bluuebunny/crossref_metadata_2025 huggingface dataset:
Place of death among foreign-born individuals: a national population-based register study
Authors: Lundberg Emma , Ozanne Anneli , Larsdotter Cecilia , Böling Susanna , Dellenborg Lisen , Enstedt Daniel , Öhlén Joakim
Published: July 2023

Background:

Relatively little is known about where foreign-born individuals die in Sweden and how birth region might influence place of death. Thus, there is a need for population-based studies investigating place of death and associated factors among foreign-born individuals.

Objectives:

The aim of this study was to identify variations in place of death among foreign-born individuals residing in Sweden and to compare place of death between the foreign- and domestic-born population. We also examine the association between place of death, underlying cause of death and sociodemographic characteristics among the foreign-born population.

Design:

A population-based register study.

Methods:

All deceased individuals ⩾18 years of age in Sweden with a registered place of death between 2012 and 2019 ( n = 682,697). Among these, 78,466 individuals were foreign-born. Univariable multinomial logistic regression modelling and multivariable multinomial logistic regression analyses were performed.

Results:

Overall, hospital was the most common place of death among the foreign-born population. However, there were variations in place of death related to region of birth. Compared to domestic-born, a higher proportion of foreign-born individuals dies at home, the majority of whom were born on the African continent.

Conclusion:

Region of birth is one of the several factors associated with place of death among foreign-born individuals. Further research is needed to explore both preferences and barriers to place of death among foreign-born individuals.
Safety analysis of new medications in clinical trials: a simulation study to assess the differences between cause-specific and subdistribution frameworks in the presence of competing events
Authors: Genet Astrid , Bogner Kathrin , Goertz Ralf , Böhme Sarah , Leverkus Friedhelm
Published: July 2023

Safety is an essential part of the evaluation of new medications and competing risks that occur in most clinical trials are a well identified challenge in the analysis of adverse events. Two statistical frameworks exist to consider competing risks: the cause-specific and the subdistribution framework. To date, the application of the cause-specific framework is the standard practice in safety analyses. Here we analyze how the safety analysis results of new medications would be affected if instead of the cause-specific the subdistribution framework was chosen. We conducted a simulation study with 600 participants, equally allocated to verum and control groups and a 30 months follow-up period. Simulated trials were analyzed for safety in a competing risk (death) setting using both the cause-specific and subdistribution frameworks. Results show that comparing safety profiles in a subdistribution setting is always more pessimistic than in a cause-specific setting. For the group with the longest survival and a safety advantage in a cause-specific setting, the advantage either disappeared or a disadvantage was found in the subdistribution analysis setting. These observations are not contradictory but show different perspectives. To evaluate the safety of a new medication over its comparator, one needs to understand the origin of both the risks and the benefits associated with each therapy. These requirements are best met with a cause-specific framework. The subdistribution framework seems better suited for clinical prediction, and therefore more relevant for providers or payers, for example.
Examining the relationship between personality traits, work experience, burnout, and intention to stay among home care aides in Taiwan
Authors: Hung Yung-Ning , Chiu Tzu-Ying
Published: July 2023

Background

Home care aides play an important role in providing long-term care services, but there is currently an insufficient supply of workers to meet the growing demand in Taiwan due to the increasing number of older adults and people with disabilities requiring care. There are numerous factors that influence the retention of home care aides. Previous research has indicated that taking employees’ individual personalities into account can enhance task delegation and organizational efficiency within an organization. Severe occupational burnout is likely to diminish vitality and disrupt sleep, which, in turn, can result in higher employee turnover rates. To date, no research has explored the correlation between personality traits, burnout, work experience, and the retention of home care aides. Given these gaps in knowledge, the present study aims to investigate how personality traits and occupational burnout are associated with the intention to stay among home care aides in Taiwan.

Methods

The study was a cross-sectional survey that utilized purposive sampling to interview 285 home care aides in Hualien County from December 2020 to January 2021. A self-report questionnaire, administered with informed consent, was used to collect data on demographics, work experience, occupational burnout, personality, and intention to stay. The researchers utilized hierarchical regression analysis to analyze the data. All measurements exhibited high reliability and consistency, with Cronbach’s α values ranging from 0.8 to 0.9.

Results

The subscales for personal burnout, work-related burnout, and client-related burnout, along with all personality scales, were highly correlated with intention to stay, except for the openness trait (p < .05). Moreover, married, full-time employment, satisfied with the promotion system and current job as home care aides on the whole, lower levels of work-related burnout, and agreeable personality type were found to be significant predictors for intention to stay (p < .05) , and the adjusted R2of the model was 29.4%.

Conclusions

This study has concluded that using personality traits as a criterion to select home care aides with a high level of agreeableness prior to recruitment, enhancing the professionalism and comprehensive of promotion system, and reducing work burnout are measures that may help home care service providers increase the intention to stay among home care aides.
A delayed spontaneous second-trimester tubo-abdominal pregnancy diagnosed and managed by laparotomy in a “self-identified” infertile woman, a case report and literature review
Authors: Zhang Yanfang , Li Mengying , Liu Xiaomei , Yang Wen , Dong Qingyun , Wang Dan , Wang Jinghua , Tian Wenyan , Song Xueru
Published: July 2023

Background

Abdominal pregnancy, a rare form of ectopic pregnancy, is associated with high morbidity and adverse consequences for future fertility. Early recognition and management reduce mortality and allow minimal invasive and conservative treatment. In modern medicine, primitive prevention to unexpected fatal pregnancies is crucial.

Case presentation

A divorced 33-year-old “self-identified” infertile polycystic ovary woman diagnosed as repeated implantation failure in previous in vitro fertilization with her ex-husband ever presented in surgery department with a history of 15-day abdominal pain, nausea, and vomiting and 3-h worsening abdominal pain. The serum beta-human chorionic gonadotropin value was more than 10,000 m-international units per milliliter. Sonogram findings were significant for the absence of intrauterine gestation; a placenta and well-formed living fetus of second-trimester gestation were seen in the abdomen, accompanied by hemoperitoneum. A unique spontaneously second-trimester tubo-abdominal pregnancy was confirmed in emergent laparotomy by gynecologists, she received a removing of the living fetus, a right total salpingectomy, resection of partial omentum and blood transfusion. The patient recovered uneventfully and her serum beta-human chorionic gonadotropin returned to normal range on the 30th postoperative day, till now, she has weak fertility awareness because of her catastrophic experiences in the unexpected abdominal pregnancy.

Conclusions

This case highlights woman with a previous in vitro fertilization history may be in is a high risk to be delayed or missed in diagnosis in an intended ectopic pregnancy due to a fixed belief in infertility. Educational interventions and contraceptive care should be provided by fertility and healthcare practitioner. The possibility of abdominal pregnancy must always be suspected and dealt with promptly and appropriately by the astute clinician.
The effect of gonadotrophin-releasing hormone agonist versus human chorionic gonadotrophin trigger on pregnancy and neonatal outcomes in Letrozole-HMG IUI cycles
Authors: Chen Li , Xi Qianwen , Jiang Shutian , Gao Yining , Long Hui , Wang Yao , Kuang Yanping
Published: July 2023

Background

GnRHa and hCG are both used for oocyte maturation and ovulation triggering. However, GnRHa have a shorter half-life than hCG, which leads to luteal phase deficiency. Letrozole (LE) has been found to improve the luteal function. Thus, the choice of triggering strategy can be different in intrauterine insemination (IUI) cycles using LE and human menopausal gonadotropin (HMG). The aim of this study was to compare the pregnancy and neonatal outcomes of patients triggered with GnRHa versus hCG versus dual trigger in LE-IUI cycles.

Methods

This retrospective cohort study included 6,075 LE-HMG IUI cycles between January 2010 and May 2021 at a tertiary-care academic medical center in China. All cycles were divided into three groups according to different trigger strategies as hCG trigger group, GnRHa trigger group and dual trigger group. The primary outcome was clinical pregnancy rate. Logistic regression analysis was performed to explore other risk factors for clinical pregnancy rate.

Results

No significant difference was observed in clinical pregnancy rate between hCG, GnRHa and dual trigger cycles in LE-HMG IUI cycles (P = 0.964). The miscarriage rate was significantly lower in the GnRHa trigger group, and higher in the dual trigger group, compared with the hCG group (P = 0.045). Logistic analysis confirmed that triggering strategy was associated with miscarriage (aOR:0.427, 95%CI: 0.183–0.996,P = 0.049; aOR:0.298, 95%CI: 0.128–0.693,P = 0.005). No significant differences were observed regarding neonatal outcomes between the three groups.

Conclusions

Our findings suggested that both GnRHa and dual trigger can be used to trigger ovulation in LE-HMG IUI cycles, but dual trigger must be used with caution.
A rare cause of air-leak syndrome in a premature newborn: a case report
Authors: Uzunhan Ozan , Yıldırım Mihriban Begüm , Eser Can , Öztarhan Kazım , Çelik Alaettin
Published: July 2023

Background

Pulmonary complications, such as airway leak syndrome, are common in preterm neonates; however, bronchial rupture is a rarely seen phenomenon.

Case Presentation

In this case, we present a preterm newborn who developed pneumomediastinum and pneumothorax. The pneumothorax persisted, despite placement of a thorax tube, requiring a thoracotomy to detect and treat the bronchial rupture.

Conclusion

Physicians should have a high suspicion of bronchial rupture in patients with persistent air leak syndrome, even after thorax tube placement and continuous negative pressure implementation.
Liver transient elastography values in healthy South African children
Authors: Rose Penelope C. , Cotton Mark F. , Otwombe Kennedy , Innes Steve , Nel Etienne D.
Published: July 2023

Background

Transient elastography (TE) is a rapid noninvasive ultrasound-based technology that measures liver stiffness as a surrogate for liver fibrosis and controlled attenuation parameter (CAP) as a measure of liver steatosis. However, normal ranges in children are not well defined in all populations. The aim of this study was to determine transient elastography values in healthy South African children.

Methods

From April 2019 to December 2021, children were recruited from the HIV negative control group of a cohort study. Only children neither overweight nor obese, without evidence of liver disease, no medical condition or medication associated with hepatic steatosis or fibrosis and normal metabolic profile were included in this cross-sectional analysis. Clinical data, anthropometry and blood samples were collected on the same day as transient elastography with controlled attenuation parameter was performed.

Results

104 children (median age 12.8 years [IQR 11.4–14.8, range 7.9–17.7 years]; 59 [57%] boys) were included. Liver stiffness was positively correlated with age (Pearson’s r = 0.39, p < 0.001). Median liver stiffness in boys (5.2 kPa [5th to 95th percentiles 3.6 to 6.8 kPa]) was greater than in girls (4.6 kPa [5th to 95th percentiles 3.6 to 6.1 kPa; p = 0.004]), but there was no difference by ethnicity. Median CAP was 179dB/m (5th to 95th percentiles 158 to 233dB/m). There was a positive correlation between CAP and body mass index (BMI) z-score, but no difference by age, sex, ethnicity or pubertal status.

Conclusion

Liver stiffness values increase with age and are higher in healthy South African boys than girls, whereas CAP values vary with BMI, but not with age or sex.
Continuity and care coordination of primary health care: a scoping review
Authors: Khatri Resham , Endalamaw Aklilu , Erku Daniel , Wolka Eskinder , Nigatu Frehiwot , Zewdie Anteneh , Assefa Yibeltal
Published: July 2023

Background

Healthcare coordination and continuity of care conceptualize all care providers and organizations involved in health care to ensure the right care at the right time. However, systematic evidence synthesis is lacking in the care coordination of health services. This scoping review synthesizes evidence on different levels of care coordination of primary health care (PHC) and primary care.

Methods

We conducted a scoping review of published evidence on healthcare coordination. PubMed, Scopus, Embase, CINAHL, Cochrane, PsycINFO, Web of Science and Google Scholar were searched until 30 November 2022 for studies that describe care coordination/continuity of care in PHC and primary care. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines to select studies. We analysed data using a thematic analysis approach and explained themes adopting a multilevel (individual, organizational, and system) analytical framework.

Results

A total of 56 studies were included in the review. Most studies were from upper-middle-income or high-income countries, primarily focusing on continuity/care coordination in primary care. Ten themes were identified in care coordination in PHC/primary care. Four themes under care coordination at the individual level were the continuity of services, linkage at different stages of health conditions (from health promotion to rehabilitation), health care from a life-course (conception to elderly), and care coordination of health services at places (family to hospitals). Five themes under organizational level care coordination included interprofessional, multidisciplinary services, community collaboration, integrated care, and information in care coordination. Finally, a theme under system-level care coordination was related to service management involving multisectoral coordination within and beyond health systems.

Conclusions

Continuity and coordination of care involve healthcare provisions from family to health facility throughout the life-course to provide a range of services. Several issues could influence multilevel care coordination, including at the individual (services or users), organizational (providers), and system (departments and sectors) levels. Health systems should focus on care coordination, ensuring types of care per the healthcare needs at different stages of health conditions by a multidisciplinary team. Coordinating multiple technical and supporting stakeholders and sectors within and beyond health sector is also vital for the continuity of care especially in resource-limited health systems and settings.
Increased prime edit rates in KCNQ2 and SCN1A via single nicking all-in-one plasmids
Authors: Dirkx N. , Weuring Wout J. , De Vriendt E. , Smal N. , van de Vondervoort J. , van ’t Slot Ruben , Koetsier M. , Zonnekein N. , De Pooter Tim , Weckhuysen S. , Koeleman B. P. C.
Published: July 2023

Background

Prime editing (PE) is the most recent gene editing technology able to introduce targeted alterations to the genome, including single base pair changes, small insertions, and deletions. Several improvements to the PE machinery have been made in the past few years, and these have been tested in a range of model systems including immortalized cell lines, stem cells, and animal models. While double nicking RNA (dncRNA) PE systems PE3 and PE5 currently show the highest editing rates, they come with reduced accuracy as undesired indels or SNVs arise at edited loci. Here, we aimed to improve single ncRNA (sncRNA) systems PE2 and PE4max by generating novel all-in-one (pAIO) plasmids driven by an EF-1α promoter, which is especially suitable for human-induced pluripotent stem cell (hiPSC) models.

Results

pAIO-EF1α-PE2 and pAIO-EF1α-PE4max were used to edit the voltage gated potassium channel gene KCNQ2 and voltage gated sodium channel gene SCN1A. Two clinically relevant mutations were corrected using pAIO-EF1α-PE2 including the homozygous truncating SCN1A R612* variant in HEK293T cells and the heterozygous gain-of-function KCNQ2 R201C variant in patient-derived hiPSC. We show that sncRNA PE yielded detectable editing rates in hiPSC ranging between 6.4% and 9.8%, which was further increased to 41% after a GFP-based fluorescence-activated cell sorting (FACS) cell sorting step. Furthermore, we show that selecting the high GFP expressing population improved editing efficiencies up to 3.2-fold compared to the low GFP expressing population, demonstrating that not only delivery but also the number of copies of the PE enzyme and/or pegRNA per cell are important for efficient editing. Edit rates were not improved when an additional silent protospacer-adjacent motif (PAM)-removing alteration was introduced in hiPSC at the target locus. Finally, there were no genome-wide off-target effects using pAIO-EF1α-PE2 and no off-target editing activity near the edit locus highlighting the accuracy of snc prime editors.

Conclusion

Taken together, our study shows an improved efficacy of EF-1α driven sncRNA pAIO-PE plasmids in hiPSC reaching high editing rates, especially after FACS sorting. Optimizing these sncRNA PE systems is of high value when considering future therapeutic in vivo use, where accuracy will be extremely important.
PARP inhibitor exerts an anti-tumor effect via LMO2 and synergizes with cisplatin in natural killer/T cell lymphoma
Authors: Wu Jiazhuo , Shi Cunzhen , Li Hongwen , Song Wenting , Huang Shuo , Zhang Jianxiang , Li Wencai , Li Zhaoming , Zhang Mingzhi
Published: July 2023

Background

PARP inhibitor (PARPi), as a kind of DNA damage repair inhibitor, has been shown to be effective in various solid tumors and hematologic malignancies. Natural killer/T cell lymphoma (NKTCL) is a highly aggressive malignancy, the treatment of which has long been a major challenge in the clinic. Here, we investigated the efficacy and mechanism of PARPi, and the therapeutic value of PARPi combined with cisplatin in NKTCL.

Methods

The cell proliferation, cell apoptosis, and cell cycle of NKTCL cells were detected respectively by CCK-8 and flow cytometry. The changes of mRNA expression and protein level were measured respectively by mRNA-sequencing, quantitative real-time PCR, western blotting, and immunofluorescence. LMO2 expression was detected by immunohistochemistry and western blotting. Targeted knockdown of LMO2 was conducted by short hairpin RNA. The tumor xenograft models were established to evaluate the efficacy of drugs in vivo.

Results

PARPi inhibited cell proliferation, promoted cell apoptosis, and induced S-phase cell cycle arrest in NKTCL cells. PARPi led to the accumulation of DNA damage by blocking DNA repair and DNA replication. Additionally, LMO2 deficiency reduced the sensitivity of NKTCL cells to PARPi. Finally, the combination of PARPi and cisplatin exhibited significant synergistic effects both in vitro and in vivo.

Conclusions

In summary, we found that PARPi exerted an anti-tumor effect via LMO2 and synergized with cisplatin in NKTCL, which provides the theoretical basis for the clinical application of PARPi.
Identification of a psychiatric risk gene NISCH at 3p21.1 GWAS locus mediating dendritic spine morphogenesis and cognitive function
Authors: Yang Zhi-Hui , Cai Xin , Ding Zhong-Li , Li Wei , Zhang Chu-Yi , Huo Jin-Hua , Zhang Yue , Wang Lu , Zhang Lin-Ming , Li Shi-Wu , Li Ming , Zhang Chen , Chang Hong , Xiao Xiao
Published: July 2023

Background

Schizophrenia and bipolar disorder (BD) are believed to share clinical symptoms, genetic risk, etiological factors, and pathogenic mechanisms. We previously reported that single nucleotide polymorphisms spanning chromosome 3p21.1 showed significant associations with both schizophrenia and BD, and a risk SNP rs2251219 was in linkage disequilibrium with a human specificAlupolymorphism rs71052682, which showed enhancer effects on transcriptional activities using luciferase reporter assays in U251 and U87MG cells.

Methods

CRISPR/Cas9-directed genome editing, real-time quantitative PCR, and public Hi-C data were utilized to investigate the correlation between theAlupolymorphism rs71052682 andNISCH. Primary neuronal culture, immunofluorescence staining, co-immunoprecipitation, lentiviral vector production, intracranial stereotaxic injection, behavioral assessment, and drug treatment were used to examine the physiological impacts of Nischarin (encoded byNISCH).

Results

Deleting theAlusequence in U251 and U87MG cells reduced mRNA expression ofNISCH, the gene locates 180 kb from rs71052682, and Hi-C data in brain tissues confirmed the extensive chromatin contacts. These data suggested that the genetic risk of schizophrenia and BD predicted elevatedNISCHexpression, which was also consistent with the observed higherNISCHmRNA levels in the brain tissues from psychiatric patients compared with controls. We then found that overexpression ofNISCHresulted in a significantly decreased density of mushroom dendritic spines with a simultaneously increased density of thin dendritic spines in primary cultured neurons. Intriguingly, elevated expression of this gene in mice also led to impaired spatial working memory in the Y-maze. Given that Nischarin is the target of anti-hypertensive agents clonidine and tizanidine, which have shown therapeutic effects in patients with schizophrenia and patients with BD in preliminary clinical trials, we demonstrated that treatment with those antihypertensive drugs could reduceNISCHmRNA expression and rescue the impaired working memory in mice.

Conclusions

We identify a psychiatric risk geneNISCHat 3p21.1 GWAS locus influencing dendritic spine morphogenesis and cognitive function, and Nischarin may have potentials for future therapeutic development.
Identification and characterization of a strong constitutive promoter stnYp for activating biosynthetic genes and producing natural products in streptomyces
Authors: Guo Wenli , Xiao Zhihong , Huang Tingting , Zhang Kai , Pan Hai-Xue , Tang Gong-Li , Deng Zixin , Liang Rubing , Lin Shuangjun
Published: July 2023

Background

Streptomyces are well known for their potential to produce various pharmaceutically active compounds, the commercial development of which is often limited by the low productivity and purity of the desired compounds expressed by natural producers. Well-characterized promoters are crucial for driving the expression of target genes and improving the production of metabolites of interest.

Results

A strong constitutive promoter, stnYp, was identified in Streptomyces flocculus CGMCC4.1223 and was characterized by its effective activation of silent biosynthetic genes and high efficiency of heterologous gene expression. The promoter stnYp showed the highest activity in model strains of four Streptomyces species compared with the three frequently used constitutive promoters ermEp*, kasOp*, and SP44. The promoter stnYp could efficiently activate the indigoidine biosynthetic gene cluster in S. albus J1074, which is thought to be silent under routine laboratory conditions. Moreover, stnYp was found suitable for heterologous gene expression in different Streptomyces hosts. Compared with the promoters ermEp*, kasOp*, and SP44, stnYp conferred the highest production level of diverse metabolites in various heterologous hosts, including the agricultural-bactericide aureonuclemycin and the antitumor compound YM-216391, with an approximately 1.4 − 11.6-fold enhancement of the yields. Furthermore, the purity of tylosin A was greatly improved by overexpressing rate-limiting genes through stnYp in the industrial strain. Further, the yield of tylosin A was significantly elevated to 10.30 ± 0.12 g/L, approximately 1.7-fold higher than that of the original strain.

Conclusions

The promoter stnYp is a reliable, well-defined promoter with strong activity and broad suitability. The findings of this study can expand promoter diversity, facilitate genetic manipulation, and promote metabolic engineering in multiple Streptomyces species.
Preclinical trial of the effectiveness of a safety nasogastric tube to detect the tube position based on tidal volume and pepsin assay results in the gastrointestinal tract of Macaca fascicularis
Authors: Nuzul Sigit Mohammad , Kartinah Neng Tine , Nur Busjra M. , Ilyas Ermita I. Ibrahim
Published: July 2023

Background

Tube misplacement into the tracheobronchial tract is associated with pneumothorax in 0.5% of cases. NGT verification only detects the position of the tube at the end of the procedure. Therefore, a safe nasogastric tube (SNGT) was created to detect the NGT position in real time in a simple and inexpensive way. This study aimed to prove the effectiveness of the SNGT prototype in Macaca fascicularis.

Result

An SNGT producing 50% of the TV had 100% sensitivity and specificity in detecting the position of the tube at 100% of the TV, with a sensitivity of 100% and a specificity of 87.5%. There was a significant difference between the movement of the SNGT 50% TV and SNGT 100% TV airbags (p ≤ 0.05). However, there was no significant difference between the accuracy of placement of the 50% TV SNGT, 100% TV SNGT, and conventional NGT (p > 0.05). The pepsin enzyme had better sensitivity (100%) than pH paper (91.66%) in detecting the end-of-procedure tube position. This research has the potential to advance into human clinical trials.

Conclusion

SNGTs are highly effective in detecting the NGT position inside the respiratory and digestive tracts to prevent misplacement.
Health-related quality of life and its associated factors among outpatients with heart failure: a cross-sectional study
Authors: Jarab Anan S. , Hamam Hanan W. , Al-Qerem Walid A. , Heshmeh Shrouq R. Abu , Mukattash Tareq L. , Alefishat Eman A.
Published: July 2023

Background

Heart Failure (HF) is a chronic disease associated with life-limiting symptoms that could negatively impact patients’ health-related quality of life (HRQOL). This study aimed to evaluate HRQOL and explore the factors associated with poor HRQOL among patients with HF in Jordan.

Methods

This cross-sectional study used the validated Arabic version of the Minnesota Living with Heart Failure Questionnaire to assess HRQOL in outpatients with HF visiting cardiology clinics at two public hospitals in Jordan. Variables were collected from medical records and custom-designed questionnaires, including socio-demographics, biomedical variables, and disease and medication characteristics. Ordinal regression analysis was used to explore variables associated with poor HRQOL among HF patients.

Results

Ordinal regression analysis showed that the number of HF medications (P < 0.05) and not taking a loop diuretic (P < 0.05) significantly increased HRQOL, while the number of other chronic diseases (P < 0.05), stage III/IV of HF (P < 0.01), low monthly income (P < 0.05), and being unsatisfied with the prescribed medications (P < 0.05) significantly decreased HRQOL of HF patients.

Conclusions

Although the current study demonstrated low HRQOL among patients with HF in Jordan, HRQOL has a considerable opportunity for improvement in those patients. Variables identified in the present study, including low monthly income, higher New York Heart Association (NYHA) classes, a higher number of comorbidities, and/or taking a loop diuretic, should be considered in future intervention programs, aiming to improve HRQOL in patients with HF.
Effect of on-site first aid for industrial injuries on healthcare utilization after medical treatment: a 4-year retrospective longitudinal study
Authors: Kim Jinhyun , Kim Hyunkyu , Park Eun-Cheol , Jang Sung-In
Published: July 2023

Background

The number of industrially injured workers (IIW) is increasing in Korea. However, little research has been conducted on whether first aid is performed at industrial sites or on the association between first aid for industrial injuries and the prognosis of IIW, including healthcare utilization.

Methods

A total of 3,092 participants (2,562 males and 530 females) were analyzed during the 4-year study period, which contributed to 11,167 observations. Healthcare utilization was evaluated based on the number of outpatient visits, hospitalizations, and duration of hospitalization using a generalized estimating equation Poisson regression. Several time-varying socioeconomic characteristics and information about the injury were adjusted, and transfer time to the medical institutions was also considered.

Results

During 4-year after the termination of medical treatment, participants who had not receive first aid visited outpatient clinics 15.243 times per year, and those who had visited 13.928 times per year, which is 16.16% less (adjusted relative risk [aRR]: 0.838, 95% CI = 0.740–0.950). Participants who had received on-site first aid with less than a 0.5-hour transfer time to the medical institutions visited outpatient clinics 14.87% less per year than those who had not received first aid (aRR: 0.851, 95% CI = 0.750–0.966).

Conclusion

To reduce the long-term outpatient utilization rate for IIW after medical treatment, on-site first aid must be provided in a timely manner. Employee education and first aid training are also necessary.
ChatGPT and large language models in academia: opportunities and challenges
Authors: Meyer Jesse G. , Urbanowicz Ryan J. , Martin Patrick C. N. , O’Connor Karen , Li Ruowang , Peng Pei-Chen , Bright Tiffani J. , Tatonetti Nicholas , Won Kyoung Jae , Gonzalez-Hernandez Graciela , Moore Jason H.
Published: July 2023

The introduction of large language models (LLMs) that allow iterative “chat” in late 2022 is a paradigm shift that enables generation of text often indistinguishable from that written by humans. LLM-based chatbots have immense potential to improve academic work efficiency, but the ethical implications of their fair use and inherent bias must be considered. In this editorial, we discuss this technology from the academic’s perspective with regard to its limitations and utility for academic writing, education, and programming. We end with our stance with regard to using LLMs and chatbots in academia, which is summarized as (1) we must find ways to effectively use them, (2) their use does not constitute plagiarism (although they may produce plagiarized text), (3) we must quantify their bias, (4) users must be cautious of their poor accuracy, and (5) the future is bright for their application to research and as an academic tool.
Decrease of thyroid function after ischemic stroke is related to stroke severity
Authors: Sidorov Evgeny , Paul Aruna , Xu Chao , Nouh Claire Delpirou , Chen Allshine , Gosmanova Albina , Gosmanov Niyaz , Gordon David Lee , Baranskaya Irina , Chainakul Juliane , Hamilton Robert , Mdzinarishvili Alexander
Published: July 2023

Background

Thyroid hormones are of fundamental importance for brain function. While low triiodothyronine levels during acute ischemic stroke (AIS) are associated with worse clinical outcomes, dynamics of thyroid function after AIS remains unknown. Thus, we longitudinally evaluated thyroid hormones after stroke and related them to stroke severity.

Methods

We prospectively traced thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxin (fT4) levels from the hyper-acute (within 24 h) to acute (3–5 days) and chronic (3–6 months) stages of ischemic stroke using a mixed regression model. Then, we analyzed whether stroke severity at presentation, expressed by National Institute of Health Stroke Scale (NIHSS), is associated with change in thyroid function.

Results

Forty-five patients were evaluated in hyper-acute and acute stages, while 29 were followed through chronic stage. TSH levels decreased from hyper-acute (2.91 ± 0.65 μIU/mL) to acute (2.86 ± 0.46 μIU/mL) and chronic stages of stroke (1.93 ± 0.35 μIU/m, p = 0.95). fT3 levels decreased from hyper-acute (2.79 ± 0.09 pg/ml) to acute (2.37 ± 0.07 pg/ml) stages, but recovered in chronic stage (2.78 ± 0.10 pg/ml, p < 0.01). fT4 levels decreased from hyper-acute (1.64 ± 0.14 ng/dl) to acute (1.13 ± 0.03 ng/dl) stages, and increased in the chronic stage (1.16 ± 0.08 ng/dl, p = 0.02). One-unit increase in presenting NIHSS was associated with 0.04-unit decrease of fT3 from hyper-acute to the acute stage (p < 0.01).

Conclusion

There is a transient decrease of thyroid hormones after ischemic stroke, possibly driven by stroke severity. Larger studies are needed to validate these findings. Correction of thyroid function in acute stroke may be investigated to improve stroke outcomes.
CD271 activation prevents low to high-risk progression of cutaneous squamous cell carcinoma and improves therapy outcomes
Authors: Quadri Marika , Tiso Natascia , Musmeci Francesco , Morasso Maria I. , Brooks Stephen R. , Bonetti Luca Reggiani , Panini Rossana , Lotti Roberta , Marconi Alessandra , Pincelli Carlo , Palazzo Elisabetta
Published: July 2023

Background

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer, showing a rapid increasing incidence worldwide. Although most cSCC can be cured by surgery, a sizeable number of cases are diagnosed at advanced stages, with local invasion and distant metastatic lesions. In the skin, neurotrophins (NTs) and their receptors (CD271 and Trk) form a complex network regulating epidermal homeostasis. Recently, several works suggested a significant implication of NT receptors in cancer. However, CD271 functions in epithelial tumors are controversial and its precise role in cSCC is still to be defined.

Methods

Spheroids from cSCC patients with low-risk (In situ or Well-Differentiated cSCC) or high-risk tumors (Moderately/Poorly Differentiated cSCC), were established to explore histological features, proliferation, invasion abilities, and molecular pathways modulated in response to CD271 overexpression or activation in vitro. The effect of CD271 activities on the response to therapeutics was also investigated. The impact on the metastatic process and inflammation was explored in vivo and in vitro, by using zebrafish xenograft and 2D/3D models.

Results

Our data proved that CD271 is upregulated in Well-Differentiated tumors as compared to the more aggressive Moderately/Poorly Differentiated cSCC, both in vivo and in vitro. We demonstrated that CD271 activities reduce proliferation and malignancy marker expression in patient-derived cSCC spheroids at each tumor grade, by increasing neoplastic cell differentiation. CD271 overexpression significantly increases cSCC spheroid mass density, while it reduces their weight and diameter, and promotes a major fold-enrichment in differentiation and keratinization genes. Moreover, both CD271 overexpression and activation decrease cSCC cell invasiveness in vitro. A significant inhibition of the metastatic process by CD271 was observed in a newly established zebrafish cSCC model. We found that the recruitment of leucocytes by CD271-overexpressing cells directly correlates with tumor killing and this finding was further highlighted by monocyte infiltration in a THP-1-SCC13 3D model. Finally, CD271 activity synergizes with Trk receptor inhibition, by reducing spheroid viability, and significantly improves the outcome of photodynamic therapy (PTD) or chemotherapy in spheroids and zebrafish.

Conclusion

Our study provides evidence that CD271 could prevent the switch between low to high-risk cSCC tumors. Because CD271 contributes to maintaining active differentiative paths and favors the response to therapies, it might be a promising target for future pharmaceutical development.
ClinVar and HGMD genomic variant classification accuracy has improved over time, as measured by implied disease burden
Authors: Sharo Andrew G. , Zou Yangyun , Adhikari Aashish N. , Brenner Steven E.
Published: July 2023

Background

Curated databases of genetic variants assist clinicians and researchers in interpreting genetic variation. Yet, these databases contain some misclassified variants. It is unclear whether variant misclassification is abating as these databases rapidly grow and implement new guidelines.

Methods

Using archives of ClinVar and HGMD, we investigated how variant misclassification has changed over 6 years, across different ancestry groups. We considered inborn errors of metabolism (IEMs) screened in newborns as a model system because these disorders are often highly penetrant with neonatal phenotypes. We used samples from the 1000 Genomes Project (1KGP) to identify individuals with genotypes that were classified by the databases as pathogenic. Due to the rarity of IEMs, nearly all such classified pathogenic genotypes indicate likely variant misclassification in ClinVar or HGMD.

Results

While the false-positive rates of both ClinVar and HGMD have improved over time, HGMD variants currently imply two orders of magnitude more affected individuals in 1KGP than ClinVar variants. We observed that African ancestry individuals have a significantly increased chance of being incorrectly indicated to be affected by a screened IEM when HGMD variants are used. However, this bias affecting genomes of African ancestry was no longer significant once common variants were removed in accordance with recent variant classification guidelines. We discovered that ClinVar variants classified as Pathogenic or Likely Pathogenic are reclassified sixfold more often than DM or DM? variants in HGMD, which has likely resulted in ClinVar’s lower false-positive rate.

Conclusions

Considering misclassified variants that have since been reclassified reveals our increasing understanding of rare genetic variation. We found that variant classification guidelines and allele frequency databases comprising genetically diverse samples are important factors in reclassification. We also discovered that ClinVar variants common in European and South Asian individuals were more likely to be reclassified to a lower confidence category, perhaps due to an increased chance of these variants being classified by multiple submitters. We discuss features for variant classification databases that would support their continued improvement.
Synthesis and preclinical evaluation of a novel fluorine-18 labeled small-molecule PET radiotracer for imaging of CXCR3 receptor in mouse models of atherosclerosis
Authors: Alluri Santosh R. , Higashi Yusuke , Berendzen Ashley , Grisanti Laurel A. , Watkinson Lisa D. , Singh Kamlendra , Hoffman Timothy J. , Carmack Terry , Devanny Elizabeth A. , Tanner Miles , Kil Kun-Eek
Published: July 2023

Background

CXCR3 is a chemokine receptor and is expressed in innate and adaptive immune cells. It promotes the recruitment of T-lymphocytes and other immune cells to the inflammatory site in response to the binding of cognate chemokines. Upregulation of CXCR3 and its chemokines has been found during atherosclerotic lesion formation. Therefore, detection of CXCR3 by positron emission tomography (PET) radiotracer can be a useful tool for detecting the development of atherosclerosis in a noninvasive manner. Herein, we report the synthesis, radiosynthesis, and characterization of a novel fluorine-18 (F-18, 18F) labeled small-molecule radiotracer for the imaging of the CXCR3 receptor in mouse models of atherosclerosis.

Results

The reference standard 1 and its precursor 9 were synthesized over 5 steps from starting materials in good to moderate yields. The measured Ki values of CXCR3A and CXCR3B were 0.81 ± 0.02 nM and 0.31 ± 0.02 nM, respectively. [18F]1 was prepared by a two-step radiosynthesis with a decay-corrected radiochemical yield of 13 ± 2%, radiochemical purity > 99%, and specific activity of 44.4 ± 3.7 GBq/µmol at the end of synthesis (n = 6). The baseline studies showed that [18F]1 displayed high uptake in the atherosclerotic aorta and brown adipose tissue in Apolipoprotein E (ApoE) knockout (KO) mice fed with a high-fat diet over 12 weeks. The uptake of [18F]1 in these regions was reduced significantly in self-blocking studies, demonstrating CXCR3 binding specificity. Contrary to this, no significant differences in uptake of [18F]1 in the abdominal aorta of C57BL/6 control mice fed with a normal diet were observed in both baseline and blocking studies, indicating increased CXCR3 expression in atherosclerotic lesions. Immunohistochemistry studies demonstrated that [18F]1-positive regions were correlated with CXCR3 expression, but some atherosclerotic plaques with significant size were not detected by [18F]1, and their CXCR3 expressions were minimal.

Conclusion

[18F]1 was synthesized with good radiochemical yield and high radiochemical purity. In PET imaging studies, [18F]1 displayed CXCR3-specific uptake in the atherosclerotic aorta in ApoE KO mice. [18F]1 visualized CXCR3 expression in different regions in mice aligned with the tissue histology studies. Taken together, [18F]1 is a potential PET radiotracer for imaging CXCR3 in atherosclerosis.
Anthelmintic activity of European fern extracts against Haemonchus contortus
Authors: Pavičić Antonio , Zajíčková Markéta , Šadibolová Michaela , Svobodová Gabriela , Matoušková Petra , Szotáková Barbora , Langhansová Lenka , Maršík Petr , Skálová Lenka
Published: July 2023

Most drugs used in the treatment of helminthiasis in humans and animals have lost their efficacy due to the development of drug-resistance in helminths. Moreover, since anthelmintics, like many pharmaceuticals, are now recognized as hazardous contaminants of the environment, returning to medicinal plants and their products represents an environmentally friendly way to treat helminthiasis. The goal of the present study was to test the anthelminthic activity of methanol extracts of eight selected European ferns from the genera Dryopteris, Athyrium and Blechnum against the nematode Haemonchus contortus, a widespread parasite of small ruminants. Eggs and adults of H. contortus drug-susceptible strain ISE and drug-resistant strain WR were isolated from experimentally infected sheep. The efficacy of fern extracts was assayed using egg hatch test and adults viability test based on ATP-level measurement. Among the ferns tested, only Dryopteris aemula extract (0.2 mg/mL) inhibited eggs hatching by 25% in comparison to control. Athyrium distentifolium, Dryopteris aemula and Dryopteris cambrensis were effective against H. contortus adults. In concentration 0.1 mg/mL, A. distentifolium, D. aemula, D. cambrensis significantly decreased the viability of females from ISE and WR strains to 36.2%, 51.9%, 32.9% and to 35.3%, 27.0%, 23.3%, respectively in comparison to untreated controls. None of the extracts exhibited toxicity in precise cut slices from ovine liver. Polyphenol’s analysis identified quercetin, kaempferol, luteolin, 3-hydroxybenzoic acid, caffeic acid, coumaric acid and protocatechuic acid as the major components of these anthelmintically active ferns.
Multi-headed deep learning-based estimator for correlated-SIRV Pareto type II distributed clutter
Authors: Kerbaa Taha Hocine , Mezache Amar , Gini Fulvio , Greco Maria S.
Published: July 2023

This paper deals with the problem of estimating the parameters of heavy-tailed sea clutter in high-resolution radar, when the clutter is modeled by the correlated Pareto type II distribution. Existing estimators based on the maximum likelihood (ML) approach, integer-order moments (IOM) approach, fractional-order moments (FOM), and log-moments (log-MoM) have shown to be sensitive to changes in data correlation. In this work, we resort to a deep learning (DL) approach based on a multi-headed architecture to overcome this problem. Offline training of the artificial neural networks (ANN) is carried out by using several combinations of the clutter parameters, with different correlation degrees. To assess the performance of the proposed estimator, we resort to Monte Carlo simulation, and we observed that it has superior performance over existing approaches in terms of estimation mean square error (MSE) and robustness to changes of the clutter correlation coefficient.
A systematic literature review of economic evaluation studies of interventions impacting antimicrobial resistance
Authors: Painter Chris , Faradiba Dian , Chavarina Kinanti Khansa , Sari Ella Nanda , Teerawattananon Yot , Aluzaite Kristina , Ananthakrishnan Aparna
Published: July 2023

Background

Antimicrobial resistance (AMR) is accelerated by widespread and inappropriate use of antimicrobials. Many countries, including those in low- and middle- income contexts, have started implementing interventions to tackle AMR. However, for many interventions there is little or no economic evidence with respect to their cost-effectiveness. To help better understand the scale of this evidence gap, we conducted a systematic literature review to provide a comprehensive summary on the value for money of different interventions affecting AMR.

Methods

A systematic literature review was conducted of economic evaluations on interventions addressing AMR. a narrative synthesis of findings was produced. Systematic searches for relevant studies were performed across relevant databases and grey literature sources such as unpublished studies, reports, and other relevant documents. All identified economic evaluation studies were included provided that they reported an economic outcome and stated that the analysed intervention aimed to affect AMR or antimicrobial use in the abstract. Studies that reported clinical endpoints alone were excluded. Selection for final inclusion and data extraction was performed by two independent reviewers. A quality assessment of the evidence used in the included studies was also conducted.

Results

28,597 articles were screened and 35 articles were identified that satisfied the inclusion criteria. The review attempted to answer the following questions: (1) What interventions to address AMR have been the subject of an economic evaluation? (2) In what types of setting (e.g. high-income, low-income, regions etc.) have these economic evaluations been focused? (3) Which interventions have been estimated to be cost-effective, and has this result been replicated in other settings/contexts? (4) What economic evaluation methods or techniques have been used to evaluate these interventions? (5) What kind and quality of data has been used in conducting economic evaluations for these interventions?

Discussion

The review is one of the first of its kind, and the most recent, to systematically review the literature on the cost-effectiveness of AMR interventions. This review addresses an important evidence gap in the economics of AMR and can assist AMR researchers’ understanding of the state of the economic evaluation literature, and therefore inform future research.

Systematic review registration PROSPERO (CRD42020190310).