bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost effectiveness of preemptive school closures to mitigate pandemic influenza outbreaks of differing severity in the United States
Authors: Dauelsberg Lori R. , Maskery Brian , Joo Heesoo , Germann Timothy C. , Del Valle Sara Y. , Uzicanin Amra
Published: January 2024

Background

Nonpharmaceutical interventions (NPIs) may be considered as part of national pandemic preparedness as a first line defense against influenza pandemics. Preemptive school closures (PSCs) are an NPI reserved for severe pandemics and are highly effective in slowing influenza spread but have unintended consequences.

Methods

We used results of simulated PSC impacts for a 1957-like pandemic (i.e., an influenza pandemic with a high case fatality rate) to estimate population health impacts and quantify PSC costs at the national level using three geographical scales, four closure durations, and three dismissal decision criteria (i.e., the number of cases detected to trigger closures). At the Chicago regional level, we also used results from simulated 1957-like, 1968-like, and 2009-like pandemics. Our net estimated economic impacts resulted from educational productivity costs plus loss of income associated with providing childcare during closures after netting out productivity gains from averted influenza illness based on the number of cases and deaths for each mitigation strategy.

Results

For the 1957-like, national-level model, estimated net PSC costs and averted cases ranged from $7.5 billion (2016 USD) averting 14.5 million cases for two-week, community-level closures to $97 billion averting 47 million cases for 12-week, county-level closures. We found that 2-week school-by-school PSCs had the lowest cost per discounted life-year gained compared to county-wide or school district–wide closures for both the national and Chicago regional-level analyses of all pandemics. The feasibility of spatiotemporally precise triggering is questionable for most locales. Theoretically, this would be an attractive early option to allow more time to assess transmissibility and severity of a novel influenza virus. However, we also found that county-wide PSCs of longer durations (8 to 12 weeks) could avert the most cases (31–47 million) and deaths (105,000–156,000); however, the net cost would be considerably greater ($88-$103 billion net of averted illness costs) for the national-level, 1957-like analysis.

Conclusions

We found that the net costs per death averted ($180,000-$4.2 million) for the national-level, 1957-like scenarios were generally less than the range of values recommended for regulatory impact analyses ($4.6 to 15.0 million). This suggests that the economic benefits of national-level PSC strategies could exceed the costs of these interventions during future pandemics with highly transmissible strains with high case fatality rates. In contrast, the PSC outcomes for regional models of the 1968-like and 2009-like pandemics were less likely to be cost effective; more targeted and shorter duration closures would be recommended for these pandemics.
Barriers and facilitators to reducing low-value care for the management of low back pain in Iran: a qualitative multi-professional study
Authors: Parvar Seyedeh Yasamin , Mojgani Parviz , Lankarani Kamran Bagheri , Poursaeed Fereshteh , Mohamadi Jahromi Leila Sadat , Mishra Vinaytosh , Abbasi Alireza , Shahabi Saeed
Published: January 2024

Introduction

Low back pain (LBP) is a prevalent musculoskeletal disorder with a wide range of etiologies, ranging from self-limiting conditions to life-threatening diseases. Various modalities are available for the diagnosis and management of patients with LBP. However, many of these health services, known as low-value care (LVC), are unnecessary and impose undue financial costs on patients and health systems. The present study aimed to explore the perceptions of service providers regarding the facilitators and barriers to reducing LVC in the management of LBP in Iran.

Methods

This qualitative descriptive study interviewed a total of 20 participants, including neurosurgeons, physiatrists, orthopedists, and physiotherapists, who were selected through purposive and snowball sampling strategies. The collected data were analyzed using the thematic content analysis approach.

Results

Thirty-nine sub-themes, with 183 citations, were identified as barriers, and 31 sub-themes, with 120 citations, were defined as facilitators. Facilitators and barriers to reducing LVC for LBP, according to the interviewees, were categorized into five themes, including: (1) individual provider characteristics; (2) individual patient characteristics; (3) social context; (4) organizational context; and (5) economic and political context. The ten most commonly cited barriers included unrealistic tariffs, provider-induced demand, patient distrust, insufficient time allocation, a lack of insurance coverage, a lack of a comprehensive referral system, a lack of teamwork, cultural challenges, a lack of awareness, and defensive medicine. Barriers such as adherence to clinical guidelines, improving the referral system, improving the cultural status of patients, and facilitators such as strengthening teamwork, developing an appropriate provider-patient relationship, improving the cultural status of the public, motivating the patients, considering an individualized approach, establishing a desirable payment mechanism, and raising the medical tariffs were most repeatedly stated by participants.

Conclusion

This study has pointed out a great number of barriers and facilitators that shape the provision of LVC in the management of LBP in Iran. Therefore, it is essential for relevant stakeholders to consider these findings in order to de-implement LVC interventions in the process of LBP management.
Lung molecular and histological changes in type 2 diabetic rats and its improvement by high-intensity interval training
Authors: Rajizadeh Mohammad Amin , Khoramipour Kayvan , Joukar Siyavash , Darvishzadeh-Mahani Fatemeh , Iranpour Maryam , Bejeshk Mohammad Abbas , Zaboli Maryam Doustaki
Published: January 2024

Background

Type 2 diabetes (T2D) leads to serious respiratory problems. This study investigated the effectiveness of high-intensity interval training (HIIT) on T2D-induced lung injuries at histopathological and molecular levels.

Methods

Forty-eight male Wistar rats were randomly allocated into control (CTL), Diabetes (Db), exercise (Ex), and Diabetes + exercise (Db + Ex) groups. T2D was induced by a high-fat diet plus (35 mg/kg) of streptozotocin (STZ) administration. Rats in Ex and Db + Ex performed HIIT for eight weeks. Tumor necrosis factor-alpha (TNFα), Interleukin 10 (IL-10), BAX, Bcl2, Lecithin, Sphingomyelin (SPM) and Surfactant protein D (SPD) levels were measured in the bronchoalveolar lavage fluid (BALF) and malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured in lung tissue. Lung histopathological alterations were assessed by using H&E and trichrome mason staining.

Results

Diabetes was significantly associated with imbalance in pro/anti-inflammatory, pro/anti-apoptosis and redox systems, and reduced the SPD, lecithin sphingomyelin and alveolar number. Performing HIIT by diabetic animals increased Bcl2 (P < 0.05) and IL10 (P < 0.01) levels as well as surfactants components and TAC (P < 0.05) but decreased fasting blood glucose (P < 0.001), TNFα (P < 0.05), BAX (P < 0.05) and BAX/Bcl2 (P < 0.001) levels as well as MDA (P < 0.01) and MDA/TAC (P < 0.01) compared to the diabetic group. Furthermore, lung injury and fibrosis scores were increased by T2D and recovered in presence of HIIT.

Conclusion

These findings suggested that the attenuating effect of HIIT on diabetic lung injury mediated by reducing blood sugar, inflammation, oxidative stress, and apoptosis as well as improving pulmonary surfactants components.

Graphical Abstract

Type 2 diabetes increased inflammation, oxidative stress and apoptosis and reduced pulmonary surfactants , while high intensity training improved these negative effects
Longitudinal analysis of quality of life in primary lung cancer patients with chlamydia pneumoniae infection: a time-to-deterioration model
Authors: Chen Zishan , Zhuang Jinman , Liu Maolin , Xu Xinying , Liu Yuhang , Yang Shuyan , Xie Jinbao , Lin Nanlong , Lai Fancai , He Fei
Published: January 2024

Background

Chlamydia pneumoniae (Cpn) IgG and IgA has been strongly linked to lung cancer, but its impact on patients' quality of life remains unclear. Our objective was to investigate the relationship between pre-treatment Cpn IgG and IgA and time to deterioration (TTD) of the HRQoL in patients with primary lung cancer.

Methods

A prospective hospital-based study was conducted from June 2017 to December 2018, enrolling 82 patients with primary lung cancer admitted to the First Affiliated Hospital of Fujian Medical University for questionnaire surveys. Cpn IgG and IgA was detected by microimmunofluorescence method. HRQoL was assessed at baseline and during follow-up using the EORTC Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13). HRQoL scores were calculated using the QoLR package, and TTD events were determined (minimum clinically significant difference = 5 points). Cox regression analysis was used to evaluate the effect of Cpn IgG and IgA on HRQoL.

Results

We investigated the relationship between Cpn IgG and IgA and quality of life in patients with primary lung cancer. The study was found that 75.61% of cases were Cpn IgG + and 45.12% were Cpn IgA + . Cpn IgA + IgG + was 41.46%. For EORTC QLQ-C30, Physical function (PF) and Pain (PA) TTD events on the functional scale and Symptom scale were the most common during follow-up. After adjusting for gender and smoking status, Pre-treatment Cpn IgA + was found to signifcantly delay TTD of Physical functioning(HR = 0.539, 95% CI: 0.291–0.996, P = 0.048). In addition, Cpn IgG + before treatment significantly delayed TTD in Emotional functioning (HR = 0.310, 95% CI: 0.115–0.836, P = 0.021). For EORTC QLQ-LC13, deterioration of dyspnea (LC-DY) was the most common event. However, Cpn IgG and IgA before treatment had no effect on the TTD of EORTC QLQ-LC13 items.

Conclusions

According to EORTC QLQ-C30 and EORTC QLQ-LC13, Cpn IgA delayed TTD in Physical functioning and Cpn IgG delayed TTD in Emotional functioning.
Risk factors for postoperative delirium in orthopaedic hip surgery patients: a database review
Authors: Callan Kylie T. , Donnelly Megan , Lung Brandon , McLellan Maddison , DiGiovanni Ryan , McMaster William , Yang Steven , Stitzlein Russell
Published: January 2024

Background

Postoperative delirium is a common problem affecting admitted patients that decreases patient satisfaction and increases the cost and complexity of care. The purpose of this study was to use the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to compare rates and risk factors of postoperative delirium for total hip arthroplasty (THA) and hemiarthroplasty patients indicated for osteoarthritis or proximal femur fracture.

Methods

The 2021 NSQIP database was queried for patients using Current Procedural Terminology (CPT) codes for THA and hemiarthroplasty and ICD-10 codes for osteoarthritis or proximal femur fracture. Demographic, past medical history, preoperative labs, and functional status data were recorded. Procedural data were also collected. Finally, postoperative outcomes and complications were reviewed.

Results

Overall, 16% of patients had postoperative delirium. Delirium patients were older on average (82.4 years vs. 80.7 years, p < 0.001), had a lower BMI (19.5 vs. 24.8, p < 0.001), were more likely to have a history of dementia (54.6% vs. 13.6%, p < 0.001), were less likely to have an independent functional status (p < 0.001) or live alone (p < 0.001), and were more likely to have sustained a recent fall (p < 0.001). Delirium patients were more likely to be hyponatremic or hypernatremic (p = 0.002), anemic (p < 0.001), and severely dehydrated (p < 0.001), among other lab abnormalities. Delirium patients were also more likely to experience additional postoperative complications, including pneumonia, pulmonary embolism, urinary tract infection, stroke, cardiac arrest, sepsis, and unplanned reoperation and readmission after discharge (all p < 0.05).

Conclusions

In this study, factors associated with postoperative delirium in patients undergoing hemiarthroplasty and THA were identified, including older age, lower BMI, certain medical conditions, decreased functional status, certain lab abnormalities, and postoperative complications. These findings can be used by clinicians to better inform care and to determine when orthopaedic joint replacement patients may be at an increased risk for postoperative delirium.
Gene sequencing applications to combat oral-cavity related disorders: a systematic review with meta-analysis
Authors: Abdul Nishath Sayed , Shenoy Mahesh , Reddy Naveen Rami , Sangappa Sunila Bukanakere , Shivakumar Ganiga Channaiah , Di Blasio Marco , Cicciù Marco , Minervini Giuseppe
Published: January 2024

Gene sequencing (GS) has numerous applications in combatting oral-cavity related disorders, including identifying genetic risk factors for diseases, developing targeted therapies, and improving diagnostic methods. It can help identify specific genetic mutations or variations that increase the risk of developing oral-cavity related disorders, such as oral cancer, periodontal disease, and cleft lip and palate. By the means of the following investigation, our primary objective was to assess the impact of GS technique in diagnosing and potentially treating diseases of the oral cavity by the means of a systematic review and meta-analysis. We commenced by defining the terms "gene sequencing," "oral cavity," and "disorders" as the important elements in our investigation's subject. Next, relevant databases like PubMed, Scopus, Embase, Web of Science, and Google Scholar were searched using keywords and synonyms for each concept, such as "genomic sequencing," "DNA sequencing," "oral health," "oral diseases," "dental caries," "periodontal disease," "oral cancer," and "salivary gland disorders." We combined several search terms, such as "gene sequencing AND oral disorders AND periodontal disease" or "oral cancer OR genomic sequencing," to further hone your search results using Boolean operators like "AND" and "OR." The oral cavity analysis obtained by CS in the selected articles revealed that most of the disorders were, in fact, a direct causal event influenced by the oral microbiome. Moreover, each sampled oral cavity evidenced a different microbial community, which predicted the precipitation of benign as well as malignant conditions, though not on a definitive basis. In the last ten years, genomic sequencing had advanced remarkably as majority of our selected studies observed, making it possible to diagnose and treat a variety of oral and maxillofacial disorders, including cancer. It was also used to ascertain a person's genetic make-up as well as to spot numerous genetic abnormalities that can predispose individuals to diseases. Understanding the different sequencing techniques and the resulting genetic anomalies may help with their clinical application and lead to an improvement in illness diagnosis and prognosis as a whole in the field of dentistry.
Evaluation of an objective staging system for assessment of cervical vertebral maturation
Authors: Alhamady Ahlam M. , Ishaq Ramy Abdul Rahman , Alhammadi Maged S. , Almashraqi Abeer A. , Alhashimi Najah
Published: January 2024

Background

The aim of this study was to evaluate an objective method for Cervical Vertebral Maturation (CVM) staging.

Methods

An initial sample of 647 Lateral Cephalometric Radiographs (LCR) were staged according to the CVM (Baccetti et al.) by 4 examiners. The final sample (n = 394) included LCR on which the staging of the 4 investigators matched. The objective staging was performed by a single operator. The sample was divided according to the maturational stages into pre-pubertal, pubertal and post-pubertal groups. Measurements were performed on the cervical vertebrae (C2, C3 and C4). The angle between posterior and superior borders for C3 and C4 was the Superior Wall Inclination Angle (SWIA). Concavity Depth (CD) for C2, C3 and C4, and Body Shape (BS) (ratio of width to height of C3 and C4). Measurements of the 3 groups were compared.

Results

Reliability of subjective staging was high (intra-observer reliability, 0.948; inter-observer reliability, 0.967). Good agreement was observed for the outcomes measured. Intra-observer reliability was good (0.918, 0.885 and 0.722 for CD, BS and SWIA, respectively). The same was for the inter-observer reliability results (0.902, 0.889 and 0.728 for CD, BS and SWIA, respectively). Significant differences were observed for mean values of SWIA and BS and median values of CD within maturational stage. Similar findings were observed when the outcomes were compared at different phases (P < 0.001).

Conclusions

A standardized, objective staging system using linear, angular measurements and ratios was applied for the determination of cervical vertebral maturation.
Two‑year clinical performance of indirect restorations fabricated from CAD/CAM nano hybrid composite versus lithium disilicate in mutilated vital teeth. A randomized controlled trial
Authors: Elmoselhy Haneen Ahmad Shafik , Hassanien Olfat EL Sayed , Haridy Mohamed Fouad , Salam El Baz Maha Abd El , Saber Shehabeldin
Published: January 2024

Trial design

This is a randomized, controlled, superiority, double-blinded, parallel-group, two-arms trial with an allocation ratio of 1:1. The aim of this trial was to compare the two-year clinical performance of partial indirect restorations fabricated from CAD/CAM nano-hybrid composite and ceramic lithium disilicate blocks using the modified USPHS criteria.

Methods

In two parallel groups (n = 50 restorations), fifty participants having mutilated vital teeth with a minimum of two remaining walls were randomly enrolled in this trial and received indirect restorations of either nano-hybrid composite resin blocks (Brilliant, Coltene, Switzerland) or Lithium Disilicate (IPS Emax CAD). The restorations were assessed using modified USPHS criteria by two independent blinded assessors at baseline, six months, one-year and two years follow-up visits. Categorical and ordinal data were presented as frequencies and percentages. Categorical data were analyzed using the chi-square test. Ordinal data were analyzed using the Mann-Whitney U test for intergroup comparisons and Freidman’s test followed by the Nemenyi post hoc test for intragroup comparisons. Numerical data were presented as mean and standard deviation values. They were analyzed for normality using the Shapiro-Wilk test. Data were found to be normally distributed and were analyzed using the independent t-test. The significance level was set at p ≤ 0.05 within all tests.

Results

Forty-eight participants received the allocated intervention and completed the follow-up periods. There was a statistically significant difference between both tested materials for all USPHS criteria regarding Marginal integrity and Marginal discoloration at six-months Follow-up, but with no statistically significant difference at one- and two-year follow-up.

Conclusions

Both materials showed an acceptable, successful clinical performance along the two-years follow-up period.

Clinical relevance

The CAD/CAM nano-hybrid composite blocks are as reliable as Lithium disilicate for restoring mutilated vital teeth.
Evaluation of micromotion in multirooted root analogue implants embedded in synthetic bone blocks: an in vitro study
Authors: Aldesoki Mostafa , Bourauel Christoph , Elshazly Tarek M. , Schkommodau Erik , Keilig Ludger
Published: January 2024

Background

While conventional threaded implants (TI) have proven to be effective for replacing missing teeth, they have certain limitations in terms of diameter, length, and emergence profile when compared to customised root analogue implants (RAI). To further investigate the potential benefits of RAIs, the aim of this study was to experimentally evaluate the micromotion of RAIs compared to TIs.

Methods

A 3D model of tooth 47 (mandibular right second molar) was segmented from an existing cone beam computed tomography (CBCT), and a RAI was designed based on this model. Four RAI subgroups were fabricated as follows: 3D-printed titanium (PT), 3D-printed zirconia (PZ), milled titanium (MT), milled zirconia (MZ), each with a sample size of n = 5. Additionally, two TI subgroups (B11 and C11) were used as control, each with a sample size of n = 5. All samples were embedded in polyurethane foam artificial bone blocks and subjected to load application using a self-developed biomechanical Hexapod Measurement System. Micromotion was quantified by analysing the load/displacement curves.

Results

There were no statistically significant differences in displacement in Z-axis (the loading direction) between the RAI group and the TI group. However, within the RAI subgroups, PZ exhibited significantly higher displacement values compared to the other subgroups (p < 0.05). In terms of the overall total displacement, the RAI group showed a statistically significant higher displacement than the TI group, with mean displacement values of 96.5 µm and 55.8 µm for the RAI and TI groups, respectively.

Conclusions

The RAI demonstrated promising biomechanical behaviour, with micromotion values falling within the physiological limits. However, their performance is less predictable due to varying anatomical designs.
Impact of the Covid-19 pandemic and ensuing online teaching on pre-clinical medical education
Authors: Goudarzi Houman , Onozawa Masahiro , Takahashi Makoto
Published: January 2024

Background

Major disruptions and changes in education have occurred worldwide as a result of the coronavirus disease (COVID-19) pandemic and the ensuing shift from in-person to online education. However, the effect of such changes on medical education, its magnitude, and the learning domains impacted by such rapid changes have not been adequately addressed, particularly with regard to objective assessment approaches.

Methods

Second-year medical students enrolled in our Medical English Course between 2019 and 2021 were recruited from Hokkaido University, Japan (N = 321) to participate in this study. We evaluated the potential impact of teaching styles on the academic performance of students before (2019; face-to-face) and during (2020; online; 2021; in-person and online) the pandemic. We examined the potential effect of three teaching styles––in-person (2019), online (2020), and a combination of these (2021) on the academic performance of medical students using: (i) subjective assessment of self-reported general English skills, including reading, writing, listening, and speaking; and (ii) objective assessment of medical terminology scores, evidence-based medicine (EBM) skills, and final written exam scores.

Results

In-person education significantly improved listening and speaking skills in 2019 (p < 0.001). This trend was observed for writing skills in an online course in 2020 (p = 0.001). With the combined teaching method, students reported significant improvements in all four English skills. In our objective assessments, medical terminology improved significantly post-test versus pre-test for all three teaching styles, and we found that the online course did not adversely affect the gain in medical terminology knowledge during the course. Additionally, we did not find any significant differences across the three applied teaching styles regarding EBM skill levels. It is noteworthy that the students taking online courses had a significantly higher final exam score (mean ± SD; 82.8 ± 8.2) than in in-person (78.6 ± 8.8) and combined (79.7 ± 12.1) teaching styles.

Conclusions

In our study, the online/combined courses showed better academic outcomes compared to the face-to-face course in the preclinical clerkship. Although the current results need to be replicated on a larger scale, online/combined courses can continue and evolve in the post-pandemic education of medical students. Medical schools and institutions should consider incorporating such courses, especially combined courses, into their curricula in the future to improve the effectiveness, accessibility, and flexibility of medical education.
A qualitative report on experiences of participants in the young innovative leadership program
Authors: Vaezi Atefeh , Khoshgoftar Mohadeseh , Teimouri-Jervekani Zahra , Haghjooy Javanmard Shaghayegh
Published: January 2024

Background

Leadership in health system is a universal challenge. The Young Innovative Leadership Program (YILP) designed for undergraduate and postgraduate medical sciences students, implemented at the Isfahan University of Medical Sciences, aimed to cultivate leadership capacities through a 16-week training program. This program comprises ten modules covering innovation, change leadership, and management skills, with mentor-facilitated group discussions. This study aimed to provide a qualitative report of the experiences of participants in the YILP.

Methods

A qualitative study was conducted in 2022, three months after the end of the training program, to investigate the participants’ perspectives. Data was extracted through in-depth, semi-structured interviews with 14 participants.

Results

In this study 14 undergraduate and postgraduate medical sciences students who had participated in the YILP the previous year were included. Four main categories emerged from the interviews: “emergence of new horizons”, “values as beacon”, “an expanded toolbox”, and “program’s structure: a learning atmosphere”.

Conclusions

The results of our study indicated that medical science students would benefit from leadership development programs. In this regard, the framework utilized to implement YILP could serve as a role model.
Strategies to prevent medical errors by nursing interns: a qualitative content analysis
Authors: Heydarikhayat Nastaran , Ghanbarzehi Nezar , Sabagh Kimiya
Published: January 2024

Background

Nursing interns often face the serious challenges and stress of clinical training. Identifying effective strategies in reducing medical errors can improve student performance and decrease patient risk and injury from errors. The purpose of this study was to identify strategies to prevent medical errors by nursing interns in Medical Universities in Sistan and Baluchistan, Southeast of Iran.

Methods

This is a qualitative study using a content analysis approach. Purposive sampling was used. The study was conducted in 3 medical universities. Ten nursing interns participated in this study. Open-ended, semi-structured, and face-to-face, interviews were used to explore the experience of nursing interns about strategies to prevent medical errors during their internship.

Results

Findings include 20 subcategories, 6 categories and one theme. The main theme is “strategies to prevent medical errors during internship”. Six categories included “strategies to prevent medical errors during internship”. These included “Professional acceptance and support”, “Revision of the implementation of the educational curriculum”, “Retraining courses for challenging skills”, ”Creating learning opportunities” “Professionalization”, and “Facilities and requirements”.

Conclusions

Preventing medical errors requires different strategies before and during nursing internship. Error prevention strategies include retraining and preparatory courses for challenging areas, evaluation of students’ performance, and accepting students as members of the health care team, respecting and supporting them and protecting their rights. Learning from medical errors, analysis and reflection on errors should be part of the curriculum during the internship.
Impact of medical insurance access negotiation on the utilization of innovative anticancer drugs in China: an interrupted time series analysis
Authors: Li Cui , Zhu Jingmin , Shan Linghan , Zhou Yingyu , Liu Gang , Zhu Hong , Wu Qunhong , Cui Yu , Kang Zheng
Published: January 2024

Background

The high costs of innovative anticancer drugs hinder a number of cancer patients’ access to these drugs in China. To address this problem, in 2018, the medical insurance access negotiation (MIAN) policy was implemented, when the prices of 17 innovative anticancer drugs were successfully negotiated and they were therefore included in the reimbursement list. This study aimed to explore the impact of the MIAN policy on the utilization of innovative anticancer drugs.

Methods

With monthly data on drug expenditures and defined daily doses (DDDs) of each innovative anticancer drug from January 2017 to December 2019, interrupted time series analysis was employed to estimate both the instant (change in the level of outcome) and long-term (change in trends of outcomes) impacts of the MIAN policy on drug utilization in terms of drug expenditures and DDDs. Our sample consists of 12 innovative anticancer drugs.

Results

From January 2017 to December 2019, the monthly drug expenditures and DDDs of 12 innovative anticancer drugs increased by about 573% (from US$8,931,809.30 to US$51,138,331.09) and 1400% (from 47,785 to 668,754), respectively. Overall, the implementation of the MIAN policy led to instant substantial increases of US$8,734,414 in drug expenditures and 158,192.5 in DDDs. Moreover, a sharper upward trend over time was reported, with increases of US$2,889,078 and 38,715.3 in the monthly growth rates of drug expenditures and DDDs, respectively. Regarding individual innovative anticancer drugs, the most prominent instant change and trend change in drug utilization were found for osimertinib, crizotinib, and ibrutinib. In contrast, the utilization of pegaspargase was barely affected by the MIAN policy.

Conclusions

The MIAN policy has effectively promoted the utilization of innovative anticancer drugs. To ensure the continuity of the effects and eliminate differentiation, supplementary measures should be carried out, such as careful selection of drugs for medical insurance negotiations, a health technology assessment system and a multichannel financing mechanism.
What preconception health services would the public find when searching the internet in Australia?: results from a simulated internet-search study
Authors: Steel Amie , Gibson Harriet , Adams Jon , Schoenaker Danielle
Published: January 2024

Background

Australian preventive health strategy outlines the importance of preconception health in improving health in the community, across multiple generations and places primary and community healthcare services as a central pillar to effective preconception care. However, there is no national implementation plan to see preconception care proactively offered in healthcare settings in Australia. Instead, there is evidence that most women search the internet for information about pregnancy planning and preparation. In response, this study explores the availability and characteristics of health services found by searching for preconception care online in Australia.

Method

Simulated Google searches were conducted using search terms ‘preconception’ and the name of a city/town with a population > 50,000. Related terms, ‘fertility’ and ‘pregnancy’ were also searched. Characteristics of the health services and the information available on relevant websites were extracted and reported descriptively.

Results

The searches identified 831 website links, including 430 websites for health services. The health services were most often located in cities/towns with populations equal to or less than 200 000 (54.2%), and housing multiple health professionals (69.8%) including a specialist doctor (66.5%), nurse (20.9%), psychologist/counsellor (2.0%) and/or naturopath (13.0%). All the health services identified online explicitly mentioned women among their target populations, while 69.1% (n = 297) also referred to providing services for men or partners. More than one third of websites included blogs (36.9%) while external links were included in 10.8% of the online sites.

Conclusions

This study provides a preliminary examination of health services that may be found through internet-based searching by Australian consumers seeking health advice or support prior to becoming pregnant. Our descriptive results suggest couples may find a variety of health professionals when seeking health services for preconception care. Future research involving co-design of search terms with consumers, ongoing monitoring of health services and ensuring access to meaningful, and accurate information found through internet-searching are all necessary to ensure people of reproductive age are able to access the preconception health information and care they need.
Application of multiple sgRNAs boosts efficiency of CRISPR/Cas9-mediated gene targeting in Arabidopsis
Authors: Li Jing , Kong Dali , Ke Yongping , Zeng Wenjie , Miki Daisuke
Published: January 2024

Background

Precise gene targeting (GT) is a powerful tool for heritable precision genome engineering, enabling knock-in or replacement of the endogenous sequence via homologous recombination. We recently established a CRISPR/Cas9-mediated approach for heritable GT in Arabidopsis thaliana (Arabidopsis) and rice and reported that the double-strand breaks (DSBs) frequency of Cas9 influences the GT efficiency. However, the relationship between DSBs and GT at the same locus was not examined. Furthermore, it has never been investigated whether an increase in the number of copies of sgRNAs or the use of multiple sgRNAs would improve the efficiency of GT.

Results

Here, we achieved precise GT at endogenous loci Embryo Defective 2410 (EMB2410) and Repressor of Silencing 1 (ROS1) using the sequential transformation strategy and the combination of sgRNAs. We show that increasing of sgRNAs copy number elevates both DSBs and GT efficiency. On the other hand, application of multiple sgRNAs does not always enhance GT efficiency. Our results also suggested that some inefficient sgRNAs would play a role as a helper to facilitate other sgRNAs DSBs activity.

Conclusions

The results of this study clearly show that DSB efficiency, rather than mutation pattern, is one of the most important key factors determining GT efficiency. This study provides new insights into the relationship between sgRNAs, DSBs, and GTs and the molecular mechanisms of CRISPR/Cas9-mediated GTs in plants.
The accumulation of modular serine protease mediated by a novel circRNA sponging miRNA increases Aedes aegypti immunity to fungus
Authors: Lu Tengfei , Ji Yannan , Chang Mengmeng , Zhang Xiaoming , Wang Yanhong , Zou Zhen
Published: January 2024

Background

Mosquitoes transmit many infectious diseases that affect human health. The fungus Beauveria bassiana is a biological pesticide that is pathogenic to mosquitoes but harmless to the environment.

Results

We found a microRNA (miRNA) that can modulate the antifungal immunity of Aedes aegypti by inhibiting its cognate serine protease. Fungal infection can induce the expression of modular serine protease (ModSP), and ModSP knockdown mosquitoes were more sensitive to B. bassiana infection. The novel miRNA-novel-53 is linked to antifungal immune response and was greatly diminished in infected mosquitoes. The miRNA-novel-53 could bind to the coding sequences of ModSP and impede its expression. Double fluorescence in situ hybridization (FISH) showed that this inhibition occurred in the cytoplasm. The amount of miRNA-novel-53 increased after miRNA agomir injection. This resulted in a significant decrease in ModSP transcript and a significant increase in mortality after fungal infection. An opposite effect was produced after antagomir injection. The miRNA-novel-53 was also knocked out using CRISPR-Cas9, which increased mosquito resistance to the fungus B. bassiana. Moreover, mosquito novel-circ-930 can affect ModSP mRNA by interacting with miRNA-novel-53 during transfection with siRNA or overexpression plasmid.

Conclusions

Novel-circ-930 affects the expression level of ModSP by a novel-circ-930/miRNA-novel-53/ModSP mechanism to modulate antifungal immunity, revealing new information on innate immunity in insects.
IGT/LAZY genes are differentially influenced by light and required for light-induced change to organ angle
Authors: Waite Jessica Marie , Dardick Christopher
Published: January 2024

Background

Plants adjust their growth orientations primarily in response to light and gravity signals. Considering that the gravity vector is fixed and the angle of light incidence is constantly changing, plants must somehow integrate these signals to establish organ orientation, commonly referred to as gravitropic set-point angle (GSA). The IGT gene family contains known regulators of GSA, including the gene clades LAZY, DEEPER ROOTING (DRO), and TILLER ANGLE CONTROL (TAC).

Results

Here, we investigated the influence of light on different aspects of GSA phenotypes in LAZY and DRO mutants, as well as the influence of known light signaling pathways on IGT gene expression. Phenotypic analysis revealed that LAZY and DRO genes are collectively required for changes in the angle of shoot branch tip and root growth in response to light. Single lazy1 mutant branch tips turn upward in the absence of light and in low light, similar to wild-type, and mimic triple and quadruple IGT mutants in constant light and high-light conditions, while triple and quadruple IGT/LAZY mutants show little to no response to changing light regimes. Further, the expression of IGT/LAZY genes is differentially influenced by daylength, circadian clock, and light signaling.

Conclusions

Collectively, the data show that differential expression of LAZY and DRO genes are required to enable plants to alter organ angles in response to light-mediated signals.
A chromosome-level genome for the nudibranch gastropod Berghia stephanieae helps parse clade-specific gene expression in novel and conserved phenotypes
Authors: Goodheart Jessica A. , Rio Robin A. , Taraporevala Neville F. , Fiorenza Rose A. , Barnes Seth R. , Morrill Kevin , Jacob Mark Allan C. , Whitesel Carl , Masterson Park , Batzel Grant O. , Johnston Hereroa T. , Ramirez M. Desmond , Katz Paul S. , Lyons Deirdre C.
Published: January 2024

Background

How novel phenotypes originate from conserved genes, processes, and tissues remains a major question in biology. Research that sets out to answer this question often focuses on the conserved genes and processes involved, an approach that explicitly excludes the impact of genetic elements that may be classified as clade-specific, even though many of these genes are known to be important for many novel, or clade-restricted, phenotypes. This is especially true for understudied phyla such as mollusks, where limited genomic and functional biology resources for members of this phylum have long hindered assessments of genetic homology and function. To address this gap, we constructed a chromosome-level genome for the gastropod Berghia stephanieae (Valdés, 2005) to investigate the expression of clade-specific genes across both novel and conserved tissue types in this species.

Results

The final assembled and filtered Berghia genome is comparable to other high-quality mollusk genomes in terms of size (1.05 Gb) and number of predicted genes (24,960 genes) and is highly contiguous. The proportion of upregulated, clade-specific genes varied across tissues, but with no clear trend between the proportion of clade-specific genes and the novelty of the tissue. However, more complex tissue like the brain had the highest total number of upregulated, clade-specific genes, though the ratio of upregulated clade-specific genes to the total number of upregulated genes was low.

Conclusions

Our results, when combined with previous research on the impact of novel genes on phenotypic evolution, highlight the fact that the complexity of the novel tissue or behavior, the type of novelty, and the developmental timing of evolutionary modifications will all influence how novel and conserved genes interact to generate diversity.
Refining and illuminating acetogenic Eubacterium strains for reclassification and metabolic engineering
Authors: Flaiz Maximilian , Poehlein Anja , Wilhelm Wiebke , Mook Alexander , Daniel Rolf , Dürre Peter , Bengelsdorf Frank R.
Published: January 2024

Background

The genus Eubacterium is quite diverse and includes several acetogenic strains capable of fermenting C1-substrates into valuable products. Especially, Eubacterium limosum and closely related strains attract attention not only for their capability to ferment C1 gases and liquids, but also due to their ability to produce butyrate. Apart from its well-elucidated metabolism, E. limosum is also genetically accessible, which makes it an interesting candidate to be an industrial biocatalyst.

Results

In this study, we examined genomic, phylogenetic, and physiologic features of E. limosum and the closest related species E. callanderi as well as E. maltosivorans. We sequenced the genomes of the six Eubacterium strains ‘FD’ (DSM 3662T), ‘Marburg’ (DSM 3468), ‘2A’ (DSM 2593), ‘11A’ (DSM 2594), ‘G14’ (DSM 107592), and ‘32’ (DSM 20517) and subsequently compared these with previously available genomes of the E. limosum type strain (DSM 20543T) as well as the strains ‘B2’, ‘KIST612’, ‘YI’ (DSM 105863T), and ‘SA11’. This comparison revealed a close relationship between all eleven Eubacterium strains, forming three distinct clades: E. limosum, E. callanderi, and E. maltosivorans. Moreover, we identified the gene clusters responsible for methanol utilization as well as genes mediating chain elongation in all analyzed strains. Subsequent growth experiments revealed that strains of all three clades can convert methanol and produce acetate, butyrate, and hexanoate via reverse β-oxidation. Additionally, we used a harmonized electroporation protocol and successfully transformed eight of these Eubacterium strains to enable recombinant plasmid-based expression of the gene encoding the fluorescence-activating and absorption shifting tag (FAST). Engineered Eubacterium strains were verified regarding their FAST-mediated fluorescence at a single-cell level using a flow cytometry approach. Eventually, strains ‘FD’ (DSM 3662T), ‘2A’ (DSM 2593), ‘11A’ (DSM 2594), and ‘32’ (DSM 20517) were genetically engineered for the first time.

Conclusion

Strains of E. limosum, E. callanderi, and E. maltosivorans are outstanding candidates as biocatalysts for anaerobic C1-substrate conversion into valuable biocommodities. A large variety of strains is genetically accessible using a harmonized electroporation protocol, and FAST can serve as a reliable fluorescent reporter protein to characterize genetically engineered cells. In total eleven strains have been assigned to distinct clades, providing a clear and updated classification. Thus, the description of respective Eubacterium species has been emended, improved, aligned, and is requested to be implemented in respective databases.
Asymptomatic Plasmodium falciparum carriage at the end of the dry season is associated with subsequent infection and clinical malaria in Eastern Gambia
Authors: Fogang Balotin , Lellouche Lionel , Ceesay Sukai , Drammeh Sainabou , Jaiteh Fatou K. , Guery Marc-Antoine , Landier Jordi , Haanappel Cynthia P. , Froberg Janeri , Conway David , D’Alessandro Umberto , Bousema Teun , Claessens Antoine
Published: January 2024

Background

Chronic carriage of asymptomatic low-density Plasmodium falciparum parasitaemia in the dry season may support maintenance of acquired immunity that protects against clinical malaria. However, the relationship between chronic low-density infections and subsequent risk of clinical malaria episodes remains unclear.

Methods

In a 2-years study (December 2014 to December 2016) in eastern Gambia, nine cross-sectional surveys using molecular parasite detection were performed in the dry and wet season. During the 2016 malaria transmission season, passive case detection identified episodes of clinical malaria.

Results

Among the 5256 samples collected, 444 (8.4%) were positive for P. falciparum. A multivariate model identified village of residence, male sex, age ≥ 5 years old, anaemia, and fever as independent factors associated with P. falciparum parasite carriage. Infections did not cluster over time within the same households or recurred among neighbouring households. Asymptomatic parasite carriage at the end of dry season was associated with a higher risk of infection (Hazard Ratio, HR = 3.0, p < 0.0001) and clinical malaria (HR = 1.561, p = 0.057) during the following transmission season. Age and village of residence were additional predictors of infection and clinical malaria during the transmission season.

Conclusion

Chronic parasite carriage during the dry season is associated with an increased risk of malaria infection and clinical malaria. It is unclear whether this is due to environmental exposure or to other factors.
Employment conditions and mental health of overseas female migrant domestic workers in Hong Kong: a parallel mediation analysis
Authors: Sumerlin Timothy S. , Kim Jean H. , Hui Alvin Yik-Kiu , Chan Dicken , Liao Tim , Padmadas Sabu , Fong Eric , Chung Roger Y.
Published: January 2024

Background

Female migrant domestic workers (MDW), approximately 8.5 million globally, often live in their employer’s home under vulnerable conditions. In Hong Kong, MDWs currently comprise 5% of the population. This study was conducted to assess the association between employment conditions and mental health, and the mediating roles stress and job satisfaction have, among female MDWs in Hong Kong.

Methods

Participants completed an online cross-sectional survey. A total of 1,965 survey were collected between August 2020 and August 2021. Questions in the survey were related to MDWs background information, employment conditions, stress, job satisfaction, and two mental health outcomes: anxiety and depression. An employment conditions score was created to assess the cumulative effect poor employment conditions had on mental health. A multicategorical parallel mediation analysis was used to assess the direct effect employment conditions have on mental health and the indirect effects through stress and job satisfaction.

Results

Overall, 17.7% of MDWs were reported to be suffering from anxiety and 30.8% from depression. An increase in poor employment conditions was statistically associated with an increase in both outcomes, while stress levels and job satisfaction mediated this association.

Conclusions

The findings call for increased scrutiny of employment conditions and mental well-being of MDWs.