bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an integrated predictive model for postoperative glioma-related epilepsy using gene-signature and clinical data
Authors: Li Lianwang , Zhang Chuanbao , Wang Zheng , Wang Yinyan , Guo Yuhao , Qi Chong , You Gan , Zhang Zhong , Fan Xing , Jiang Tao
Published: January 2023

Background

This study aimed to develop an integrated model for predicting the occurrence of postoperative seizures in patients with diffuse high-grade gliomas (DHGGs) using clinical and RNA-seq data.

Methods

Patients with DHGGs, who received prophylactic anti-epileptic drugs (AEDs) for three months following surgery, were enrolled into the study. The patients were assigned randomly into training (n = 166) and validation (n = 42) cohorts. Differentially expressed genes (DEGs) were identified based on preoperative glioma-related epilepsy (GRE) history. Least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to construct a predictive gene-signature for the occurrence of postoperative seizures. The final integrated prediction model was generated using the gene-signature and clinical data. Receiver operating characteristic analysis and calibration curve method were used to evaluate the accuracy of the gene-signature and prediction model using the training and validation cohorts.

Results

A seven-gene signature for predicting the occurrence of postoperative seizures was developed using LASSO logistic regression analysis of 623 DEGs. The gene-signature showed satisfactory predictive capacity in the training cohort [area under the curve (AUC) = 0.842] and validation cohort (AUC = 0.751). The final integrated prediction model included age, temporal lobe involvement, preoperative GRE history, and gene-signature-derived risk score. The AUCs of the integrated prediction model were 0.878 and 0.845 for the training and validation cohorts, respectively.

Conclusion

We developed an integrated prediction model for the occurrence of postoperative seizures in patients with DHGG using clinical and RNA-Seq data. The findings of this study may contribute to the development of personalized management strategies for patients with DHGGs and improve our understanding of the mechanisms underlying GRE in these patients.
Contextual, maternal, and infant factors in preventable infant deaths: a statewide ecological and cross-sectional study in Rio Grande do SUL, Brazil
Authors: Kreutz Ivete Maria , Santos Iná S.
Published: January 2023

Background

Ending preventable deaths of newborns and children under five by 2030 is among the United Nations Sustainable Development Goals. This study aimed to describe infant mortality rate due to preventable causes in Rio Grande do Sul (RS), the Southernmost state in Brazil. With 11,329,605 inhabitants and 141,568 live births in 2017, RS was the fifth most populous state in the country.

Method

An ecological and cross-sectional statewide study, with data extracted from records of the Mortality Information System, Death Certificates, and Live Birth Certificates for the year 2017. Preventability was estimated by applying the List of Causes of Deaths Preventable through Intervention of SUS (acronym for Sistema Unico de Saude - Brazilian Unified Health System) Intervention. Rates of preventable infant mortality (PIMR), preventable early neonatal mortality (PENMR), preventable late neonatal mortality (PLNMR), and preventable post-neonatal mortality (PPNMR) per 1000 live births (LB) were quantified. Incidence ratios, according to contextual characteristics (human development index of the health region and of the municipality; Gini index of the municipality), maternal characteristics at the time of delivery (age, education, self-reported skin color, presence of a partner, number of antenatal care consultations, and type of delivery), and characteristics of the child at the time of birth (gestational age, weight, and pregnancy type) were calculated.

Results

In 2017, there were 141,568 live births and 1425 deaths of infants younger than 1 year old, of which 1119 were preventable (PIMR = 7.9:1000 LB). The PENMR, PLNMR, and PPNMR were 4.1:1000 LB; 1.5:1000 LB; and 2.3:1000 LB, respectively. More than 60% of deaths in the first week and 57.5% in the late neonatal period could be reduced through adequate care of the woman during pregnancy. The most frequent preventable neonatal causes were related to prematurity, mainly acute respiratory syndrome, and non-specified bacterial septicemia. In the post-neonatal period, 31.8% of deaths could be prevented through adequate diagnostic and treatment.

Conclusions

The strategies needed to reduce preventable infant deaths should preferably focus on preventing prematurity, through adequate care of the woman during pregnancy.
Development of inferiority-compensation scale among high school students
Authors: Yang Di , Qiu Baiyang , Jiang Jin , Xia Youkui , Li Lingxiao , Li Yanting , Luo Longli , Liu Xiaocui , Meng Jing
Published: January 2023

An increasing number of high school students are inflicted by different degrees of mental disorders in learning, such as moodiness, learning difficulties, test anxiety, difficulty coping with frustration, etc., which are one of the factors leading to the inferiority of students. In the present study, the initial scale of inferiority compensation for high school students was developed through literature searching, expert evaluation, interviews, and an open scale. 1187 high school students were tested in different periods, after deleting an invalid 83 scales, including 461 copies of valid scale of exploratory factor analysis in the first stage and 643 copies of valid scale of confirmatory factor analysis in the second stage. The results showed that the inferiority compensation scale for high school students consisted of two sub-scale: self-compensation and others-compensation, ach two were composed of five dimensions including academic performance, physical fitness, social communication, appearance, and self-esteem. Confirmatory factor analysis showed that the total scale and the two sub-scale all had good structural validity (RMSEA≤0.08; CFI&IFI ≥ 0.9), and the combined reliability and values (such as the correlation coefficient of each dimension) of the two sub-scale were within the ideal range. With good reliability and validity (Cronbacα&KMO ≥ 0.90), and meeting the requirements of psychometrics, the scale can be used in the relevant research and practice of inferiority compensation for high school students.
Incivility in medical education: a scoping review
Authors: Abate Laura E. , Greenberg Larrie
Published: January 2023

Incivility in the workplace, school and political system in the United States has permeated mass and social media in recent years and has also been recognized as a detrimental factor in medical education. In this scoping review, we use the term incivility to encompass a spectrum of behaviors that occur across the continuum of medical education, and which include verbal abuse including rude or dismissive conduct, sexual and racial harassment and discrimination, and sexual and physical assault. We identified research on incivility involving medical students, residents and fellows, and faculty in North America to describe multiple aspects of incivility in medical education settings published since 2000. Our results reinforce that incivility is likely under-reported across the continuum of medical education and also confirmed incidences of incivility involving nursing personnel and patients, not emphasized in previous reviews. The authors suggest a zero-tolerance national policy if this problem is to be resolved.
Clinical decision-making and adaptive expertise in residency: a think-aloud study
Authors: Gamborg Maria Louise , Mehlsen Mimi , Paltved Charlotte , Vetter Sigrid Strunge , Musaeus Peter
Published: January 2023

Clinical decision-making (CDM) is the ability to make clinical choices based on the knowledge and information available to the physician. It often refers to individual cognitive processes that becomes more dependent with the acquisition of experience and knowledge. Previous research has used dual-process theory to explain the cognitive processes involved in how physicians acquire experiences that help them develop CDM. However, less is known about how CDM is shaped by the physicians’ situated cognition in the clinical environment. This is especially challenging for novice physicians, as they need to be adaptive to compensate for the lack of experience. The adaptive expert framework has been used to explain how novice physicians learn, but it has not yet been explored, how adaptive expertise is linked to clinical decision-making amongst novice physicians.

This study aimed to analyse how residents utilize and develop adaptive expert cognition in a natural setting. By describing cognitive processes through verbalization of thought processes, we sought to explore their CDM strategies considering the adaptive expert framework.

We used concurrent and retrospective think-aloud interviews in a natural setting of an emergency department (ED) at a university hospital, to query residents about their reasoning during a patient encounter. We analysed data using protocol analysis to map cognitive strategies from these verbalizations. Subsequently in a narrative analysis, we compared these strategies with the literature on adaptive expertise.

Fourteen interviews were audio recorded over the course for 17 h of observation. We coded 78 informational concepts and 46 cognitive processes. The narrative analysis demonstrated how epistemic distance was prevalent in the initial CDM process and self-regulating processes occurred during hypothesis testing. However, residents who too quickly moved on to hypothesis testing tended to have to redirect their hypothesis more often, and thus be more laborious in their CDM. Uncertainty affected physicians’ CDM when they did not reconcile their professional role with being allowed to be uncertain. This allowance is an important feature of orientation to new knowledge as it facilitates the evaluation of what the physician does not know.

For the resident to learn to act as an adaptive decision-maker, she relied on contextual support. The professional role was crucial in decisional competency. This supports current literature, which argues that role clarification helps decisional competency. This study adds that promoting professional development by tolerating uncertainty may improve adaptive decisional competency.
Empirical studies on how ethical recommendations are translated into practice: a cross-section study on scope and study objectives
Authors: Schwietering Johannes , Langhof Holger , Strech Daniel
Published: January 2023

Background

Empirical research can become relevant for bioethics in at least two ways. First, by informing the development or refinement of ethical recommendations. Second, by evaluating how ethical recommendations are translated into practice. This study aims to investigate the scope and objectives of empirical studies evaluating how ethical recommendations are translated into practice.

Methods

A sample of the latest 400 publications from four bioethics journals was created and screened. All publications were included if they met one of the following three criteria: (1) evaluative empirical research, (2) non-evaluative empirical research and (3) borderline cases. For all publications categorized as evaluative empirical research we analyzed which objects (norms and recommendations) had been evaluated.

Results

234 studies were included of which 54% (n = 126) were categorized as non-evaluative empirical studies, 36% (n = 84) as evaluative empirical studies, and 10% (n = 24) as borderline cases. The object of evaluation were aspirational norms in 5 of the 84 included evaluative empirical studies, more specific norms in 14 (16%) studies and concrete best practices in 65 (77%) studies. The specific best practices can be grouped under five broader categories: ethical procedures, ethical institutions, clinical or research practices, educational programs, and legal regulations.

Conclusions

This mapping study shows that empirical evaluative studies can be found at all stages in the translational process from theory to best practices. Our study suggests two intertwined dimensions for structuring the field of evaluative/translational empirical studies in bioethics: First, three broader categories of evaluation objects and second five categories for types of best practices.

Trial registration: The methodology used was described in a study protocol that was registered publicly on the Open Science Framework (https://osf.io/r6h4y/).
Investigating nurses’ knowledge and attitudes about delirium in older persons: a cross-sectional study
Authors: Papaioannou Maria , Papastavrou Evridiki , Kouta Christiana , Tsangari Haritini , Merkouris Anastasios
Published: January 2023

Introduction

Delirium is the most common emergency for older hospitalized patients that demands urgent treatment, otherwise it can lead to more severe health conditions. Nurses play a crucial part in diagnosing delirium and their competencies facilitate the appropriate treatment and management of the condition.

Aim

This study aims to enhance the understanding of delirium care by exploring both knowledge and attitudes of nurses toward patients in acute care hospital wards and the possible association between these two variables.

Method

The Nurses Knowledge of Delirium Questionnaire (NKD) and the Attitude Tool of Delirium (ATOD) that were created for the said inquiry, were disseminated to 835 nurses in the four largest Public Hospitals of the Republic. These tools focused particularly on departments with increased frequency of delirium (response rate = 67%).

Results

Overall nurses have limited knowledge of acute confusion/delirium. The average of correct answers was 42.2%. Only 38% of the participants reported a correct definition of delirium, 41.6 correctly reported the tools to identify delirium and 42.5 answered correctly on the factors leading to delirium development. The results of the attitudes’ questionnaire confirmed that attitudes towards patients with delirium may not be supportive enough. A correlation between the level of nurses’ knowledge and their attitude was also found. The main factors influencing the level of knowledge and attitudes were gender, education, and workplace.

Conclusion

The findings of this study are useful for the international audience since they can be used to develop and modify educational programmes in order to rectify the knowledge deficits and uninformed attitudes towards patients with delirium. The development of a valid and reliable instrument for the evaluation of attitudes will help to further assess nurses’ attitudes. Furthermore, the results are even more important and useful on a national level since there is no prior data on the subject area, making this study the first of its kind.
Comparison of clinician diagnosis of COVID-19 with real time polymerase chain reaction in an adult-representative population in Sweden
Authors: Quraishi Eman , Jibuaku Chiamaka , Lisik Daniil , Wennergren Göran , Lötvall Jan , Nyberg Fredrik , Ekerljung Linda , Rådinger Madeleine , Kankaanranta Hannu , Nwaru Bright I.
Published: January 2023

Background

Due to the high transmissibility of SARS-CoV-2, accurate diagnosis is essential for effective infection control, but the gold standard, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), is costly, slow, and test capacity has at times been insufficient. We compared the accuracy of clinician diagnosis of COVID-19 against RT-PCR in a general adult population.

Methods

COVID-19 diagnosis data by 30th September 2021 for participants in an ongoing population-based cohort study of adults in Western Sweden were retrieved from registers, based on positive RT-PCR and clinician diagnosis using recommended ICD-10 codes. We calculated accuracy measures of clinician diagnosis using RT-PCR as reference for all subjects and stratified by age, gender, BMI, and comorbidity collected pre-COVID-19.

Results

Of 42,621 subjects, 3,936 (9.2%) and 5705 (13.4%) had had COVID-19 identified by RT-PCR and clinician diagnosis, respectively. Sensitivity and specificity of clinician diagnosis against RT-PCR were 78% (95%CI 77–80%) and 93% (95%CI 93–93%), respectively. Positive predictive value (PPV) was 54% (95%CI 53–55%), while negative predictive value (NPV) was 98% (95%CI 98–98%) and Youden’s index 71% (95%CI 70–72%). These estimates were similar between men and women, across age groups, BMI categories, and between patients with and without asthma. However, while specificity, NPV, and Youden’s index were similar between patients with and without chronic obstructive pulmonary disease (COPD), sensitivity was slightly higher in patients with (84% [95%CI 74–90%]) than those without (78% [95%CI 77–79%]) COPD.

Conclusions

The accuracy of clinician diagnosis for COVID-19 is adequate, regardless of gender, age, BMI, and asthma, and thus can be used for screening purposes to supplement RT-PCR.
Durable wall lining for malaria control in Liberia: results of a cluster randomized trial
Authors: Giesbrecht David , Belleh Tuwuyor G. , Pontarollo Julie , Hinneh Victor S. , Pratt Oliver , Kamal Sajid , Allan Richard
Published: January 2023

Background

Malaria control in Liberia depends upon universal coverage with pyrethroid-impregnated long-lasting insecticidal nets (LLINs). Despite regular mass distribution, LLIN coverage and usage is patchy. Pyrethroid resistance in malaria vectors may further reduce LLIN efficacy. Durable Wall Lining (DWL), a novel material treated with two non-pyrethroid class insecticides, was designed to be installed onto the surface of inner walls, and cover openings and ceiling surfaces of rural houses.

Objectives

Aim

To determine the malaria control efficacy of DWL.

Primary objective

To determine if DWL has an additional protective effect in an area of pyrethroid resistance.

Secondary objectives

To compare surface bio-availability of insecticides and entomological effectiveness over the study duration.

Design

A cluster randomized trial.

Participants

Children aged 2–59 months.

Control arm

50 houses per 20 clusters, all of which received LLIN within the previous 12 months.

Active arm

50 houses per 20 experimental clusters, all of which received LLINs with the previous 12 months, and had internal walls and ceilings lined with DWL.

Randomisation

Cluster villages were randomly allocated to control or active arms, and paired on 4 covariates.

Main outcome measures

Primary measure

Prevalence of infection with P. falciparum in children aged 2 to 59 months.

Secondary measure

Surface bioavailability and entomological effectiveness of DWL active ingredients.

Results

Plasmodium falciparum prevalence in active clusters after 12 months was 34.6% compared to 40.1% in control clusters (p = 0.052). The effect varied with elevation and was significant (RR = 1.3, p = 0.022) in 14 pairs of upland villages. It was not significant (RR = 1.3, p = 0.344) in 6 pairs of coastal villages. Pooled risk ratio (RR) was calculated in SAS (Cary, NC, USA) using the Cochran–Mantel–Haenszel (CMH) test for upland and coastal cluster pairs. DWL efficacy was sustained at almost 100% for 12 months.

Conclusions

Findings indicate that DWL is a scalable and effective malaria control intervention in stable transmission areas with pyrethroid-resistant vectors, where LLIN usage is difficult to achieve, and where local housing designs include large gable and eve openings.

Trial registration ClinicalTrials.gov identifier: NCT02448745 (19 May 2015): https://clinicaltrials.gov/ct2/show/NCT02448745
Automated wearable cameras for improving recall of diet and time use in Uganda: a cross-sectional feasibility study
Authors: Bulungu Andrea L. S. , Palla Luigi , Nambooze Joweria , Priebe Jan , Forsythe Lora , Katic Pamela , Varley Gwen , Galinda Bernice D. , Sarah Nakimuli , Wellard Kate , Ferguson Elaine L.
Published: January 2023

Background

Traditional recall approaches of data collection for assessing dietary intake and time use are prone to recall bias. Studies in high- and middle-income countries show that automated wearable cameras are a promising method for collecting objective health behavior data and may improve study participants’ recall of foods consumed and daily activities performed. This study aimed to evaluate the feasibility of using automated wearable cameras in rural Eastern Ugandan to collect dietary and time use data.

Methods

Mothers of young children (n = 211) wore an automated wearable camera on 2 non-consecutive days while continuing their usual activities. The day after wearing the camera, participants’ dietary diversity and time use was assessed using an image-assisted recall. Their experiences of the method were assessed via a questionnaire.

Results

Most study participants reported their experiences with the automated wearable camera and image-assisted recall to be good (36%) or very good (56%) and would participate in a similar study in the future (97%). None of the eight study withdrawals could be definitively attributed to the camera. Fifteen percent of data was lost due to device malfunction, and twelve percent of the images were "uncodable" due to insufficient lighting. Processing and analyzing the images were labor-intensive, time-consuming, and prone to human error. Half (53%) of participants had difficulty interpreting the images captured by the camera.

Conclusions

Using an automated wearable camera in rural Eastern Uganda was feasible, although improvements are needed to overcome the challenges common to rural, low-income country contexts and reduce the burdens posed on both participants and researchers. To improve the quality of data obtained, future automated wearable camera-based image assisted recall studies should use a structured data format to reduce image coding time; electronically code the data in the field, as an output of the image review process, to eliminate ex post facto data entry; and, ideally, use computer-assisted personal interviews software to ensure completion and reduce errors. In-depth formative work in partnership with key local stakeholders (e.g., researchers from low-income countries, representatives from government and/or other institutional review boards, and community representatives and local leaders) is also needed to identify practical approaches to ensuring that the ethical rights of automated wearable camera study participants in low-income countries are adequately protected.
Application of probabilistic methods to address variability and uncertainty in estimating risks for non-cancer health effects
Authors: Nielsen Greylin H. , Heiger-Bernays Wendy J. , Levy Jonathan I. , White Roberta F. , Axelrad Daniel A. , Lam Juleen , Chartres Nicholas , Abrahamsson Dimitri Panagopoulos , Rayasam Swati D. G. , Shaffer Rachel M. , Zeise Lauren , Woodruff Tracey J. , Ginsberg Gary L.
Published: January 2023

Human health risk assessment currently uses the reference dose or reference concentration (RfD, RfC) approach to describe the level of exposure to chemical hazards without appreciable risk for non-cancer health effects in people. However, this “bright line” approach assumes that there is minimal risk below the RfD/RfC with some undefined level of increased risk at exposures above the RfD/RfC and has limited utility for decision-making. Rather than this dichotomous approach, non-cancer risk assessment can benefit from incorporating probabilistic methods to estimate the amount of risk across a wide range of exposures and define a risk-specific dose. We identify and review existing approaches for conducting probabilistic non-cancer risk assessments. Using perchloroethylene (PCE), a priority chemical for the U.S. Environmental Protection Agency under the Toxic Substances Control Act, we calculate risk-specific doses for the effects on cognitive deficits using probabilistic risk assessment approaches. Our probabilistic risk assessment shows that chronic exposure to 0.004 ppm PCE is associated with approximately 1-in-1,000 risk for a 5% reduced performance on the Wechsler Memory Scale Visual Reproduction subtest with 95% confidence. This exposure level associated with a 1-in-1000 risk for non-cancer neurocognitive deficits is lower than the current RfC for PCE of 0.0059 ppm, which is based on standard point of departure and uncertainty factor approaches for the same neurotoxic effects in occupationally exposed adults. We found that the population-level risk of cognitive deficit (indicating central nervous system dysfunction) is estimated to be greater than the cancer risk level of 1-in-100,000 at a similar chronic exposure level. The extension of toxicological endpoints to more clinically relevant endpoints, along with consideration of magnitude and severity of effect, will help in the selection of acceptable risk targets for non-cancer effects. We find that probabilistic approaches can 1) provide greater context to existing RfDs and RfCs by describing the probability of effect across a range of exposure levels including the RfD/RfC in a diverse population for a given magnitude of effect and confidence level, 2) relate effects of chemical exposures to clinical disease risk so that the resulting risk assessments can better inform decision-makers and benefit-cost analysis, and 3) better reflect the underlying biology and uncertainties of population risks.
Advancing the science on chemical classes
Authors: Maffini Maricel V. , Rayasam Swati D. G. , Axelrad Daniel A. , Birnbaum Linda S. , Cooper Courtney , Franjevic Shari , MacRoy Patrick M. , Nachman Keeve E. , Patisaul Heather B. , Rodgers Kathryn M. , Rossi Mark S. , Schettler Ted , Solomon Gina M. , Woodruff Tracey J.
Published: January 2023

Background

Hazard identification, risk assessment, regulatory, and policy activity are usually conducted on a chemical-by-chemical basis. Grouping chemicals into categories or classes is an underutilized approach that could make risk assessment and management of chemicals more efficient for regulators.

Objective and methods

While there are some available methods and regulatory frameworks that include the grouping of chemicals (e.g.,same molecular mechanism or similar chemical structure) there has not been a comprehensive evaluation of these different approaches nor a recommended course of action to better consider chemical classes in decision-making. This manuscript: 1) reviews current national and international approaches to grouping; 2) describes how groups could be defined based on the decision context (e.g., hazard/risk assessment, restrictions, prioritization, product development) and scientific considerations (e.g., intrinsic physical-chemical properties); 3) discusses advantages of developing a decision tree approach for grouping; 4) uses ortho-phthalates as a case study to identify and organize frameworks that could be used across agencies; and 5) discusses opportunities to advance the class concept within various regulatory decision-making scenarios.

Results

Structural similarity was the most common grouping approach for risk assessment among regulatory agencies (national and state level) and non-regulatory organizations, albeit with some variations in its definition. Toxicity to the same target organ or to the same biological function was also used in a few cases. The phthalates case study showed that a decision tree approach for grouping should include questions about uses regulated by other agencies to encourage more efficient, coherent, and protective chemical risk management.

Discussion and conclusion

Our evaluation of how classes of chemicals are defined and used identified commonalities and differences based on regulatory frameworks, risk assessments, and business strategies. We also identified that using a class-based approach could result in a more efficient process to reduce exposures to multiple hazardous chemicals and, ultimately, reduce health risks. We concluded that, in the absence of a prescribed method, a decision tree approach could facilitate the selection of chemicals belonging to a pre-defined class (e.g., chemicals with endocrine-disrupting activity; organohalogen flame retardants [OFR]) based on the decision-making context (e.g., regulatory risk management).
Photochemically-driven highly efficient intracellular delivery and light/hypoxia programmable triggered cancer photo-chemotherapy
Authors: Zhang Wei , Zhang Cuncheng , Yang Chao , Wang Xingyue , Liu Weiwei , Yang Mi , Cao Yang , Ran Haitao
Published: January 2023

Background

Using nanotechnology to improve the efficiency of tumor treatment represents a major research interest in recent years. However, there are paradoxes and obstacles in using a single nanoparticle to fulfill all the requirements of complex tumor treatment.

Results

In this paper, a programmed-triggered nanoplatform (APP NPs), which is sequentially responsive to light and hypoxia, is rationally integrated for photoacoustic (PA) imaging-guided synergistic cancer photo-chemotherapy. The nanoplatform is constructed by in situ hybridization of dopamine monomer in the skeleton of PCN-224 and loading prodrug banoxantrone (AQ4N). Upon first-stage irradiation with a 660 nm laser, cellular internalization was effectively promoted by a photosensitizer-mediated photochemical effect. Furthermore, under second-stage irradiation, APP NPs exhibit a notably high photothermal conversion efficiency and sufficient reactive oxygen species (ROS) production for photothermal therapy (PTT) and photodynamic therapy (PDT), respectively, which not only triggers rapid intercellular drug release but also consequently aggravates tumor hypoxia levels, and aggravated hypoxia can further active the cytotoxicity of AQ4N for chemotherapy. Both in vitro and in vivo studies confirm that the dual-stage light guided photo-chemotherapy strategy exhibits a greatly enhanced anticancer effects and superior therapeutic safety.

Conclusion

This work represents a versatile strategy to construct a dual-stage light induced PDT/PTT and hypoxia-activated chemotherapy nanoplatform and will be promising for the development of multistimuli-responsive nanosystems with programmable functions for precise cancer therapy.
Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development
Authors: Rjiba Khouloud , Mougou-Zerelli Soumaya , Hamida Imen hadj , Saad Ghada , Khadija Bochra , Jelloul Afef , Slimani Wafa , Hasni Yosra , Dimassi Sarra , khelifa Hela Ben , Sallem Amira , Kammoun Molka , Abdallah Hamza Hadj , Gribaa Moez , Bignon-Topalovic Joelle , Chelly Sami , Khairi Hédi , Bibi Mohamed , Kacem Maha , Saad Ali , Bashamboo Anu , McElreavey Kenneth
Published: January 2023

Background

Forty-six ,XY Differences/Disorders of Sex Development (DSD) are characterized by a broad phenotypic spectrum ranging from typical female to male with undervirilized external genitalia, or more rarely testicular regression with a typical male phenotype. Despite progress in the genetic diagnosis of DSD, most 46,XY DSD cases remain idiopathic.

Methods

To determine the genetic causes of 46,XY DSD, we studied 165 patients of Tunisian ancestry, who presented a wide range of DSD phenotypes. Karyotyping, candidate gene sequencing, and whole-exome sequencing (WES) were performed.

Results

Cytogenetic abnormalities, including a high frequency of sex chromosomal anomalies (85.4%), explained the phenotype in 30.9% (51/165) of the cohort. Sanger sequencing of candidate genes identified a novel pathogenic variant in theSRYgene in a patient with 46,XY gonadal dysgenesis. An exome screen of a sub-group of 44 patients with 46,XY DSD revealed pathogenic or likely pathogenic variants in 38.6% (17/44) of patients.

Conclusion

Rare or novel pathogenic variants were identified in theAR, SRD5A2, ZNRF3, SOX8, SOX9andHHATgenes. Overall our data indicate a genetic diagnosis rate of 41.2% (68/165) in the group of 46,XY DSD.
Raising the contraceptive prevalence rate to 50% by 2025 in Pakistan: an analysis of number of users and service delivery channels
Authors: Abdullah Mujahid , Bilal Faiq , Khan Romesa , Ahmed Azadeh , Khawaja Aamir Ashraf , Sultan Faisal , Khan Adnan Ahmad
Published: January 2023

Background

Pakistan is the fifth most populous country in the world, with a population that is growing at 2.4% annually. Despite considerable political will, including a national commitment that was endorsed by the president to raise the contraceptive prevalence rate (CPR) to 50% by 2025, it has stagnated at around 30–35%. Much of the dialogue on raising CPR is hypothetical and revolves around percentage point change rather than an actual number of women that must be served.

Methods

The Demographic and Health Survey 2017–18 (DHS 2017–18) provides information about the channels through which users receive family planning (FP) services and disaggregates this information at the provincial level. Proportions of users from each of these channels were multiplied by the Pakistan Census-2017 populations to arrive at the number of users. These users were compared with the total FP users and the number of women that had used any FP service in the past 12 months. Linear estimations of population were applied to calculate population numbers in 2025.

Results

The national target of 50% CPR by 2025 translates to a population of 20.02 million users. Currently, 11.26 million married women of reproductive age (MWRA) use any method, 8.22 million use a modern method and 4.94 million received this service in the past 12 months. Of these, 2.7 million did so from social marketing outlets, 0.76 million from public sector outreach through lady health workers (LHWs), 0.55 million from private sector and 0.88 million from public sector facilities. However, arriving at the CPR target means expanding annual service delivery from 4.94 to 13.7 million users. Since social marketing and LHW outreach may have become saturated, only public and private health facilities are the likely channels for such an expansion.

Conclusions

We demonstrate triangulation of the survey data with the census data as a simple policy analysis tool that can help decision-makers estimate the quantum of services they must provide. Such an analysis also allows an understanding of the utilization patterns of each of these channels. In Pakistan’s context, underutilization of funds and existing facilities suggests that increased funding or more providers will likely not be helpful. The policy changes that will likely be most effective include adding outreach to support existing public and private sector facilities while ensuring that procurement of commodities is prioritized.
Clinical and economic benefits of image-guided system in functional endoscopicsinus surgery: a retrospective chart review study in China
Authors: Wang Zaixing , Liu Chunling , Tan Baoying , Sun Guoqing , Pang Poucheok , lv Kangchen , Xie Hui , Ou Xiong , Zeng Xianhai , Xuan Jianwei
Published: January 2023

Background

Image-guided system (IGS) has been gradually applied in the field of rhinology, making functional endoscopic sinus surgery (FESS) a truly minimally invasive and precise surgery. This study was based on real-world data from China hospitals and aimed to evaluate the clinical and economic benefits of the IGS navigation system in FESS.

Methods

This was a two-center retrospective chart review of patients with chronic rhinosinusitis who underwent FESS, including open frontal sinus between July 1, 2018 and December 31, 2019 in China. The intervention group consisted of 100 patients who underwent FESS with the IGS navigation system (IGS group), and the control group consisted of 100 patients who underwent conventional FESS (Non-IGS group). Data were collected from surgical notes and hospital medical records. The primary endpoints for clinical effectiveness and safety were avoid rehospitalization due to bleeding, avoid reoperation due to bleeding, and avoid reoperation due to recurrence.

Results

There were no cases of rehospitalization due to bleeding, reoperation due to bleeding, and reoperation due to recurrence in the IGS group, with an avoidance rate of 100%. In the non-IGS group, there were four cases of rehospitalization and reoperation due to bleeding, with an avoidance rate 96.00% (P = 0.121). No cases of reoperation due to recurrence were in the non-IGS group. The total hospitalization cost was 17,391.51 CNY in the IGS group and 17,742.41 CNY in the non-IGS group per patient, with no statistical difference between the two groups (P = 0.715). Compared with the non-IGS group, the IGS group had an overall cost saving of 350.90 CNY per patient. Although the procedure-related medical costs of IGS group were increased by 1,286.12 CNY compared with the non-IGS group, this was more than offset by other costs.

Conclusion

The results of the study indicated that the IGS may avoid occurrence of rehospitalization and reoperation due to postoperative bleeding. Although the use of navigation technology increased the cost of surgery, its clinical effectiveness brought other medical cost savings, resulting in no significant difference in the overall cost of navigation surgery compared to conventional surgery. The IGS should be considered cost-effectiveness in the treatment of FESS.
Detrimental consequences after intimal disruption of subclavian artery during transcathether aortic valve implantation
Authors: Reuthebuch Oliver T. , Vasiloi Ion , Nestelberger Thomas , Wolff Thomas , Eckstein Friedrich S.
Published: January 2023

Background

TAVI via the left subclavian artery is considered a bail-out strategy in cases where a transfemoral approach is not feasible. However, since this route is only scarcely used, major complications can arise. We describe such an adverse course and present our proceeding.

Case presentation

A 65-year-old man with severe aortic valve stenosis (AS) was referred for transcatheter aortic valve implantation (TAVI) via left subclavian artery. After uneventful deployment of the TAVI prosthesis, consequent valve assessment with transeosophageal echocardiography and angiography showed a highly mobile and tubular structure shifting within the valve. We went for a surgical extraction via sternotomy on cardiopulmonary bypass (CPB). A 6 cm longish intimal cylinder was hassle-free extracted. 4 days postoperatively the left sided radial pulse was missing. In a subsequent computed tomography angiography (CTA) scan a proximal dissection as well as an intimal flap, causing a subtotal stenosis of the left subclavian artery, was detected. Consecutively the intimal cylinder was removed using a Fogarty-balloon. Pre-discharge control revealed recurrence of peripheral radial pulse and an unimpeded function of the TAVI prosthesis. The patient presented no sequela at discharge.

Conclusion

Though TAVI is a well-advanced technique complications are not completely avertable. It is thus advisable to have patients discussed in the heart team encompassing all potentially involved specialties.
Frequent copy number variants in a cohort of Mexican-Mestizo individuals
Authors: Sánchez Silvia , Juárez Ulises , Domínguez Julieta , Molina Bertha , Barrientos Rehotbevely , Martínez-Hernández Angélica , Carnevale Alessandra , Grether-González Patricia , Mayen Dora Gilda , Villarroel Camilo , Lieberman Esther , Yokoyama Emiy , Del Castillo Victoria , Torres Leda , Frias Sara
Published: January 2023

Background

The human genome presents variation at distinct levels, copy number variants (CNVs) are DNA segments of variable lengths that range from several base pairs to megabases and are present at a variable number of copies in human genomes. Common CNVs have no apparent influence on the phenotype; however, some rare CNVs have been associated with phenotypic traits, depending on their size and gene content. CNVs are detected by microarrays of different densities and are generally visualized, and their frequencies analysed using the HapMap as default reference population. Nevertheless, this default reference is inadequate when the samples analysed are from people from Mexico, since population with a Hispanic genetic background are minimally represented. In this work, we describe the variation in the frequencies of four common CNVs in Mexican-Mestizo individuals.

Results

In a cohort of 147 unrelated Mexican-Mestizo individuals, we found that the common CNVs 2p11.2 (99.6%), 8p11.22 (54.5%), 14q32.33 (100%), and 15q11.2 (71.1%) appeared with unexpectedly high frequencies when contrasted with the HapMap reference (ChAS). Yet, while when comparing to an ethnically related reference population, these differences were significantly reduced or even disappeared.

Conclusion

The findings in this work contribute to (1) a better description of the CNVs characteristics of the Mexican Mestizo population and enhance the knowledge of genome variation in different ethnic groups. (2) emphasize the importance of contrasting CNVs identified in studied individuals against a reference group that—as best as possible—share the same ethnicity while keeping this relevant information in mind when conducting CNV studies at the population or clinical level.
Hypertension contributes to exacerbated osteoarthritis pathophysiology in rats in a sex-dependent manner
Authors: Yeater Taylor D. , Griffith Jacob L. , Cruz Carlos J. , Patterson Folly M. , Aldrich Jessica L. , Allen Kyle D.
Published: January 2023

Background

Hypertension is a common comorbidity of osteoarthritis (OA) with known autonomic dysregulation; thus, the autonomic nervous system may provide a shared underlying mechanism. The objective of this study was to examine the role of the autonomic nervous system in a preclinical model of OA and hypertension.

Methods

Experiments were conducted in spontaneously hypertensive rats and a normotensive control strain, including male and female rats. OA was surgically induced via medial meniscus transection with skin incision used as a sham control (n= 7–8/strain/sex/surgery). Tactile sensitivity, anxiety-related behavior, and serum corticosterone were measured at baseline then bi-weekly across 8 weeks. At weeks 9–10, cardiovascular responses to a chemical vagal nerve agonist were determined to indirectly evaluate vagus nerve function. The joint structure was assessed via grading of histological sections.

Results

In males, OA resulted in thinner cartilage in both hypertensive (OA vs. non-OAp< 0.001) and normotensive (OA vs. non-OAp< 0.001). Only females with comorbid hypertension and OA displayed thinner cartilage (p= 0.013). Male hypertensive OA animals had increased calcified subchondral bone compared to normotensive OA animals (p= 0.043) while female hypertensive OA animals had increased calcified subchondral bone compared to hypertensive sham animals (p< 0.001). All MCLT+MMT groups developed low-grade synovitis; interestingly, hypertensive OA females had higher synovitis scores than normotensive OA females (p= 0.046). Additionally, hypertension led to larger drops in blood pressure with vagal activation in both OA (hypertensive vs. normotensivep= 0.018) and sham (hypertensive vs. normotensivep< 0.001) male animals. In females, this trend held true only in OA animals (normotensive vs. hypertensivep= 0.005).

Conclusion

These data provide preliminary evidence that hypertension influences OA progression and encourages further study into the autonomic nervous system as a possible mechanism.
Biochemical and molecular biomarkers: unraveling their role in gestational diabetes mellitus
Authors: Karami Masoumeh , Mousavi Seyyed Hossein , Rafiee Mohammad , Heidari Reza , Shahrokhi Seyedeh Zahra
Published: January 2023

Gestational diabetes mellitus (GDM) is the most prevalent metabolic disorder during pregnancy, causing short- and long-term complications for both mother and baby. GDM is a multifactorial disease, and it may be affected by interactions between genetic, epigenetic, and environmental factors. However, the exact etiology is poorly understood. Despite the high prevalence of GDM, there is still debate regarding the optimal time for screening, the diagnostic threshold to apply, and the best strategies for treatment. Identifying effective strategies for therapeutic purposes as well as accurate biomarkers for prognostic and diagnostic purposes will reduce the GDM incidence and improve its management. In recent years, new biochemical and molecular biomarkers such as microRNAs, single-nucleotide polymorphisms, and DNA methylation have received great interest in the diagnosis of GDM. In this review, we discuss current and future diagnostic approaches for the detection of GDM and evaluate lifestyle and pharmacological strategies for GDM prevention.
Laser-activated autologous adipose tissue-derived stromal vascular fraction restores spinal cord architecture and function in multiple sclerosis cat model
Authors: Farid Mariam F. , Abouelela Yara S. , Yasin Noha A. E. , Al-Mokaddem Asmaa K. , Prince Abdelbary , Ibrahim Marwa A. , Rizk Hamdy
Published: January 2023

Background

Multiple sclerosis (MS) is the most frequent non-traumatic neurological debilitating disease among young adults with no cure. Over recent decades, efforts to treat neurodegenerative diseases have shifted to regenerative cell therapy. Adipose tissue-derived stromal vascular fraction (SVF) comprises a heterogeneous cell population, considered an easily accessible source of MSCs with therapeutic potential in autoimmune diseases. This study aimed to assess the regenerative capacity of low-level laser-activated SVF in an MS cat model.

Methods

Fifteen adult Persian cats were used in this study: Group I (control negative group, normal cats), Group II (EB-treated group, induced for MS by ethidium bromide (EB) intrathecal injection), and Group III (SVF co-treated group, induced for MS then treated with SVF on day 14 post-induction). The SVF was obtained after digesting the adipose tissue with collagenase type I and injecting it intrathecal through the foramen magnum.

Results

The results showed that the pelvic limb’s weight-bearing locomotion activity was significantly (P ≤ 0.05) recovered in Group III, and the Basso, Beattie, and Bresnahan (BBB) scores of hindlimb locomotion were significantly higher in Group III (14 ± 0.44) than Group II (4 ± 0.31). The lesion’s extent and intensity were reduced in the magnetic resonance imaging (MRI) of Group III. Besides, the same group showed a significant increase in the expression of neurotrophic factors: BDNF, SDF and NGF (0.61 ± 0.01, 0.51 ± 0.01 and 0.67 ± 0.01, respectively) compared with Group II (0.33 ± 0.01, 0.36 ± 0.006 and 0.2 ± 0.01, respectively). Furthermore, SVF co-treated group revealed a significant (P ≤ 0.05) increase in oligodendrocyte transcription factor (Olig2) and myelin basic protein (4 ± 0.35 and 6 ± 0.45, respectively) that was decreased in group II (1.8 ± 0.22 and 2.9 ± 0.20, respectively). Moreover, group III showed a significant (P ≤ 0.05) reduction in Bax and glial fibrillary acidic protein (4 ± 0.53 and 3.8 ± 0.52, respectively) as compared with group II (10.7 ± 0.49 and 8.7 ± 0.78, respectively). The transmission electron microscopy demonstrated regular more compact, and markedly (P ≤ 0.05) thicker myelin sheaths (mm) in Group III (0.3 ± 0.006) as compared with group II (0.1 ± 0.004). Based on our results, the SVF co-treated group revealed remyelination and regeneration capacity with a reduction in apoptosis and axonal degeneration.

Conclusion

SVF is considered an easy, valuable, and promising therapeutic approach for treating spinal cord injuries, particularly MS.