bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Variation in the FAAH Gene Is Directly Associated with Subjective Well-Being and Indirectly Associated with Problematic Alcohol Use
Authors: Bornscheuer Lisa , Lundin Andreas , Forsell Yvonne , Lavebratt Catharina , Melas Philippe A.
Published: September 2023

Fatty acid amide hydrolase (FAAH) is an enzyme that degrades anandamide, an endocannabinoid that modulates mesolimbic dopamine release and, consequently, influences states of well-being. Despite these known interactions, the specific role of FAAH in subjective well-being remains underexplored. Since well-being is a dynamic trait that can fluctuate over time, we hypothesized that we could provide deeper insights into the link between FAAH and well-being using longitudinal data. To this end, we analyzed well-being data collected three years apart using the WHO (Ten) Well-Being Index and genotyped a functional polymorphism in the FAAH gene (rs324420, Pro129Thr) in a sample of 2822 individuals. We found that the A-allele of rs324420, which results in reduced FAAH activity and elevated anandamide levels, was associated with lower well-being scores at both time points (Wave I, B: −0.52, p = 0.007; Wave II, B: −0.41, p = 0.03, adjusted for age and sex). A subsequent phenome-wide association study (PheWAS) affirmed our well-being findings in the UK Biobank (N = 126,132, alternative C-allele associated with elevated happiness, p = 0.008) and revealed an additional association with alcohol dependence. In our cohort, using lagged longitudinal mediation analyses, we uncovered evidence of an indirect association between rs324420 and problematic alcohol use (AUDIT-P) through the pathway of lower well-being (indirect effect Boot: 0.015, 95% CI [0.003, 0.030], adjusted for AUDIT in Wave I). We propose that chronically elevated anandamide levels might influence disruptions in the endocannabinoid system—a biological contributor to well-being—which could, in turn, contribute to increased alcohol intake, though multiple factors may be at play. Further genetic studies and mediation analyses are needed to validate and extend these findings.
Au-Cu Resources in Some Mines from Antiquity in the South Gabal Um Monqul and Gabal Al Kharaza Prospects, North Eastern Desert, Egypt
Authors: Atef Abdallah , Surour Adel A. , Madani Ahmed A. , Azer Mokhles K.
Published: September 2023

Since Antiquity, sustainable resources of gold and copper have been mined at two prominent prospects in the north Eastern Desert of Egypt, namely the south Gabel Um Monqul (SGUM) and Gabal Al Kharaza (GKZ). Mineralization is hosted by Neoproterozoic shield rocks represented by dacite and monzo- to syenogranite at the SGUM prospect whereas they are diorite, granodiorite, and quartz feldspar porphyry at the GKZ prospect. These hosts have been emplaced in an island arc environment from calc-alkaline magmas with a peraluminous to metaluminous signature. They are hydrothermally altered including albitization, sericitization, silicification, epidotization, and chloritization. The Au and Cu mineralizations are confined to shear zones that lately filled with auriferous quartz veins adjacent to mineralized alteration zones. In the GKZ prospect, the old trenches trend mainly in a NW–SE direction whereas it is NE–SW and NW–SE in the SGUM prospect. Evidence of shearing ranges from megascopic conjugate fractures and shear planes in the outcrops to microscopic sheared and crumbled Au-Cu ore assemblages dominated by Fe-Cu sulfides, specularite, and barite. Microscopic investigation suggests that the formation of specularite is due to the shearing of early existing magnetite. The ore textures and paragenetic sequence indicate that pyrite in the alteration zones is oxidized, leading to the liberation of gold up to 3.3 g/t. The formulae of the analyzed electrum lie in the range Au74.5-76.8 Ag22.2-24.5. Integration of the field, geochemistry, and mineral chemistry data, combined with the gold fire assay data prove the presence of sustainable amounts of disseminated Au and Cu, not only in the mineralized quartz veins, but also in the alteration zones. Data materialized in our paper show similarities in the style of mineralization at the SGUM and the GKZ prospects with iron oxide-copper-gold (IOCG) deposits elsewhere in the Arabian-Nubian Shield (ANS) and other world examples.
Salt Production and the Geoheritage of the Huesca Province (Spain): Context, History, and Potential as an Educational Resource
Authors: Calvo Guiomar , Carrasquer-Álvarez Beatriz , Martínez-Aznar Javier
Published: September 2023

Salt harvesting through natural solar evaporation of salt brines is a practice notably abundant in the Iberian Peninsula. Such activity has been relevant for human consumption, food preservation, livestock feed, and various industries throughout history. The objective of this research is to analyze the productive history and conservation state of the salt evaporation ponds located in Naval and Peralta de la Sal (Huesca, Spain), as well as their didactic potential. These saltworks are associated with clay and gypsum levels from the Upper Triassic (Keuper). The earliest written records of salt production in the area date back to the 10th century, but they were exploited as early as the Bronze Age. Remains of most of the ponds and some buildings are still preserved and are easily accessed, which makes them very interesting from an educational perspective. Both on-site and off-site activities can be carried out to analyze their historical and current significance through modeling and argumentation practices. This can lead to a better understanding of how geology relates to everyday life and facilitate the development of positive attitudes among students towards geoheritage while raising awareness about its preservation and preventing its degradation.
Gender Differences in Psychosocial Outcomes and Coping Strategies of Patients with Colorectal Cancer: A Systematic Review
Authors: Zhou Junrui , Wang Zhiming , Chen Xuan , Li Qiuping
Published: September 2023

(1) Background: Gender is an important factor impacting cancer experience. This review mainly aimed to summarize colorectal cancer (CRC) patients’ gender differences in psychosocial outcomes and coping strategies. (2) Methods: Relevant studies were searched for in four electronic databases from 2007 to July 2023. And manual searching was performed on the included studies’ reference lists to identify additional eligible studies. (3) Results: A total of 37 eligible articles were included in this review. These studies were conducted in 19 countries, and they targeted CRC patients at various treatment stages. Significant results showed that female patients tended to have more psychological distress, complex social functioning, and less sexual distress and to choose more positive coping strategies than male patients. But there was no gender difference in psychosocial outcomes and/or coping strategies in some studies, which implied that gender similarity also existed. (4) Conclusions: The findings support the fact that there are both gender differences and similarities in CRC patients’ psychosocial outcomes and coping strategies. A perspective beyond the simple masculine–feminine binary improved our in-depth understanding of gender tendency. Importantly, taking gender tendency into account is critical for medical staff to provide more personalized support and communication interventions.
Clinical Effectiveness of Renal Transplant Outpatient Pharmaceutical Care Services in Korea
Authors: Jang Ha Young , Kim Yon Su , Oh Jung Mi
Published: September 2023

Background: The necessity and importance of pharmaceutical care services (PCS) are well recognized, yet the concept and scope of PCS have not yet been clearly defined in Korea, particularly in kidney transplantation outpatient clinics. Aim: The main purpose of this study is to evaluate whether PCS is effective in the outpatient setting for kidney transplant patients. Methods: For three years, a clinical pharmacist provided PCS to kidney transplant patients in an outpatient setting to evaluate the clinical effectiveness of PCS. Results: A total of 302 patients were matched in a 1:1 ratio, with 151 in the PCS group and 151 in the control group. These patients were followed, and a total of 476 interventions were provided to them, including medication reconciliation (n = 113, 23.7%), medication evaluation and management (n = 186, 39.1%), and pharmaceutical care transition (n = 177, 37.2%) services. The estimated glomerular filtration rate (eGFR) exhibited a notable difference between the control and PCS groups when comparing the pre- and post-study periods measurements. In the control group, there was a decline of 7.0 mL/min/1.73 m2 in eGFR. In contrast, the PCS group showed a smaller decline of 2.5 mL/min/1.73 m2 (p = 0.03). The adjusted odds ratio for end stage renal disease development in the PCS group was 0.51 (95% confidence interval: 0.26–0.96), indicating a significantly lower risk compared to the control group. Conclusion: Our study highlights the promising potential of PCS implementation in kidney transplantation outpatient clinics. Further research is needed to validate and expand upon these findings, especially in diverse clinical settings.
Evolution of Tunneling Hydro-Technology: From Ancient Times to Present and Future
Authors: Angelakis Andreas N. , Passchier Cees W. , Valipour Mohammad , Krasilnikoff Jens A. , Tzanakakis Vasileios A. , Ahmed Abdelkader T. , Baba Alper , Kumar Rohitashw , Bilgic Esra , Capodaglio Andrea G. , Dercas Nicholas
Published: September 2023

Water tunnels are one of the oldest hydro-technologies for extracting water resources and/or transmitting them through water distribution systems. In the past, human societies have used tunneling for various purposes, including development, as a measure to enable underground resource extraction and the construction of transportation networks in challenging landscapes and topographies. The development of hydro-technology potentially involves the construction of tunnels to feed aqueducts, irrigation and waste water systems. Thus, the ability to make and maintain tunnels became an important component in creating lasting and sustainable water systems, which increased water supply and security, minimized construction costs, and reduced environmental impact. Thus, this review asks how, when and why human societies of the past included tunneling for the development of lasting water supply systems. This review presents a comprehensive overview across time and space, covering the history of tunneling in hydro technology from antiquity to the present, and it ponders how past experiences could impact on future hydro-technological projects involving tunneling. A historical review of tunnel systems enhances our understanding of the potential, performance, challenges, and prospects associated with the use of hydro-techniques. In the past, as the different examples in time and space demonstrate, tunneling was often dedicated to solving local problems of supply and disposal. However, across the world, some features were repeated, including the need for carving through the living rock or digging to create tunnels covered with stone slabs. Also, the world-wide use of extensive and costly tunnel systems indicates the high level of investment which human societies are willing to make for securing control over and with its water resources. This study helps us to gather inspiration from proven technologies of the past and more recent knowledge of water tunnel design and construction. As we face global warming and its derivate problems, including problems of water scarcity and flooding, the ability to create and maintain tunnels remains an important technology for the future.
Knowledge, Attitude, Behavior Practices and Compliance of Workers Exposed to Respirable Dust in a Zambian Copper Mine
Authors: Sifanu Mwaba , Taylor Thomas K. , Kalebaila Kennedy K. , Hayumbu Patrick , Nabiwa Lubinda , Linde Stephanus J. L.
Published: September 2023

Work in the copper mining industry is often associated with exposure to respirable dust and respirable crystalline silica. This exposure has the potential to cause silicosis, an incurable occupational respiratory lung disease. This study aimed at establishing the relationship between knowledge, attitudes, work behavioral practices and compliance with safety standards and workers’ exposure to respirable dust. A cross-sectional descriptive survey was conducted on 528 mine workers. The Statistical Package for Social Sciences (SPSS) was used for the descriptives. Structural equation modeling (SEM) with latent variables and partial least squares (LVPLS) analysis were employed to determine the relationship among these variables. The results indicated that of the four hypotheses, two were supported, and two were rejected, showing that there is a significant relationship between exposure to respirable dust and work behavioral practices, as well as compliance with safety standards. Knowledge and attitudes toward respirable dust exposure did not significantly influence exposure. According to the results from the survey, positive work behavioral practices as well as compliance with safety standards were significantly associated with exposure to respirable dust. It is recommended that mines should focus on the miners’ work behavioral practices and compliance with safety standards.
Mental Health Clinician Attitudes about Service User and Family Agency and Involvement in Recovery-Oriented Practice
Authors: Chisholm Janice , Hope Judy , Fossey Ellie , Petrakis Melissa
Published: September 2023

Background: Recovery-oriented practice (ROP) is a framework focusing on recovery through hope, choice, and meaning, to live with or without enduring symptoms and challenges. Aims: To examine clinicians’ attitudes about the involvement of service users and family or supporters in ROP. Methods: A bespoke Qualtrics survey obtained views of mental health clinicians working in an Australian public mental health service about service user and family involvement in ROP, using a five-point Likert scale of agreement and free-text responses. Data were analysed with descriptive statistics and content analysis methods. Results: Two hundred and three clinicians completed the survey. Most (79%) clinicians agreed with the statement that service users want clinicians to use ROP principles, and the majority (63%) also ‘strongly believed’ that ROP made a difference to service users’ mental health outcomes. Only 15% ‘strongly agreed’ and 57% somewhat agreed with the statement that service users know what treatment is best for them, and only 20% of clinicians ‘strongly agreed’ that supporters of service users believed in and wanted ROP for their family member or friend. Future directions: This study adds to the literature on clinicians’ views about ROP and shows that although clinicians are supportive of ROP, they also express substantial ambivalence about whether service users and families know what treatment is best. For ROP implementation to be successful, workforce training needs to support clinicians to reflect on these views with service users and families, and to encourage supported decision making. Future studies should focus on changes in clinicians’ views and practice post ROP training.
Large-Emitting-Area Quantum Dot Light-Emitting Diodes Fabricated by an All-Solution Process
Authors: Tu Ning , Lee S. W. Ricky
Published: September 2023

Quantum dots (QDs) have attracted a lot of attention over the past decades due to their sharp emission spectrum and color, which can be tuned by changing just the particle size and chromophoric stability. All these advantages of QDs make quantum dot light-emitting diodes (QLEDs) promising candidates for display and light-source applications. This paper demonstrates a large-emitting-area QLED fabricated by a full-solution process. This QLED is composed of indium tin oxide (ITO) as the anode, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT: PSS) as the hole injection layer (HIL), and poly(N,N′-bis-4-butylphenyl-N,N′-bisphenyl)benzidine (poly-TPD) as the hole-transport layer (HTL). The light-emitting layer (EML) is composed of green CdSe/ZnS quantum dots. By applying the ZnO nanoparticles as the electron-injection/transport layer, QLED devices are prepared under a full-solution process. The large-emitting-area QLED exhibits a low turn-on voltage of around 2~3 V, and the International Commission on Illumination (CIE) 1931 coordinate value of the emission spectrum was (0.31, 0.66). The large emitting area and the unique QLED structure of the device make it possible to apply these features to inkjet printing quantum dot light sources and quantum dot display applications.
miR-30a-3p Regulates Autophagy in the Involution of Mice Mammary Glands
Authors: Tian Lei , Guo Shancheng , Zhao Zhiye , Chen Yuxu , Wang Chunmei , Li Qingzhang , Li Ye
Published: September 2023

The mammary gland undergoes intensive remodeling during the lactation cycle, and the involution process of mammary gland contains extensive epithelial cells involved in the process of autophagy. Our studies of mice mammary glands suggest that miR-30a-3p expression was low during involution compared with its high expression in the mammary glands of lactating mice. Then, we revealed that miR-30a-3p negatively regulated autophagy by autophagy related 12 (Atg12) in mouse mammary gland epithelial cells (MMECs). Restoring ATG12, knocking down autophagy related 5 (Atg5), starvation, and Rapamycin were used to further confirm this conclusion. Overexpression of miR-30a-3p inhibited autophagy and altered mammary structure in the involution of the mammary glands of mice, which was indicative of alteration in mammary remodeling. Taken together, these results elucidated the molecular mechanisms of miR-30a-3p as a key induction mediator of autophagy by targeting Atg12 within the transition period between lactation and involution in mammary glands.
ASAP1 Expression in Invasive Breast Cancer and Its Prognostic Role
Authors: Park Hosub , Son Hwangkyu , Cha Hyebin , Song Kihyuk , Bang Seongsik , Jee Seungyun , Kim Hyunsung , Myung Jaekyung , Shin Su-Jin , Cha Chihwan , Chung Min Sung , Paik Seungsam
Published: September 2023

Breast cancer is a major global health burden with high morbidity and mortality rates. Previous studies have reported that increased expression of ASAP1 is associated with poor prognosis in various types of cancer. This study was conducted on 452 breast cancer patients who underwent surgery at Hanyang University Hospital, Seoul, South Korea. Data on clinicopathological characteristics including molecular pathologic markers were collected. Immunohistochemical staining of ASAP1 expression level were used to classify patients into high and low groups. In total, 452 cases low ASAP1 expression group was associated with significantly worse recurrence-free survival (p = 0.029). In ER-positive cases (n = 280), the low ASAP1 expression group was associated with significantly worse overall survival (p = 0.039) and recurrence-free survival (p = 0.029). In multivariate cox analysis, low ASAP1 expression was an independent significant predictor of poor recurrence-free survival in the overall patient group (hazard ratio = 2.566, p = 0.002) and ER-positive cases (hazard ratio = 4.046, p = 0.002). In the analysis of the TCGA dataset, the low-expression group of ASAP1 protein demonstrated a significantly poorer progression-free survival (p = 0.005). This study reports that low ASAP1 expression was associated with worse recurrence-free survival in invasive breast cancer.
Therapeutic Effects of Curcumin Derivatives against Obesity and Associated Metabolic Complications: A Review of In Vitro and In Vivo Studies
Authors: Moetlediwa Marakiya T. , Ramashia Rudzani , Pheiffer Carmen , Titinchi Salam J. J. , Mazibuko-Mbeje Sithandiwe E. , Jack Babalwa U.
Published: September 2023

Obesity is a major cause of morbidity and mortality globally, increasing the risk for chronic diseases. Thus, the need to identify more effective anti-obesity agents has spurred significant interest in the health-promoting properties of natural compounds. Of these, curcumin, the most abundant and bioactive constituent of turmeric, possesses a variety of health benefits including anti-obesity effects. However, despite its anti-obesity potential, curcumin has demonstrated poor bioavailability, which limits its clinical applicability. Synthesizing curcumin derivatives, which are structurally modified analogs of curcumin, has been postulated to improve bioavailability while maintaining therapeutic efficacy. This review summarizes in vitro and in vivo studies that assessed the effects of curcumin derivatives against obesity and its associated metabolic complications. We identified eight synthetic curcumin derivatives that were shown to ameliorate obesity and metabolic dysfunction in diet-induced obese animal models, while five of these derivatives also attenuated obesity and associated metabolic complications in cell culture models. These curcumin derivatives modulated adipogenesis, lipid metabolism, insulin resistance, steatosis, lipotoxicity, inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis, autophagy, fibrosis, and dyslipidemia to a greater extent than curcumin. In conclusion, the findings from this review show that compared to curcumin, synthetic curcumin derivatives present potential candidates for further development as therapeutic agents to modulate obesity and obesity-associated metabolic complications.
Evolution End Classification of tfd Gene Clusters Mediating Bacterial Degradation of 2,4-Dichlorophenoxyacetic Acid (2,4-D)
Authors: Iasakov Timur
Published: September 2023

The tfd (tfdI and tfdII) are gene clusters originally discovered in plasmid pJP4 which are involved in the bacterial degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) via the ortho-cleavage pathway of chlorinated catechols. They share this activity, with respect to substituted catechols, with clusters tcb and clc. Although great effort has been devoted over nearly forty years to exploring the structural diversity of these clusters, their evolution has been poorly resolved to date, and their classification is clearly obsolete. Employing comparative genomic and phylogenetic approaches has revealed that all tfd clusters can be classified as one of four different types. The following four-type classification and new nomenclature are proposed: tfdI, tfdII, tfdIII and tfdIV(A,B,C). Horizontal gene transfer between Burkholderiales and Sphingomonadales provides phenomenal linkage between tfdI, tfdII, tfdIII and tfdIV type clusters and their mosaic nature. It is hypothesized that the evolution of tfd gene clusters proceeded within first (tcb, clc and tfdI), second (tfdII and tfdIII) and third (tfdIV(A,B,C)) evolutionary lineages, in each of which, the genes were clustered in specific combinations. Their clustering is discussed through the prism of hot spots and driving forces of various models, theories, and hypotheses of cluster and operon formation. Two hypotheses about series of gene deletions and displacements are also proposed to explain the structural variations across members of clusters tfdII and tfdIII, respectively. Taking everything into account, these findings reconstruct the phylogeny of tfd clusters, have delineated their evolutionary trajectories, and allow the contribution of various evolutionary processes to be assessed.
Molecular Markers for Bladder Cancer Screening: An Insight into Bladder Cancer and FDA-Approved Biomarkers
Authors: Flores Monar Gabriela Vanessa , Reynolds Thomas , Gordon Maxie , Moon David , Moon Chulso
Published: September 2023

Bladder cancer is one of the most financially burdensome cancers globally, from its diagnostic to its terminal stages. The impact it imposes on patients and the medical community is substantial, exacerbated by the absence of disease-specific characteristics and limited disease-free spans. Frequent recurrences, impacting nearly half of the diagnosed population, require frequent and invasive monitoring. Given the advancing comprehension of its etiology and attributes, bladder cancer is an appealing candidate for screening strategies. Cystoscopy is the current gold standard for bladder cancer detection, but it is invasive and has the potential for undesired complications and elevated costs. Although urine cytology is a supplementary tool in select instances, its efficacy is limited due to its restricted sensitivity, mainly when targeting low-grade tumors. Although most of these assays exhibit higher sensitivity than urine cytology, clinical guidelines do not currently incorporate them. Consequently, it is necessary to explore novel screening assays to identify distinctive alterations exclusive to bladder cancer. Thus, integrating potential molecular assays requires further investigation through more extensive validation studies. Within this article, we offer a comprehensive overview of the critical features of bladder cancer while conducting a thorough analysis of the FDA-approved assays designed to diagnose and monitor its recurrences.
Parallel Losses of Blue Opsin Correlate with Compensatory Neofunctionalization of UV-Opsin Gene Duplicates in Aphids and Planthoppers
Authors: Friedrich Markus
Published: September 2023

Expanding on previous efforts to survey the visual opsin repertoires of the Hemiptera, this study confirms that homologs of the UV- and LW-opsin subfamilies are conserved in all Hemiptera, while the B-opsin subfamily is missing from the Heteroptera and subgroups of the Sternorrhyncha and Auchenorrhyncha, i.e., aphids (Aphidoidea) and planthoppers (Fulgoroidea), respectively. Unlike in the Heteroptera, which are characterized by multiple independent expansions of the LW-opsin subfamily, the lack of B-opsin correlates with the presence of tandem-duplicated UV-opsins in aphids and planthoppers. Available data on organismal wavelength sensitivities and retinal gene expression patterns lead to the conclusion that, in both groups, one UV-opsin paralog shifted from ancestral UV peak sensitivity to derived blue sensitivity, likely compensating for the lost B-opsin. Two parallel bona fide tuning site substitutions compare to 18 non-corresponding amino acid replacements in the blue-shifted UV-opsin paralogs of aphids and planthoppers. Most notably, while the aphid blue-shifted UV-opsin clade is characterized by a replacement substitution at one of the best-documented UV/blue tuning sites (Rhodopsin site 90), the planthopper blue-shifted UV-opsin paralogs retained the ancestral lysine at this position. Combined, the new findings identify aphid and planthopper UV-opsins as a new valuable data sample for studying adaptive opsin evolution.
Update on Anticoagulation Strategies in Patients with ECMO—A Narrative Review
Authors: Šoltés Ján , Skribuckij Michal , Říha Hynek , Lipš Michal , Michálek Pavel , Balík Martin , Pořízka Michal
Published: September 2023

The use of extracorporeal membrane oxygenation (ECMO) has recently increased exponentially. ECMO has become the preferred mode of organ support in refractory respiratory or circulatory failure. The fragile balance of haemostasis physiology is massively altered by the patient’s critical condition and specifically the aetiology of the underlying disease. Furthermore, an application of ECMO conveys another disturbance of haemostasis due to blood-circuit interaction and the presence of an oxygenator. The purpose of this review is to summarise current knowledge on the anticoagulation management in patients undergoing ECMO therapy. The unfractionated heparin modality with monitoring of activated partial thromboplastin tests is considered to be a gold standard for anticoagulation in this specific subgroup of intensive care patients. However, alternative modalities with other agents are comprehensively discussed. Furthermore, other ways of monitoring can represent the actual state of coagulation in a more complex fashion, such as thromboelastometric/graphic methods, and might become more frequent. In conclusion, the coagulation system of patients with ECMO is altered by multiple variables, and there is a significant lack of evidence in this area. Therefore, a highly individualised approach is the best solution today.
Limb Salvage and Survival in Chronic Limb-Threatening Ischemia: The Need for a Fast-Track Team-Based Approach
Authors: Ventoruzzo Giorgio , Mazzitelli Giulia , Ruzzi Umberto , Liistro Francesco , Scatena Alessia , Martelli Eugenio
Published: September 2023

Chronic limb-threatening ischemia (CLTI) represents the end-stage form of peripheral arterial disease (PAD) and is associated with a very poor prognosis and high risk of limb loss and mortality. It can be considered very similar to a terminal cancer disease, reflecting a large impact on quality of life and healthcare costs. The aim of this study is to offer an overview of the relationship between CLTI, limb salvage, and mortality, with a focus on the need of a fast-track team-based management that is a driver to achieve better survival results. This review can be useful to improve management of this growing impact disease, and to promote the standardisation of care and communication between specialist and non-specialist healthcare professionals.
Haematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease
Authors: Slatter M. , Gennery A.
Published: September 2023

Chronic granulomatous disease (CGD) is an inborn error of immunity due to defects in the transport or function of subunits of nicotinamide adenine dinucleotide phosphate oxidase, the enzyme that generates the phagocyte respiratory burst responsible for intracellular killing of engulfed micro-organisms. Patients present with infectious or inflammatory complications. Common bacterial pathogens include Staphylococcus aureus and Burkholderia cepacia complex. Fungal pathogens include Aspergillus species, particularly Aspergillus fumigatus. Inflammatory complications most commonly manifest as inflammatory bowel disease or lung disease. Granulomata are the distinguishing histological feature. Haematopoietic stem cell transplantation (HSCT) was first considered for CGD in the early 1970’s. Since then, refinements in transplant technique, donor selection, conditioning regimens, and graft engineering have widened the option of HSCT to most patients with CGD. This review charts the progress made in HSCT for CGD.
Common Diagnostic Challenges and Pitfalls in Segmental Colitis Associated with Diverticulosis (SCAD)
Authors: Sbarigia Caterina , Ritieni Camilla , Annibale Bruno , Carabotti Marilia
Published: September 2023

Segmental colitis associated with diverticulosis (SCAD) is characterized by inflammation involving the sigmoid inter-diverticular mucosa, sparing the proximal colon and rectum. Due to the heterogeneity of clinical manifestations and endoscopic and histological findings, SCAD diagnosis might be challenging in clinical practice. This narrative review aimed to report the SCAD diagnostic criteria adopted in different studies, highlighting the current challenges and main pitfalls in its diagnosis. We analysed fourteen studies, mainly prospective observational studies. Haematochezia and rectal bleeding were the main complaints leading to diagnosis, followed by diarrhoea. An accurate endoscopic description was performed in 86% of studies, while a standardised biopsy sampling protocol (sigma, proximal colon and rectum) was scarcely adopted, being complete only in 28.5% of studies. The evaluation of concomitant drugs potentially inducing colitis was carried out in only 57% of studies. Great heterogeneity in sigmoid endoscopic (edema, erythema, erosions, ulcers, mucosal friability) and histological findings (chronic and/or acute inflammatory infiltrate) was observed. We showed that SCAD diagnosis is often based on not fully adequate macroscopic colonic description and scant biopsy protocol sampling. An accurate clinical and endoscopic evaluation, with an adequate sampling biopsy protocol, with attention to differential diagnosis, seemed to be crucial for a prompt SCAD diagnosis.
Nonspecific Gastrointestinal Symptoms as the First Sign of Ganglioneuroblastoma Intermixed—Case Report and Literature Review
Authors: Lipiński Łukasz , Lipińska Justyna , Kowalczuk Maria , Kopeć Izabela , Woźniak Magdalena Maria , Mitek-Palusińska Joanna , Mitura-Lesiuk Małgorzata
Published: September 2023

Nonspecific gastrointestinal symptoms remain a problem for pediatricians because, out of a thousand trivial cases, there are rare diseases that require in-depth diagnostics and extensive knowledge to identify them. These complaints may be caused by a neoplastic process. We present the case of a 5-year-old boy whose diagnostic pathway lasted about 3 months. He was admitted to hospital due to severe abdominal pain. Physical examination revealed a bloated, hard, and painful abdomen. In the standing X-ray, the features of intestinal obstruction were visualized. An ultrasound examination showed a possible malignant lesion in the location of the left adrenal gland. After the surgical removal of the pathological mass and histopathological examination, the diagnosis of ganglioneuroblastoma intermixed was made. This tumor, along with neuroblastoma, ganglioneuroma, and ganglioneuroblastoma nodular, belongs to neuroblastic tumors (NTs), which originate from primitive cells of the sympathetic nervous system. NTs are quite rare, but they are still the majority of extracranial solid tumors in children, and their symptoms often appear relatively late when the neoplastic process is already advanced. The purpose of this review is to present current information about ganglioneuroblastoma, with a special emphasis on nonspecific gastrointestinal symptoms as first sign of this tumor and its diagnostics.
Similar Patient Satisfaction and Quality of Life Improvement Achieved with TKA and THA According to the Goodman Scale: A Comparative Study
Authors: Barahona Maximiliano , Bustos Felipe , Navarro Tomás , Chamorro Pablo , Barahona Macarena Alejandra , Carvajal Sebastián , Brañes Julian , Hinzpeter Jaime , Barrientos Cristian , Infante Carlos
Published: September 2023

Background: Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are effective treatments for severe knee and hip osteoarthritis. Historically, TKA has been associated with lower satisfaction than THA, but recent advances in knee surgery have led to lower dissatisfaction rates. This study aimed to compare the satisfaction and self-reported improvement in the quality of life of two cohorts of patients who underwent TKA and THA, respectively. Methods: This observational study compared two previously published cohorts of patients who underwent THA and TKA in a single university center. The Goodman scale was used to assess satisfaction and self-perception of improved quality of life after TKA and THA at a minimum one-year follow-up. Propensity score matching was used to balance age, gender, and follow-up between groups. Significance was set at 0.05. Results: The study included a total of 105 THAs and 131 TKAs. Both groups had high levels of satisfaction with pain relief, ability to do house/yard work, and overall satisfaction, with above 90% satisfaction rates. Regarding improvement in quality of life, both groups had 86% of patients reporting improvement as “much better.” After propensity score matching, no significant difference was found between THA and TKA for any of the comparisons made using the Goodman scale. Conclusions: The study showed that both TKA and THA resulted in high levels of satisfaction and improvement in quality of life. There was no significant difference in satisfaction rates between TKA and THA, contrary to the historical trend of lower satisfaction rates for TKA.
Perinatal Outcomes of Monochorionic Twin Pregnancies Conceived Naturally Versus through Assisted Reproductive Techniques
Authors: Martínez-Varea Alicia , Martínez-Gómez Martha , Novillo Blanca , Domenech Josep , Morales-Roselló José , Diago-Almela Vicente
Published: September 2023

Objective: It has been reported that monochorionic twin pregnancies conceived through assisted reproductive techniques (ART) display a higher risk of second-trimester miscarriage, cesarean delivery, and neonatal death than those conceived naturally. The aim of this study was to compare the perinatal outcomes of monochorionic diamniotic (MCDA) twin pregnancies conceived naturally and through ART in a tertiary hospital. Methods: This was a retrospective cohort study of all MCDA twin pregnancies that received obstetric care and delivered at La Fe University and Polytechnic Hospital between 2015 and 2021. MCDA pregnancies that were referred to the tertiary hospital for specialized management, follow-up, and delivery were also included. The study was approved by The Health Research Institute Hospital La Fe (IIS La Fe). Results: Among the 184 MCDA pregnancies, 149 (81%) had a natural conception, and 35 (19%) were conceived through ART. Patients with an MCDA pregnancy who conceived through ART had a significantly older maternal age (38.0 [35.5–42.5] vs. 32.0 [29.0–36.0], p < 0.001) and an elevated rate of nulliparity (80.0% vs. 50.3%, p = 0.001). Regarding pregnancy complications, MCDA pregnancies through ART were associated with a significantly higher incidence of gestational diabetes (22.9% vs. 2.7%, p < 0.001), hypertensive disorders during pregnancy (22.9% vs. 9.4%, p = 0.04), and other pregnancy complications such as threatened labor or preterm prelabor rupture of membranes (14.3% vs. 36.2%, p = 0.015), than naturally conceived MCDA pregnancies. No differences were found in the incidence of twin-to-twin transfusion syndrome (20% vs. 33.6%, p = 0.155). MCDA pregnancies through natural conception had a greater rate of vaginal delivery than MCDA through ART (16.8% vs. 2.9%, p = 0.032). When adjusted for confounding factors, MCDA pregnancies through ART were only more likely to develop gestational diabetes than those naturally conceived (aOR 7.86, 95% CI 1.55–39.87). No differences were found regarding neonatal outcomes between groups. Conclusions: Compared with naturally conceived MCDA twin pregnancies, those conceived through ART displayed a significantly higher risk of developing gestational diabetes. No differences regarding other pregnancy complications, mode of delivery, or neonatal outcomes were found between groups.
Morphological Effect on the Surface Activity and Hydrogen Evolution Catalytic Performance of Cu2O and Cu2O/rGO Composites
Authors: Ramirez-Ubillus Manuel A. , Wang Ankai , Zou Shengli , Chumbimuni-Torres Karin Y. , Zhai Lei
Published: September 2023

Different cuprous oxide (Cu2O) particle forms, including the octahedron, truncated octahedron, cube, and star-like forms, are synthesized through chemical reduction under different reaction conditions. The correlation between the morphology and the catalytic activity of hydrogen evolution reactions (HERs) is investigated. It is discovered that the Cu2O particles with a higher 111/100 facets (r) ratio have a higher oxidation resistance and higher activity in HER catalysis, as supported by the density functional theory (DFT) calculation results. This improvement is attributed to the fact that more Cu+ terminated atoms on facet 111 provide more active sites, as measured using their electroactive area, as well as the lower H2 adsorption energy on that facet. To enhance Cu2O’s HER performance, cuprous oxide particles are deposited on reduced graphene oxide (rGO) through a hydrothermal method. XPS and XRD show a CuO layer on the composite surface, which reduces the Cu2O corrosion in the reaction. Overall, Cu2O/rGO composites exhibit a better particle distribution, increased active sites, and improved charge separation. The best electrocatalyst in this study is the Cu2O/rGO with a star-shaped form, with an overpotential of −458 mV. Its improved performance is attributed to the presence of unsaturated active sites with a higher reactivity, such as the edges and corners. SEM studies of this composite after catalysis indicate that Cu2O undergoes structural reconstruction during the reaction and reaches a more stable structure.
Recent Advances in Stem Cell Differentiation Control Using Drug Delivery Systems Based on Porous Functional Materials
Authors: Eom Yun-Sik , Park Joon-Ha , Kim Tae-Hyung
Published: September 2023

The unique characteristics of stem cells, which include self-renewal and differentiation into specific cell types, have paved the way for the development of various biomedical applications such as stem cell therapy, disease modelling, and drug screening. The establishment of effective stem cell differentiation techniques is essential for the effective application of stem cells for various purposes. Ongoing research has sought to induce stem cell differentiation using diverse differentiation factors, including chemicals, proteins, and integrin expression. These differentiation factors play a pivotal role in a variety of applications. However, it is equally essential to acknowledge the potential hazards of uncontrolled differentiation. For example, uncontrolled differentiation can give rise to undesirable consequences, including cancerous mutations and stem cell death. Therefore, the development of innovative methods to control stem cell differentiation is crucial. In this review, we discuss recent research cases that have effectively utilised porous functional material-based drug delivery systems to regulate stem cell differentiation. Due to their unique substrate properties, drug delivery systems based on porous functional materials effectively induce stem cell differentiation through the steady release of differentiation factors. These ground-breaking techniques hold considerable promise for guiding and controlling the fate of stem cells for a wide range of biomedical applications, including stem cell therapy, disease modelling, and drug screening.
Crack Propagation and Fatigue Performance of Partial Posterior Indirect Restorations: An Extended Finite Element Method Study
Authors: Demirel Mehmet Gökberkkaan , Mohammadi Reza , Keçeci Murat
Published: September 2023

Dental ceramics are susceptible to slow, progressive crack growth after cyclic loading. The purpose of this study was to investigate the progressive patterns of cracks in two different types of CAD/CAM ceramic materials used with three different partial posterior indirect restoration (PPIR) designs and to determine the materials’ failure risk using a fatigue test. Standard initial cracks were formed in Standard Tessellation Language (STL) files prepared for three different PPIRs. The materials chosen were monolithic lithium disilicate (LS) and polymer-infiltrated ceramic networks (PICNs). The extended finite element method (XFEM) was applied, and the fatigue performance was examined by applying a 600 N axial load. The cracks propagated the most in onlay restorations, where the highest displacement was observed. In contrast, the most successful results were observed in overlay restorations. Overlay restorations also showed better fatigue performance. LS materials exhibited more successful results than PICN materials. LS materials, which can be used in PPIRs, yield better results compared to PICN materials. While inlay restorations demonstrated relatively successful results, overlay and onlay restorations can be specified as the most and the least successful PPIR types, respectively.
Return of Participants’ Incidental Genetic Research Findings: Experience from a Case-Control Study of Asthma in an American Indian Community
Authors: Best Lyle G. , O’Leary Marcia , O’Leary Rae , Lawrence Wendy , Torgerson Dara G.
Published: September 2023

The proper communication of clinically actionable findings to participants of genetic research entails important ethical considerations, but has been challenging for a variety of reasons. We document an instance of the return of individual genetic results in the context of a very rural American Indian community, in hopes of providing insight to other investigators about potentially superior or inferior courses of action. This was a case/control study of asthma among 324 pediatric participants. Subsequently, microarray genotype data became available, providing over 2 million variants, incidentally including some conferring risk for conditions for which the American College of Medical Genetics recommends return of results. The study investigators engaged in extensive consultation with the IRB, the tribal government, and local clinicians to better inform our approach. We were able to notify the two participants heterozygous for the one clinically actionable variant identified. One participant welcomed this information and proceeded to obtain further clinical work-up; the other participant declined further follow-up. While demanding considerable time and effort, the return of clinically actionable genetic results is important from both an ethical perspective and to provide an improved trust relationship with the community of research participants.
Systemic Inflammatory Response Index (SIRI) at Baseline Predicts Clinical Response for a Subset of Treatment-Resistant Bipolar Depressed Patients
Authors: Murata Stephen , Baig Nausheen , Decker Kyle , Halaris Angelos
Published: September 2023

Background: in a recent double-blind, placebo controlled RCT we demonstrated that selective inhibition of cyclo-oxygenase 2 (COX2) is an effective adjunctive strategy in treatment-resistant bipolar depression (TRBDD). To better clarify the mechanisms underlying TRBDD and treatment response, we conducted a retrospective exploratory analysis of the systemic inflammatory response index (SIRI = absolute neutrophils × absolute monocytes/absolute lymphocytes) in relation to other biomarkers and clinical outcomes after escitalopram (ESC), combined with the COX-2 inhibitor, celecoxib (CBX), versus placebo. Methods: Baseline measures of SIRI were compared between TRBDD and healthy controls (HC), and correlated with blood-based inflammatory cytokines, kynurenines, and growth factors. Post-treatment Hamilton Depression Rating Scale 17 (HAMD-17) total scores (clinical outcome) were modelled according to SIRI adjusting for demographics (including relevant interactions with SIRI), baseline depression, treatment arm, and treatment timepoint using multiple linear regression and robust linear mixed effects models. Results: Baseline SIRI did not distinguish TRBDD from HC groups. Baseline SIRI was significantly correlated with lower baseline MCP-1. The relationship between SIRI and HAMD-17 was significant at treatment week 8, in contrast to baseline. Finally, baseline SIRI predicted elevated post-treatment HAMD-17 scores, amongst patients with elevated depression scores at baseline. Significance: High pre-treatment SIRI may predict poorer depressive outcomes amongst TRBDD patients with baseline elevated depression.
The Role of Uric Acid in Human Health: Insights from the Uricase Gene
Authors: Roman Youssef M.
Published: September 2023

Uric acid is the final product of purine metabolism and is converted to allantoin in most mammals via the uricase enzyme. The accumulation of loss of function mutations in the uricase gene rendered hominoids (apes and humans) to have higher urate concentrations compared to other mammals. The loss of human uricase activity may have allowed humans to survive environmental stressors, evolution bottlenecks, and life-threatening pathogens. While high urate levels may contribute to developing gout and cardiometabolic disorders such as hypertension and insulin resistance, low urate levels may increase the risk for neurodegenerative diseases. The double-edged sword effect of uric acid has resurrected a growing interest in urate’s antioxidant role and the uricase enzyme’s role in modulating the risk of obesity. Characterizing both the effect of uric acid levels and the uricase enzyme in different animal models may provide new insights into the potential therapeutic benefits of uric acid and novel uricase-based therapy.