bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital leadership: Norwegian healthcare managers’ attitudes towards using digital tools
Authors: Oksavik Jannike Dyb , Vik Erlend , Kirchhoff Ralf
Published: September 2024

Background

Health services are undergoing digitalization and applying new digital tools. These changes may provide healthcare managers with opportunities to exercise digital leadership. However, managers’ attitudes may influence the extent to which they demonstrate digital leadership. This study explores the attitudes of Norwegian healthcare managers towards: (1) digital tools and change and (2) to what extent digital tools are applicable to various tasks of managers.

Methods

Cross-sectional study including 154 managers in hospitals and municipal health services in a Norwegian county. The questionnaire was about management and digital tools, and the data was analyzed by descriptive statistics, correlations, and content analysis.

Results

The healthcare managers perceived that digital tools facilitated a positive change in organizational work processes aligned with values and goals. Digital tools supported administrative tasks such as gaining control over responsibilities. However, 76 managers stated that certain tasks, including interactions with employees (e.g. performance appraisals and sick leave follow-up) and the building of an organizational culture, should not be performed using digital tools or using them only to a limited extent; for these tasks, they preferred in-person meetings.

Discussion

Norwegian healthcare managers’ attitudes toward digital tools are generally positive, but there are areas where they find the tools less suitable.

Conclusions

The results provide new insights into healthcare by indicating that many managers may have positive attitudes toward digital tools. However, digital leadership may not be applicable equally in all areas of healthcare managers’ work. This raises the question of whether digital leadership can or should be exercised uniformly in every area of health services.
Double-Outlet Right Ventricle With Intact Ventricular Septum and Left Atrioventricular Valve Regurgitation in a Patient With Right Atrial Isomerism
Authors: Nakata Tomohiro , Tachi Maiko , Yasuda Kenji , Nakashima Shigeki , Minamoto Toshiko , Yamazaki Kazuhiro
Published: September 2024

We present a very rare case of right atrial isomerism, double-outlet right ventricle, and incomplete atrioventricular septal defect (intact ventricular septum). In the neonatal period, the right ventricle was compressed by a “blind-ended” left ventricle with mild-to-moderate left atrioventricular valve regurgitation. The regurgitation gradually decreased from mild-to-moderate to mild with body weight gain. The patient underwent systemic-to-pulmonary shunt at three months of age and bilateral bidirectional Glenn at eight months of age. Although the echocardiogram demonstrated that the right ventricle was still compressed by the left ventricle, over time the size of the left ventricle reduced significantly and the left atrioventricular valve regurgitation became trivial.
Building Construction In Princely State Bikaner: Form, Style And Architecture
Authors: Kumar Rajender
Published: September 2024

This article explores the significance of building construction in the evolution of human civilisation, tracing its origins from mountain caves to sophisticated structures in the Indus Valley Civilisation. It highlights the advancements in materials and techniques, noting the grandeur and artistic merit of ancient and medieval buildings. Focusing on the princely state of Bikaner, it details the use of local resources like red sandstone from Dulmera and Khari. The Khari quarry stone was a key construction material in Bikaner from the era of Rao Bika Ji to the nineteenth century. In Besides Khari, stones from Dulmera and other villages such as Hansera and Aalsar were used. The involvement of various professional castes and artisans such as gajdhar, karigar, chejara, usta, Sika, Suthar, Luhar and labourers in construction could be seen. The raw material for building construction was available locally. Brick-making was another important activity in building construction, which was done by potters mixing yellow clay with straw. Other important materials were lime, kankar, and murad, which were managed by the Kumhar and Chungar communities. Fuel for lime kilns came from local sources such as dry khejri wood. Colouring materials such as lime-based kalli were obtained locally. Water for construction was supplied from wells, which were managed by malis and sikas. Iron, obtained locally from outside states, played an important role, with blacksmiths making the necessary tools. Various professional castes were involved in the construction process, reflecting a mix of local resources and skilled labour, leading to distinct architectural features in Bikaner buildings. This article emphasises the durability of pre-modern buildings due to natural materials and examines archival documents like Kamthana Bahis for insights into the eighteenth–nineteenth-century Bikaner’s construction practices. These documents provide comprehensive information on building methods, materials and the socio-economic aspects of construction, illustrating the structural and aesthetic differences between government and non-government buildings. The study underscores the cultural heritage and architectural legacy of Bikaner, offering a detailed analysis of its historical building techniques and materials.
Chronic Conditions and Resilience: Adolescent Health Behaviors in the Midst of the COVID-19 Pandemic in Thailand
Authors: Thitamethee Phatchara , Likhitweerawong Narueporn , Louthrenoo Orawan , Boonchooduang Nonglak
Published: September 2024

Objective. To assess the impact of chronic illnesses on risk behaviors and psychosocial adjustments among adolescents during the COVID-19 pandemic in Thailand. Methods. A cross-sectional study was conducted between June 2021 and September 2022, including adolescents aged 10 to 18 years. Participants completed the Thai Youth Risk Behavior Survey and the Strengths and Difficulties Questionnaire (SDQ). Data were analyzed using descriptive statistics, Student’s t-test, Chi-square test, and logistic regression. Results. Adolescents with chronic illnesses (n = 120) were more likely to exhibit risk behaviors related to violence (38.3%) and mental health issues (18.3%). They also scored higher on total difficulties (mean = 12.23, SD = 5.14) and emotional symptoms (mean = 3.08, SD = 2.45) than the healthy group (n = 120). Conclusion. During the COVID-19 pandemic, adolescents with chronic illnesses in Thailand demonstrated increased risk behaviors related to violence and mental health issues, highlighting the need for tailored interventions.
The (Not-So) Easy Puzzle Competition: An Exercise in Planning and Rewarding Teamwork
Authors: Shaffer Jonathan A.
Published: September 2024

This article presents a classroom exercise that highlights critical aspects of promoting effective teamwork. In this exercise, teams compete against one another to be the first to complete 100-piece puzzles. During the exercise, teams discover that the task is not as easy as it seems, and the experience highlights the impact that suboptimal planning, limited resources, and zero-sum competition between teams can have on team and organizational effectiveness. The exercise provides an opportunity for instructors to discuss the responsibility that managers have to make sure that their teams fully understand how to complete their tasks, to provide the resources their teams needs to be successful, and to distribute rewards such that teams are encouraged to cooperate rather than compete against one another.
Investigating effectiveness of inverted classroom in undergraduate statistics education: A small sample HLM approach
Authors: Ma Xin , Zhang Jing , Karkelanova Petya , Osborne Michael C. , Karkelanova Anushka
Published: September 2024

Data collected from an educational experiment were analyzed to investigate the effectiveness of an instructional reform referred to as the inverted classroom (learning activities traditionally taking place inside the classroom now take place outside the classroom and vice versa) in undergraduate statistics education. Students were taught the same statistics course in the inverted classroom (135 students) and the traditional classroom (135 students) over one semester. A small sample HLM (hierarchical linear modeling) approach was used to account for the data structure of students nested within 12 sections of the course and small sample sizes at both student and section levels. The treatment effects were adjusted for individual background characteristics and high school performances. There were positive treatment effects of the inverted classroom across all three outcome measures of coursework, attendance, and final grade. After adjustment, the inverted classroom would increase scores in coursework, attendance, and final grade by 3.47, 2.14, and 1.18 percentage points respectively, representing a limited success of the inverted classroom.
A Critical Appraisal on China's Blocking Statutes from a Private Actor's Perspective
Authors: Liu Guiqiang
Published: September 2024

This article examines the potential repercussions of China's blocking statutes on private actors. In recent years, China's strategy for countering unilateral sanctions has evolved from mere diplomatic protests to utilizing a legal toolkit, most notably through the promulgation of three blocking statutes between 2019 and 2021. This article argues that while a primary goal of China's blocking statutes is to protect the interests of private actors, this objective remains only partially fulfilled. Rather, the enforcement of these statutes may inadvertently precipitate additional challenges for private parties, such as heightened legal uncertainty, risk of exposure to conflicting legal obligations, and increased complexity in private dispute resolution. Given these predicaments, the article advocates that Chinese authorities give due consideration to the interests of private actors in the enforcement of blocking statutes. Specifically, it is recommended that Chinese authorities adopt a prudent enforcement approach and concurrently enhance the procedural support mechanisms for these statutes.
A novelin vitrotubular model to recapitulate features of distal airways: the bronchioid
Authors: Maurat Elise , Raasch Katharina , Leipold Alexander M. , Henrot Pauline , Zysman Maeva , Prevel Renaud , Trian Thomas , Krammer Tobias , Bergeron Vanessa , Thumerel Matthieu , Nassoy Pierre , Berger Patrick , Saliba Antoine-Emmanuel , Andrique Laetitia , Recher Gaëlle , Dupin Isabelle
Published: September 2024

Background

Airflow limitation is the hallmark of obstructive pulmonary diseases, with the distal airways representing a major site of obstruction. Although numerousin vitromodels of bronchi already exist, there is currently no culture system for obstructive diseases that reproduces the architecture and function of small airways. Here, we aimed to engineer a model of distal airways to overcome the limitations of current culture systems.

Methods

We developed a so-called bronchioid model by encapsulating human bronchial adult stem cells derived from clinical samples in a tubular scaffold made of alginate gel.

Results

This template drives the spontaneous self-organisation of epithelial cells into a tubular structure. Fine control of the level of contraction is required to establish a model of the bronchiole, which has a physiologically relevant shape and size. Three-dimensional imaging, gene expression and single-cell RNA-sequencing analysis of bronchioids made of bronchial epithelial cells revealed tubular organisation, epithelial junction formation and differentiation into ciliated and goblet cells. Ciliary beating was observed, at a decreased frequency in bronchioids made of cells from COPD patients. The bronchioid could be infected by rhinovirus. An air–liquid interface was introduced that modulated gene expression.

Conclusion

Here, we provide a proof of concept of a perfusable bronchioid with proper mucociliary and contractile functions. The key advantages of our approach, such as the air‒liquid interface, lumen accessibility, recapitulation of pathological features and possible assessment of clinically relevant end-points, will make our pulmonary organoid-like model a powerful tool for preclinical studies.
Neonatal cardiorespiratory failure caused by splenic hemorrhages: a case report on a fatal and a rescued case
Authors: Jansen Nadieh A. , T M Dittrich Anne , Backes Manouk , Kusters Benno , M Klein Willemijn , Hundscheid Tim
Published: September 2024

Two cases of neonatal splenic hemorrhage with acute cardiorespiratory failure are described in this report. The first case involves a full-term neonate who was found unresponsive without any witnesses and could not be successfully resuscitated. A postmortem diagnosis revealed a splenic hemorrhage. Second case is an extremely premature neonate who experienced a witnessed cardiovascular collapse on the 14th day of life. Rapid cardiovascular support was administered, resulting in a positive outcome. While splenic hemorrhage is commonly associated with traumatic events, these cases highlight the need of considering spontaneous splenic hemorrhages as a potential cause of acute neonatal compromise, even in the absence of birth-related trauma (e.g., asphyxia, prolonged labor, clavicle fractures, brachial plexus injuries). This report emphasizes the importance of including splenic hemorrhage timely in the differential diagnosis of neonatal cardiorespiratory instability, especially in the absence of more common diagnoses, and discusses the challenges associated with its recognition and treatment.
Liver resection for hepatocellular carcinoma in elderly patients: does age matter?
Authors: Shehta Ahmed , Medhat Mohamed , Farouk Ahmed , Monier Ahmed , Said Rami , Salah Tarek , Fouad Amgad , Ali Mahmoud Abdelwahab
Published: September 2024

Background

Evaluation of the influence of the age of the patients upon the outcomes of liver resection (LR) for hepatocellular carcinoma (HCC).

Methods

HCC patients who underwent LR between 2010 and 2020 were analyzed. They were divided into 3 groups depending on the patient’s age. Group I (patients less than 60 years), Group II (patients between 60 and 69 years), and Group III (patients equal to or more than 70 years).

Results

364 patients were included. A significantly higher serum bilirubin and alpha feto-protein were noted in Group I and serum creatinine was noted in Group III. The study groups did not show any significant differences regarding HCC site, number, macrovascular invasion, the extent of LR, Pringle maneuver, and perioperative blood transfusions. Longer operation time was found in Groups II and III, while more blood loss was noted in Group (I) Group I patients had longer hospital stays. Higher postoperative morbidities were noted in both Group I and Group (II) Higher incidence of post-hepatectomy liver dysfunction was noted in Group I. More early mortalities were found in Group I, related to liver failure. We did not experience early mortality in Group (III) Late Mortalities occurred in 117 patients (32.1%). HCC recurrence occurred in 165 patients (45.3%). Regarding the overall- and tumor-free survival, we did not experience any significant differences among the 3 groups (Log Rank: p = 0.371 and 0.464 respectively).

Conclusions

Curative LR can be safely performed in selected elderly patients with HCC. An advanced patient’s age should not be considered as a contraindication for curative LR.
Exploring the feasibility and acceptability of community paramedicine programs in achieving vaccination equity: a qualitative study
Authors: Kasting Monica L. , Laily Alfu , Smith Sidney J. , Sembian Sathveka , Head Katharine J. , Usidame Bukola , Zimet Gregory D. , Schwab-Reese Laura M.
Published: September 2024

Background

Mobile Integrated Health-Community Paramedicine (MIH-CP) is a novel approach that may reduce the rural-urban disparity in vaccination uptake in the United States. MIH-CP providers, as physician extenders, offer clinical follow-up and wrap-around services in homes and communities, uniquely positioning them as trusted messengers and vaccine providers. This study explores stakeholder perspectives on feasibility and acceptability of community paramedicine vaccination programs.

Methods

We conducted semi-structured qualitative interviews with leaders of paramedicine agencies with MIH-CP, without MIH-CP, and state/regional leaders in Indiana. Interviews were audio recorded, transcribed verbatim, and analyzed using content analysis.

Results

We interviewed 24 individuals who represented EMS organizations with MIH-CP programs (MIH-CP; n = 10), EMS organizations without MIH-CP programs (non-MIH-CP; n = 9), and state/regional administrators (SRA; n = 5). Overall, the sample included professionals with an average of 19.6 years in the field (range: 1–42 years). Approximately 75% (n = 14) were male, and all identified as non-Hispanic white. MIH-CPs reported they initiated a vaccine program to reach underserved areas, operating as a health department extension. Some MIH-CPs integrated existing services, such as food banks, with vaccine clinics, while other MIH-CPs focused on providing vaccinations as standalone initiatives. Key barriers to vaccination program initiation included funding and vaccinations being a low priority for MIH-CP programs. However, participants reported support for vaccine programs, particularly as they provided an opportunity to alleviate health disparities and improve community health. MIH-CPs reported low vaccine hesitancy in the community when community paramedics administered vaccines. Non-CP agencies expressed interest in launching vaccine programs if there is clear guidance, sustainable funding, and adequate personnel.

Conclusions

Our study provides important context on the feasibility and acceptability of implementing an MIH-CP program. Findings offer valuable insights into reducing health disparities seen in vaccine uptake through community paramedics, a novel and innovative approach to reduce health disparities in rural communities.
Tudor-SN exacerbates pathological vascular remodeling by promoting the polyubiquitination of PTEN via NEDD4-1
Authors: Wu Yichen , Chen Zilong , Zheng Zhe , Li Xiaoguang , Shu Jiangcheng , Mao Ruiqi , An Jie , Fan Siyuan , Luo Ruijie , Guo Yi , Xu Wenjing , Liang Minglu , Huang Kai , Wang Cheng
Published: September 2024

Background

Dysregulation of vascular homeostasis can induce cardiovascular diseases and increase global mortality rates. Although lineage tracing studies have confirmed the pivotal role of modulated vascular smooth muscle cells (VSMCs) in the progression of pathological vascular remodeling, the underlying mechanisms are still unclear.

Methods

The expression of Tudor-SN was determined in VSMCs of artery stenosis, PDGF-BB-treated VSMCs and atherosclerotic plaque. Loss- and gain-of-function approaches were used to explore the role of Tudor-SN in the modulation of VSMCs phenotype both in vivo and in vitro.

Results

In this study, we demonstrate that Tudor-SN expression is significantly elevated in injury-induced arteries, atherosclerotic plaques, and PDGF-BB-stimulated VSMCs. Tudor-SN deficiency attenuates, but overexpression aggravates the synthetic phenotypic switching of VSMCs and pathological vascular remodeling. Loss of Tudor-SN also reduces atherosclerotic plaque formation and increases plaque stability. Mechanistically, PTEN, the major regulator of the MAPK and PI3K-AKT signaling pathways, plays a vital role in Tudor-SN-mediated regulation on proliferation and migration of VSMCs. Tudor-SN facilitates the polyubiquitination and degradation of PTEN via NEDD4-1, thus exacerbating vascular remodeling under pathological conditions. BpV (HOpic), a specific inhibitor of PTEN, not only counteracts the protective effect of Tudor-SN deficiency on proliferation and migration of VSMCs, but also abrogates the negative effect of carotid artery injury-induced vascular remodeling in mice.

Conclusions

Our findings reveal that Tudor-SN deficiency significantly ameliorated pathological vascular remodeling by reducing NEDD4-1-dependent PTEN polyubiquitination, suggesting that Tudor-SN may be a novel target for preventing vascular diseases.
Developing a systems-focused tool for modeling lung cancer screening resource needs
Authors: Reddy Aparna , Abe-Nornes Fumiya , Haskell Alison , Saito Momoka , Schumacher Matthew , Venkat Advaidh , Venkatasubramanian Krithika , Woodhouse Kira , Zhang Yiran , Niktafar Hooman , Leveque Anthony , Kedroske Beth , Ramnath Nithya , Cohn Amy
Published: September 2024

Background

Early detection through screening dramatically improves lung cancer survival rates, including among war Veterans, who are at heightened risk. The effectiveness of low dose computed tomography scans in lung cancer screening (LCS) prompted the Veteran’s Affairs Lung Precision Oncology Program (VA LPOP) to increase screening rates. We aimed to develop an adaptive population health tool to determine adequate resource allocation for the program, with a specific focus on primary care providers, nurse navigators, and radiologists.

Methods

We developed a tool using C + + that uses inputs that represents the process of the VA LCS program in Ann Arbor, Michigan to calculate FTEs of human resource needs to screen a given population. Further, we performed a sensitivity analysis to understand how resource needs are impacted by changes in population, screening eligibility, and time allocated for the nurse navigators’ tasks.

Results

Using estimates from the VA LCS Program as demonstrative inputs, we determined that the greatest number of full-time equivalents required were for radiologists, followed by nurse navigators and then primary care providers, for a target population of 75,000. An increase in the population resulted in a linear increase of resource needs, with radiologists experiencing the greatest rate of increase, followed by nurse navigators and primary care providers. These resource requirements changed with primary care providers, nurse navigators and radiologists demonstrating the greatest increase when 1–20, 20–40 and > 40% of Veterans accepted to be screened respectively. Finally, when increasing the time allocated to check eligibility by the nurse navigator from zero to three minutes, there was a linear increase in the full-time equivalents required for the nurse navigator.

Conclusion

Variation of resource utilization demonstrated by our user facing tool emphasizes the importance of tailored strategies to accommodate specific population demographics and downstream work. We will continue to refine this tool by incorporating additional variability in system parameters, resource requirements following an abnormal test result, and resource distribution over time to reach steady state. While our tool is designed for a specific program in one center, it has wider applicability to other cancer screening programs.
A rare case of ventricular tachycardia caused by an intramyocardial fibroma with successful surgical resection in an adult
Authors: Binder M. Scott , Roby Matthew , Chancellor William , Yarboro Leora , Arnold Scott , Hodge Kyle , Kern John , Sane David
Published: September 2024

Background

Cardiac fibromas are extremely rare in adults. The preferred treatment is surgical resection, but antiarrhythmic medications or heart transplantation have also been used previously. The cardiac imaging, particularly MRI, can be useful to help delineate between primary cardiac tumors, and surgical factors such as the extent/size of the fibroma, involvement of the coronary arteries or mitral apparatus and amount of residual myocardium influence whether surgical resection is feasible.

Case presentation

A 42-year-old male presented with a wide-complex tachycardia, unresponsive to amiodarone. An echocardiogram was performed which showed a possible posterior wall mass. A cardiac MRI showed a well circumscribed lateral wall intracardiac fibroma, measuring 5.2 × 5.1 × 3.8 cm with preserved function. Surgical resection was successful, and he was discharged without a defibrillator.

Conclusions

Cardiac fibromas are encapsulated tumors which do not infiltrate myocardium and should be surgically resected if possible.
Diagnostic utility of acute phase proteins and their ability to guide antibiotic usage in pigs, horses, and cattle: a mapping review
Authors: Jakobsen Nadia , Weber Nicolai Rosager , Larsen Inge , Pedersen Ken Steen
Published: September 2024

To mitigate the use of antibiotics for many of the multifactorial diseases seen in pigs, horses and cattle, new diagnostic tools are needed. Acute phase protein (APP) measurements can, in humans, be used to guide antibiotic treatment initiation, evaluate treatment efficacy, and make a prognosis. The aim of this review is to collect evidence on the clinical functionality of APP measurements as a tool to guide antibiotic treatment in pigs, horses, and cattle. Literature was retrieved using Medline, CAB Abstracts and Google Scholar. The acute phase response has been investigated for a plethora of diseases and clinical signs and the major acute phase proteins are elevated in diseased compared to healthy animals. Few studies correlated acute phase response with aetiology, antibiotic treatment efficacy, prognosis, or severity of disease. The existing research does not support that APP can be used to guide antibiotic treatment, but the reported studies indicate that C-reactive protein (CRP) might be able to differentiate between bacterial and non-bacterial causes of disease in pigs. Serum amyloid A (SAA) might reflect underlying aetiology in horses and infectious or non-infectious cases of mastitis in cows.
Control of swine dysentery at national level in Sweden
Authors: Wallgren Per
Published: September 2024

Background

Swine dysentery, caused by Brachyspira hyodysenteriae, is a severe pig disease. Resistance to tylosins is common and resistance to tiamulin has been reported since the 1990s. Still, dysentery is not notifiable to authorities. The disease therefore escapes control from an overall population perspective. In Sweden, a program that aimed to control dysentery at national level was initiated in 2020, mainly due to the unexpected diagnosis of tiamulin resistant Brachyspira hyodysenteriae in 2016.

Results

Through joint efforts of a network including farmers, government, animal health organisations and abattoirs it was concluded that outbreaks of dysentery had taken place in 25 herds between 2016 and 2019. By 1 January 2020, nine of these herds were still not declared free from the disease. From that date, the network decided that Brachyspira hyodysenteriae was to be cultured whenever dysentery could be suspected. Thus, 148, 157 and 124 herds were scrutinised for Brachyspira hyodysenteriae in 2020, 2021 and 2022, respectively, whereof five, three and two new herds were confirmed positive. By 31 December 2022, four herds were judged as impossible to sanitise. However, they posed no problem since they were identified by the network, pigs to and from these enterprises could be transported without jeopardising other herds. When Brachyspira hyodysenteriae was diagnosed in fattening herds purchasing growers, Brachyspira hyodysenteriae could not be detected in the delivering herds. That result, together with other observations, indicated that Brachyspira hyodysenteriae ought to be regarded as ubiquitous, although at a low level in healthy pigs.

Conclusions

Eradication of dysentery contributed to substantial welfare and financial improvements in affected herds. Dysentery was controlled successfully at national level through the united efforts from competing stake holders, such as different abattoirs and animal health organisations. However, as Brachyspira hyodysenteriae was assumed to be ubiquitous, although at a low level in healthy pigs, the duration of the successful control of dysentery was concluded to only be transient. Without permanent monitoring for Brachyspira hyodysenteriae, the knowledge of the national status will rapidly decline to the level prior to the initiation of the control program.
Contactless hand biometrics for forensics: review and performance benchmark
Authors: Gonzalez-Soler Lazaro Janier , Zyla Kacper Marek , Rathgeb Christian , Fischer Daniel
Published: September 2024

Contactless hand biometrics has emerged as an alternative to traditional biometric characteristics, e.g., fingerprint or face, as it possesses distinctive properties that are of interest in forensic investigations. As a result, several hand-based recognition techniques have been proposed with the aim of identifying both wanted criminals and missing victims. The great success of deep neural networks and their application in a variety of computer vision and pattern recognition tasks has led to hand-based algorithms achieving high identification performance on controlled images with few variations in, e.g., background context and hand gestures. This article provides a comprehensive review of the scientific literature focused on contactless hand biometrics together with an in-depth analysis of the identification performance of freely available deep learning-based hand recognition systems under various scenarios. Based on the performance benchmark, the relevant technical considerations and trade-offs of state-of-the-art methods are discussed, as well as further topics related to this research field.
Gene therapy for polygenic or complex diseases
Authors: Wu Tingting , Hu Yu , Tang Liang V.
Published: September 2024

Gene therapy utilizes nucleic acid drugs to treat diseases, encompassing gene supplementation, gene replacement, gene silencing, and gene editing. It represents a distinct therapeutic approach from traditional medications and introduces novel strategies for genetic disorders. Over the past two decades, significant advancements have been made in the field of gene therapy, leading to the approval of various gene therapy drugs. Gene therapy was initially employed for treating genetic diseases and cancers, particularly monogenic conditions classified as orphan diseases due to their low prevalence rates; however, polygenic or complex diseases exhibit higher incidence rates within populations. Extensive research on the etiology of polygenic diseases has unveiled new therapeutic targets that offer fresh opportunities for their treatment. Building upon the progress achieved in gene therapy for monogenic diseases and cancers, extending its application to polygenic or complex diseases would enable targeting a broader range of patient populations. This review aims to discuss the strategies of gene therapy, methods of gene editing (mainly CRISPR-CAS9), and carriers utilized in gene therapy, and highlight the applications of gene therapy in polygenic or complex diseases focused on applications that have either entered clinical stages or are currently undergoing clinical trials.

Graphical Abstract
Etiology and antimicrobial susceptibility patterns of bacteria causing pneumonia among adult patients with signs and symptoms of lower respiratory tract infections during the COVID-19 pandemic in Mwanza, Tanzania: a cross-sectional study
Authors: Rukyaa Johannes , Mushi Martha F. , Silago Vitus , Damiano Prisca , Keenan Katherine , Sabiiti Wilber , Holden Matthew T. G. , Seni Jeremiah , Mshana Stephen E.
Published: September 2024

Background

Bacterial pneumonia is among the leading causes of morbidity and mortality worldwide. The extensive misuse and overuse of antibiotics observed during the Corona Virus Disease 2019 (COVID-19) pandemic may have changed the patterns of pathogens causing bacterial pneumonia and their antibiotic susceptibility profiles. This study was designed to establish the prevalence of culture-confirmed bacterial pneumonia and describe their antimicrobial susceptibility profile in adult patients who presented with signs and symptoms of lower respiratory tract infections (LRTIs) during the COVID-19 pandemic.

Methodology

This hospital-based cross-sectional study was conducted from July 2021 to July 2022 at a zonal referral hospital and two district hospitals in Mwanza, Tanzania. Demographic and clinical data were collected using a standardized questionnaire. Sputum samples were processed by conventional culture followed by the identification of isolates and antibiotic susceptibility testing. Descriptive data analysis was performed using STATA version 15.0.

Results

A total of 286 patients with a median age of 40 (IQR 29–60) years were enrolled in the study. More than half of the patients enrolled were females (52.4%, n = 150). The overall prevalence of bacterial pneumonia was 34.3% (n = 98). The majority of the bacterial pathogens isolated were Gram-negative bacteria (GNB) (61.2%, 60/98), with a predominance of Klebsiella spp., 38.8% (38/98), followed by Streptococcus pyogenes (21.4%, 21/98). Multi drug resistant (MDR) bacteria were detected in 72/98 (73.5%) of the isolates. The proportions of GNB-resistant strains were 60.0% (36/60) for ciprofloxacin, 60% (36/60) for amoxicillin, 60% (36/60) for amoxicillin, 68.3% (41/60) for trimethoprim-sulfamethoxazole and 58.3% (35/60) for ceftriaxone.

Conclusion

One-third of the patients with signs and symptoms of LRTIs had laboratory-confirmed bacterial pneumonia with a predominance of Gram negative MDR bacteria. This calls for continuous antimicrobial resistance (AMR) surveillance and antimicrobial stewardship programs in the study setting and other settings in developing countries as important strategies for tackling AMR.
Design and Evaluation of Microemulsion-Based Drug Delivery Systems for Biofilm-Based Infection in Burns
Authors: Biswas Avirup , A Jesil Mathew , Lewis Shaila Angela , Raja Selvaraj , Paul Arpita , Ghosal Kajal , Mahmood Syed , Ansari Mohd Danish
Published: September 2024

Normal skin is the first line of defense in the human body. A burn injury makes the skin susceptible to bacterial infection, thereby delaying wound healing and ultimately leading to sepsis. The chances of biofilm formation are high in burn wounds due to the presence of avascular necrotic tissue. The most common pathogen to cause burn infection and biofilm is Pseudomonas aeruginosa. The purpose of this study was to create a microemulsion (ME) formulation for topical application to treat bacterial burn infection. In the present study, tea tree oil was used as the oil phase, Tween 80 and transcutol were used as surfactants, and water served as the aqueous phase. Pseudo ternary phase diagrams were used to determine the design space. The ranges of components as suggested by the design were chosen, optimization of the microemulsion was performed, and in vitro drug release was assessed. Based on the characterization studies performed, it was found that the microemulsion were formulated properly, and the particle size obtained was within the desired microemulsion range of 10 to 300 nm. The I release study showed that the microemulsion followed an immediate release profile. The formulation was further tested based on its ability to inhibit biofilm formation and bacterial growth. The prepared microemulsion was capable of inhibiting biofilm formation.

Graphical Abstract
Serum Steroid Profiling in the Diagnosis of Adrenocortical Carcinoma: A Prospective Cohort Study
Authors: Yu Kai , Athimulam Shobana , Saini Jasmine , Kaur Ravinder Jeet , Xue Qingping , McKenzie Travis J , Singh Ravinder J , Grebe Stefan , Bancos Irina
Published: September 2024

Context

Guidelines suggest performing urine steroid profiling in patients with indeterminate adrenal tumors to make a noninvasive diagnosis of adrenocortical carcinoma (ACC). However, urine steroid profiling is not widely available.

Objective

To determine the accuracy of clinically available serum 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone in diagnosing ACC.

Methods

We conducted a prospective single-center cohort study of patients with adrenal masses evaluated between 2015 and 2023. Serum was analyzed by liquid chromatography–mass spectrometry for 17OH-pregnenolone, 17OH-progesterone, and 11-deoxycortisol. Reference standard for adrenal mass included histopathology, imaging characteristics, imaging follow up of 2 years, or clinical follow up of 5 years. Localized Generalized Matrix Learning Vector Quantization analysis was used to develop serum steroid score and assessed with area under receiver operating curve.

Results

Of 263 patients with adrenal masses, 44 (16.7%) were diagnosed with ACC, 161 (61%) with adrenocortical adenomas (ACAs), 27 (10%) with other adrenal malignancies, and 31 (12%) with other. Hounsfield unit ≥ 20 was demonstrated in all ACCs, in all but 1 other adrenal malignancy, and in 58 (31%) ACAs. All 3 steroids were higher in patients with ACCs vs non-ACCs, including when comparing ACCs with functioning ACAs, and with ACAs with Hounsfield unit ≥ 20 (P < .0001 for all). Localized Generalized Matrix Learning Vector Quantization analysis yielded a serum steroid score that discriminated between ACC and non-ACC groups with a mean threshold fixed area under receiver operating curve of 0.823.

Conclusion

We showed that measurements of 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone could be valuable in diagnosing ACC. After appropriate validation, serum steroid score could be integrated in clinical practice.
Postbiotic Impact on Host Metabolism and Immunity Provides Therapeutic Potential in Metabolic Disease
Authors: Fang Han , Rodrigues e-Lacerda Rodrigo , Barra Nicole G , Kukje Zada Dana , Robin Nazli , Mehra Alina , Schertzer Jonathan D
Published: September 2024

The gut microbiota influences aspects of metabolic disease, including tissue inflammation, adiposity, blood glucose, insulin, and endocrine control of metabolism. Prebiotics or probiotics are often sought to combat metabolic disease. However, prebiotics lack specificity and can have deleterious bacterial community effects. Probiotics require live bacteria to find a colonization niche sufficient to influence host immunity or metabolism. Postbiotics encompass bacterial-derived components and molecules, which are well-positioned to alter host immunometabolism without relying on colonization efficiency or causing widespread effects on the existing microbiota. Here, we summarize the potential for beneficial and detrimental effects of specific postbiotics related to metabolic disease and the underlying mechanisms of action. Bacterial cell wall components, such as lipopolysaccharides, muropeptides, lipoteichoic acids and flagellin, have context-dependent effects on host metabolism by engaging specific immune responses. Specific types of postbiotics within broad classes of compounds, such as lipopolysaccharides and muropeptides, can have opposing effects on endocrine control of host metabolism, where certain postbiotics are insulin sensitizers and others promote insulin resistance. Bacterial metabolites, such as short-chain fatty acids, bile acids, lactate, glycerol, succinate, ethanolamine, and ethanol, can be substrates for host metabolism. Postbiotics can fuel host metabolic pathways directly or influence endocrine control of metabolism through immunomodulation or mimicking host-derived hormones. The interaction of postbiotics in the host-microbe relationship should be considered during metabolic inflammation and metabolic disease.
Lrig1 regulates cell fate specification of glutamatergic neurons via FGF-driven Jak2/Stat3 signaling in cortical progenitors
Authors: De Vincenti Ana Paula , Bonafina Antonela , Ledda Fernanda , Paratcha Gustavo
Published: September 2024

The cell-intrinsic mechanisms underlying the decision of a stem/progenitor cell to either proliferate or differentiate remain incompletely understood. Here, we identify the transmembrane protein Lrig1 as a physiological homeostatic regulator of FGF2-driven proliferation and self-renewal of neural progenitors at early-to-mid embryonic stages of cortical development. We show that Lrig1 is expressed in cortical progenitors (CPs), and its ablation caused expansion and increased proliferation of radial/apical progenitors and of neurogenic transit-amplifying Tbr2+ intermediate progenitors. Notably, our findings identify a previously unreported EGF-independent mechanism through which Lrig1 negatively regulates neural progenitor proliferation by modulating the FGF2-induced IL6/Jak2/Stat3 pathway, a molecular cascade that plays a pivotal role in the generation and maintenance of CPs. Consistently, Lrig1 knockout mice showed a significant increase in the density of pyramidal glutamatergic neurons placed in superficial layers 2 and 3 of the postnatal neocortex. Together, these results support a model in which Lrig1 regulates cortical neurogenesis by influencing the cycling activity of a set of progenitors that are temporally specified to produce upper layer glutamatergic neurons.
Off- and On-Bike Resistance Training in Cyclists: A Randomized Controlled Trial
Authors: BARRANCO-GIL DAVID , HERNÁNDEZ-BELMONTE ALEJANDRO , RODRÍGUEZ-RIELVES VÍCTOR , IRIBERRI JON , MARTÍNEZ-CAVA ALEJANDRO , BUENDÍA-ROMERO ÁNGEL , ALEJO LIDIA B. , FRANCO-LOPEZ FRANCISCO , SANCHEZ-REDONDO IVÁN R. , DE PABLOS RAÚL , LUCIA ALEJANDRO , VALENZUELA PEDRO L. , PALLARES JESÚS G.
Published: September 2024

Purpose

This study compared the effects of off- and on-bike resistance training (RT) on endurance cycling performance as well as muscle strength, power, and structure.

Methods

Well-trained male cyclists were randomly assigned to incorporate two sessions/week of off-bike (full squats, n = 12) or on-bike (all-out efforts performed against very high resistances and thus at very low cadences, n = 12) RT during 10 wk, with all RT-related variables (number of sessions, sets, and repetitions, duration of recovery periods, and relative loads [70% of one-repetition maximum]) matched between the two groups. A third, control group (n = 13), did not receive any RT stimulus, but all groups completed a cycling training regime of the same volume and intensity. Outcomes included maximum oxygen uptake (V̇O2max), off-bike muscle strength (full squat) and on-bike (“pedaling”) muscle strength, and peak power capacity (Wingate test), dual-energy X-ray absorptiometry-determined body composition (muscle/fat mass), and muscle structure (cross-sectional area, pennation angle).

Results

No significant within/between-group effect was found for V̇O2max. Both the off-bike (mean Δ = 2.6%–5.8%) and on-bike (4.5%–7.3%) RT groups increased squat and pedaling-specific strength parameters after the intervention compared with the control group (−5.8% to –3.9%) (P < 0.05) with no significant differences between them. The two RT groups also increased Wingate performance (4.1% and 4.3%, respectively, vs –4.9% in the control group, P ≤ 0.018), with similar results for muscle cross-sectional area (2.5% and 2.2%, vs –2.3% in the control group, P ≤ 0.008). No significant within/between-group effect was found for body composition.

Conclusions

The new proposed on-bike RT could be an effective alternative to conventional off-bike RT training for improving overall and pedaling-specific muscle strength, power, and muscle mass.
Η καταγωγή και η σημασία του παλαιοχριστιανικού συνθρόνου
Authors: ΧΑΤΖΗΛΑΖΑΡΟΥ ( Dimitriοs Th. CHATZILAZAROU) Δημήτριος Θ.
Published: September 2024

H ομοιότητα του παλαιοχριστιανικού συνθρόνου με τις καθηγητικές εξέδρες που αποκαλύφθηκαν σε διδασκαλεία στην Αλεξάνδρεια, αναδεικνύει τη σημασία της έννοιας της διδασκαλίας για τη χριστιανική πίστη. Στην πρώιμη χριστιανική εικονογραφία και αυτοκρατορική ιδεολογία ανιχνεύονται τα τεκμήρια ενός εγχειρήματος της Εκκλησίας να προσεγγίσει τον εθνικό κόσμο μέσα από το ιδεολογικό, εικονογραφικό και συμβολικό λεξιλόγιό του. Η μεταφορά της καθηγητικής εξέδρας στην αψίδα του χριστιανικού ναού τον ανέδειξε συμβολικά σε διδασκαλείο της Θείας Σοφίας.
Προκαταρκτική παρουσίαση των αποτελεσμάτων της αρχαιολογικής έρευνας στον ναό του Αγίου Τίτου Γόρτυνας κατά τα έτη 2013-2015
Authors: ΣΥΘΙΑΚΑΚΗ (Vassiliki SΥΤΗΙΑΚΑΚΙ) Βασιλική
Published: September 2024

Ο ημιερειπωμένος ναός που διατηρεί το όνομα του ιδρυτή της κρητικής Εκκλησίας αποστόλου Τίτου στη Γόρτυνα, απασχολεί τη διεθνή επιστημονική κοινότητα για περισσότερο από έναν αιώνα. Μια δοκιμαστική ανασκαφική έρευνα που πραγματοποιήθηκε το 2010, η επανεξέταση των λειψάνων του γλυπτού διακόσμου, αλλά κυρίως η συστηματική διερεύνηση κατά το διάστημα 2013-2015 στο πλαίσιο εργασιών συντήρησης και αποκατάστασης, αποκάλυψαν εξόχως ενδιαφέροντα στοιχεία για την οικοδομική ιστορία του μνημείου. Επιχειρείται εδώ μια προκαταρκτική παρουσίαση των αποτελεσμάτων της έρευνας, που ρίχνουν νέο φως στα παλαιότερα ερωτήματα.
Παλαιολόγειες εικόνες στη Βουλγαρία
Authors: Trifonova Alexandra
Published: September 2024

Στη μελέτη θα παρουσιαστούν επιλεκτικά 11 παλαιολόγειες εικόνες, οι οποίες χρονολογούνται από το δεύτερο μισό του 13ου έως το τελευταίο τέταρτο του 14ου αιώνα. Οι εικόνες αυτές βρίσκονται σε διάφορα μέρη στη Βουλγαρία και έχουν διαφορετική προέλευση. Ωστόσο, οι περισσότερες προέρχονται από τη Μεσημβρία, πόλη στη Μαύρη Θάλασσα. Οι εικόνες αυτές, σύμφωνά με την έρευνά μας, ανήκουν σε ζωγράφους καλλιτεχνικών εργαστηρίων κυρίως της Κωνσταντινούπολης και δευτερευόντως της Θεσσαλονίκης
Panayota Assimakopoulou-Atzaka, Corpus of the Early Christian Mosaic Pavements of Greece, III.2. The Mosaic Pavements of Macedonia and Thrace.
Authors: OVADIAH Asher
Published: September 2024

Panayota Assimakopoulou-Atzaka, Corpus of the Early Christian Mosaic Pavements of Greece, III.2. The Mosaic Pavements of Macedonia and Thrace (in Greek), Part A and Part B (Aristotle University of Thessaloniki / Centre for Byzantine Research, Byzantine Monuments 18), Thessaloniki: Aristotle University of Thessaloniki / Centre for Byzantine Research and the National Bank Cultural Foundation, 2017, 624 + 660 pp., 566 mostly colour pls and maps, bibliography, indexes (in Greek with a preface, an introduction, and a list of plates in English). ISBN: 978-618-83505-0-2, ISSN: 1791-9630.
Yuliana Boycheva, «Αl. Kuyumdzhiev, Emm. Mutafov (επιμ.), Corpus of Mural Paintings from the first half of 19th century in Bulgaria (στα βουλγαρικά) (Corpora of Pre-Modern Christian Orthodox Mural Painting, Bulgaria 3)».
Authors: BOYCHEVA Yuliana
Published: September 2024

Αl. Kuyumdzhiev, Emm. Mutafov (επιμ.), Corpus of Mural Paintings from the first half of 19th century in Bulgaria (Corpora of Pre-Modern Christian Orthodox Mural Painting, Bulgaria 3), Institute of Art Studies, Bulgarian Academy of Sciences, Σόφια 2018, 900 σελ., 1.200 εικ., 46 αρχιτ. και 50 σχέδ. τοιχογραφιών (στα βουλγαρικά, ο πρόλογος και το εικονογραφικό ευρετήριο στα βουλγαρικά και τα αγγλικά). ISBN: 978-954-8594-73-8.
Μεταμορφώσεις του αστικού τοπίου της Θεσσαλονίκης απο τον 4ο στον 9ο αι. στη διασταύρωση του decumanus maximus με τον cardo της οδού Βενιζέλου (ανασκαφή σταθμού Βενιζέλου ‒ μετρό Θεσσαλονίκης)
Authors: ΚΩΝΣΤΑΝΤΙΝΙΔΗ (Krino KONSTANTINIDOU) Κρινώ , ΜΙΖΑ (Maria MIZA) Μαρία
Published: September 2024

Στην παρούσα μελέτη παρουσιάζονται οι μεταμορφώσεις του πολεοδομικού ιστού της Θεσσαλονίκης στη διασταύρωση του decumanus maximus με τον cardo της οδού Βενιζέλου, βάσει των ανασκαφικών δεδομένων που ήρθαν στο φως από την έρευνα που διεξήχθη στο σταθμό Βενιζέλου, στο πλαίσιο της κατασκευής του Μητροπολιτικού Σιδηροδρόμου. Mέσα στον 4ο αιώνα στη συμβολή των μαρμαρόστρωτων δρόμων ανεγείρεται μνημειακό τετράπυλο, ενώ κατά τον πολεοδομικό ανασχεδιασμό του 6ου αιώνα, νότια του διερυμένου decumanus maximus, διαμορώνεται ορθογώνια μαρμαρόστρωτη πλατεία πλαισιωμένη με στοές. Σταδιακά, εκατέρωθεν της χαλικόστρωτης πλέον οριζόντιας οδικής αρτηρίας, της Μέσης ή Λεωφόρου των βυζαντινών χρόνων, αναπτύσσονται νησίδες της κεντρικής αγοράς της πόλης (8ος-9ος αιώνας).
Μελίνα Π. Παϊσίδου, Η Παναγία Ελεούσα της Μεγάλης Πρέσπας
Authors: ΚΑΛΟΠΙΣΗ-ΒΕΡΤΗ(Sofia KALOPISSI-VERTI) Σοφία
Published: September 2024

Μελίνα Π. Παϊσίδου, Η Παναγία Ελεούσα της Μεγάλης Πρέσπας. Μελέτη μνημειακής τοπογραφίας, αρχιτεκτονικής και ζωγραφικής των αρχών του 15ου αιώνα στην περιοχή των Πρεσπών, Μακεδονική Βιβλιοθήκη, αρ. 110, Εταιρεία Μακεδονικών Σπουδών, Θεσσαλονίκη 2019, 238 σελ., 2 σχέδ., 99 έγχρ. εικ., περίληψη στα γαλλικά, βιβλιογραφία, ευρετήρια. ISBN: 978-960-9458-27-6.