bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Posterior Cord Compression From the Ligamentum Flavum Influence Clinical Outcomes After Anterior Cervical Discectomy and Fusion?
Authors: Lee Dong-Ho , Hwang Chang Ju , Cho Jae Hwan , Cho Sung Tan , Nam Hyun Wook , Park Sehan
Published: July 2023

Study Design.

Retrospective cohort study.

Objective.

To clarify whether outcomes of anterior cervical discectomy and fusion (ACDF) differ according to the presence of posterior cord compression from the ligamentum flavum (CCLF)

Summary of Background Data.

Although ACDF effectively addresses anterior cord compression from disc material and bone spurs, it cannot address posterior compression. Whether ACDF could result in favorable outcomes when CCLF is present remains unclear.

Patients and Methods.

A total of 195 consecutive patients who underwent ACDF and were followed up for >2 years were included. CCLF was graded based on magnetic resonance imaging findings. Patients with CCLF grade 2 were classified as such, whereas patients with CCLF grades 0 to 1 were classified as the no-CCLF group. Patient characteristics, cervical sagittal parameters, neck pain visual analog scale, arm pain visual analog scale, and Japanese Orthopedic Association (JOA) score were assessed. Categorical variables were analyzed using a χ2 test, whereas continuous variables were analyzed using the Student t test. Multivariable logistic regression analysis was performed to elucidate factors associated with JOA recovery rates of >50%.

Results.

One hundred sixty-seven patients (85.6%) were included in the no-CCLF group, whereas the remaining 28 patients (14.4%) were included in the CCLF group. Among patients in the CCLF group, 14 patients (50.0%) achieved clinical improvement. JOA score significantly improved in the no-CCLF group after the operation (P < 0.001), whereas improvement was not appreciated in the CCLF group (P = 0.642). JOA scores at 3 months (P = 0.037) and 2 years (P = 0.001) postoperatively were significantly higher in the no-CCLF group. Furthermore, the JOA recovery rate at 2 years after surgery was significantly higher in the no-CCLF group (P = 0.042). Logistic regression demonstrated that CCLF was significantly associated with a JOA recovery rate of >50% at 2 years after surgery (odds ratio: 2.719; 95% CI: 1.12, 6.60).

Conclusion.

ACDF performed for patients with CCLF grade 2 showed inferior JOA score improvement compared with those with CCLF grade 0 or 1. ACDF cannot remove posterior compressive structures, which limits its utility when ligamentum flavum significantly contributes to cord compression.
Updating the Fitzpatrick Classification: The Skin Color and Ethnicity Scale
Authors: Coleman William , Mariwalla Kavita , Grimes Pearl
Published: July 2023

BACKGROUND

There has been a significant increase in submissions to scientific journals addressing a broad spectrum of medical and surgical conditions in subjects grouped under the classification of “Skin of Color.” Authors, reviewers, and editors have struggled with accurate terminology.

OBJECTIVE

To update the Fitzpatrick scale to make it more accurate in stratifying various shades of skin color.

MATERIALS AND METHODS

A thorough literature review was performed using PubMed and Embase to assess existing skin color scales, and an extensive internet search was conducted using makeup foundation ranges as a starting point for skin tone matching.

RESULTS

The research resulted in a consensus that Fitzpatrick types 4 and 5 ratings were the most confusing in that these included a broad range of skin types with different responses to solar radiation, lasers, surgery, and cosmetic products. The authors reached a consensus that subdividing skin types 4 and 5 into “A” and “B” better defined them. The new scale that resulted was labeled the SCE scale (for Skin Color Ethnicity).

CONCLUSION

This new updated SCE scale should assist authors in better reporting scientific data in skin of color.
Association of the L3MBTL3 rs1125970 and rs4897367 Gene Polymorphisms With Coronary Heart Disease Susceptibility in the Chinese Population: A Case–Control Study
Authors: Li Yongdong , Zhang Jiaqiang , He Jun , Chen Xiaoyu , Zhang Xianbo , Wu Haiqing , Ding Yipeng
Published: July 2023

Coronary heart disease (CHD) is a prevalent heart disease with high incidence and mortality rates worldwide, and its pathogenesis is related to genetic factors. L3MBTL3 has been reported to be potentially linked to CHD susceptibility. This study aims to explore the correlation between L3MBTL3 single nucleotide polymorphisms (SNPs) and CHD risk in the Chinese population. Three SNPs (rs1125970 A/T, rs4897367 T/C, and rs2068957 A/G) in L3MBTL3 from 649 patients with CHD and 649 healthy controls were genotyped using the Agena MassARRAY platform. The relationship between SNPs and CHD risk was evaluated by logistic regression analysis. Our study indicated that rs1125970 (TT: odds ratio [OR] = 0.76, P = 0.014) and rs4897367 (TT: OR = 0.74, P = 0.021) were related to a decreased susceptibility to CHD. Stratified analyses showed that rs1125970 could reduce the risk of CHD in males, subjects aged <60 years, with a body mass index <24 kg/m2, and nonhypertensive patients. rs4897367 exerted a risk-decreasing influence on CHD in nondiabetic patients. In the haplotype analysis, individuals with the Trs4897367Ars2068957 haplotype were less likely to develop CHD (OR = 0.74, P = 0.024). In summary, L3MBTL3 rs1125970 and rs4897367 were significantly correlated with a decreased susceptibility to CHD in the Chinese population.
Inclisiran and cardiovascular events: a comprehensive review of efficacy, safety, and future perspectives
Authors: Mohamed Ahmed A. , Ray Kausik K.
Published: July 2023

Purpose of review

This review aims to offer an up-to-date evaluation of Inclisiran's (a small interfering RNA treatment) ability to decrease low-density lipoprotein cholesterol (LDL-C), as well as its safety and potential effects on decreasing cardiovascular risk.

Recent findings

Inclisiran significantly lowers LDL-C levels, as shown by phase III studies, by inhibiting hepatic synthesis of proprotein convertase subtilisin kexin 9 (PCSK-9), a protein implicated in the degradation of LDL receptors. Inclisiran has the benefit of subcutaneous injection twice a year, which may reduce patient nonadherence when compared with other LDL-C reducing therapies such as statins and ezetimibe, which require daily dosing. When added on top of statins, a greater proportion of patients achieved recommended cholesterol goals. It has also demonstrated a good safety profile with few adverse effects.

Inclisiran is a promising treatment for lowering LDL-C levels in people at high risk of atherosclerotic cardiovascular disease. It is a practical and well tolerated option for those who struggle to stick to medication regimes because of its twice-yearly dosage schedule and a good safety profile. Although it has been demonstrated to be effective in decreasing LDL-C, further research is needed to determine its impact on reducing cardiovascular events. Nonetheless, Inclisiran is a significant advancement in lipid-lowering medication and could improve patient outcomes.
Glaucoma Treatment Patterns in Sub-Saharan Africa
Authors: Olawoye Olusola , Washaya Jennifer , Gessesse Girum W. , Balo Komi , Agre Jeremie , Macheka Boniface , Kizor-Akaraiwe Nkiru , Pons Jonathan , Sarimiye Tarela , Ashaye Adeyinka , Garba Farouk , Chitedze Richard , Ibanga Affiong , Mahdi Abdull , Ogunro Adunola , Budengeri Patrick , Ajibode Haroun Adetunji , Tamrat Lemlem , Onakoya Adeola , Okeke Suhanyah , Giorgis Abeba T. , Okosa Chimdi Chuka , Fowobaje Kayode , Cook Stephen , Lawrence Scott , Chan Ving Fai , Azuara-Blanco Augusto , Congdon Nathan , Realini Tony ,   The STAGE Research Group
Published: July 2023

Précis:

Physicians were most likely to recommend primary medical therapy upon diagnosis of glaucoma. Laser therapy was underutilized where they were available. Physicians were more likely to recommend surgery in severe glaucoma, laser therapy in mild glaucoma, while recommendation of medical therapy did not depend on glaucoma severity.

Purpose:

To characterize treatment patterns for newly diagnosed glaucoma in sub-Saharan Africa (SSA).

Methods:

This was a multicenter cross-sectional study of adults newly diagnosed with glaucoma at 27 eye care centers in 10 African countries. In addition to demographic and clinical data, physician treatment recommendations (medication, laser, surgery, or no treatment) were recorded. Statistical analyses were performed using STATA version 14.0.

Results:

Data from 1201 patients were analyzed. Physicians were most likely to recommend primary medical therapy upon diagnosis of glaucoma (69.4%), with laser (13.2%), surgery (14.9%), and no treatment (2.5%) recommended to the remaining patients. All sites had medical therapy available and most (25/27, 92.6%) could provide surgical treatment; only 16/27 (59.3%) sites offered laser, and at these sites, 30.8% of eyes were recommended to undergo primary laser procedures. As glaucoma severity increased, the laser was recommended less, surgery more, and medications unchanged. Patient acceptance of medical therapy was 99.1%, laser 88.3%, and surgery 69.3%.

Conclusions:

Medical therapy for first-line glaucoma management is preferred by most physicians in SSA (69%). Laser therapy may be underutilized at centers where it is available. These findings underscore the need for comparative studies of glaucoma treatments in SSA to inform the development of evidence-based treatment guidelines and of programs to reduce glaucoma blindness in SSA. Strategic approaches to glaucoma therapy in SSA must address the question of whether medical therapy is the most optimal first-line approach in this setting.
Association Between Optic Disc Perfusion Determined by Swept-Source Optical Coherence Tomography Angiography and Visual Field Progression in Glaucoma
Authors: Lee Jin Yeong , Sung Kyung Rim , Kim Joon Mo , Shin Joong Won , Kim Ko Eun
Published: July 2023

Précis:

Reduced optic disc vessel density determined by swept-source optical coherence tomography angiography (SS-OCTA) was associated with visual field (VF) deterioration in glaucomatous eyes, which suggested that this parameter can be a potential biomarker that correlates well with functional deterioration.

Purpose:

The purpose of this study was to identify the association between optic disc perfusion evaluated by SS-OCTA and VF progression in primary open angle glaucoma (POAG) eyes.

Methods:

A total of 266 POAG eyes of 266 patients (5.4 y of mean follow-up) were included. Optic nerve head SS-OCTA was performed to evaluate the optic disc vessel density (dVD), parapapillary choroidal vessel density (pcVD), choroidal microvascular dropout (cMvD), and optic disc microvascular dropout (dMvD). VF progression was defined using Early Manifest Glaucoma Trial criteria. Factors associated with VF worsening were assessed by Cox proportional hazard analysis.

Results:

Eighty (30.1%) out of the 266 POAG eyes showed VF progression. The progression group showed a significantly higher proportion of disc hemorrhage, cMvD, and dMvD but lower dVD and pcVD than the stable group (all P<0.05). Considering the strong association between the parameters [dMvD vs. dVD (r = −0.757, P=0.010], cMvD vs. pcVD (r = −0.745, P=0.012), dMvD vs. cMvD (r = 0.802, P<0.001], dVD vs. pcVD (r = 0.862, P<0.001), CMvD vs. dVD (r= −0.698, P=0.031), and dMvD vs. pcVD (r= −0.688, P=0.034)], 6 models with different combinations of covariates compensating for multicollinearity were developed. Younger age, presence of disc hemorrhage, and lower dVD were consistently associated with progression in all models that included these parameters.

Conclusions:

Optic disc perfusion, represented as dVD, may be a useful biomarker that correlates well with functional deterioration in POAG eyes.
Successful Use of Cefiderocol to Treat a Multidrug-resistant Stenotrophomonas maltophilia Ventilator-associated Pneumonia in an Extremely Preterm Neonate
Authors: Koirala Archana , Krishnappa Bharath , Banh Caroline , Brandenburg Ulrike , Findlay Michael , Williams Phoebe C. M.
Published: July 2023

Background:

Ventilator-associated pneumonia (VAP) caries a morbidity and mortality risk in the preterm neonate, particularly in the context of rising global antimicrobial resistance driving infections due to multidrug-resistant Gram-negative bacteria. Cefiderocol, a siderophilic cephalosporin, has broad Gram-negative antimicrobial activity and central nervous system penetration and is used for the treatment of hospital-acquired pneumonia or VAP in adults. Scarce data exists on its use in neonates.

Case:

A female neonate born at 26 + 6 weeks developed VAP at 21 days of life. She was commenced on corticosteroids, vancomycin and ceftazidime but continued to deteriorate. Sputum cultures yielded Stenotrophomonas maltophilia resistant to trimethoprim/sulfamethoxazole, ciprofloxacin and ceftazidime, with potential susceptibility to cefiderocol. Cerebrospinal fluid showed an elevated white cell count. In view of worsening respiratory and hemodynamic status, antibiotic treatment was changed to cefiderocol monotherapy at 30 mg/kg/dose every 8 hours. Within 72 hours of commencing cefiderocol, the neonate was successfully extubated to variable-flow continuous positive airway pressure and showed ongoing clinical improvement.

Conclusions:

Cefiderocol was integral for the care of our neonate without any immediate adverse safety consequences. We relied on dosing data from a conference abstract, due to the paucity of evidence on the use of novel antimicrobials. This lack of evidence is particularly concerning given preterm neonates are particularly vulnerable to infections with multidrug-resistant Gram-negative organisms due to their immature immune systems, prolonged hospital stay, repeated interventions and antimicrobial exposure.
Clinical Outcomes of Ceftaroline Fosamil in the Treatment of Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia
Authors: El-Lababidi Rania , Abdelsalam Manal , Hassan Amal , El Nekidy Wasim S. , Alatoom Adnan , Nusair Ahmad Rakad
Published: July 2023

Background

Limited evidence exists in the management of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with ceftaroline as salvage therapy. This retrospective study aims to evaluate the use of ceftaroline as salvage therapy in the treatment of persistent MRSA bacteremia (MRSAB).

Methods

Electronic medical charts of patients who received ceftaroline for the treatment of persistent MRSAB at an academic, quaternary care medical center from January 1, 2015, to December 31, 2021, were reviewed for clinical cure, reinfection, prior antibiotic use, source of infection, microbiological culture clearance, patient mortality, and adverse effects. Primary endpoints included clinical and microbiological success, and secondary endpoints were recurrence of infection and 60-day all-cause mortality.

Results

Nineteen patient charts were identified, and 9 patients met the inclusion criteria for this analysis. Vancomycin or daptomycin was given for a median of 7 ± 2.3 days, respectively, before the initiation of ceftaroline. The total daily dose of ceftaroline ranged from 400 to 1800 mg depending on the patients' kidney function. Five patients achieved clinical cure and 4 patients died. No patients experienced a recurrence. Three patients (33%) experienced adverse effects while on ceftaroline therapy.

Conclusions

The use of ceftaroline in persistent MRSAB demonstrated microbiological cure, clinical cure, and minimal reinfection in the reviewed patient population. Ceftaroline may be a potential treatment option for patients with persistent MRSAB as salvage therapy.
Dietary Management in Individuals With Serious Mental Illness and Comorbid Diabetes: A Focused Ethnography Study
Authors: TZENG Wen-Chii , FENG Hsin-Pei
Published: July 2023

Background

Patients with serious mental illness (SMI) are more likely to have Type 2 diabetes mellitus (T2DM). However, studies that discuss the eating habits of patients with both T2DM and SMI are lacking.

Purpose

This study was designed to explore the beliefs and experiences of Taiwanese patients with SMI who also have T2DM.

Methods

Fieldwork for this study included 2 years of participant observation and individual interviews with 13 patients with SMI. Data from transcripts of observational field notes and interviews were transcribed verbatim and analyzed.

Results

The participants described their experiences and concerns regarding dietary management during the period after receiving their T2DM diagnosis. The results of the data analysis were distinguished into three categories, including (a) increased difficulty in life, (b) positive view of dietary control, and (c) inability to abide by dietary restrictions.

Conclusions

The findings suggest that healthcare professionals should work to better understand the challenges faced by patients with SMI and T2DM in implementing changes and resisting the temptation to eat unhealthy food and provide suggestions tailored to their cultural background, lifestyle, and eating characteristics.
Quantifying physical activity energy expenditure based on doubly labelled water and basal metabolism calorimetry: what are we actually measuring?
Authors: Speakman John R. , Pontzer Herman
Published: July 2023

Purpose of review

Physical activity impacts energy balance because of its contribution to total energy expenditure. Measuring physical activity energy expenditure (PAEE) is often performed by subtracting the estimated 24 h expenditure on basal metabolism (called basal energy expenditure or BEE) from the total energy expenditure (TEE) measured by doubly labelled water minus an estimate of the thermic effect of food (TEF). Alternatively it can be measured as the ratio of TEE/BEE, which is commonly called the physical activity level (PAL).

Recent findings

PAEE and PAL are widely used in the literature but their shortcomings are seldom addressed. In this review, we outline some of the issues with their use.

TEE and BEE are both measured with error. The estimate of PAEE by difference magnifies these errors and consequently the precision of estimated PAEE is about 3× worse than TEE and 25–35× worse than BEE. A second problem is that the component called PAEE is actually any component of TEE that is not BEE. We highlight how the diurnal variation of BEE, thermoregulatory expenditure and elevations of RMR because of stress will all be part of what is called PAEE and will contribute to a disconnect between what is measured and what energy expenditure is a consequence of physical activity. We emphasize caution should be exerted when interpreting these measurements of PAEE and PAL.
Composition of healthy diets for older persons
Authors: Yeung Suey S.Y. , Kwan Michelle , Woo Jean
Published: July 2023

Purpose of review

This study aims to review recent evidence (2022–2023) on the role of diet in promoting healthy aging in older adults.

Recent findings

Current evidence of diet and healthy aging is limited to epidemiological studies. A healthy diet is beneficial for individual domains of intrinsic capacity, that is, cognition, locomotion, vitality, psychological, and/or sensory functions, with sex-specific differences reported. Only a few studies used the multidimensional concept of intrinsic capacity as an outcome. This review supports that a healthy diet for older adults consists of plenty of plant-based foods, adequate protein-rich foods, and healthy fats. Next to quantity, improving the quality and variety within food groups play a role in optimizing health. Data on the associations between adherence to national food-based dietary guidelines and intrinsic capacity are scarce.

A healthy diet, centered on plant-based foods, adequate protein-rich foods and healthy fats, potentially promotes healthy aging. Future studies may evaluate the association between adherence to healthy dietary patterns (particularly national food-based dietary guidelines) and the multidimensional concept of intrinsic capacity, with consideration of sex-specific differences. Clinical trials are warranted to inform the causal effects of diet and outcomes related to intrinsic capacity.
Evaluating the Proportion of Low-Value Blood Cultures Obtained in a Pediatric Emergency Department
Authors: Graham John , Ahmad Fahd A. , Bram Sarah , Srinivasan Mythili
Published: July 2023

Background

Existing literature suggests that for some pediatric conditions, blood cultures may be of low value in specific clinical circumstances. The goals of our study were to: 1) identify common pediatric illnesses and define criteria for low-value blood cultures in children aged from 91 days to 19 years, 2) apply these criteria retrospectively to identify the patients in our emergency department (ED) who had low-value blood cultures obtained, and 3) describe this cohort and assess the proportion of true bacteremia in low-value blood cultures.

Method

The study team reviewed the literature and developed consensus criteria to identify conditions in which blood cultures were of low value for our study population. The criteria were applied retrospectively to well-appearing patients aged from 91 days to 19 years, without a central venous catheter, and evaluated in our ED with a peripheral blood culture from June 2018 to April 2020. Children admitted to the intensive care/hematology-oncology/cardiology/pulmonary units, those transferred from our ED to an outside facility, who transferred to our ED due to a positive blood culture from an outside facility, and repeat visits of a patient within 30 days from a previous visit were excluded from the study. After chart review, children with fever for 7 days or more, who were unvaccinated, immunosuppressed, had implanted devices, had a complex medical history, or had provider concerns for bacteremia/sepsis were excluded.

Results

The study population consisted of 1436 children. Children at risk for bacteremia (n = 718) were excluded. Four hundred twenty-four children had discharge diagnoses not included in our study. There were 294 (20.5%) patients who had low-value cultures per our study criteria. Nine children (9/294, 3.1%) had false-positive blood cultures, and three (3/294, 1.0%) had true-positive blood cultures.

Conclusions

We identified a cohort of patients in our ED with blood cultures obtained when available literature indicates they were of low value.
Understanding the interaction of Hsp70 with NK cells
Authors: Sahni Ruchir , Multhoff Gabriele
Published: July 2023

Heat Shock Protein 70 (Hsp70) is a highly conserved and ubiquitous molecular chaperone that plays a central role in cellular protein machinery and stress response. Membrane-bound HSP70 has emerged as an important cancer biomarker and acts as a danger signal and elicits immune response. Hsp70 membrane expression is correlated to increased sensitivity to lysis carried out by NK cells. This study uses computational approaches to decode the interaction of Hsp70 with NK cells and determines the binding site for Hsp70 on the surface of NK cells. Our findings identified CD69 and NKP46 as the most probable binding sites for Hsp70. Additionally, we confirmed the strong binding affinity between Hsp70 and the CD94-NKG2A complex.
Proneural genes form a combinatorial code to diversify neocortical neural progenitor cells
Authors: Moffat Alexandra , Oproescu Ana-Maria , Okawa Satoshi , Han Sisu , Vasan Lakshmy , Ghazale Hussein , Dennis Daniel J , Zinyk Dawn , Guillemot François , del Sol Antonio , Schuurmans Carol
Published: July 2023

Neocortical neural progenitor cells (NPCs) are molecularly heterogeneous, yet the genes that confer distinct neuronal morphologies and connectivities during development are poorly understood. Here, we determined that a proneural gene combinatorial code diversifies cortical NPCs. By mining scRNA-seq data from murine embryonic and early postnatal cortices and generating trajectory inference models, we found that Neurog2 is predominant, and is transiently co-expressed with Ascl1 and/or Neurog1 during an apical-to-basal NPC transition state in NPCs with early pseudotime identities. To assess whether proneural gene pairs confer distinct properties, we first used Neurog2/Ascl1 reporter mice expressing unique reporters, revealing that NPCs have distinct cell division modes and cell cycle dynamics dependent on their proneural gene profile. To assess Neurog2/Neurog1 interactions, we used double knock-out mice and novel split-Cre transgenics crossed to a Rosa-diptheria-toxin-A line to delete double+cells, showing Neurog1/Neurog2 are specifically required to generate early-born neurons and to maintain NPCs. Finally, in silico mutation of a cortical Neurog2-gene regulatory network and validation using Neurog1/Neurog2 mutant and ‘deleter’ mice, identified Bclllb and Nhlh2, expressed in early-born neurons, as dependent on Neurog1/Neurog2. Our data explains how proneural genes act combinatorically to diversify gene regulatory networks, thereby lineage restricting NPCs and creating cortical neuronal diversity.
Bacterial risk evaluation of widely consumed fast foods by the younger population in Bangladesh and its potential health effects
Authors: Masud Lamia Bintay , Hossain Md. Imran , Faruk Md. Omor , Tuha Md. Akber Subahan Mahbub , Akash Sajidur Rahman , Islam Khondakar Raisul , Sahabuddin Md. , Ali Md. Sarafat
Published: July 2023

Food-borne illness is a significant public health concern in Bangladesh, especially among the younger generation. They often consume spicy street foods, such as Fusca, Hog plum bedfellow, and Chotpoti. These foods can be contaminated with harmful bacteria, which can cause various diseases, including diarrhea, cholera, and dysentery. This study investigated the microbiological quality of three commonly consumed street foods in Bangladesh. We collected samples of Fusca, Hog plum bedfellow, and Chotpoti from different vendors in Dhaka and analyzed them in a laboratory. We found that all three of the food samples were contaminated with a variety of bacteria, including Bacillus spp., Haemophilus spp., Salmonella spp., Klebsiella spp., Staphylococcus spp., and Streptococcus spp. Some of these bacteria, such as Haemophilus spp., were resistant to the antibiotic ciprofloxacin. Our findings suggest that there is a high risk of food-borne illness associated with the consumption of street foods in Bangladesh. We urge vendors and consumers to take steps to improve food safety, such as proper food handling and cooking and clean water and utensils.
Heterogeneity and Functional Analysis of Cardiac Fibroblasts in Heart Development
Authors: Deng Yiting , He Yuanhang , Xu Juan , He Haoting , Li Guang
Published: July 2023

Background

As one of the major cell types in the heart, fibroblasts play critical roles in multiple biological processes. Cardiac fibroblasts are known to develop from multiple sources, but their transcriptional profiles have not been systematically compared. Furthermore, while the function of a few genes in cardiac fibroblasts has been studied, the overall function of fibroblasts as a cell type remains uninvestigated.

Methods

Single-cell mRNA sequencing (scRNA-seq) and bioinformatics approaches were used to analyze the genome-wide genes expression and extracellular matrix genes expression in fibroblasts, as well as the ligand-receptor interactions between fibroblasts and cardiomyocytes. Single molecular in situ hybridization was employed to analyze the expression pattern of fibroblast subpopulation-specific genes. The Diphtheria toxin fragment A (DTA) system was utilized to ablate fibroblasts at each developmental phase.

Results

Using RNA staining ofCol1a1at different stages, we grouped cardiac fibroblasts into four developmental phases. Through the analysis of scRNA-seq profiles of fibroblasts at 18 stages from two mouse strains, we identified significant heterogeneity, preserving lineage gene expression in their precursor cells. Within the main fibroblast population, we found differential expressions of Wt1, Tbx18, and Aldh1a2 genes in various cell clusters. Lineage tracing studies showed Wt1- and Tbx18-positive fibroblasts originated from respective epicardial cells. Furthermore, using a conditional DTA system-based elimination, we identified the crucial role of fibroblasts in early embryonic and heart growth, but not in neonatal heart growth. Additionally, we identified the zone- and stage-associated expression of extracellular matrix genes and fibroblast-cardiomyocyte ligand-receptor interactions. This comprehensive understanding sheds light on fibroblast function in heart development.

Conclusion

We observed cardiac fibroblast heterogeneity at embryonic and neonatal stages, with preserved lineage gene expression. Ablation studies revealed their distinct roles during development, likely influenced by varying extracellular matrix genes and ligand-receptor interactions at different stages.
Methyl 4-amino-3-methoxyisoxazole-5-carboxylate
Authors: Abdul Manan Mohd Abdul Fatah , Cordes David B. , Slawin Alexandra M. Z.
Published: July 2023

The title compound, C6H8N2O4, a new derivative of isoxazole, has been synthesized and structurally characterized. The crystal structure shows the molecule to be almost planar (r.m.s. deviation for the non-hydrogen atoms = 0.029 Å), this conformation being supported by an intramolecular N—H...O hydrogen bond. In the extended structure, the molecules are linked by N—H...O hydrogen bonds into chains propagating along [010].
An investigation of the effect of sensitization on the metallurgical characteristics of dissimilarly welded austenitic-ferritic stainless steel
Authors: Sharma Anand , Shukla Sourabh , Thombre Manish , Bansod Ankur , Untawale Sachin
Published: July 2023

Purpose

The purpose of this study is to examine the effects of sensitization on the metallurgical characteristics of weld joints made up of austenitic stainless steel (AISI 316L) and ferritic stainless steel (AISI 430), using the gas tungsten arc welding (GTAW) process with ER316L filler wires.

Design/methodology/approach

A non-consumable tungsten electrode with a diameter of 1.6 mm was used during the GTAW procedure. The filler wire, ER316L, was selected based on the recommendation provided in literature. To explore the interconnections among the structure and properties of these weldments, the techniques including scanning electron microscopy and optical analysis have been used. In addition, the sensitization behaviour of the weldments was investigated using the double loop electrochemical potentio-kinetic reactivation (DLEPR) test.

Findings

Microstructural analyses revealed the occurrences of coarsened grains with equiaxed columnar grains and migrating grain boundaries in the weld zone. The results of the DLEPR test demonstrated that heat affected zone (HAZ) of AISI 430 was more susceptible to sensitization than HAZ of AISI 316L. Microstructure analysis also revealed the precipitation of large amounts of chromium carbide at the grain boundaries region of AISI 430 welded steel, causing more sensitization and, as a result, more failure or breaking at the side of AISI 430 weld in the dissimilar weldment of AISI 316L–AISI 430.

Originality/value

The present work has been carried out to determine the appropriate welding conditions for joining AISI 316L and AISI 430, as well as the metallurgical properties of the dissimilar weldment formed between AISI 316L and AISI 430. Owing to the difficulties in measuring the performance of these types of dissimilar joints given their unique mechanical and microstructural characteristics, research on the subject is limited.
Association between cardio‐cerebrovascular disease and systemic antipsoriatic therapy in psoriasis patients using population‐based data: A nested case–control study
Authors: Kim Bo Ri , Lee Kun Hee , Kim Jinseob , Kim Jee Woo , Paik Kyungho , Myung Woojae , Lee Hyewon , Choi Chong Won , Youn Sang Woong
Published: July 2023

The effect of antipsoriatic therapy on cardio‐cerebrovascular disease (CCVD) is not well described. Thus, we performed a population‐based nested case–control study to investigate the effect of systemic antipsoriatic therapy on CCVD in psoriasis patients. Using nationwide cohort data from the Korean National Health Insurance Claims database, newly diagnosed psoriasis patients were identified. Among the enrolled participants, postenrollment development of CCVD events (ischemic heart disease, myocardial infarction, cerebral infarction, and cerebral hemorrhage) was investigated. To evaluate the effect of systemic antipsoriatic therapy on CCVD risk, we calculated the proportion of the treatment period with systemic antipsoriatic therapy during the study period (PTP [%]: the sum of all systemic antipsoriatic therapy durations divided by total observation period). Among 251 813 participants, 6262 experienced CCVD events during the study period (CCVD group). Controls included 245 551 patients without CCVD history during the study period (non‐CCVD group). The non‐CCVD group had greater PTP than the CCVD group (CCVD 2.12 ± 7.92, non‐CCVD 2.64 ± 9.64; P < 0.001). In multiple logistic regression analysis, PTP was inversely associated with the CCVD risk after adjusting for age, sex, diabetes, hypertension, and dyslipidemia. A 10% increase in PTP reduced CCVD risk by 0.96 (95% confidence interval 0.93 to 0.99). Reduced CCVD risk was robust for both conventional antipsoriatic therapy and biologics. Our study found that systemic antipsoriatic therapy use was inversely associated with CCVD risk in psoriasis patients. These findings suggested that systemic antipsoriatic therapy could reduce CCVD development in patients with psoriasis.
Adverse events associated with postoperative outcomes of adjuvant anti‐PD‐1 antibody therapy in both acral and non‐acral cutaneous melanomas: A multicenter, observational, post hoc analysis study
Authors: Muto Yusuke , Kambayashi Yumi , Kato Hiroshi , Fukushima Satoshi , Ito Takamichi , Maekawa Takeo , Fujisawa Yasuhiro , Yoshino Koji , Uchi Hiroshi , Matsushita Shigeto , Yamamoto Yuki , Amagai Ryo , Ohuchi Kentaro , Hashimoto Akira , Asano Yoshihide , Fujimura Taku
Published: July 2023

Since anti‐PD‐1 Abs can cause irreversible immune‐related adverse events (irAEs), the associations between their efficacies and the incidence of irAEs are important to evaluate the use of anti‐PD‐1Abs for the treatment of melanoma, especially in the adjuvant setting. The purpose of this post hoc analysis study was to retrospectively analyze the associations between recurrence‐free survival (RFS) at 12 months and the onset of any irAEs in 31 non‐acral cutaneous and 30 acral melanoma cases treated with anti‐PD‐1 Abs therapy at the adjuvant setting in Asians. There were 20 cases with greater than grade 1 AEs in both the acral and non‐acral cutaneous groups. Of the acral melanoma, 10 cases were nails or toes, and 20 cases were soles and heels. The log‐rank test showed that RFS was better in cases with AEs than in cases without AEs. The present study suggested that the different profiles of irAEs between non‐acral cutaneous and acral melanoma might correlate with the different response to anti‐PD1 Abs of melanoma in the adjuvant setting.
Phylogenetic diversity is a weak proxy for functional diversity but they are complementary in explaining community assembly patterns in temperate vegetation
Authors: E‐Vojtkó Anna , de Bello Francesco , Lososová Zdeňka , Götzenberger Lars
Published: July 2023

Ecological differences between coexisting species within plant communities can be assessed by considering functional and phylogenetic dissimilarities either separately or in a complementary way. Here, we studied (a) the potential overlap between functional (FD) and phylogenetic diversities (PD) and (b) their combined and unique roles in explaining community assembly patterns across different temperate vegetation types and across functional traits representing multiple dimensions of plant strategy (plant size, leaf, floral and reproductive, clonal and bud bank traits).

We tested the strength of the PD–FD relationship within and across vegetation types and functional traits (Pearson correlations) and tested whether it depended on the strength of the phylogenetic signal (Pagel's lambda and Blomberg'sK). We tested deviations from random expectations in FD and ‘decoupled FD’ (i.e. functional dissimilarity after accounting for the effect of phylogenetic distances between species) to reveal the importance of ecological differences for community assembly.

PD–FD correlations were predominantly significant but rarely strong, and largely depended on the studied functional trait and vegetation type. Phylogenetic signals were partially but inconsistently related to the overlap between FD and PD.

Community assembly patterns tended to shift from under‐dispersion (FD lower than random expectations) towards over‐dispersion (FD higher than random expectations) when functional distances were decoupled from phylogenetic distances indicating that species within the same clade were dissimilar to each other regarding their traits. However, we found the opposite pattern as well, mainly for floral and below‐ground traits, which indicated functional differentiation across clades.

Synthesis. Decoupling functional and phylogenetic differences between species might provide further information on plant community assembly: showing cases where the strongest ecological differentiation between coexisting species occurs between phylogenetically related species rather than between phylogenetically unrelated ones.
Neoadjuvant chemotherapy for ovarian cancer: Avoiding ‘needless hurt’?
Authors: Morrison Jo
Published: July 2023

Linked article: This is a mini commentary on C. Marchetti et al., pp.1579–1588 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17558.
Genetic variants in key necroptosis regulators predict prognosis of non‐small cell lung cancer after surgical resection
Authors: Lee Jang Hyuck , Park Ji Eun , Hong Mi Jeong , Choi Jin Eun , Kang Hyo‐Gyoung , Do Sook Kyung , Lee Sunwoong , Jeong Ji Yun , Shin Kyung Min , Do Young Woo , Lee Eung Bae , Lee Won Kee , Oh In‐Jae , Kim Young‐Chul , Choi Sun Ha , Lee Yong Hoon , Seo Hyewon , Lee Jaehee , Cha Seung Ick , Kim Chang Ho , Yoo Seung Soo , Lee Shin Yup , Park Jae Yong
Published: July 2023

Background

Necroptosis is a regulated inflammatory cell death which plays a significant role in cancer development and progression. In this study, we evaluated whether genetic variants in key regulators of necroptosis may affect survival outcome of non‐small cell lung cancer (NSCLC) patients after surgical resection.

Methods

A total of 674 patients who underwent curative surgery were included. Fifteen genetic variants in key regulators of necroptosis (RIPK1, RIPK3, and MLKL) were selected. The association of these variants with survival outcomes was evaluated.

Results

Two variants, RIPK1 rs17548629C > T and MLKL rs877375G > C, were associated with better overall survival and disease‐free survival in multivariate analyses. When the patients were divided according to histology, the associations were significant only in adenocarcinoma, but not in squamous cell carcinoma. RIPK1 rs17548629 C‐to‐T change was associated with significantly increased luciferase activity by modulating the binding of miR‐642a. Promoter assays showed a significantly increased promoter activity in MLKL rs877375C allele compared to G allele. Consistently, the mRNA expression level of RIPK1 and MLKL showed significant positive correlation with RIPK1 rs17548629C‐to‐T and MLKL rs877375G‐to‐C changes.

Conclusion

Two genetic variants in key regulators in necroptosis, RIPK1 rs17548629C > T and MLKL rs877375G > C, may be used as biomarkers to predict survival outcomes in surgically resected NSCLC patients.
Gegen‐Qinlian decoction—A traditional Chinese medicine formula—Alleviates methamphetamine withdrawal induced anxiety by targeting GABAergic interneuron‐pyramidal neuron pathway in mPFC
Authors: Song Hongxiu , Lu Xue , Du Demin , Peng Yaqin , Pan Weichao , Xu Xing , Fan Yu , Yang Xin , Ge Feifei , Guan Xiaowei
Published: July 2023

Methamphetamine (Meth) withdrawal elicits anxiety, which is a public health concern with limited therapeutic options. Previous studies implied a strong correlation between mPFC and Meth withdrawal. Here, we examined the role of Gegen‐Qinlian decoction (GQD) in Meth withdrawal anxiety and explored potential therapeutic targets in mPFC. We found that intra‐gastric administration of GQD during the withdrawal period efficiently alleviated anxiety‐like behaviours in Meth‐withdrawn mice. Further, GQD could restore Meth withdrawal‐triggered pathway of GABAergic interneurons (GABA IN)‐pyramidal neurons (PN) in the mPFC of Meth‐withdrawn mice, especially the prelimbic cortex (PrL) sub‐region and PV‐positive GABA IN. While, GQD had no obvious effects on the glial cells in the mPFC of Meth‐withdrawn mice. By transcriptomic analysis and validation of several gene candidates, we found that genes in the MAPK signalling pathway, especially those related to heat shock proteins, including Hspa1a, Hspa1b and Hspb1, might be GQD‐targeting genes in mPFC to treat Meth withdrawal anxiety, as indicated that these genes were up‐regulated by Meth withdrawal but rescued by GQD in mPFC. Collectively, our findings identified for the first time that GQD could efficiently alleviate Meth withdrawal anxiety, partially through regulating the local GABA IN‐PN pathway and transcriptomic profile of mPFC. The present study confirms that TCM, such as GQD, will be a desirable therapeutic approach in the treatment of drug addiction and related emotional deficits.
Diabetes impairs the haemodynamic response to non‐selective betablockers in compensated cirrhosis and predisposes to hepatic decompensation
Authors: Paternostro Rafael , Jachs Mathias , Hartl Lukas , Simbrunner Benedikt , Scheiner Bernhard , Bauer David , Schwabl Philipp , Semmler Georg , Trauner Michael , Mandorfer Mattias , Reiberger Thomas
Published: July 2023

Background

Non‐selective betablockers (NSBBs) reduce the risk of hepatic decompensation in patients with compensated advanced chronic liver disease (cACLD). Metabolic co‐morbidities (MetC) are increasingly observed in cACLD patients.

Aims

To investigate the impact of MetC on the haemodynamic effects of NSBB and hepatic decompensation in cACLD.

Methods

cACLD patients undergoing paired hepatic venous pressure gradient (HVPG) measurements before/under NSBB therapy were retrospectively considered for this study. We recorded baseline characteristics on MetC (obesity, dyslipidaemia and diabetes), as well as hepatic decompensation and liver‐related mortality during follow‐up.

Results

We included 92 patients (Child‐A n = 80, 87%; Child‐B n = 12, 13%). MetC were found in 34 (37%) patients: 19 (20.7%) with obesity, 14 (15.2%) with dyslipidaemia and 23 (34.8%) with diabetes. The median baseline HVPG of 18 (IQR:15–21) mmHg decreased to 15 (IQR:9–12) mmHg under NSBB. HVPG‐response (decrease ≥10% or to ≤12 mmHg) was achieved in 60 (65.2.%) patients. Patients with diabetes (OR: 0.35, p = 0.021) and higher BMI (OR: 0.89 per kg/m2, p = 0.031) were less likely to achieve HVPG‐response.

During a median follow‐up of 2.3 (0.5–4.2) years, 18 (19.5%) patients experienced hepatic decompensation. Child‐B (adjusted subdistribution hazard ratio, aSHR: 4.3 [95% CI:1.5–12.2], p = 0.006), HVPG‐response (aSHR: 0.3 [95% CI:0.1–0.9], p = 0.037) and diabetes (aSHR: 2.8 [95% CI:1.1–7.2], p = 0.036) were independently associated with hepatic decompensation.

Conclusions

In patients with cACLD, diabetes and a higher BMI impair the HVPG‐response to NSBB. Furthermore, diabetes‐independently from Child B and lack of HVPG‐response‐increases the risk of hepatic decompensation.
Laparoscopic completion gastrectomy: A single‐institution case series and systematic review of the literature
Authors: Heng Wei , Lye Jian Ying Tiffany , Lee Zhen Jin , Chan Weng Hoong , Tan Jeremy Tian Hui
Published: July 2023

Introduction

Completion gastrectomy with lymphadenectomy for remnant gastric cancer (RGC) is currently the gold standard for patients with resectable disease. Multiple surgical approaches can be adopted; however, there exists no agreement on the best choice due to the low incidence of RGC. With its anticipated increase in prevalence, we thus sought to evaluate the feasibility and efficacy of the laparoscopic approach versus conventional laparotomy via a pooled analysis of existing literature.

Methods

A retrospective review of five consecutive patients who underwent laparoscopic completion gastrectomy from August 2017 to June 2022 was performed following Institutional Review Board waiver. A comprehensive systematic review of literature on laparoscopic completion gastrectomy from the Pubmed, Embase, MEDLINE, Web of Science and Cochrane databases was conducted to supplement the experience from our institution.

Results

Four patients had prior benign gastric disease and one had prior gastric cancer. Two patients experienced severe postoperative complications but there were otherwise no reports of conversion to laparotomy or mortality. Mean operative duration was 295 minutes. Mean duration to oral intake and discharge was 6.8 and 14.6 days respectively. Results from our pooled analysis of 591 cases suggested that the laparoscopic approach was associated with longer operative durations but delivered fewer postoperative complications, shorter duration to dietary resumption and shorter lengths of stay over conventional laparotomy.

Conclusion

Laparoscopic completion gastrectomy is indeed a more challenging procedure due to the presence of dense adhesions from previous surgery. However, the procedure can be performed safely with superior outcomes as compared to conventional laparotomy.
Novel enhancers of guanylyl cyclase‐A activity acting via allosteric modulation
Authors: Andresen Henriette , Pérez‐Ternero Cristina , Robinson Jerid , Dickey Deborah M. , Hobbs Adrian J. , Potter Lincoln R. , Levy Finn Olav , Cataliotti Alessandro , Moltzau Lise Román
Published: July 2023

Background and Purpose

Guanylyl cyclase‐A (GC‐A), activated by endogenous atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), plays an important role in the regulation of cardiovascular and renal homeostasis and is an attractive drug target. Even though small molecule modulators allow oral administration and longer half‐life, drug targeting of GC‐A has so far been limited to peptides. Thus, in this study we aimed to develop small molecular activators of GC‐A.

Experimental Approach

Hits were identified through high‐throughput screening and optimized by in silico design. Cyclic GMP was measured in QBIHEK293A cells expressing GC‐A, GC‐B or chimerae of the two receptors using AlphaScreen technology. Binding assays were performed in membrane preparations or whole cells using 125I‐ANP. Vasorelaxation was measured in aortic rings isolated from Wistar rats.

Key Results

We have identified small molecular allosteric enhancers of GC‐A, which enhanced ANP or BNP effects in cellular systems and ANP‐induced vasorelaxation in rat aortic rings. The mechanism of action appears novel and not mediated through previously described allosteric binding sites. In addition, the selectivity and activity depend on a single amino acid residue that differs between the two similar receptors GC‐A and GC‐B.

Conclusion and Implications

We describe a novel allosteric binding site on GC‐A, which can be targeted by small molecules to enhance ANP and BNP effects. These compounds will be valuable tools in further development and proof‐of‐concept of GC‐A enhancement for the potential use in cardiovascular therapy.