bluuebunny/crossref_metadata_2025 huggingface dataset:
Awareness of HIV functional cure and willingness in participating in related clinical trials: comparison between antiretroviral naïve and experienced men who have sex with men living with HIV
Authors: Kwan Tsz Ho , Chan Chin Pok , Wong Ngai Sze , Lee Shui Shan
Published: April 2022

Background

Human immunodeficiency virus (HIV) functional cure is a novel biomedical strategy characterized by sustained viral suppression without the need for life-long medications. The attitude of people living with HIV (PLHIV) towards functional cure and clinical trials are understudied. We aimed to examine the awareness and levels of anticipation for HIV functional cure among men who have sex with men (MSM) living with HIV, and their willingness to join trials as differentiated by their antiretroviral treatment status.

Methods

MSM living with HIV with and those without treatment history were recruited from Hong Kong’s HIV specialist clinics. Self-administered questionnaires covering behavioral profile, perceived impact of HIV cure, attitude towards HIV functional cure and related clinical trials were collected. Clinical data were separately transcribed. Determinants of perceptions and attitudes were identified by logistic regression models.

Results

Of 356 MSM living with HIV recruited, less than half (42%) were aware of HIV functional cure, but they had a high level of anticipation for it. Treatment-experienced participants were more likely to be aware of HIV functional cure. Awareness was associated with continued engagement in sexual activities after HIV diagnosis and sexually transmitted infection (STI) diagnosis. Higher anticipation was observed among older MSM living with HIV but it was negatively associated with one’s awareness. Over 90% were willing to join functional cure trials, especially those who had previously been diagnosed with STI and had engaged in chemsex in the past year. Advice from healthcare professional was an important factor considered by those willing to join clinical trials. Younger, better educated MSM, and those with lower CD4 counts were more concerned about potential risk of AIDS and potential complications upon trial participation.

Conclusions

MSM living with HIV, especially those sexually active, showed positive attitude towards functional cure and willingness to join related clinical trials despite low awareness. To enhance preparedness for HIV functional cure trials, community education, updated information and appropriate medical advice would be needed. Safety is a major concern for potential enrollees in HIV functional cure trials.
Does current ovarian endometrioma increase the time for DOR patients to reach live birth in IVF?
Authors: Deng Yu , Ou Zhanhui , Yin Minna , Chen Zhiheng , Chen Shiling , Sun Ling
Published: April 2022

Background

The contents of ovarian endometrioma (OMA) such as inflammatory mediators, reactive oxygen species, and iron may disrupt normal folliculogenesis and result in subsequent oocyte apoptosis. Therefore, women with OMA have a potential risk of diminished ovarian reserve (DOR). The purpose of this study is to compare the in vitro fertilization (IVF) outcomes and efficiency between DOR patients with and without current OMA.

Methods

This retrospective case-control study included a total of 493 women with DOR (serum anti-Müllerian hormone level < 1.1 ng/mL). Ninety patients with OMA (Group A) underwent 191 IVF cycles and 403 patients without ovarian OMA (Group B) underwent 888 IVF cycles in our center between January 2014 and December 2018. Basal characteristics and IVF outcomes were compared between Group A and Group B. Time to achieve live birth were compared between patients with live birth in two groups (Group A1, 31 patients; Group B1, 132 patients).

Results

Clinical and demographic characteristics of patients were similar respectively between groups (A vs. B, A1 vs. B1). There were no statistically significant differences in implantation rate, live birth rate per OPU and per ET cycle and the cumulative live birth rate per patient and per patient with good-quality embryos between Group A and Group B (P > 0.05). Total time to achieve live birth has no statistically significant difference between Group A1 and Group B1 (P > 0.05).

Conclusion

For DOR women, presence of endometrioma did not affect the IVF outcomes. Even the time to get live birth was not prolonged by current OMA.
Phase I study of [131I] ICF01012, a targeted radionuclide therapy, in metastatic melanoma: MELRIV-1 protocol
Authors: Thivat Emilie , Rouanet Jacques , Auzeloux Philippe , Sas Nicolas , Jouberton Elodie , Levesque Sophie , Billoux Tommy , Mansard Sandrine , Molnar Ioana , Chanchou Marion , Fois Giovanna , Maigne Lydia , Chezal Jean-Michel , Miot-Noirault Elisabeth , D’Incan Michel , Durando Xavier , Cachin Florent
Published: April 2022

Background

Benzamide-based radioligands targeting melanin were first developed for imaging melanoma and then for therapeutic purpose with targeted radionuclide therapy (TRT).

[131I]ICF01012 presents a highly favorable pharmacokinetics profile in vivo for therapy. Tumour growth reduction and increase survival have been established in preclinical models of melanoma. According the these preclinical results, we initiate a first-in-human study aimed to determine the recommended dose of [131I]ICF01012 to administer for the treatment of patients with pigmented metastatic melanoma.

Methods

The MELRIV-1 trial is an open-label, multicentric, dose-escalation phase I trial. The study is divided in 2 steps, a selection part with an IV injection of low activity of [131I]ICF01012 (185 MBq at D0) to select patients who might benefit from [131I]ICF01012 TRT in therapeutic part, i.e. patient presenting at least one tumour lesion with [131I]ICF01012 uptake and an acceptable personalized dosimetry to critical organs (liver, kidney, lung and retina). According to dose escalation scheme driven by a Continual Reassessment Method (CRM) design, a single therapeutic injection of 800 MBq/m2, or 1600 MBq/m2, or 2700 MBq/m2 or 4000 MBq/m2 of [131I]ICF01012 will be administered at D11 (± 4 days). The primary endpoint is the recommended therapeutic dose of [131I]ICF01012, with DLT defined as any grade 3-4 NCI-CT toxicity during the 6 weeks following therapeutic dose. Safety, pharmacokinetic, biodistribution (using planar whole body and SPECT-CT acquisitions), sensitivity / specificity of [131I]ICF01012, and therapeutic efficacy will be assessed as secondary objectives. Patients who received therapeutic injection will be followed until 3 months after TRT. Since 6 to 18 patients are needed for the therapeutic part, up to 36 patients will be enrolled in the selection part.

Discussion

This study is a first-in-human trial evaluating the [131I]ICF01012 TRT in metastatic malignant melanomas with a diagnostic dose of the [131I]ICF01012 to select the patients who may benefit from a therapeutic dose of [131I]ICF01012, with at least one tumor lesion with [131I]ICF01012 uptake and an acceptable AD to healthy organ.

Trial registration

Clinicaltrials.gov: NCT03784625. Registered on December 24, 2018.

Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°EudraCT 2016-002444-17.
Diagnostic value of tumor markers in identifying favorable or unfavorable subsets in patients with cancer of unknown primary: a retrospective study
Authors: Takamizawa Shigemasa , Shimoi Tatsunori , Yoshida Masayuki , Tokura Momoko , Yazaki Shu , Mizoguchi Chiharu , Saito Ayumi , Kita Shosuke , Yamamoto Kasumi , Kojima Yuki , Sumiyoshi-Okuma Hitomi , Nishikawa Tadaaki , Noguchi Emi , Sudo Kazuki , Yonemori Kan
Published: April 2022

Background

Routine measurement of tumor markers is not recommended in daily clinical practice for patients with cancer of unknown primary (CUP). We evaluated the diagnostic value of tumor markers in identifying favorable or unfavorable subsets in patients with CUP.

Methods

We retrospectively reviewed the medical records of patients who were diagnosed with CUP between October 2010 and July 2015 at the National Cancer Center Hospital. The tumor markers of the patients were examined, including squamous cell carcinoma antigen, cytokeratin fraction, carcinoembryonic antigen, sialyl Lewis X, neuron-specific enolase, pro-gastrin-releasing peptide, α-fetoprotein, protein induced by vitamin K absence or antagonist II, prostate-specific antigen, soluble interleukin-2 receptor, carbohydrate antigen 19–9, cancer antigen 125, cancer antigen 15–3, NCC-ST-439 (ST439), elastase-1, human chorionic gonadotropin, and sialyl-Tn (STN).

Results

Among 199 patients with suspected CUP, 90 were diagnosed with confirmed CUP (12 in the favorable subset and 78 in the unfavorable subset). No tumor markers showed 100% sensitivity for unfavorable subsets. ST439 (p = 0.03) and STN (p = 0.049) showed 100% specificity for unfavorable subsets.

Conclusions

For patients with suspected CUP who show elevated ST439 or STN levels, the treatment strategy should be based on the premise that the patient is likely to be placed in the unfavorable subset.
Reversed scleral tunnel technique for repair of iridodialysis after blunt force trauma: a retrospective clinical study
Authors: Lin Zushun , Song Zongming , Zhao Zhenquan , Ke Zhisheng
Published: April 2022

Background

To investigate the efficacy and safety of reversed scleral tunnel technique for repairing iridodialysis after blunt force trauma.

Methods

A total of 51 eyes of 51 patients with iridodialysis undergoing surgery were included in this study. Patients were divided into 2 groups: group A (the reversed scleral tunnel technique) and group B (the control group). Before the procedure and at 1, 3, and 6 months afterward, data on the patients’ age, gender, treatments, diagnosis, mechanism of injury, best-corrected visual acuity (BCVA), intraocular pressure (IOP), degree of iridodialysis, lens status, concomitant ocular damage, number of sutures, complications, and follow-up time were collected and compared between the 2 groups.

Results

Iridodialysis was repaired and the pupil shape was restored to nearly round in all eyes. Standard phacoemulsification or lens removal was performed in all eyes. A final BCVA ≥20/60 was achieved in 13 eyes (48.1%) in Group A and 13 eyes (54.2%) in Group B. The IOP remained stable during the follow-up period in all eyes except 2 eyes (7.4%) in Group A and 3 eyes (12.5%) in Group B with angle recession. There were no statistically significant differences in BCVA and IOP between group A and group B. Intraoperatively, A significantly lower percentage of extensive subconjunctival hemorrhage occurred in Group A compared to Group B (1 eye versus 24 eyes, χ2 = 47.1, P = 0.00). Hyphema was observed in 2 eyes (7.4%) in Group A and 1 eye (4.2%) in Group B. Postoperatively, two eyes (7.4%) in Group A and 2 eyes (8.3%) in Group B developed retinal detachment. No other complications were noted during the follow-up period.

Conclusions

The reversed scleral tunnel technique is a safe and effective approach for repairing iridodialysis after blunt force trauma with few complications, favorable cosmetic and visual outcomes.
Domestic violence and associated factors during COVID-19 epidemic: an online population-based study in Iran
Authors: Bagheri Lankarani Kamran , Hemyari Camellia , Honarvar Behnam , Khaksar Elahe , Shaygani Fatemeh , Rahmanian Haghighi Mohammad Reza , Shaygani Mohammad Reza
Published: April 2022

Background

The novel coronavirus disease 2019 has severely affected communities around the world. Fear and stress of being infected, along with pressure caused by lockdown, prevention protocols, and the economic downturn, increased tension among people, which consequently led to the rise of domestic violence (DV). Therefore, this study was conducted to determine the rate of change in DV and its associated factors during the COVID-19 epidemic in Shiraz, Iran.

Methods

In this cross-sectional study, 653 individuals with the age of over 15 years from Shiraz were participated through snowball sampling and filled out an online questionnaire through the WhatsApp platform. A 51-item, self-administered and multidimensional (knowledge, attitude, and practice) questionnaire was designed and assessed 653 participants. The gathered data was analyzed using SPSS software (version 25), and variables with a p-value of less than 0.05 were considered statistically significant.

Results

In this study, 64.2% of the respondents were within the age range of 31–50 years, and 72.6% of the subjects were female. Furthermore, 73.8 and 73.0% of the individuals were married and educated for over 12 years, respectively. The DV increased by 37.5% during the quarantine period, compared to before the pandemic. The emotional type was the most common type of violence; the sexual type was the least frequent. Multivariate analysis indicated that infection with COVID-19, drug use, high level of co-living observation of anti-COVID prevention protocols, and lower level of physical activity during the quarantine period had a positive and significant association with the occurrence of DV.

Conclusion

Based on the obtained results, it is required to implement effective harm-reduction policies and measures in the community due to the increasing rate of DV during the COVID-19 epidemic.
Factors contributing to household wealth inequality in under-five deaths in low- and middle-income countries: decomposition analysis
Authors: Fagbamigbe Adeniyi Francis , Adeniji Folashayo Ikenna Peter , Morakinyo Oyewale Mayowa
Published: April 2022

Background

The burden of under-5 deaths is disproportionately high among poor households relative to economically viable ones in developing countries. Despite this, the factors driving this inequality has not been well explored. This study decomposed the contributions of the factors associated with wealth inequalities in under-5 deaths in low- and middle-income countries (LMICs).

Methods

We analysed data of 856,987 children from 66,495 neighbourhoods across 59 LMICs spanning recent Demographic and Health Surveys (2010-2018). Under-5 mortality was described as deaths among live births within 0 to 59 months of birth and it was treated as a dichotomous variable (dead or alive). The prevalence of under-five deaths was stratified using household wealth status. A Fairlie decomposition analysis was utilized to investigate the relative contribution of the factors associated with household wealth inequality in under-5 deaths at p<0.05. The WHO health equity assessment toolkit Plus was used to assess the differences (D) ratios (R), population attributable risk (PAR), and population attributable fraction (PAF) in household wealth inequalities across the countries.

Results

The proportion of children from poor households was 45%. The prevalence of under-5 deaths in all samples was 51 per 1000 children, with 60 per 1000 and 44 per 1000 among children from poor and non-poor households (p<0.001). The prevalence of under-5 deaths was higher among children from poor households than those from non-poor households in all countries except in Ethiopia, Tanzania, Zambia, Lesotho, Gambia and Sierra Leone, and in the Maldives. Thirty-four of the 59 countries showed significantly higher under-5 deaths in poor households than in non-poor households (pro-non-poor inequality) and no significant pro-poor inequality. Rural-urban contexts, maternal education, neighborhood socioeconomic status, sex of the child, toilet kinds, birth weight and preceding birth intervals, and sources of drinking water are the most significant drivers of pro-poor inequities in under-5 deaths in these countries.

Conclusions

Individual-level and neighbourhood-level factors were associated with a high prevalence of under-5 deaths among poor households in LMICs. Interventions in countries should focus on reducing the gap between the poor and the rich as well as improve the education and livelihood of disadvantaged people.
Examining the sustainability and effectiveness of co-created physical activity interventions in vocational education and training: a multimethod evaluation
Authors: Grüne Eva , Popp Johanna , Carl Johannes , Semrau Jana , Pfeifer Klaus
Published: April 2022

Background

Co-creation approaches are increasingly used in physical activity promotion to develop interventions tailored to the target group and setting. The resulting complexity of such interventions raises challenges in evaluation. Accordingly, little is known about the effectiveness of co-created interventions and the underlying processes that impact their sustainable implementation. In this study, we attempt to fill this gap by evaluating co-created multi-component physical activity interventions in vocational education and training in nursing care and automotive mechatronics regarding (1) their sustainable implementation at the institutional level and (2) the effectiveness of single intervention components at the individual level.

Methods

Following a multimethod design, we conducted a questionnaire survey (n = 7) and semi-structured interviews (n = 4) to evaluate the sustainability of the interventions. Quantitative data were analyzed descriptively, and qualitative data were analyzed using qualitative content analysis. To examine the interventions’ effectiveness, we conducted two non-randomized controlled trials (n = 111). Analysis of variance was used to examine differences between groups.

Results

At the institutional level, long-term implementation of single intervention components in nursing care was observed; in contrast, long-term implementation in automotive mechatronics was not observed. In this context, various factors at the outer contextual (e.g., COVID-19 pandemic), inner contextual (e.g., health-promoting leadership), intervention (e.g., acceptance), and personal levels (e.g., champion) influenced sustainability. At the individual level, no significant intervention effects were found for changes in physical activity behavior and physical activity-related health competence.

Conclusion

The role of co-creation on the effectiveness and sustainability of physical activity promotion in vocational education and training cannot be answered conclusively. Only in the nursing care sector, a co-creation approach appeared promising for long-term intervention implementation. Sustainable implementation depends on various influencing factors that should be considered from the outset. Demonstrating effectiveness at the individual level was challenging. To conclusively clarify both the role and impact of co-creation, methodologically complex and elaborate evaluation designs will be required in future research projects.

Trial registration

This study was retrospectively registered at clinicaltrials.gov on 24/08/2021 (NCT05018559).
Association between maternal exposure to indoor air pollution and offspring congenital heart disease: a case–control study in East China
Authors: Sun Jing , Wang Jian , Yang Jing , Shi Xin , Li Shujing , Cheng Jinping , Chen Sun , Sun Kun , Wu Yurong
Published: April 2022

Background

Previous research suggested an association between maternal exposure to ambient air pollutants and the risk of congenital heart disease (CHD). However, the effect of individual prenatal exposure to indoor air pollutants on CHD occurrence was not reported.

Methods

We performed a hospital-based case–control study to investigate the association between personal air pollution exposure during pregnancy and the risk of CHD in offspring. A total of 44 cases and 75 controls were included from two hospitals in East China. We investigated maternal and residential environmental characteristics using a questionnaire and obtained personal indoor air samples to assess particulate matter (PM) and volatile organic compounds (VOCs) from 22–30 gestational weeks. Formaldehyde, benzene, toluene, xylene, total volatile organic compounds (TVOCs), PM2.5, and PM10 were assessed. Logistic regression was performed to assess associations and interactions between individual indoor air pollutants and CHD after adjusting for confounders. The potential residential environmental factors affecting the risks of indoor air pollutants on CHD were also assessed.

Results

Median TVOC (0.400 vs. 0.005 mg/m3, P < 0.001) exposure levels in cases were significantly higher than controls. A logistic regression model adjusted for confounders revealed that exposure to high levels of indoor TVOCs (AOR 7.09, 95% CI 2.10–23.88) during pregnancy was associated with risks for CHD and the occurrence of some major CHD subtype in offspring. These risk effects were enhanced in pregnant women living in a newly renovated house but were mitigated by household use of smoke ventilators when cooking. We observed a positive interaction of maternal exposure to TVOCs and PM2.5 and the risk for CHD.

Conclusions

Maternal exposure to indoor VOCs and PMs may increase the risk of giving birth to foetuses with CHD.
Development and validation of an occlusal cant index
Authors: Alhuwaish Hessah A. , Almoammar Khalid A.
Published: April 2022

Background

Occlusal cant (OC) is a malocclusion trait lacking indexing or classification that describes the extent and severity of tilt in the occlusal plane. The aims of this study were to develop an occlusal cant index (OCI) based on the degree of OC detection among orthodontists and laypeople and to validate the newly developed OCI by a panel of experts using content validity.

Methods

The ability to perceive OC was assessed in 134 participants (orthodontists = 67 and laypeople = 67). A frontal photograph of a model with an ideal smile with 0° of OC was obtained and manipulated to create various degrees of OC from 1–5° at the right and left sides. A set of 11 electronic photographs was displayed to the participants. The participants were asked to report whether they detected an OC in each photograph. The collected data was used as a baseline to develop an OCI. Then, a content validation of the OCI was performed using a questionnaire provided to a panel of experts comprising ten orthodontists.

Results

The OCI was designed based on the threshold of OC detection. In both orthodontists and laypeople, the accuracy of OC detection increased as the amount of tilt increased. The threshold point of OC detection in orthodontists was at 2°, while in laypeople it was at 4°. There was a significant difference between orthodontists and laypeople in their ability to detect OC at 2–3° of tilt. The content validity index (CVI) showed excellent validity between the item-level CVI and the scale-level CVI of the OCI.

Conclusion

The OCI was developed and implemented for diagnostic, communication, and research purposes. The index showed strong evidence supporting content validity.
Regulatory emotional self-efficacy and psychological distress among medical students: multiple mediating roles of interpersonal adaptation and self-acceptance
Authors: Zhang Xuemin , Yue Heng , Sun Junfang , Liu Min , Li Cuiyun , Bao Hugejiletu
Published: April 2022

Background

Psychological distress (depression, anxiety and stress) is more common among medical students than in the general population, and is an important cause of insomnia, internet addiction, substance abuse, decreased academic performance and increased suicidality in medical students.

Methods

To examine the mechanism by which regulatory emotional self-efficacy affects medical students' psychological distress, a questionnaire of 539 medical students using an interpersonal adaptability scale, regulatory emotional self-efficacy scale, self-acceptance scale and depression-anxiety-stress scale was conducted.

Results

① Regulatory emotional self-efficacy, interpersonal adaptability and self-acceptance are positively correlated, but they are negatively correlated with psychological distress. ② The mediation model shows that interpersonal adaptation and self-acceptance are the mediation variables of the effect of regulatory emotional self-efficacy on psychological distress, and the total mediation effect value is -0.37, accounting for 86.05% of the total effect (-0.43). Specifically, the effect involves three paths: first, regulatory emotional self-efficacy indirectly affects psychological distress through interpersonal adaptation (effect value-0.24); second, regulatory emotional self-efficacy indirectly affects psychological distress through interpersonal adaptation and self-acceptance (effect value-0.08); and third, regulatory emotional self-efficacy indirectly affects psychological distress through self-acceptance (effect value -0.05).

Conclusions

Interpersonal adaptation and self-acceptance have a significant mediating effect between regulatory emotional self-efficacy and psychological distress, and the chain mediating effect of interpersonal adaptation and self-acceptance is also significant.
A pattern-discovery-based outcome predictive tool integrated with clinical data repository: design and a case study on contrast related acute kidney injury
Authors: Li Yuxi , Chan Tak-Ming , Feng Jinghan , Tao Liang , Jiang Jie , Zheng Bo , Huo Yong , Li Jianping
Published: April 2022

Background

Clinical data repositories (CDR) including electronic health record (EHR) data have great potential for outcome prediction and risk modeling. We built a prediction tool integrated with CDR based on pattern discovery and demonstrated a case study on contrast related acute kidney injury (AKI).

Methods

Patients undergoing cardiac catheterization from January 2015 to April 2017 were included. AKI was identified based on Acute Kidney Injury Network definition. Predictive model including 16 variables covered in existing AKI models was built. A visual analytics tool based on pattern discovery was trained on 70% data up to August 2016 with three interactive knowledge incorporation modes to develop 3 models: (1) pure data-driven, (2) domain knowledge, and (3) clinician-interactive, which were tested and compared on 30% consecutive cases dated afterwards.

Results

Among 2560 patients in the final dataset, 189 (7.3%) had AKI. We measured 4 existing models, whose areas under curves (AUCs) of receiver operating characteristics curve for the test dataset were 0.70 (Mehran's), 0.72 (Chen's), 0.67 (Gao's) and 0.62 (AGEF), respectively. A pure data-driven machine learning method achieves AUC of 0.72 (Easy Ensemble). The AUCs of our 3 models are 0.77, 0.80, 0.82, respectively, with the last being top where physician knowledge is incorporated.

Conclusions

We developed a novel pattern-discovery-based outcome prediction tool integrated with CDR and purely using EHR data. On the case of predicting contrast related AKI, the tool showed user-friendliness by physicians, and demonstrated a competitive performance in comparison with the state-of-the-art models.
Allergens sensitization among children with allergic diseases in Shanghai, China: age and sex difference
Authors: Ying Xiaolan , Qi Xinyi , Yin Yong , Wang Hongmei , Zhang Hao , Jiang Haohua , Yang Lin , Wu Jinhong
Published: April 2022

Background

The distribution of allergens has geographic characteristics. Local epidemiological data provides evidence-based strategies for the prevention and management of allergic diseases. Age and sex differences may exist in the prevalence of sensitivity to various allergens. We investigated the distribution of common allergens in allergic children in Shanghai, southeastern China.

Methods

39,926 children 1 month to 18 years of age diagnosed with allergic diseases were tested for the presence of serum-specific Immunoglobulins E (sIgE) to 17 allergens common to this region, using a reversed enzyme allergosorbent test.

Results

25,757 (64.5%) of the subjects showed elevated sIgE to at least one of the tested allergens. House mite and dust mite were the most common aeroallergens, while egg and milk were the most common food allergens. The most common aeroallergens and food allergens were similar among each allergic disease. By age-group analysis, the positive rates of aeroallergens were higher at older age. Several peaks of sensitization to food allergens were observed in children between 1 and 3 years of age for eggs, milk, nut, crab and shrimp. In addition, the sensitization to beef and mango was highest in children 3–6 years of age. The rate of positive sIgE detection was higher in males than females for all the tested allergens except cockroach, trees and beef. Considering the interplay between sex and ages and other related components (including season, monthly temperature, humidity, air quality index, test rate of patients), the sIgE positive rates of the main aeroallergens increased with age, while the main food allergens decreased; males are more sensitive to several aeroallergens (including dust mite, house mite, cat epithelium, dog epithelium and mulberry).

Conclusions

House mite, dust mite, milk, and egg are major allergens in Shanghai. Children at younger age are more sensitive to food allergens, while increasing overall prevalence of sensitization can be found with increasing age. Boys have higher positive rates of sIgE responses than girls. Knowledge of the prevalence of allergen sensitization in different age groups and sex may help facilitate diagnosis and intervention efforts to mitigate the impact of allergic diseases in this large geographical region. This approach may be extrapolated to other regions.
Endoplasmic reticulum stress downregulates PGC-1α in skeletal muscle through ATF4 and an mTOR-mediated reduction of CRTC2
Authors: Montori-Grau Marta , Aguilar-Recarte David , Zarei Mohammad , Pizarro-Delgado Javier , Palomer Xavier , Vázquez-Carrera Manuel
Published: April 2022

Background

Peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) downregulation in skeletal muscle contributes to insulin resistance and type 2 diabetes mellitus. Here, we examined the effects of endoplasmic reticulum (ER) stress on PGC-1α levels in muscle and the potential mechanisms involved.

Methods

The human skeletal muscle cell line LHCN-M2 and mice exposed to different inducers of ER stress were used.

Results

Palmitate- or tunicamycin-induced ER stress resulted in PGC-1α downregulation and enhanced expression of activating transcription factor 4 (ATF4) in human myotubes and mouse skeletal muscle. Overexpression of ATF4 decreased basal PCG-1α expression, whereas ATF4 knockdown abrogated the reduction of PCG-1α caused by tunicamycin in myotubes. ER stress induction also activated mammalian target of rapamycin (mTOR) in myotubes and reduced the nuclear levels of cAMP response element-binding protein (CREB)-regulated transcription co-activator 2 (CRTC2), a positive modulator of PGC-1α transcription. The mTOR inhibitor torin 1 restored PCG-1α and CRTC2 protein levels. Moreover, siRNA against S6 kinase, an mTORC1 downstream target, prevented the reduction in the expression of CRTC2 and PGC-1α caused by the ER stressor tunicamycin.

Conclusions

Collectively, these findings demonstrate that ATF4 and the mTOR-CRTC2 axis regulates PGC-1α transcription under ER stress conditions in skeletal muscle, suggesting that its inhibition might be a therapeutic target for insulin resistant states.
The effect of unemployment and post-natal care on the exclusive breast-feeding practice of women in Ethiopia: a systematic review and meta-analysis
Authors: Habte Mekdes Hailegebreal , Seid Seada Jemal , Alemu Ayinalem , Hailemariam Hanna Abera , Wudneh Birhanu Asrat , Kasa Rahel Nega , Bitew Zebenay Workneh
Published: April 2022

Background

Promoting exclusive breastfeeding (EBF) is a major child survival strategy in developing countries like Ethiopia. Studies in EBF are found in a fragmented and inconclusive way in Ethiopia. Therefore, the aim of this study was to examine evidences on the effect of post natal care counseling and maternal employment status on exclusive breastfeeding practice of women in Ethiopia.

Methods

A systematic literature search was conducted from PubMed (contains MEDLINE), CINAHL (EBSCO), Global Health, Food Science and Technology Abstracts (FSTA) (EBSCO) and Grey literature sources such as Google and Google scholar. All primary studies on the effects of employment status and/or post-natal care utilization on EBF practices of women in Ethiopia were included. Data analyses were performed using STATA software. Forest plot, I2 test and the Cochrane Q statistics were used to detect heterogeneity among studies. Heterogeneity was considered significant when the I2 value was ≥ 50%, with p-value < 0.05. Publication bias was checked by looking the asymmetry of funnel and confirmed by Egger’s regression test at a 5% significant level. The pooled odds ratio (POR) with 95% confidence interval (CI) was used to report the measures of associations.

Result

A total of 622 studies were identified in the initial search of which 42 articles were included this systematic review and meta-analysis. A meta-analysis of 24 studies indicated that maternal employment status was significantly associated (POR = 0.51, 95% CI 0.16, 0.86) EBF practice in that employed mother were less likely to practice to practice EBF. Post-natal care service utilization significantly increases (POR = 1.76, 95% CI 1.32, 2.34) the EBF practice in Ethiopia and it was computed using 25 eligible articles. Besides, the pooled estimates of EBF practice was found to be 62.58% (95% CI 56.98, 68.19, I2 = 96.4%, p < 0.001).

Conclusion

This review found that post-natal care service utilization and maternal employment status has a significant effect on EBF practice. The findings from this review may be used to inform for better supportive and promotive strategies for EBF practice in Ethiopia.
Three-dimensional alignment of the upper extremity in the standing neutral position in healthy subjects
Authors: Yoshida Yuki , Matsumura Noboru , Yamada Yoshitake , Hiraga Satoshi , Ishii Kazunori , Oki Satoshi , Yokoyama Yoichi , Yamada Minoru , Nakamura Masaya , Nagura Takeo , Jinzaki Masahiro
Published: April 2022

Background

Though alignment of the spine and lower extremities in the standing neutral position has been evaluated, a few studies evaluating the alignment of the upper extremities have also been made. This study assessed the normal alignment of the upper extremities in the standing neutral position and clarified the three-dimensional angular rotations of the upper extremity joints.

Methods

Computed tomography (CT) images of 158 upper extremities from 79 healthy volunteers were prospectively acquired in the standing neutral position using an upright CT scanner. Three-dimensional coordinate systems of the thorax, scapula, humerus, and forearm were designated, and three-dimensional angular rotations of the scapulothoracic, glenohumeral, and elbow joints were calculated.

Results

The median angle of the scapulothoracic joint was 9.2° (interquartile range [IQR], 5.2°–12.5°) of upward rotation, 29.0° (IQR, 24.9°–33.3°) of internal rotation, and 7.9° (IQR, 4.3°–11.8°) of anterior tilt. The median angle of the glenohumeral joint was 4.5° (IQR, 0.9°–7.8°) of abduction, 9.0° (IQR, 2.2°–19.0°) of internal rotation, and 0.3° (IQR, − 2.6°–3.1°) of extension. The median angle of the elbow joint was 9.8° (IQR, 6.9°–12.4°) of valgus, 90.2° (IQR, 79.6°–99.4°) of pronation, and 15.5° (IQR, 13.2°–18.1°) of flexion. Correlations in angular rotation values were found between the right and left upper extremities and between joints.

Conclusions

This study clarified the three-dimensional angular rotation of upper extremity joints in the standing neutral position using an upright CT scanner. Our results may provide important insights for the functional evaluation of upper extremity alignment.
Transformation of lymphoid interstitial pneumonia (LIP) into malignant lymphoma in patients with Sjogren's syndrome: a case report and literature review
Authors: Zhu Chengyuan , Hu Jibo , Wu Jun , Cheng Lingxiao
Published: April 2022

Background

Lymphoid interstitial pneumonia (LIP) is a very rare disease and its malignant transformation is even more rare. LIP is easily misdiagnosed by clinicians and radiologists.

Case presentation

The medical record of a 64-year-old female with Sjogren's syndrome was reviewed. The clinical and pathological data along with chest CT images were obtained. The literature related to the transformation was reviewed. There were no specific clinical manifestations of LIP and its transformation into malignant lymphoma in the patient. The chest CT mainly displayed multiple cystic foci, with multiple nodules and ground-glass shadows in both lungs.

Conclusions

Malignant transformation to lymphoma is suspected with findings of large nodules (> 11 mm) or their sizes doubly increased, pleural effusion and alveolar consolidation.
Compassion fatigue in a health care worker treating COVID-19 patients: a case report
Authors: Nishihara Tomoe , Ohashi Ayako , Nakashima Yuko , Yamashita Takafumi , Hiyama Kazutoshi , Kuroiwa Mika
Published: April 2022

Background

Doctors treating COVID-19 are under extreme stress. It was reported that healthcare workers providing palliative care could present elevated levels of compassion fatigue. We herein report a case if the attending doctor of severe COVID-19 cases who felt extreme psychological difficulty and suffered from compassion fatigue.

Case presentation

A 29-year-old female doctor presented with anxiety and insomnia. Her stress from overwork was exacerbated during the treatment of two related COVID-19 patients, a 47-year-old man with COVID-19 and his 76-year-old mother, who suffered acute stress disorder after the death of her son. The mother first refused treatment, but with psychiatric intervention she was able to recover and be discharged. In the course of these cases of COVID-19, their attending physician felt psychological distress and presented with insomnia and anticipatory anxiety due to the poor prognosis of the mother. After being presented with a systematic approach to improve her work situation by the hospital executive staff and undergoing psychotherapy for compassion fatigue, she recovered and was able to return to work.

Conclusions

We report a physician in charge of severe cases of COVID-19, who suffered an adverse impact on her mental health. Excessively empathic engagement in the care of patients who do not survive and their relatives provides high risk for compassion fatigue. The stress-related distress of HCWs should be more widely recognized in order to improve support systems for them.
Reactive oxygen species-inducing titanium peroxide nanoparticles as promising radiosensitizers for eliminating pancreatic cancer stem cells
Authors: Salah Mohammed , Akasaka Hiroaki , Shimizu Yasuyuki , Morita Kenta , Nishimura Yuya , Kubota Hikaru , Kawaguchi Hiroki , Sogawa Tomomi , Mukumoto Naritoshi , Ogino Chiaki , Sasaki Ryohei
Published: April 2022

Background

Despite recent advances in radiotherapy, radioresistance in patients with pancreatic cancer remains a crucial dilemma for clinical treatment. Cancer stem cells (CSCs) represent a major factor in radioresistance. Developing a potent radiosensitizer may be a novel candidate for the eradication of pancreatic CSCs.

Methods

CSCs were isolated from MIA PaCa-2 and PANC1 human pancreatic cancer cell lines. Titanium peroxide nanoparticles (TiOxNPs) were synthesized from titanium dioxide nanoparticles (TiO2NPs) and utilized as radiosensitizers when added one hour prior to radiation exposure. The antitumor activity of this novel therapeutic strategy was evaluated against well-established pancreatic CSCs model both in vitro and in vivo.

Results

It is shown that TiOxNPs combined with ionizing radiation exhibit anti-cancer effects on radioresistant CSCs both in vitro and in vivo. TiOxNPs exhibited a synergistic effect with radiation on pancreatic CSC-enriched spheres by downregulating self-renewal regulatory factors and CSC surface markers. Moreover, combined treatment suppressed epithelial-mesenchymal transition, migration, and invasion properties in primary and aggressive pancreatic cancer cells by reducing the expression of proteins relevant to these processes. Notably, radiosensitizing TiOxNPs suppressed the growth of pancreatic xenografts following primary or dissociating sphere MIA PaCa-2 cell implantation. It is inferred that synergy is formed by generating intolerable levels of reactive oxygen species (ROS) and inactivating the AKT signaling pathway.

Conclusions

Our data suggested the use of TiOxNPs in combination with radiation may be considered an attractive therapeutic strategy to eliminate pancreatic CSCs.
Rapid chest compression effects on intracranial pressure in patients with acute cerebral injury
Authors: Rodrigues-Gomes Ricardo Miguel , Martí Joan-Daniel , Rolán Rosa Martínez , Gelabert-González Miguel
Published: April 2022

Background

Patients with acute brain injury often require invasive mechanical ventilation, increasing the risk of developing complications such as respiratory secretions retention. Rapid chest compression is a manual chest physiotherapy technique that aims to improve clearance of secretions in these patients. However, the rapid chest compression technique has been suggested to be associated with increased intracranial pressure in patients with acute brain injury. The aim of this work is to elucidate the effects of the technique on intracranial pressure in mechanically ventilated patients with acute brain injury. Furthermore, the effects of the technique in different volumes and flows recorded by the ventilator and the relationship between the pressure applied in the intervention group and the different variables will also be studied.

Methods

Randomized clinical trial, double-blinded. Patients with acute brain injury on invasive mechanical ventilation > 48 h will be included and randomized in two groups. In the control group, a technique of passive hallux mobilization will be applied, and in the intervention group, it will be performed using the rapid chest compression technique. Intracranial pressure (main variable) will be collected with an intracranial pressure monitoring system placed at the lateral ventricles (Integra Camino).

Discussion

The safety of chest physiotherapy techniques in patients at risk of intracranial hyperpressure is still uncertain. The aim of this study is to identify if the rapid manual chest compression technique is safe in ventilated patients with acute brain injury.

Trial registration

NCT03609866. Registered on 08/01/2018.
Efficacy and safety of Mydriatic Microdrops for Retinopathy Of Prematurity Screening (MyMiROPS): study protocol for a non-inferiority crossover randomized controlled trial
Authors: Seliniotaki Aikaterini K. , Haidich Anna-Bettina , Lithoxopoulou Maria , Gika Helen , Boutou Eleftheria , Virgiliou Christina , Nikolaidou Martha , Dokoumetzidis Aristides , Raikos Nikolaos , Diamanti Elisavet , Ziakas Nikolaos , Mataftsi Asimina
Published: April 2022

Background

Retinopathy of prematurity (ROP) eye examination screening presupposes adequate mydriasis for an informative fundoscopy of preterm infants at risk, on a weekly basis. Systemic absorption of the instilled mydriatic regimens has been associated with various adverse events in this fragile population. This report aims to present the fully developed protocol of a full-scale trial for testing the hypothesis that the reduced mydriatic drop volume achieves adequate mydriasis while minimizing systemic adverse events.

Methods

A non-inferiority crossover randomized controlled trial will be performed to study the efficacy and safety of combined phenylephrine 1.67% and tropicamide 0.33% microdrops compared with standard drops in a total of 93 preterm infants requiring ROP screening. Primary outcome will be the pupil diameter at 45 (T45) min after instillation. Pupil diameter at T90 and T120 will constitute secondary efficacy endpoints. Mixed-effects linear regression models will be developed, and the 95% confidence interval approach will be used for assessing non-inferiority. Whole blood samples will be analyzed using hydrophilic liquid chromatography–tandem mass spectrometry method (HILIC–MS/MS), for gathering pharmacokinetic (PK) data on the instilled phenylephrine, at nine specific time points within 3 h from mydriasis. Pooled PK data will be used due to ethical restrictions on having a full PK profile per infant. Heart rate, oxygen saturation, blood pressure measurements, and 48-h adverse events will also be recorded.

Discussion

This protocol is designed for a study powered to assess non-inferiority of microdrops compared with standard dilating drops. If our hypothesis is confirmed, microdrops may become a useful tool in ROP screening.

Trial registration

ClinicalTrials.govNCT05043077. Registered on 2 September 2021
Variation in targetable genomic alterations in non-small cell lung cancer by genetic ancestry, sex, smoking history, and histology
Authors: Adib Elio , Nassar Amin H. , Abou Alaiwi Sarah , Groha Stefan , Akl Elie W. , Sholl Lynette M. , Michael Kesi S. , Awad Mark M. , Jӓnne Pasi A. , Gusev Alexander , Kwiatkowski David J.
Published: April 2022

Background

Genomic alterations in 8 genes are now the targets of FDA-approved therapeutics in non-small cell lung cancer (NSCLC), but their distribution according to genetic ancestry, sex, histology, and smoking is not well established.

Methods

Using multi-institutional genetic testing data from GENIE, we characterize the distribution of targetable genomic alterations in 8 genes among 8675 patients with NSCLC (discovery cohort: DFCI, N = 3115; validation cohort: Duke, Memorial Sloan Kettering Cancer Center, Vanderbilt, N = 5560). For the discovery cohort, we impute genetic ancestry from tumor-only sequencing and identify differences in the frequency of targetable alterations across ancestral groups, smoking pack-years, and histologic subtypes.

Results

We identified variation in the prevalence of KRASG12C, sensitizing EGFR mutations, MET alterations, ALK, and ROS1 fusions according to the number of smoking pack-years. A novel method for computing continental (African, Asian, European) and Ashkenazi Jewish ancestries from panel sequencing enables quantitative analysis of the correlation between ancestry and mutation rates. This analysis identifies a correlation between Asian ancestry and EGFR mutations and an anti-correlation between Asian ancestry and KRASG12C mutation. It uncovers 2.7-fold enrichment for MET exon 14 skipping mutations and amplifications in patients of Ashkenazi Jewish ancestry. Among never/light smokers, targetable alterations in LUAD are significantly enriched in those with Asian (80%) versus African (49%) and European (55%) ancestry. Finally, we show that 5% of patients with squamous cell carcinoma (LUSC) and 17% of patients with large cell carcinoma (LCLC) harbor targetable alterations.

Conclusions

Among patients with NSCLC, there was significant variability in the prevalence of targetable genomic alterations according to genetic ancestry, histology, and smoking. Patients with LUSC and LCLC have 5% rates of targetable alterations supporting consideration for sequencing in those subtypes.