bluuebunny/crossref_metadata_2025 huggingface dataset:
Life expectancy and healthy life expectancy of Korean registered disabled by disability type in 2014–2018: Korea National Rehabilitation Center database
Authors: Jang Hyuna , Choi Kyung-Hwa , Kim Jung-Ae , Choi Yong-jun
Published: September 2023

Background

Conducting a distinct comparison between the life expectancy (LE) and healthy life expectancy (HALE) of people with disabilities (PWDs) and the general population is necessary due to the various environmental and health conditions they encounter. Therefore, this study aimed to develop the life table for PWDs and calculate those of LE and HALE based on sex, severity, and disability types among the registered Korean PWDs.

Methods

We used aggregated data of registered PWDs from the Korea National Rehabilitation Center database between 2014 and 2018. Overall, 345,595 deaths were included among 12,627,428 registered PWDs. First, we calculated the LE for total PWDs and non-disabled people using a standard life table, extending the old age mortality among nine models. Subsequently, we calculated the LE for each type of disability using the relationship between the mortality of total PWDs and those of each type of disability. Finally, HALE was calculated using the Sullivan method for three types as follows: disability-free and perceived health (PH) using the National Survey, and hospitalized for  ≥ 7 days using the Korea National Health Insurance System (NHIS) database.

Results

The calculated LE/HALE–NHIS (years) at registration in males and females were 81.32/73.32 and 87.38/75.58, 68.54/58.98 and 71.43/59.24, 73.87/65.43 and 78.25/67.51, and 61.53/50.48 and 62.41/49.72 years among non-disabled, total PWDs, mild disabled, and severe disabled, respectively. LE/HALE-NHIS was lowest and highest in respiratory dysfunction and hearing disabilities, respectively.

Conclusions

Males with disabilities had shorter LE and HALE at registration than females, except for those with severe disabilities, and there were variabilities in the LE based on the disability types.
A cytodiagnosis of adenoid cystic carcinoma of the tracheobronchial tree through a systematic clinical case comparison and analysis
Authors: Zhou Bing , Duan Ting , Liu Xianwei , Peng Lizi
Published: September 2023

Background

Primary adenoid cystic carcinoma (AdCC) of the tracheobronchial tree is very rare with a high risk for recurrence and metastasis. The diagnosis of AdCC by histologic and immunohistochemical means has been well studied clinically. However, the identification of AdCC by cytologic features remains elusive due to the atypical features the cancer presents. This study aimed to describe the cytologic features of AdCC by using bronchial brushing, which could aid in distinguishing AdCC from other pulmonary carcinomas.

Methods

The cytopathological features of bronchial brushing smears collected from seven cases were histologically diagnosed as AdCC. The defined cytologic features, which could potentially be diagnostic, were systemically analyzed.

Results

Four out of the seven cytologic cases were inconcordance with the histologic diagnosis and cytologically classified as positive for malignant cells, small cell carcinoma, or atypical cells. Three cases showed a characteristic adenoid structure and magenta stroma forming globule, which was distinguished from the four cases. Cytologically, the above mentioned three cases were uniform with relatively small bland nuclei and little cytoplasm. In this study, only one case showed atypical polygonal medium-sized cells with conspicuous nucleoli.

Conclusions

Unlike fine-needle aspiration cytology, magenta stroma globules might offer an alternate clue for cytodiagnosis of AdCC clinically. Bronchial brushings cytology was more present in bland uniform cells with high nuclear to cytoplasmic ratios and background mucoid substance. More cases should be collected and confirmed using histopathology with careful film reading to reduce the rate of misdiagnosis.
Effects of three spontaneous ventilation modes on respiratory drive and muscle effort in COVID-19 pneumonia patients
Authors: Simón José Manuel Serrano , Montosa Carolina Joya , Carmona Juan Francisco Martínez , Amaya Manuel Jesús Delgado , Castro Javier Luna , Carmona Ashlen Rodríguez , Pérez José Castaño , Delgado Marina Rodríguez , Centeno Guillermo Besso , Lozano José Antonio Benítez
Published: September 2023

Background

High drive and high effort during spontaneous breathing can generate patient self-inflicted lung injury (P-SILI) due to uncontrolled high transpulmonary and transvascular pressures, with deterioration of respiratory failure. P-SILI has been demonstrated in experimental studies and supported in recent computational models. Different treatment strategies have been proposed according to the phenotype of elastance of the respiratory system (Ers) for patients with COVID-19. This study aimed to investigate the effect of three spontaneous ventilation modes on respiratory drive and muscle effort in clinical practice and their relationship with different phenotypes. This was achieved by obtaining the following respiratory signals: airway pressure (Paw), flow (V´) and volume (V) and calculating muscle pressure (Pmus).

Methods

A physiologic observational study of a series of cases in a university medical-surgical ICU involving 11 mechanically ventilated patients with COVID-19 pneumonia at the initiation of spontaneous breathing was conducted. Three spontaneous ventilation modes were evaluated in each of the patients: pressure support ventilation (PSV), airway pressure release ventilation (APRV), and BiLevel positive airway pressure ventilation (BIPAP). Pmus was calculated through the equation of motion. For this purpose, we acquired the signals of Paw, V´ and V directly from the data transmission protocol of the ventilator (Dräger). The main physiological measurements were calculation of the respiratory drive (P0.1), muscle effort through the ΔPmus, pressure‒time product (PTP/min) and work of breathing of the patient in joules multiplied by respiratory frequency (WOBp, J/min).

Results

Ten mechanically ventilated patients with COVID-19 pneumonia at the initiation of spontaneous breathing were evaluated. Our results showed similar high drive and muscle effort in each of the spontaneous ventilatory modes tested, without significant differences between them: median (IQR): P0.1 6.28 (4.92–7.44) cm H2O, ∆Pmus 13.48 (11.09–17.81) cm H2O, PTP 166.29 (124.02–253.33) cm H2O*sec/min, and WOBp 12.76 (7.46–18.04) J/min. High drive and effort were found in patients even with low Ers. There was a significant relationship between respiratory drive and WOBp and Ers, though the coefficient of variation widely varied.

Conclusions

In our study, none of the spontaneous ventilatory methods tested succeeded in reducing high respiratory drive or muscle effort, regardless of the Ers, with subsequent risk of P-SILI.
A participatory ergonomics intervention to re-design work and improve the musculoskeletal health of paramedics: protocol for a cluster randomised controlled trial
Authors: Davies Karen , Weale Victoria , Oakman Jodi
Published: September 2023

Background

In this paper, we present the protocol for a cluster randomised controlled trial to evaluate the effectiveness and implementation of a participative risk management intervention to address work-related musculoskeletal disorders (WMSDs). The aims of the study include to evaluate the implementation process and the impact of the intervention on work related musculoskeletal pain and discomfort and exposure to physical and psychosocial hazards in paramedics over a 12-month period.

Methods

The intervention in this study is to implement A Participative Hazard Identification and Risk Management (APHIRM) toolkit in an ambulance service. Eighteen work groups containing eligible participants (registered paramedics) will be randomised into the intervention or wait-list control arm in one of three rolling recruitment periods. The APHIRM toolkit survey will be offered at baseline and 12 months later, to all current eligible participants in each work group allocated to the trial. The intervention work groups will receive the remainder of the APHIRM toolkit procedures. Identifying data about individual participants will not be collected in the survey, to protect participant privacy and encourage participation. Changes in primary (musculoskeletal pain and discomfort) and secondary (exposure to physical and psychosocial hazards at work) outcomes measured in the survey will be analysed comparing the baseline and follow up response of the cluster. A process evaluation is included to analyse the implementation and associated barriers or facilitators.

Discussion

This study is important in providing a comprehensive approach which focusses on both physical and psychosocial hazards using worker participation, to address WMSDs, a well-known and significant problem for ambulance services. The effectiveness of the intervention in work groups will be rigorously evaluated. If significant positive results are observed, the intervention may be adopted in ambulance services, both nationally and internationally.

Trial registration

ISRCTN77150219. Registered 21 November 2021.
An extraoral approach to intraoral cooling–a feasibility study in non-cancer patients
Authors: Najaf L. , Borgvall N. , Vennman K. , Walladbegi J.
Published: September 2023

Background

Cryotherapy, using ice chips (IC) is an effective strategy to prevent chemotherapy-induced oral mucositis (OM) in selected cancer patient cohorts. However, although effective, use of IC may cause adverse reactions, e.g., nausea, numbness, and shooting pain in the teeth, which could have an adverse impact on the medical treatment. Furthermore, IC requires water of good quality to minimize risk of serious systemic infections. To eliminate these disadvantages, novel cooling devices have emerged as alternative cooling modalities. Thus, the aim was to evaluate the efficacy and tolerability profile of extraoral cooling for intraoral temperature reduction.

Subjects and Methods

This experimental pilot study was conducted at the Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. In total, six healthy volunteers were enrolled in this study. At baseline and following 30-, and 60 min of cooling with the extraoral cooling device, intraoral mucosal temperatures were measured using a thermographic camera, and a questionnaire related to tolerability was completed.

Results

Following 30-, and 60 min of cooling, the intraoral temperature decreased with 2.0 °C and 2.3 °C, respectively. Extraoral cooling was well tolerated, and all subjects endured the entire cooling session of 60 min.

Conclusion

Extraoral cooling reduces intraoral mucosal temperatures and is a well-tolerated cooling modality.
Effect of forceful suction and air disinfection machines on aerosol removal
Authors: Du Yaru , Zhao Fei , Tao Ran , Liu Bing
Published: September 2023

Backgrounds

Dental procedures involving drilling and grinding can produce a significant amount of suspended aerosol particles (PM) and bioaerosols. This study aims to analyze the size and concentration of aerosol particles generated during drilling and to investigate the effectiveness of two air exchange systems, namely forceful suction (FS) and air disinfection machines (DM), in removing PM.

Methods

For this study, 100 extracted permanent teeth were collected and divided into three groups: without suction (n = 50), suction with forceful suction (n = 25), and suction with air disinfection machines (n = 25). The removal rate of suspended aerosol particles was analyzed using particle counters and air data multimeter.

Results

When drilling and grinding were performed without vacuum, 0.75% of the aerosol particles generated were PM2.5-10, 78.25% of total suspended aerosol particles (TSP) were PM2.5, and 98.68% of TSP were PM1. The nanoanalyzer measurements revealed that the aerodynamic diameter of most aerosol particles was below 60 nm, with an average particle diameter of 52.61 nm and an average concentration of 2.6*1011 ultrafine aerosol particles. The air change per hour (ACH) was significantly lower in the air disinfection machines group compared to the forceful suction group. Additionally, the number of aerosol particles and mass concentration was significantly lower in the air disinfection machines group compared to the forceful suction group in terms of PM2.5 levels. However, the forceful suction group also reduced the mass concentration in PM10 level than the air disinfection machines group.

Conclusion

In conclusion, the air exchange system can reduce the aerosol particles generated during drilling and grinding. Comparing the two air exchange systems, it was found that the air disinfection machines group reduces the number of aerosol particles and mass concentration in PM2.5 levels, while the forceful suction group reduces the mass concentration in PM10 level.
Computational biology and in vitro studies for anticipating cancer-related molecular targets of sweet wormwood (Artemisia annua)
Authors: Dawood Hend , Celik Ismail , Ibrahim Reham S.
Published: September 2023

Background

Cancer is one of the leading causes of death worldwide. Recently, it was shown that many natural extracts have positive effects against cancer, compared with chemotherapy or recent hormonal treatments. A. annua is an annual medicinal herb used in the traditional Chinese medicine. It has also been shown to inhibit the proliferation of various cancer cell lines.

Methods

Multi-level modes of action of A. annua constituents in cancer therapy were investigated using an integrated approach of network pharmacology, molecular docking, dynamic simulations and in-vitro cytotoxicity testing on both healthy and cancer cells.

Results

Network pharmacology-based analysis showed that the hit Artemisia annua constituents related to cancer targets were 3-(2-methylpropanoyl)-4-cadinene-3,11-diol, artemisinin G, O-(2-propenal) coniferaldehyde, (2-glyceryl)-O-coniferaldehyde and arteamisinin III, whereas the main cancer allied targets were NFKB1, MAP2K1 and AR. Sixty-eight significant signaling KEGG pathways with p < 0.01 were recognized, the most enriched of which were prostate cancer, breast cancer, melanoma and pancreatic cancer. Thirty-five biological processes were mainly regulated by cancer, involving cellular response to mechanical stimulus, positive regulation of gene expression and transcription. Molecular docking analysis of the top hit compounds against the most enriched target proteins showed that 3-(2-methylpropanoyl)-4-cadinene-3,11-diol and O-(2-propenal) coniferaldehyde exhibited the most stabilized interactions. Molecular dynamics simulations were performed to explain the stability of these two compounds in their protein-ligand complexes. Finally, confirmation of the potential anticancer activity was attained by in-vitro cytotoxicity testing of the extract on human prostate (PC-3), breast (MDA-MB-231), pancreatic (PANC-1) and melanoma (A375) cancerous cell lines.

Conclusion

This study presents deeper insights into A. annua molecular mechanisms of action in cancer for the first time using an integrated approaches verifying the herb’s value.
Exploring the attitudes of general medical students toward older adult’s care in a lower middle-income country: implications for medical education
Authors: Nojomi Marzieh , Goharinezhad Salime , Saraei Rasoul , Goharinejad Saeideh , Ramezani Ghobad , Aalaa Maryam
Published: September 2023

Objective

The motivation for this study stemmed from the growing population of older adults and the increasing demand for healthcare professionals who possess the necessary skills and knowledge to provide quality care to this demographic. By exploring the attitudes, perceptions, and beliefs of medical students towards older adult care, the study aimed to identify gaps in their training and areas where improvements can be made to better equip them for this critical aspect of healthcare.

Method

This study was a qualitative thematic analysis. The participants of this research were selected from among the general medicine internship students of Iran University of Medical Sciences by purposive sampling method. In-depth individual semi-structured interviews were used to collect data. Sampling continued until data saturation. The interviews were recorded, transcribed, and analyzed using a hybrid approach of inductive and deductive thematic analysis. Using this approach, the analysis of the data became more adaptable and open-ended, free from the restrictions of pre-existing theoretical frameworks. MAXQDA 22 was used to analyze qualitative data.

Results

A total of 27 medical students were interviewed semi-structured, and audio files were transcribed immediately after the interview. In the process of reading the interviews carefully and separating the conceptual units into codes, 167 primary codes were obtained, and these codes were divided into five main categories under the title of root factors after constant comparison analysis. Five main themes are including discrimination in service delivery, a lack of inter-professional training, interpersonal communication skills, inadequate infrastructure and human resources, and enhancing attitudes towards older person care through experiential learning.

Conclusion

This study sheds light on the attitudes and perceptions of medical students toward older adult care in a lower-middle-income country. The findings reveal that there are significant gaps in their training and preparation for providing quality care to this demographic profile. The four main categories identified as root factors highlight key areas where improvements can be made in medical education. It is recommended that medical schools in low and middle-income countries consider incorporating these themes into their curricula to better equip future healthcare professionals with the necessary skills and knowledge to provide quality care to older adults.
Additional considerations before using a ctDNA-guided approach for informing adjuvant chemotherapy in colorectal cancer
Authors: Olivier Timothée , Haslam Alyson , Prasad Vinay
Published: September 2023

Background

The DYNAMIC trial investigated the use of circulating tumor DNA (ctDNA) to guide adjuvant treatment decisions in stage II colon cancer. Despite the DYNAMIC trial’s assertion that a ctDNA-guided approach could minimize the use of adjuvant treatment without compromising recurrence-free survival (RFS), we raised concerns regarding the trial’s methodology and the practical implications of its findings in a Debate article. Here, we expand upon these concerns in a response to a correspondence by the authors of the DYNAMIC trial.

Main body

We dispute the choice of a large non-inferiority margin in the DYNAMIC trial, simply because an 8.5 percentage points decrease in recurrence-free survival could result in significant harm to patients. We challenge the authors’ comparisons of the DYNAMIC trial outcomes with observational studies. Such comparison is subject to selection bias and changes over time that limit their relevance. The prognostic role of ctDNA do not automatically imply that more treatment in patients with ctDNA positivity would improve outcomes, which we highlight. In real-world settings, we anticipate a potential rise in chemotherapy use due to clinicians utilizing ctDNA alongside existing clinicopathologic factors, rather than using ctDNA as an entire replacement. Lastly, a key concern in DYNAMIC was an 350% higher use of oxaliplatin in the ctDNA arm compared with standard management (9.5% versus 2.7%, respectively), which poses a risk for long-term neuropathy.

Conclusion

We look forward improvements in patient selection in the adjuvant setting, but we maintain our reservations about the DYNAMIC trial and the real-life implementation of its results. As an alternative to exploring de-escalation strategies with large margins non-inferiority trials, we propose that superiority trials in stage II patients could be a more effective strategy.
A duplex nested RT-PCR method for monitoring porcine epidemic diarrhea virus and porcine delta-coronavirus
Authors: Li Chun Qi , Hu Li Qun , Liu Guo Ping , Wang Yan , Li Tong , Chen Shao Xian , Yang Xiao Lin , Ma Li Xin , Zeng Jian Guo
Published: September 2023

Background

Porcine epidemic diarrhea virus (PEDV) and porcine delta-coronavirus (PDCoV) are economically important pathogens that cause diarrhea in sows and acute death of newborn piglets. Moreover, the emerging PDCoV was reported to infect children. The current situation is that vaccine prevention has not met expectations, and emergency containment strategies following outbreaks cannot prevent the damages and losses already incurred. Therefore, a more sensitive detection method, that is both convenient and enables accurate and effective sequencing, that will provide early warning of PEDV and PDCoV is necessary. This will enable active, effective, and comprehensive prevention and control, which will possibly reduce disease occurrences.

Results

Duplex nested RT-PCR (dnRT-PCR) is an ideal method to achieve early warning and monitoring of PEDV and PDCoV diseases, and to additionally investigate any molecular epidemiological characteristics. In this study, two pairs of primers were designed for each virus based upon the highly conserved N protein sequences of both PEDV and PDCoV strains retrieved from the NCBI Genbank. After optimization of the reaction conditions, the dnRT-PCR assay amplified a 749-bp fragment specific to PEDV and a 344-bp fragment specific to PDCoV. Meanwhile, the specificity and sensitivity of the primers and clinical samples were tested to verify and establish this dnRT-PCR method. The limit of detection (LoD)for both PEDV and PDCoV was 10 copies/µL. The results showed that among 251 samples, 1 sample contained PEDV infection, 19 samples contained a PDCoV infection, and 8 samples were infected with both viruses, following the use of dnRT-PCR. Subsequently, the positive samples were sent for sequencing, and the sequencing results confirmed that they were all positive for the viruses detected using dnRT-PCR, and conventional RT-PCR detection was conducted again after the onset of disease. As these results were consistent with previous results, a detection method for PEDV and PDCoV using dnRT-PCR was successfully established. In conclusion, the dnRT-PCR method established in this study was able to detect both PEDV and PDCoV, concomitantly.

Conclusions

The duplex nested RT-PCR method represents a convenient, reliable, specific, sensitive and anti-interference technique for detecting PEDV and PDCoV, and can additionally be used to simultaneously determine the molecular epidemiological background.
Copy number variations (CNVs) and karyotyping analysis in males with azoospermia and oligospermia
Authors: Xin Xing , Xu Peng , Wang Nan , Jiang Yi , Zhang Jiaqiao , Li Shufang , Zhu Ying , Zhang Cong , Zhang Long , Huang Hailong , Feng Ling , Wang Shaoshuai
Published: September 2023

Background

Considering the essential roles that genetic factors play in azoospermia and oligospermia, this study aims to identify abnormal chromosomes using karyotyping and CNVs and elucidate the associated genes in patients.

Methods

A total of 1157 azoospermia and oligospermia patients were recruited, of whom, 769 and 674 underwent next-generation sequencing (NGS) to identify CNVs and routine G-band karyotyping, respectively.

Results

First, 286 patients were co-analyzed using CNV sequencing (CNV-seq) and karyotyping. Of the 725 and 432 patients with azoospermia and oligospermia, 33.8% and 48.9% had abnormal karyotypes and CNVs, respectively. In particular, 47,XXY accounted for 44.18% and 26.33% of abnormal karyotypes and CNVs, respectively, representing the most frequent genetic aberration in azoospermia and oligospermia patients. Nevertheless, big Y and small Y accounted for 7.46% and 16.67% of abnormal karyotypes, respectively. We also identified high-frequency CNVs-loci, such as Xp22.31 and 2p24.3, in azoospermia and oligospermia patients.

Conclusion

Sex chromosome and autosomal CNV loci, such as Xp22.31 and 2p24.3, as well as the associated genes, such as VCX and NACAP9, could be candidate spermatogenesis genes. The high-frequency abnormal karyotypes, CNV loci, and hot genes represent new targets for future research.
“Just another thing for me to stress off of”: Responses to unintentional fentanyl use in a community-based study of people who use opioids
Authors: Lorvick Jennifer , Hemberg Jordana L. , George Madeleine J. , Piontak Joy R. , Comfort Megan L.
Published: September 2023

The unintentional consumption of fentanyl is a serious health risk for people who use illicit drugs. In an ongoing community-based study regarding polysubstance use among people who use opioids, we found that 17 of 58 (29%) of participants who did not endorse fentanyl use in the past thirty days tested positive for fentanyl during point-of-care urinalysis (UA). This paper describes the reactions and experiences of participants who were informed they had consumed fentanyl unintentionally, as well as how the research team handled the unanticipated occurrence of discordant results. Consistent with other recent studies, we found that people learning of unintentional fentanyl use expressed strong concerns about accidental overdose. It was common for participants to reflect on recent substance use experiences that were atypical and might have involved fentanyl, as well as to examine sources of recent drug purchases. While not all participants were surprised that they had unintentionally consumed fentanyl, all felt that learning their positive results was important due to risk of overdose. Research and medical staff have an opportunity to promote awareness of possible contamination by sharing and discussing UA test results with people who use drugs in non-judgmental manner. In addition to the widely promoted harm reduction strategy of testing drugs with fentanyl test strips, self-administered point-of-care UA, particularly after an unexpected reaction to using a drug, could provide useful information for people buying and using illicit drugs.
Methods of ex vivo analysis of tissue status in vascularized composite allografts
Authors: Ton Carolyn , Salehi Sara , Abasi Sara , Aggas John R. , Liu Renee , Brandacher Gerald , Guiseppi-Elie Anthony , Grayson Warren L.
Published: September 2023

Vascularized composite allotransplantation can improve quality of life and restore functionality. However, the complex tissue composition of vascularized composite allografts (VCAs) presents unique clinical challenges that increase the likelihood of transplant rejection. Under prolonged static cold storage, highly damage-susceptible tissues such as muscle and nerve undergo irreversible degradation that may render allografts non-functional. Skin-containing VCA elicits an immunogenic response that increases the risk of recipient allograft rejection. The development of quantitative metrics to evaluate VCAs prior to and following transplantation are key to mitigating allograft rejection. Correspondingly, a broad range of bioanalytical methods have emerged to assess the progression of VCA rejection and characterize transplantation outcomes. To consolidate the current range of relevant technologies and expand on potential for development, methods to evaluate ex vivo VCA status are herein reviewed and comparatively assessed. The use of implantable physiological status monitoring biochips, non-invasive bioimpedance monitoring to assess edema, and deep learning algorithms to fuse disparate inputs to stratify VCAs are identified.
Long-term outcomes of offspring from multiple gestations: a two-sample Mendelian randomization study on multi-system diseases using UK Biobank and FinnGen databases
Authors: Jiang Yi , Du Yuanyuan , Su Rui , Zhou Xuan , Wei Lijie , Zhang Jingyi , Zhu Shenglan , Zhang Huiting , Fang Chenyun , Chen Yuting , Gao Peng , Zhang Liangnan , Wang Shaoshuai , Yu Jun , He Mengzhou , Ding Wencheng , Feng Ling
Published: September 2023

Background

Assisted reproductive technologies (ART) have increased the incidence of multiple births, which can have a negative impact on maternal and offspring health. The study aimed to investigate the association between genetically predicted multiple birth and the risk of 42 common diseases of the nervous, psychiatric, cardiovascular, respiratory, digestive, and endocrine systems.

Methods

The study utilized two-sample Mendelian randomization (MR) analysis to explore the potential causal relationship between genetically predicted multiple birth and the genetically predicted risk of diseases. The study used the FinnGen and UK Biobank datasets for analysis.

Results

The study found no significant causal relationship between multiple birth and psychiatric disorders. However, the lower limits of the 95% confidence intervals for bipolar affective disorder and anxiety disorders were not robust, indicating a need for further investigation. The study found that multiple birth may be a strong risk factor for infantile cerebral palsy, and caution is necessary in both natural and ART multiple births. The study revealed a potential causal relationship between multiple birth and coronary heart disease, ischemic heart disease, and deep vein thrombosis, which may be related to abnormal intrauterine environments in multiple pregnancies. Surprisingly, multiple birth appears to have a protective effect against some respiratory diseases, such as chronic obstructive pulmonary disease and asthma.

Conclusions

The study highlights the need for caution regarding the risk of infantile cerebral palsy, cardiovascular diseases, and psychiatric disorders in multiple birth. Our study can lead to the development of preventive strategies and improved clinical management for affected infants.
Viral suppression rate at operation triple zero (Otz) and regular art follow-Up programs and associated factors among adolescent clients of Addis Ababa Ethiopia: a comparative cross-sectional study
Authors: Tafere Getahun Wedaje , Hunduma Fufa , Yesuf Aman
Published: September 2023

Background

- Viral suppression is the main goal of currently available treatment and it is used as a primary indicator of successful treatment for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). This ensures a reduction in AIDS-associated morbidity and mortality and decreases the risk of both vertical and horizontal viral transmission. This study aimed to investigate the magnitude of viral suppression and its associated factors among adolescents, comparing the operation triple zero (OTZ) program to regular antiretroviral therapy (ART) follow-up programs.

Methods

- The research consisted of a comparative cross-sectional study, which included a total sample size of 446 adolescents on Active Antiretroviral Therapy (ART) — 223 enrolled in OTZ, and 223 in regular ART from public hospitals. Sociodemographic data were obtained using a self-administered semi-structured questionnaire, and clinical data were extracted from medical records. To examine the prevalence of viral suppression (VS) the latest status was used and multivariate logistic regression analysis was performed to identify factors associated with VS.

Results

- Overall, the adolescent viral suppression was 88.3%, with 92.4% in the OTZ group and 84.3% in the regular ART group. Among OTZ participants, the factors that significantly reduced the odds of viral suppression were having a history of admission in the last year, alcohol use, biological mother not alive, cigarette smoking, social discrimination, and current medication regimen TDF/3TC/EFZ. Among those in regular ART, factors associated with a lesser chance of viral suppression were alcohol use, social discrimination, unscheduled appointments, and current medication regimen TDF/3TC/EFZ when compared to their counterparts. When we compared the two programs, OTZ had a 26.1 times greater chance of suppressing HIV viral load (AOR = 26.1, 95% CI: 3.499–133.9; P = 0.041).

Conclusion

- The overall VS was 88.3%, while viral suppression is better achieved through the OTZ program than through regular ART services. Alcohol use, biological mother not alive, cigarette smoking, social discrimination, and current medication regimen TDF/3TC/EFZ were identified to be factors associated with viral nonsuppression. Therefore, it is advisable to implement the OTZ program in all HIV care centers and focus on factors reducing viral suppression.
The burden of hospital admissions for skeletal dysplasias in Sri Lanka: a population-based study
Authors: Kolambage Yasas D. , Walpita Yasaswi N. , Liyanage Udari A. , Dayaratne Buddika M.K.D.R. , Dissanayake Vajira H.W.
Published: September 2023

Background

Skeletal dysplasias are a diverse group of rare disorders in the chondro-osseous tissue that can have a significant impact on patient’s functionality. The worldwide prevalence of skeletal dysplasias at birth is approximately 1:5000 births. To date, disease burden and trends of skeletal dysplasias in the Sri Lankan population have not been described in any epidemiological study. Our aim was to evaluate the burden and the current trends in hospital admissions for skeletal dysplasias in the Sri Lankan population. A retrospective evaluation of hospital admissions for skeletal dysplasia during 2017–2020 was performed using population-based data from the eIMMR database which covers government hospitals in the entire country. The trends in hospital admissions for skeletal dysplasias by calendar year, age, and types of skeletal dysplasia were described using appropriate summary statistics.

Results

Respective crude admission rates of skeletal dysplasias in the years 2017, 2018, 2019 and 2020 were 5.2, 8.1, 8.0, and 6.5 per million population. A female predominance (1.4:1) was noted during the studied period. Of all reported cases the majority (n = 268; 44.2%) were children less than 4 years. Each year, 0–4 years age group represented 40–47% of the total hospital admissions. More than half of the cases were reported from Colombo (28.1%) and Kandy (25.4%) districts combined. 60% of cases were diagnosed as osteogenesis imperfecta (OI). Rising trends were observed in the hospital admissions for osteogenesis imperfecta, achondroplasia and osteopetrosis, while other skeletal dysplasia types collectively showed a relatively stable trend.

Conclusion

This preliminary study revealed a female predominance of skeletal dysplasias and a relatively high admission rate of osteogenesis imperfecta in the Sri Lankan population. A distinct trend was not visible in the studied years probably due to the impact on hospital services due to COVID- Pandemic. Future research on the healthcare burden on families affected by skeletal dysplasia is required to better understand the overall cost of care and identify therapies that reduce admission rates. This study highlights the value of analysing population-based data on rare diseases to improve healthcare in low-resource countries.
Preliminary study of noninvasive prenatal screening for 22q11.2 deletion/duplication syndrome using multiplex dPCR assay
Authors: Wang Jing , Wang Wei , Zhou Wenbo , Zhou Yan , Zhou Linna , Wang Xinyue , Yu Bin , Zhang Bin
Published: September 2023

Objective

This study aimed to establish a cell-free fetal DNA (cffDNA) assay using multiplex digital PCR (dPCR) for identifying fetuses at increased risk of 22q11.2 deletion/duplication syndrome.

Methods

Six detection sites and their corresponding probes were designed for the 22q11.2 recurrent region. A dPCR assay for the noninvasive screening of 22q11.2 deletion/duplication syndrome was established. A total of 130 plasma samples from pregnant women (including 15 samples with fetal 22q11.2 deletion/duplication syndrome) were blindly tested for evaluating the sensitivity and specificity of the established assay.

Results

DNA with different sizes of 22q11.2 deletion/duplication was detected via dPCR, indicating that the designed probes and detection sites were reasonable and effective. In the retrospective clinical samples, 11 out of 15 samples of pregnant women with 22q11.2 deletion/duplication were detected during the cffDNA assay, and accurate regional localization was achieved. Among the 115 normal samples, 111 were confirmed to be normal. Receiver operating characteristic curves were used for assessing the cut-off values and AUC for these samples. The sensitivity, specificity, and positive as well as negative predictive values were 73.3%, 96.5%, 73.3%, and 96.5%, respectively.

Conclusion

The cffDNA assay based on dPCR technology for the noninvasive detection of 22q11.2 recurrent copy number variants in fetuses detected most affected cases, including smaller but relatively common nested deletions, with a low false-positive rate. It is a potential, efficient and simple method for the noninvasive screening of 22q11.2 deletion/duplication syndrome.
SENP5 promotes homologous recombination-mediated DNA damage repair in colorectal cancer cells through H2AZ deSUMOylation
Authors: Liu Tingting , Wang Hang , Chen Yuanyuan , Wan Zhijie , Du Zhipeng , Shen Hui , Yu Yue , Ma Shengzhe , Xu Ying , Li Zhuqing , Yu Nanxi , Zhang Fangxiao , Cao Kun , Cai Jianming , Zhang Wei , Gao Fu , Yang Yanyong
Published: September 2023

Background

Neoadjuvant radiotherapy has been used as the standard treatment of colorectal cancer (CRC). However, radiotherapy resistance often results in treatment failure. To identify radioresistant genes will provide novel targets for combined treatments and prognostic markers.

Methods

Through high content screening and tissue array from CRC patients who are resistant or sensitive to radiotherapy, we identified a potent resistant gene SUMO specific peptidase 5 (SENP5). Then, the effect of SENP5 on radiosensitivity was investigated by CCK8, clone formation, comet assay, immunofluorescence and flow cytometric analysis of apoptosis and cell cycle to investigate the effect of SENP5 on radiosensitivity. SUMO-proteomic mass spectrometry combined with co-immunoprecipitation assay were used to identify the targets of SENP5. Patient-derived organoids (PDO) and xenograft (PDX) models were used to explore the possibility of clinical application.

Results

We identified SENP5 as a potent radioresistant gene through high content screening and CRC patients tissue array analysis. Patients with high SENP5 expression showed increased resistance to radiotherapy. In vitro and in vivo experiments demonstrated that SENP5 knockdown significantly increased radiosensitivity in CRC cells. SENP5 was further demonstrated essential for efficient DNA damage repair in homologous recombination (HR) dependent manner. Through SUMO mass spectrometry analysis, we characterized H2AZ as a deSUMOylation substrate of SENP5, and depicted the SUMOylation balance of H2AZ in HR repair and cancer resistance. By using PDO and PDX models, we found targeting SENP5 significantly increased the therapeutic efficacy of radiotherapy.

Conclusion

Our findings revealed novel role of SENP5 in HR mediated DNA damage repair and cancer resistance, which could be applied as potent prognostic marker and intervention target for cancer radiotherapy.
The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells
Authors: Sun Lei , Ji Wei-Xue , Li Yan , Li Ze-Lian , Duan Can-Can , Xia Bai-rong , Xiao Lan
Published: September 2023

Background

Cancer cells may develop resistance to cisplatin by various mechanisms. Yet, the exact mechanism of cisplatin in ovarian cancer remains unclear. Recent studies have shown that 3’-phospoadenosine 5’-phosphosulfate synthase 1 (PAPSS1) inhibition combined with low-dose cisplatin increases DNA damage. The aim of this study was to determine the value of targeting PAPSS1 as a cisplatin modulator in epithelial ovarian cancer (EOC).

Results

Increased expression of PAPSS1 was observed in both EOC cells and tissues. Also, its higher nuclear expression was distinctly associated with FIGO (The International Federation of Gynecology and Obstetrics) stage, histological subtype, metastasis, and recurrence. Down-regulation of the PAPSS1 gene increased the cisplatin sensitivity of EOC in vitro and in vivo. Expression of PAPSS1 was negatively correlated with estrogen receptor α (ERα) in EOC. Also, low nuclear PAPSS1 and high nuclear ERα expression in EOC were associated with longer overall survival and progression-free survival in all ovarian cancer and ovarian cancer patients who received platinum-based chemotherapy. PAPSS1 silencing increased the activity of ERα-signaling in EOC cells, thus sensitizing tumors to cisplatin.

Conclusions

These findings characterize a novel interplay between PAPSS1-mediated sulfation and ERα-signaling in EOC cisplatin resistance. PAPSS1 may be exploited as a cisplatin-sensitizing therapeutic target.
Advances for pediatricians in 2022: allergy, anesthesiology, cardiology, dermatology, endocrinology, gastroenterology, genetics, global health, infectious diseases, metabolism, neonatology, neurology, oncology, pulmonology
Authors: Caffarelli Carlo , Santamaria Francesca , Piro Ettore , Basilicata Simona , D’Antonio Lorenzo , Tchana Bertrand , Bernasconi Sergio , Corsello Giovanni
Published: September 2023

The last year saw intensive efforts to advance knowledge in pediatric medicine. This review highlights important publications that have been issued in the Italian Journal of Pediatrics in 2022. We have chosen papers in the fields of allergy, anesthesiology, cardiology, dermatology, endocrinology, gastroenterology, genetics, global health, infectious diseases, metabolism, neonatology, neurology, oncology, pulmonology. Novel valuable developments in epidemiology, pathophysiology, prevention, diagnosis and treatment that can rapidly change the approach to diseases in childhood have been included and discussed.
Distinct requirements for Tcf3 and Tcf12 during oligodendrocyte development in the mouse telencephalon
Authors: Talley Mary Jo , Nardini Diana , Ehrman Lisa A. , Lu Q. Richard , Waclaw Ronald R.
Published: September 2023

Background

E-proteins encoded by Tcf3, Tcf4, and Tcf12 are class I basic helix-loop-helix (bHLH) transcription factors (TFs) that are thought to be widely expressed during development. However, their function in the developing brain, specifically in the telencephalon remains an active area of research. Our study examines for the first time if combined loss of two E-proteins (Tcf3 and Tcf12) influence distinct cell fates and oligodendrocyte development in the mouse telencephalon.

Methods

We generated Tcf3/12 double conditional knockouts (dcKOs) using Olig2Cre/+ or Olig1Cre/+ to overcome compensatory mechanisms between E-proteins and to understand the specific requirement for Tcf3 and Tcf12 in the ventral telencephalon and during oligodendrogenesis. We utilized a combination of in situ hybridization, immunohistochemistry, and immunofluorescence to address development of the telencephalon and oligodendrogenesis at embryonic and postnatal stages in Tcf3/12 dcKOs.

Results

We show that the E-proteins Tcf3 and Tcf12 are expressed in progenitors of the embryonic telencephalon and throughout the oligodendrocyte lineage in the postnatal brain. Tcf3/12 dcKOs showed transient defects in progenitor cells with an enlarged medial ganglionic eminence (MGE) region which correlated with reduced generation of embryonic oligodendrocyte progenitor cells (OPCs) and increased expression of MGE interneuron genes. Postnatal Tcf3/12 dcKOs showed a recovery of OPCs but displayed a sustained reduction in mature oligodendrocytes (OLs). Interestingly, Tcf4 remained expressed in the dcKOs suggesting that it cannot compensate for the loss of Tcf3 and Tcf12. Generation of Tcf3/12 dcKOs with Olig1Cre/+ avoided the MGE morphology defect caused by Olig2Cre/+ but dcKOs still exhibited reduced embryonic OPCs and subsequent reduction in postnatal OLs.

Conclusion

Our data reveal that Tcf3 and Tcf12 play a role in controlling OPC versus cortical interneuron cell fate decisions in MGE progenitors in addition to playing roles in the generation of embryonic OPCs and differentiation of postnatal OLs in the oligodendrocyte lineage.
Characterization of human Ccser2 as a protein tracking the plus-ends of microtubules
Authors: Shirai Yuko , Okuda Tomohiro , Oshima Kenzi , Nadano Daita
Published: September 2023

Objective

Microtubules, which are closely related to cell proliferation, have been the promising therapeutic target of cancer. Therefore, it is necessary to understand the intracellular control mechanisms of microtubules, the whole picture of which is still unclear though. Intracellular dynamics of microtubules are regulated by various microtubule-associated proteins, one group of which is microtubule plus-end-tracking proteins (+ TIPs), localizing to the extending tips of microtubules. Here, we report the identification and analysis of Ccser2 as a new + TIP in human breast cancer MCF-7 cells.

Results

Ccser2 was found to be a member of + TIPs by microscopic observations including time-lapse imaging. The C-terminal region of Ccser2, including two SxIP motifs, was likely to be important for the tracking function. In MCF-7 cells, endogenous Ccser2 was mainly detected in the peripheral regions of microtubule fibers, suggesting that Ccser2 functions in cell projections.
Role of authentication factors in Fin-tech mobile transaction security
Authors: Khan Habib Ullah , Sohail Muhammad , Nazir Shah , Hussain Tariq , Shah Babar , Ali Farman
Published: September 2023

Fin-Tech is the merging of finance and technology, to be considered a key term for technology-based financial operations and money transactions as far as Fin-Tech is concerned. In the massive field of business, mobile money transaction security is a great challenge for researchers. The user authentication schemes restrict the ability to enforce the authentication before the account can access and operate. Although authentication factors provide greater security than a simple static password, financial transactions have potential drawbacks because cybercrime expands the opportunities for fraudsters. The most common enterprise challenge is mobile-based user authentication during transactions, which addresses the security issues against fraudsters. The confirmation of a user legitimation before the money transaction is highlighted by mechanisms and technologies from previous studies that may be helpful in user authentication. This study aims to identify the technologies for user authentication and the opportunity for their transformation to mobile money transaction security despite having all the legally required data for a transaction. This proposed review has identified the role of multifactor authentication techniques for authentication to mitigate the risk of fraudulent transactions—the analysis through 92 articles taken from famous publishers. The most relevant articles address authentication problems, of which 54 percent describe money transaction security, and the rest highlight the supporting technology for user authentication. The study platform described the technology-based approaches with the appreciation of new ideas for secure money transactions. The QR code and multifactor authentication are key terms that increased security by 46%. In addition, this also ensures the user is legitimate using advanced technologies and algorithms to predict and discover transaction risks and discourage fraudsters from trying.