulated myosin heavy chain expression (MyHC). It also reduced the phosphorylation of nuclear factor kappa B, and downregulated Smad3 proteins, which are involved in protein ubiquitination. When we examined whether GU exhibits antioxidant activities. GU suppressed TNF-α-induced muscle atrophy by increasing the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates the expression of antioxidant factors such as heme oxygenase-1 (HO-1) as well as apoptosis-related factors, such as caspase-3/7. These results suggest that GU extract is potentially an important agent in the regulation of TNF-an induced muscle atrophy.
Distinct outcomes, ABL1 mutation profile, and transcriptome features between p190 and p210 transcripts in adult Philadelphia-positive acute lymphoblastic leukemia in the TKI era
Authors: Shi Ting , Xie Mixue , Chen Li , Yuan Wei , Wang Yungui , Huang Xin , Xie Wanzhuo , Meng Haitao , Lou Yinjun , Yu Wenjuan , Tong Hongyan , Ye Xiujin , Huang Jinyan , Jin Jie , Zhu Honghu
Published: March 2022

Background

The differential signaling and outcome of patients with p190 or p210 transcripts of BCR-ABL1 have been systematically investigated in chronic myeloid leukemia rather than in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

Methods

We analyzed the outcomes and ABL1 mutation profiles in 305 consecutive adult patients with Ph+ ALL treated with chemotherapy plus tyrosine kinase inhibitors. We also studied transcriptome features in two newly diagnosed patients with p190 and p210 using single-cell RNA sequencing (scRNA-seq).

Results

P190 and p210 were found in 199 (65%) and 106 (35%) patients, respectively. Compared to patients with p190, a higher white blood cell count (p = 0.05), platelet count (p = 0.047), BCR-ABL1 transcript level (p < 0.001), and lower bone marrow blasts (p = 0.003) were found in patients with p210. Patients with p210 had fewer types of ABL1 mutations (4 vs. 16) and a higher prevalence of T315I and E225K/V mutations (91.3% vs. 68.6%; p = 0.031). Patients with p210 had a similar complete remission rate (91.0% vs. 90.1%; p = 0.805) but a lower complete molecular remission rate at 1 month (9.9% vs. 22.0%; p = 0.031) compared with p190. Patients with p210 had lower 3-year overall survival (OS) and disease-free survival (DFS) rates than those with p190 (3-year DFS: 10.4% vs. 9.2%, p = 0.069, 3-year OS: 44.3% vs. 38.2%, p = 0.018, respectively). Multivariate analysis revealed that p210 was independently associated with worse OS [HR 1.692 (95% CI 1.009–2.838), p = 0.046]. Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) was associated with a better prognosis in patients with p210 (p < 0.0001). In addition, scRNA-seq data showed distinct molecular and cellular heterogeneity between bone marrow cells of the two transcripts.

Conclusions

Ph+ ALL patients with p190 and p210 had different clinical characteristics, outcomes, ABL1 mutation profiles, and transcriptome features. Allo-HSCT could improve the outcomes of patients with p210.
Graphic representation of the degree of historical-archaeological evidence: the 3D reconstruction of the “Baker’s House”
Authors: Cáceres-Criado Irene , García-Molina Diego Francisco , Mesas-Carrascosa Francisco-Javier , Triviño-Tarradas Paula
Published: March 2022

Over the years, the methodologies used for graphic representation in archaeology have evolved. The substantial change in representation was achieved with the use of computer software. Currently, 3D sketch scanning and photogrammetry are predominating tools used in this field. A new methodology, i.e., the use of the historical-archaeological evidence level scale, has entered this discipline to show the veracity of archaeological studies, as well as that of the vestiges found. The present study is focused on the virtual reconstruction of the ‘Baker’s House’ in the archaeological site of Torreparedones (Córdoba, Spain). The main aim of this study was to show and identify the veracity of the obtained reconstruction, through the use of the historical-archaeological evidence scale and the elaboration of a typological rank. The methodology used shows the evidence level employed by experts in the creation of virtual representations. The dissemination of the proposed historical-archaeological evidence scale entails the graphical identification of the veracity of reconstructions in this type of representations, always complying with the scientific quality criteria established by the Seville Letter.
Towards a biological definition of ARDS: are treatable traits the solution?
Authors: Bos Lieuwe D. J. , Laffey John G. , Ware Lorraine B. , Heijnen Nanon F. L. , Sinha Pratik , Patel Brijesh , Jabaudon Matthieu , Bastarache Julie A. , McAuley Daniel F. , Summers Charlotte , Calfee Carolyn S. , Shankar-Hari Manu
Published: March 2022

The pathophysiology of acute respiratory distress syndrome (ARDS) includes the accumulation of protein-rich pulmonary edema in the air spaces and interstitial areas of the lung, variable degrees of epithelial injury, variable degrees of endothelial barrier disruption, transmigration of leukocytes, alongside impaired fluid and ion clearance. These pathophysiological features are different between patients contributing to substantial biological heterogeneity. In this context, it is perhaps unsurprising that a wide range of pharmacological interventions targeting these pathophysiological processes have failed to improve patient outcomes. In this manuscript, our goal is to provide a narrative summary of the potential methods to capture the underlying biological heterogeneity of ARDS and discuss how this information could inform future ARDS redefinitions. We discuss what biological tests are available to identify patients with any of the following predominant biological patterns: (1) epithelial and/or endothelial injury, (2) protein rich pulmonary edema and (3) systemic or within lung inflammatory responses.
Evaluating Diuretics in Normal Care (EVIDENCE): a feasibility report of a pilot cluster randomised trial of prescribing policy in primary care to compare the effectiveness of thiazide-type diuretics in hypertension
Authors: Flynn Angela , Rogers Amy , McConnachie Lewis , Barr Rebecca , Flynn Robert W. V. , Mackenzie Isla S. , MacDonald Thomas M. , Doney Alexander S. F.
Published: March 2022

Background

Obtaining evidence on comparative effectiveness and safety of widely prescribed drugs in a timely and cost-effective way is a major challenge for healthcare systems. Here, we describe the feasibility of the Evaluating Diuretics in Normal Care (EVIDENCE) study that compares a thiazide and thiazide-like diuretics for hypertension as an exemplar of a more general framework for efficient generation of such evidence. In 2011, the UK NICE hypertension guideline included a recommendation that thiazide-like diuretics (such as indapamide) be used in preference to thiazide diuretics (such as bendroflumethiazide) for hypertension. There is sparse evidence backing this recommendation, and bendroflumethiazide remains widely used in the UK.

Methods

Patients prescribed indapamide or bendroflumethiazide regularly for hypertension were identified in participating general practices. Allocation of a prescribing policy favouring one of these drugs was then randomly applied to the practice and, where required to comply with the policy, repeat prescriptions switched by pharmacy staff. Patients were informed of the potential switch by letter and given the opportunity to opt out. Practice adherence to the randomised policy was assessed by measuring the amount of policy drug prescribed as a proportion of total combined indapamide and bendroflumethiazide. Routinely collected hospitalisation and death data in the NHS will be used to compare cardiovascular event rates between the two policies.

Results

This pilot recruited 30 primary care practices in five Scottish National Health Service (NHS) Boards. Fifteen practices were randomised to indapamide (2682 patients) and 15 to bendroflumethiazide (3437 patients), a study population of 6119 patients. Prior to randomisation, bendroflumethiazide was prescribed to 78% of patients prescribed either of these drugs. Only 1.6% of patients opted out of the proposed medication switch.

Conclusion

The pilot and subsequent recruitment confirms the methodology is scalable within NHS Scotland for a fully powered larger study; currently, 102 GP practices (> 12,700 patients) are participating in this study. It has the potential to efficiently produce externally valid comparative effectiveness data with minimal disruption to practice staff or patients. Streamlining this pragmatic trial approach has demonstrated the feasibility of a random prescribing policy design framework that can be adapted to other therapeutic areas.

Trial registration

ISRCTN Registry, ISRCTN46635087. Registered on 11 August 2017
eHealth supported multi-months dispensing of antiretroviral therapy: a mixed-methods preference assessment in rural Lesotho
Authors: Scherrer Ramona , Tschumi Nadine , Lejone Thabo Ishmael , Kopo Mathebe , Motaboli Lipontso , Mothobi Buoang , Amstutz Alain , Deml Michael J. , Lerotholi Malebanye , Labhardt Niklaus Daniel
Published: March 2022

Background

Multi-month dispensing (MMD) of antiretroviral therapy (ART) represents one approach of differentiated service delivery (DSD) aiming to improve quality and cost-effectiveness for HIV services in resource-limited settings. However, reduction in clinic visits for people living with HIV (PLWH) should go along with out-of-clinic care tailored to PLWH`s preferences and comorbidities to maintain quality of care. eHealth supported MMD offers a potential solution.

Methods

Between October 2019 and January 2020 we assessed preferences on an eHealth supported MMD package among adult PLWH attending routine ART care at a rural clinic in Lesotho using a mixed-methods approach. Participants reported their preferences among different refill and eHealth options. They were invited to test automated text messages (SMS) informing about their viral load results, an automated tuberculosis symptoms screening call and telemedical support by an expert nurse. Telemedical service comprised a call-back option if participants required any additional support and adherence counselling for closer follow-up of participants with unsuppressed viral loads. After 6 weeks, participants were followed-up to assess perception of the chosen eHealth support using a qualitative approach.

Results

Among 112 participants (median age = 43 years; 74% female), 83/112 (75%) preferred MMD for 6–12 months (median = 9 months, IQR = [5, 12]). Neither sex, age, employment, costs and time for travel to clinic, nor the duration of taking ART correlated with the MMD preference. All 17 participants attending routine viral load measurement wished to receive the result via SMS. Fifteen (19.2%) participants requested a telemedical nurse call-back during the study period. All participants with recent unsuppressed viral load (N = 13) requested telemedical adherence counselling for closer follow-up. Among 78 participants followed-up, 76 (97%) would appreciate having the call-back option in future. Seventy-five participants (67%) received and evaluated the automated symptomatic tuberculosis screening call, overall 71 (95%) appreciated it.

Conclusions

The great majority of PLWH in this study preferred 6–12 months MMD and appreciated the additional eHealth support, including viral load results via SMS, telemedical nurse consultations and automated tuberculosis symptom screening calls. eHealth supported MMD packages appear to be a promising approach for DSD models and should be assessed for clinical endpoints and cost-effectiveness in larger studies.
Cardiotoxicity risk factors with immune checkpoint inhibitors
Authors: Brumberger Zachary L. , Branch Mary E. , Klein Max W , Seals Austin , Shapiro Michael D. , Vasu Sujethra
Published: March 2022

Background

Checkpoint-inhibitor immunotherapies have had a profound effect in the treatment of cancer by inhibiting down-regulation of T-cell response to malignancy. The cardiotoxic potential of these agents was first described in murine models and, more recently, in numerous clinical case reports of pericarditis, myocarditis, pericardial effusion, cardiomyopathy, and new arrhythmias. The objective of our study was to determine the frequency of and associated risk factors for cardiotoxic events in patients treated with immune checkpoint inhibitors.

Methods

Medical records of patients who underwent immunotherapy with durvalumab, ipilimumab, nivolumab, and pembrolizumab at Wake Forest Baptist Health were reviewed. We collected retrospective data regarding sex, cancer type, age, and cardiovascular disease risk factors and medications. We aimed to identify new diagnoses of heart failure, atrial fibrillation, ventricular fibrillation/tachycardia, myocarditis, and pericarditis after therapy onset. To assess the relationship between CVD risk factors and the number of cardiac events, a multivariate model was applied using generalized linear regression. Incidence rate ratios were calculated for every covariate along with the adjusted P-value. We applied a multivariate model using logistic regression to assess the relationship between CVD risk factors and mortality. Odds ratios were calculated for every covariate along with the adjusted P-value. Adjusted P-values were calculated using multivariable regression adjusting for other covariates.

Results

Review of 538 medical records revealed the following events: 3 ventricular fibrillation/tachycardia, 12 pericarditis, 11 atrial fibrillation with rapid ventricular rate, 0 myocarditis, 8 heart failure. Significant risk factors included female gender, African American race, and tobacco use with IRR 3.34 (95% CI 1.421, 7.849; P = 0.006), IRR 3.39 (95% CI 1.141, 10.055; P = 0.028), and IRR 4.21 (95% CI 1.289, 13.763; P = 0.017) respectively.

Conclusions

Our study revealed 34 significant events, most frequent being pericarditis (2.2%) and atrial fibrillation (2.0%) with strongest risk factors being female gender, African American race, and tobacco use. Patients who meet this demographic, particularly those with planned pembrolizumab treatment, may benefit from early referral to a cardio-oncologist. Further investigation is warranted on the relationship between CTLA-4 and PD-L1 expression and cardiac adverse events with ICIs, particularly for these subpopulations.
Is there any difference between the obstetric and perinatal complications of pregnancy in patients with and without repeated implantation failure in fresh and frozen-thawed embryo transfer cycles?
Authors: Dashti Saeideh , Mirzaei Maryam , Eftekhar Maryam , Mangoli Esmat
Published: March 2022

Background

Repeated implantation failure (RIF) is the main challenge in assisted reproduction; the present study aimed to compare the obstetric and perinatal outcomes between RIF and control patients who experienced a successful pregnancy after fresh embryo transfer (ET) or frozen-thawed embryo transfer (FET) cycles. Data were obtained from 1150 women experiencing embryo transfer(s), consisting of 720 fresh ET and 430 FET cycles, at the Research and Clinical Center for Infertility, Yazd, Iran. The 370 women, in total, reached chemical pregnancies and finally 321 cases in fresh ET (n=216) and FET (n=105) cycles with singleton deliveries divided into two groups of control and RIF according to the number of last implantation failures. Then, the rate of obstetric and prenatal complications was compared between two groups in fresh ET and FET cycles.

Results

The results showed a higher abortion rate in the RIF group compared to the control group in fresh and FET cycles. In the assessment of the data from the cases with singleton pregnancies in fresh and FET cycles, the results showed almost similar obstetric and perinatal complications in the patients of RIF and control groups. Although the rates of some complications like vaginal bleeding, PROM, preterm delivery, and NICU administration were higher in the RIF patients, these were not significant (P> 0.05).

Conclusion

There was some variation in the normal rates of obstetric and perinatal outcomes between RIF patients compared to control. But, it seems necessary to run studies on more patients to endorse this conclusion.
Creating a Global Community of Practice for Oncofertility
Authors: Ataman Lauren M. , Rodrigues Jhenifer K. , Marinho Ricardo M. , Caetano João P.J. , Chehin Maurício B. , Alves da Motta Eduardo L. , Serafini Paulo , Suzuki Nao , Furui Tatsuro , Takae Seido , Sugishita Yodo , Morishige Ken-Ichiro , Almeida-Santos Teresa , Melo Cláudia , Buzaglo Karen , Irwin Kate , Wallace W. Hamish , Anderson Richard A. , Mitchell Roderick T. , Telfer Evelyn E. , Adiga Satish K. , Anazodo Antoinette , Stern Catharyn , Sullivan Elizabeth , Jayasinghe Yasmin , Orme Lisa , Cohn Richard , McLachlan Rob , Deans Rebecca , Agresta Franca , Gerstl Brigitte , Ledger William L. , Robker Rebecca L. , de Meneses e Silva João M. , Melo e Silva Lígia H.F. , Lunardi Franciele O. , Lee Jung R. , Suh Chang S. , De Vos Michael , Van Moer Ellen , Stoop Dominic , Vloeberghs Veerle , Smitz Johan , Tournaye Herman , Wildt Ludwig , Winkler-Crepaz Katharina , Andersen Claus Y. , Smith Brigid M. , Smith Kristin , Woodruff Teresa K.
Published: March 2022

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.
Tailored Immunotherapy Approach With Nivolumab in Advanced Transitional Cell Carcinoma
Authors: Grimm Marc-Oliver , Schmitz-Dräger Bernd Jürgen , Zimmermann Uwe , Grün Christine Barbara , Baretton Gustavo Bruno , Schmitz Marc , Foller Susan , Leucht Katharina , Schostak Martin , Zengerling Friedemann , Schumacher Ulrike , Loidl Wolfgang , Meran Johannes
Published: March 2022

PURPOSE

Several anti–programmed cell death (ligand)-1 (PD-[L]1) immune checkpoint inhibitors are approved in advanced/metastatic urothelial carcinoma (mUC). Recently, improved activity of an anti–PD-1/anticytotoxic T-cell lymphocyte-4 (CTLA-4) combination versus anti–PD-1 monotherapy has been reported. We report a response-based approach starting treatment with nivolumab monotherapy with nivolumab/ipilimumab as immunotherapeutic boost.

METHODS

After four doses of nivolumab induction, responders continued with nivolumab maintenance therapy. Patients with stable/progressive disease received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks for 2 doses followed by nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 2 doses, if not responding to the initial boost. Responders to boosts continued with nivolumab maintenance. Between July 2017 and April 2019, 86 patients were enrolled. The median follow-up is 7.7 months. The primary end point is objective response rate (ORR) per RECIST1.1. Secondary end points include efficacy of nivolumab induction, remission rate with nivolumab/ipilimumab boosts, overall survival, and safety.

RESULTS

Of all patients, 42, 39, and five were first- (1L), second- (2L), and third-line (3L), respectively. The median age was 68 years. The ORR with nivolumab monotherapy (assessed at week 8) was 29% in 1L and 23% in 2/3L, respectively. Forty-one patients received early (week 8) and 11 received later nivolumab/ipilimumab boosts. ORRs with nivolumab with or without nivolumab/ipilimumab (best overall response) were 45% and 27% in 1L and 2/3L, respectively. In 1L, 7 of 17 patients receiving boosts at week 8 improved, compared with 2 of 24 in 2/3L.

CONCLUSION

The tailored approach of TITAN-TCC shows meaningful clinical activity supporting dual checkpoint inhibition in 1L mUC. However, starting therapy with nivolumab exclusively appears inadequate given the aggressive nature of mUC. In 2/3L, nivolumab/ipilimumab boosts with escalating ipilimumab dose did not improve efficacy outcomes versus nivolumab monotherapy. An independent 2L cohort of TITAN-TCC receiving nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 4 doses is ongoing.