bluuebunny/crossref_metadata_2025 huggingface dataset:
Absence of Proviral Human Immunodeficiency Virus (HIV) Type 1 Evolution in Early-Treated Individuals With HIV Switching to Dolutegravir Monotherapy During 48 Weeks
Authors: Jörimann Lisa , Tschumi Jasmin , Zeeb Marius , Leemann Christine , Schenkel Corinne D , Neumann Kathrin , Chaudron Sandra E , Zaheri Maryam , Frischknecht Paul , Neuner-Jehle Nadia , Kuster Herbert , Braun Dominique L , Grube Christina , Kouyos Roger , Metzner Karin J , Günthard Huldrych F ,   for the Swiss HIV Cohort Study (SHCS)
Published: July 2023

Human immunodeficiency virus type 1 (HIV-1) infection is treated with antiretroviral therapy (ART), usually consisting of 2–3 different drugs, referred to as combination ART (cART). Our recent randomized clinical trial comparing a switch to dolutegravir monotherapy with continuation of cART in early-treated individuals demonstrated sustained virological suppression over 48 weeks. Here, we characterize the longitudinal landscape of the HIV-1 reservoir in these participants, with particular attention to potential differences between treatment groups regarding evidence of evolution as a proxy for low-level replication. Near full-length HIV-1 proviral polymerase chain reaction and next-generation sequencing was applied to longitudinal peripheral blood mononuclear cell samples to assess proviral evolution and the potential emergence of drug resistance mutations (DRMs). Neither an increase in genetic distance nor diversity over time was detected in participants of both treatment groups. Single proviral analysis showed high proportions of defective proviruses and low DRM numbers. No evidence for evolution during dolutegravir monotherapy was found in these early-treated individuals.
A Green-and-White Integrative Analytical Strategy Combining Univariate and Chemometric Techniques for Quantifying Recently Approved Multi-Drug Eye Solution and Potentially Cancer-Causing Impurities: Application to the Aqueous Humor
Authors: Attia Khalid A M , El-Olemy Ahmed , Eid Sherif M , Abbas Ahmed Emad F
Published: July 2023

Background

Drug impurities are now seen as a major threat to the production of pharmaceuticals around the world and a major part of the global contamination problem, especially when it comes to carcinogenic impurities.

Objective

We present the first spectrophotometric strategy based on a combination of univariate and multivariate methods as impurity profiling methods for the estimation of lignocaine (LIG) and fluorescein (FLS) with their carcinogenic impurities: 2,6-xylidine (XYL) and benzene-1,3-diol (BZD).

Method

The data processing strategy depends on overcoming unresolved bands by employing five affordable, accurate, selective, and sensitive methods. The methods applied were a direct UV univariate spectrophotometric analysis (D0) and four multivariate chemometric methods, including classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), and genetic algorithm (GA-PLS). FLS analysis (1–16 μg/mL) was performed using the D0 method at 478 nm; then, the application of the ratio subtraction method (RSM) allowed the removal of interference caused by the FLS spectrum. From the resulting ratio spectra, LIG, XYL, and BZD can be efficiently determined by chemometrics. The calibration set was carefully selected at five concentration levels using a partial factorial training design, resulting in 25 mixtures with central levels of 160, 40, and 3 μg/mL for LIG, XYL, and BZD, respectively. Another 13 samples were applied to validate the predictive ability.

Results

The statistical parameters demonstrated exceptional recoveries and smaller prediction errors, confirming the experimental model’s predictive power.

Conclusions

The proposed approach was effectively tested using newly FDA-approved LIG and FLS pharmaceutical preparation and aqueous humor. Additionally, it was effectively assessed for whiteness, greenness, and sustainability using five assessment tools.

Highlights

With its remarkable analytical performance, sustainability, affordability, simplicity, and cost-efficiency, the proposed strategy is an indispensable tool for quality control and in situ analysis in little-equipped laboratories, increasing the proposed approach’s surveillance ability.
Estimation of population size with heterogeneous catchability and behavioural dependence: applications to air- and water-borne disease surveillance
Authors: Bhuyan Prajamitra , Chatterjee Kiranmoy
Published: July 2023

Population size estimation based on the capture–recapture experiment is an interesting problem in various fields including epidemiology, criminology, demography, etc. In many real-life scenarios, there exists inherent heterogeneity among the individuals and dependency between capture and recapture attempts. A novel trivariate Bernoulli model is considered to incorporate these features, and the Bayesian estimation of the model parameters is suggested using data augmentation. Simulation results show robustness under model misspecification and the superiority of the performance of the proposed method over existing competitors. The method is applied to analyse real case studies on epidemiological surveillance. The results provide interesting insight on the heterogeneity and dependence involved in the capture–recapture mechanism. The methodology proposed can assist in effective decision-making and policy formulation.
Defective kernel 66 encodes a GTPase essential for kernel development in maize
Authors: Wei Yi Ming , Wang Bo Hui , Shao Dong Jie , Yan Ru Yu , Wu Jia Wen , Zheng Guang Ming , Zhao Ya Jie , Zhang Xian Sheng , Zhao Xiang Yu
Published: July 2023

The mitochondrion is a semi-autonomous organelle that provides energy for cell activities through oxidative phosphorylation. In this study, we identified a defective kernel 66 (dek66)-mutant maize with defective kernels. We characterized a candidate gene, DEK66, encoding a ribosomal assembly factor located in mitochondria and possessing GTPase activity (which belongs to the ribosome biogenesis GTPase A family). In the dek66 mutant, impairment of mitochondrial structure and function led to the accumulation of reactive oxygen species and promoted programmed cell death in endosperm cells. Furthermore, the transcript levels of most of the key genes associated with nutrient storage, mitochondrial respiratory chain complex, and mitochondrial ribosomes in the dek66 mutant were significantly altered. Collectively, the results suggest that DEK66 is essential for the development of maize kernels by affecting mitochondrial function. This study provides a reference for understanding the impact of a mitochondrial ribosomal assembly factor in maize kernel development.
Introduction to Women in Combat
Authors: Trego Lori L , Deuster Patricia A
Published: July 2023

This is an introduction to the second Women in Combat Supplement and provides an editorial on the topic.
Lyman α emitters in ionized bubbles: constraining the environment and ionized fraction
Authors: Trapp A C , Furlanetto Steven R , Davies Frederick B
Published: July 2023

Lyman α emitters (LAEs) are excellent probes of the reionization process, as they must be surrounded by large ionized bubbles in order to be visible during the reionization era. Large ionized regions are thought to correspond to overdense regions and may be protoclusters, making them interesting test-beds for early massive structures. Close associations containing several LAEs are often assumed to mark overdense, ionized bubbles. Here, we develop the first framework to quantify the ionization and density fields of high-z galaxy associations. We explore the interplay between (i) the large-scale density of a survey field, (ii) Poisson noise due to the small number density of bright sources at high redshifts (z ∼ 7), and (iii) the effects of the ionized fraction on the observation of LAEs. We use Bayesian statistics, a simple model of reionization, and a Monte Carlo simulation to construct a more comprehensive method for calculating the large-scale density of LAE regions than previous works. We find that Poisson noise has a strong effect on the inferred density of a region and show how the ionized fraction can be inferred. We then apply our framework to the strongest association yet identified: Hu et al. found 14 LAEs in a volume of ∼50 000 cMpc3 inside the COSMOS field at z ∼ 7. We show that this is most likely a 2.4σ overdensity inside of an ionized or nearly ionized bubble. We also show that this LAE association implies that the global ionized fraction is $\bar{Q} = 0.59^{+0.10}_{-0.11}$, within the context of a simple reionization model.
Gas-phase formation route for trans-HC(O)SH and its isomers under interstellar conditions: a state-of-the-art quantum-chemical study
Authors: Ye Hexu , Alessandrini Silvia , Puzzarini Cristina
Published: July 2023

Sulphur is an important and ubiquitous element of the interstellar medium (ISM). Despite its importance, its chemistry still needs to be elucidated, with one of the main issues being the missing sulphur problem. In this work, small molecular species, already detected in the ISM (SH, OH, H2CS, H2CO, H2S, H2O, HCS/HSC, and HCO), were combined to set five different gas-phase reactions for the formation of isomers belonging to the CH2SO family, with one of its member, namely trans-HC(O)SH, already identified as well. Through a state-of-the-art computational study, it has been found that, thermochemically, only one of the reactions considered is open in the ISM conditions: H2CS + OH can produce cis/trans-HC(S)OH and cis/trans-HC(O)SH via hydrogen-atom loss. Kinetically, the favoured product is trans-HC(S)OH followed by trans-HC(O)SH. In view of the recent detection of this latter, our study suggests that trans-HC(S)OH is a good candidate for astronomical observations. Since this species has never been studied experimentally, as a first step towards its laboratory characterization, accurate estimates of the rotational constants have been provided.
The evolution of preferences and charitable giving: a panel study of the university years
Authors: Eckel Catherine , Sinha Nishita , Wilson Rick
Published: July 2023

Economic preferences are often taken as given, yet evidence shows that preferences respond to life events and change over time. We examine the evolution of other-regarding preferences for a cohort of university students over 5 years, starting before they matriculate and extending one year beyond graduation. Using survey and incentivized measures of preferences, we show that altruism declines over the university years. This decline is reflected in changes in charitable giving over three donation opportunities. We rule out several alternative explanations for the observed change, including cohort differences, perceptions of the charities, and experience with experiments. We show evidence of a ‘giving type’ in charitable giving, with consistency in behavior across giving opportunities. Methodologically, we also show that the incentivized and survey measures are similar at predicting giving types. We conclude that preferences reflect common tendencies over time, while simultaneously showing an overall decline in generosity during the university years.
Facilitators and Barriers for Chlamydia and Gonorrhea Testing in Female Sex Workers: A Scoping Review
Authors: Xu Wenqian , Liang Peng , Wang Cheng
Published: July 2023

We conducted a scoping review to examine the barriers and facilitators accessing Chlamydia trachomatis and Neisseria gonorrhoeae testing among female sex workers. A literature search was conducted in Embase, Medline, and Web of Science for studies published from the date of creation of database to 17 March 2023, without restrictions for publication date. We used thematic synthesis to identify common affecting factors across included studies and then linked them into categories of the socioecological framework. Among the 14 articles included, 3 utilized qualitative methods, 7 utilized quantitative surveys, 2 were mixed methods, and 2 were randomized controlled trials. Several important affecting factors stood out during this review, including stigma and discrimination, as well as social support at the societal level, and financial costs at the service level. This review suggested that interventions on addressing societal- and service-level determinants are needed, which includes reducing stigma and discrimination toward sex work and cost for facility testing, as well as increasing social support and community engagement.
Melioidosis in Timor-Leste: First Case Description and Phylogenetic Analysis
Authors: Guterres Helio , Gusmao Celia , Pinheiro Mateus , Martins Joana , Odio Gustavo , Maia Carolina , da Conceicao Virginia , Soares Messias , Osorio Celita , da Silva Endang Soares , Tilman Arijayanti , Givney Rodney , Oakley Tessa , Yan Jennifer , Toto Lucia , Amaral Elfiana , James Rodney , Buising Kirsty , Mayo Mark , Kaestli Mirjam , Webb Jessica R , Baird Robert W , Currie Bart J , Francis Joshua R , Muhi Stephen
Published: July 2023

Burkholderia pseudomallei, the causative agent of melioidosis, has not yet been reported in Timor-Leste, a sovereign state northwest of Australia. In the context of improved access to diagnostic resources and expanding clinical networks in the Australasian region, we report the first 3 cases of culture-confirmed melioidosis in Timor-Leste. These cases describe a broad range of typical presentations, including sepsis, pneumonia, multifocal abscesses, and cutaneous infection. Phylogenetic analysis revealed that the Timor-Leste isolates belong to the Australasian clade of B. pseudomallei, rather than the Asian clade, consistent with the phylogeographic separation across the Wallace Line. This study underscores an urgent need to increase awareness of this pathogen in Timor-Leste and establish diagnostic laboratories with improved culture capacity in regional hospitals. Clinical suspicion should prompt appropriate sampling and communication with laboratory staff to target diagnostic testing. Local antimicrobial guidelines have recently been revised to include recommendations for empiric treatment of severe sepsis.
Spatial Distribution and Densities of CD103+ and FoxP3+ Tumor Infiltrating Lymphocytes by Digital Analysis for Outcome Prediction in Breast Cancer
Authors: Chan Ronald , Aphivatanasiri Chaiwat , Poon Ivan K , Tsang Julia Y , Ni Yunbi , Lacambra Maribel , Li Joshua , Lee Conrad , Tse Gary M
Published: July 2023

Background

The evaluation of tumor-infiltrating lymphocytes (TILs) for breast cancer prognosis is now established. However, the clinical value for their spatial distributions of specific immune subsets, namely CD103+ tissue-resident memory T cells FoxP3+ regulatory T ells, have not been thoroughly examined.

Method

Representative whole sections of breast cancers were subjected to CD103 and FoxP3 double staining. Their density, ratio, and spatial features were analyzed in tumor area and tumor-stromal interface. Their associations with clinicopathological parameters and patient’s prognosis were analyzed.

Results

CD103 TILs were closer to tumor nests than FoxP3 TILs in the tumor-stromal interface. Their densities were associated with high-grade disease, TNBC, and stromal TILs. High stromal FoxP3 (sFoxP3) TILs and close proximity of sCD103 TILs to tumor were independently associated with better survival at multivariate analysis. Subgroup analysis showed the high FoxP3 TILs density associated better survival was seen in HER2-OE and TNBC subtypes while the proximity of CD103 TILs to tumor nests associated better survival was seen in luminal cancers.

Conclusion

The prognostic impact of CD103 and FoxP3 TILs in breast cancer depends on their spatial localization. High sFoxP3 TIL density and the lower distance of CD103 TILs from the tumor nests had independent favorable prognostic values.
Suzaku spectral analysis of an X-ray emitting plasma in the supernova remnant G352.7−0.1
Authors: Fujishige Asahi , Yamauchi Shigeo , Nobukawa Kumiko K , Nobukawa Masayoshi
Published: July 2023

The results of a Suzaku observation of the supernova remnant (SNR) G352.7−0.1 are presented in this paper. We conducted spectral analysis based on careful sky background estimation and found an emission line from Al at 1.6 keV, in addition to previously detected emission lines from Mg, Si, S, Ar, Ca, and Fe ions. The X-ray spectrum in the 0.7–10 keV band is represented by a two-component ionizing plasma model with different temperatures and ionization timescales. Based on the results, properties of the X-ray emitting plasma and the explosion type are discussed.
The D14 and KAI2 Orthologs of Gymnosperms Sense Strigolactones and KL Mimics, Respectively, and the Signals Are Transduced to Control Downstream Genes
Authors: Kodama Kyoichi , Xie Xiaonan , Kyozuka Junko
Published: July 2023

Strigolactones (SLs), lactone-containing carotenoid derivatives, function as signaling molecules in the rhizosphere, inducing symbiosis with arbuscular mycorrhizal. In addition, as a class of plant hormones, SLs control plant growth and development in flowering plants (angiosperms). Recent studies show that the ancestral function of SLs, which precede terrestrialization of plants, is as rhizosphere signaling molecules. SLs were then recruited as a class of plant hormones through the step-by-step acquisition of signaling components. The D14 gene encoding the SL receptor arose by gene duplication of KARRIKIN INSENSITIVE2 (KAI2), the receptor of karrikins and KAI2 ligand (KL), an unknown ligand, in the common ancestor of seed plants. KL signaling targets SMAX1, a repressor protein. On the other hand, the SL signaling targets SMXL78 subclade repressors, which arose by duplication of SMAX1 in angiosperms. Thus, gymnosperms contain the SL receptor D14 but not SMXL78, the SL signaling–specific repressor proteins. We studied two gymnosperm species, ginkgo (Ginkgo biloba) and Japanese umbrella pine (Sciadopitys verticillata), to clarify whether SLs are perceived and the signals are transduced in gymnosperms. We show that D14 and KAI2 of ginkgo and Japanese umbrella pine specifically perceive an SL analog and KL mimic, respectively. Furthermore, our results suggest that both SL signaling and KL signaling target SMAX1, and the specific localization of the receptor may result in the specificity of the signaling in gymnosperms.
Evidence for positive long- and short-term effects of vaccinations against COVID-19 in wearable sensor metrics
Authors: Wiedermann Marc , Rose Annika H , Maier Benjamin F , Kolb Jakob J , Hinrichs David , Brockmann Dirk
Published: July 2023

Vaccines are among the most powerful tools to combat the COVID-19 pandemic. They are highly effective against infection and substantially reduce the risk of severe disease, hospitalization, ICU admission, and death. However, their potential for attenuating long-term changes in personal health and health-related wellbeing after a SARS-CoV-2 infection remains a subject of debate. Such effects can be effectively monitored at the individual level by analyzing physiological data collected by consumer-grade wearable sensors. Here, we investigate changes in resting heart rate, daily physical activity, and sleep duration around a SARS-CoV-2 infection stratified by vaccination status. Data were collected over a period of 2 years in the context of the German Corona Data Donation Project with around 190,000 monthly active participants. Compared to their unvaccinated counterparts, we find that vaccinated individuals, on average, experience smaller changes in their vital data that also return to normal levels more quickly. Likewise, extreme changes in vitals during the acute phase of the disease occur less frequently in vaccinated individuals. Our results solidify evidence that vaccines can mitigate long-term detrimental effects of SARS-CoV-2 infections both in terms of duration and magnitude. Furthermore, they demonstrate the value of large-scale, high-resolution wearable sensor data in public health research.
Non-typhoidal salmonella contamination along the pork value chain in a rural East African setting: a cross-sectional study
Authors: Gichuyia Cianjo M , Thomas Lian F , Makena Christine , Ochieng Linnet , Gathura Peter B , Onono Joshua O , Fèvre Eric M
Published: July 2023

Background

Non-typhoidal Salmonella (NTS) is a serious foodborne pathogen that has previously been isolated from pigs presented for slaughter in a rural pork value chain in western Kenya.

Methods

To understand varying NTS contamination along the value chain we assessed prevalence at slaughter, transport and retail. Suspect isolates from culture were confirmed using matrix-assisted laser desorption-ionization time of flight mass spectrometry.

Results

Prevalence on pig carcasses, meat transportation containers, retailed raw and cooked pork and accompanying side salads was 18.1%, 23.9%, 28.0%, 1.9% and 8.6%, respectively.

Conclusion

NTS contamination is propagated along the pork value chain in rural western Kenya, demonstrating the need for improved hygiene measures to prevent human exposure.
Dietary interventions improve diabetic kidney disease, but not peripheral neuropathy, in a db/db mouse model of type 2 diabetes
Authors: Eid Stephanie A. , O'Brien Phillipe D. , Kretzler Katharina H. , Jang Dae‐Gyu , Mendelson Faye E. , Hayes John M. , Carter Andrew , Zhang Hongyu , Pennathur Subramaniam , Brosius Frank C. , Koubek Emily J. , Feldman Eva L.
Published: July 2023

Patients with type 2 diabetes often develop the microvascular complications of diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN), which decrease quality of life and increase mortality. Unfortunately, treatment options for DKD and DPN are limited. Lifestyle interventions, such as changes to diet, have been proposed as non‐pharmacological treatment options for preventing or improving DKD and DPN. However, there are no reported studies simultaneously evaluating the therapeutic efficacy of varying dietary interventions in a type 2 diabetes mouse model of both DKD and DPN. Therefore, we compared the efficacy of a 12‐week regimen of three dietary interventions, low carbohydrate, caloric restriction, and alternate day fasting, for preventing complications in a db/db type 2 diabetes mouse model by performing metabolic, DKD, and DPN phenotyping. All three dietary interventions promoted weight loss, ameliorated glycemic status, and improved DKD, but did not impact percent fat mass and DPN. Multiple regression analysis identified a negative correlation between fat mass and motor nerve conduction velocity. Collectively, our data indicate that these three dietary interventions improved weight and glycemic status and alleviated DKD but not DPN. Moreover, diets that decrease fat mass may be a promising non‐pharmacological approach to improve DPN in type 2 diabetes given the negative correlation between fat mass and motor nerve conduction velocity.
Nuclear proteostasis imbalance in laminopathy‐associated premature aging diseases
Authors: Pande Shruti , Ghosh Debasish Kumar
Published: July 2023

Laminopathies are a group of rare genetic disorders with heterogeneous clinical phenotypes such as premature aging, cardiomyopathy, lipodystrophy, muscular dystrophy, microcephaly, epilepsy, and so on. The cellular phenomena associated with laminopathy invariably show disruption of nucleoskeleton of lamina due to deregulated expression, localization, function, and interaction of mutant lamin proteins. Impaired spatial and temporal tethering of lamin proteins to the lamina or nucleoplasmic aggregation of lamins are the primary molecular events that can trigger nuclear proteotoxicity by modulating differential protein–protein interactions, sequestering quality control proteins, and initiating a cascade of abnormal post‐translational modifications. Clearly, laminopathic cells exhibit moderate to high nuclear proteotoxicity, raising the question of whether an imbalance in nuclear proteostasis is involved in laminopathic diseases, particularly in diseases of early aging such as HGPS and laminopathy‐associated premature aging. Here, we review nuclear proteostasis and its deregulation in the context of lamin proteins and laminopathies.
Translation, cross-cultural adaptation, and validation of the Persian version of the Attitude Towards Menopause scale
Authors: Bahri Narjes , Sajjadi Moosa , Hunter Myra S. , Mohammadzadeh Fatemeh
Published: July 2023

Objectives

This study describes translation, cross-cultural adaptation, and validation of the Attitude Towards Menopause (ATM) scale in Persian.

Methods

A standard process was followed for translation and cross-cultural adaptation of the ATM scale into Persian. The content validity index and content validity ratio were used to measure content validity. The construct validity was tested using exploratory factor analysis and confirmatory factor analysis. The average variance extracted and construct reliability were used to indicate convergent and discriminant validity, respectively. Internal consistency and test-retest reliability of the Persian ATM scale were assessed using Cronbach α and intraclass correlation coefficient (ICC).

Results

A revised version of the ATM scale, including 26 items assigned to seven factors, was obtained in exploratory factor analysis. The factors were interpreted as negative affect, postmenopausal recovery, control of symptoms, sexuality, psychological losses, unpleasant confrontation, and menstrual freedom, explaining 66.18% of the total variance. The factor structure of the scale was confirmed using confirmatory factor analysis (Comparative Fit Index = 0.90, Tucker-Lewis Index = 0.88, Goodness-of-Fit Index = 0.90, Adjusted Goodness-of-Fit Index = 0.86, Root Mean Square Error of Approximation = 0.07, χ
2/df = 4.56). The values of Cronbach α coefficient and ICC indicated an acceptable level of reliability (α = 0.70, ICC = 0.89). The construct reliability for all factors was more than or equal to 0.7 except for psychological losses, indicating good discriminating validity. The values of average variances extracted for subscales varied from 0.48 to 0.99, representing adequate convergent validity.

Conclusions

The Persian version of the ATM scale is a reliable and valid tool to evaluate the attitudes of Iranian women toward menopause.
Racial and Ethnic Disparities in Selected Speakers at Plastic Surgery Conferences
Authors: Ha Grace , Benyamein Paige , Reghunathan Meera , Vatsia Sohrab , Blum Jessica , Gosman Amanda A.
Published: July 2023

Background:

Disparities in representation amongst academic physicians continue to persist at multiple levels, including the resident selection process and faculty career advancement. This study aimed to evaluate the racial and ethnic representation amongst plastic surgeons who are selected to speak at national and regional plastic surgery conferences.

Methods:

The researchers evaluated selected speakers at 12 plastic surgery annual meetings over 7 years (2014–2020). Racial and ethnic distribution in selected speakers at conferences were compared with those of medical school graduates, plastic surgery residents, and practicing plastic surgeons.

Results:

There were a total of 79 meetings, with 8931 total speaking opportunities and 1276 unique speakers. The percentage of individuals underrepresented in medicine (UIM) is 15.2% in matriculating medical students, 8.9% in active PRS residents, 8.3% in practicing PRS physicians, and 4.7% in invited conference speakers. Within racial/ethnic groups of invited speakers, there was no significant difference in either the average number of fellowships completed or average number of plastic surgery publications (P = 0.44 and 0.39, respectively). No individual UIM speaker had more than 20 speaking opportunities over these 7 years, compared with 17.0% in non-UIM speakers.

Conclusion:

Given the results of the study, the researchers conclude that racial minorities are disproportionately underrepresented as selected speakers at plastic surgery conferences, despite similarities in qualifications such as fellowship training, publication number, and years since board certification.
Inflammatory cell activity in treated neovascular age-related macular degeneration, a histologic case study
Authors: Berlin Andreas , Messinger Jeffrey D , Ramtohul Prithvi , Balaratnasingam Chandrakumar , Mendis Randev , Ferrara Daniela , Freund K. Bailey , Curcio Christine A
Published: July 2023

Background:

Imaging indicators of macular neovascularization (MNV) risk can help determine patient eligibility for new treatments for geographic atrophy secondary to age-related macular degeneration (AMD). Because type 1 MNV includes inflammation, we assessed by histology the distribution of cells with inflammatory potential in two fellow eyes with AMD.

Methods:

Two eyes of a white woman in her 90’s with type 3 MNV treated with anti-vascular endothelial growth factor were prepared for high-resolution histology. Eye-tracked spectral-domain optical coherence tomography (OCT) applied to the preserved donor eyes linked in vivo imaging to histology. Cells were enumerated in the intraretinal, subretinal and sub-retinal pigment epithelium (RPE)-basal lamina (BL) compartments on 199 glass slides. Cells with numerous organelles were considered to RPE-derived; cells with sparse RPE organelles were considered non-RPE phagocytes.

Results:

Both eyes had soft drusen and abundant SDD. In the retina and subretinal space, RPE-derived cells, including hyperreflective foci, were common (n=125, 73, respectively). Non-RPE phagocytes were infrequent (n=5 in both). Over drusen, RPE morphology transitioned smoothly from the age-normal layer towards the top, suggesting transdifferentiation. The sub-RPE-BL space had RPE-derived cells (n=87) and non-RPE phagocytes (n=49), including macrophages and giant cells.

Conclusions:

Numerous sub-RPE-BL cells of several types are consistent with the documented presence of pro-inflammatory lipids in drusen and aged Bruch’s membrane. The relatively compartmentalized abundance of infiltrating cells suggests that drusen contents are more inflammatory than SDD, perhaps reflecting their environments. Ectopic RPE occur frequently. Some manifest as hyperreflective foci. More cells may be visible as OCT technologies evolve.
USE OF ADDITIONAL FACEDOWN POSITIONING WITH SILICONE OIL TAMPONADE FOR THE TREATMENT OF RETINAL REDETACHMENT
Authors: Somisetty Aditya , Hoyek Sandra , Yuan Melissa , Somisetty Swathi , Kim Leo A. , Patel Nimesh A.
Published: July 2023

Purpose:

The purpose of this study was to highlight a potential alternative to additional surgery for management of retinal redetachment through the use of additional facedown positioning with silicone oil tamponade.

Methods:

Retrospective case series of two patients evaluated with examination, multimodal imaging, including fundus photography, optical coherence tomography, and fluorescein angiography.

Results:

In Case 1, a 70-year-old female patient underwent surgery for a full-thickness macular hole with associated macula-off retinal detachment, but experienced a recurrent detachment and underwent a second surgery with silicone oil placement. Another recurrent detachment was found. The case was managed conservatively with facedown positioning, resulting in resolution of subretinal fluid and improvement in vision. At follow-up, the retina remained attached with stable vision. In Case 2, a 25-year-old male patient underwent a surgical repair for proliferative vitreoretinopathy retinal detachment with a scleral buckle, cryotherapy, and external drainage. After multiple redetachment surgeries with retinectomy and oil placement, another tractional redetachment of the fovea was noted. Management was with facedown positioning, and follow-up evaluation showed resolution of the subretinal fluid and improvement in vision with stability for greater than 2 months.

Conclusion:

For recurrent retinal redetachments with silicone oil in place, an additional week of facedown positioning can result in anatomical success and be a viable alternative or bridge to invasive surgical interventions. This approach may have greatest utility for patients who are poor surgical candidates without new peripheral pathology.
External validation and updating of prognostic prediction models for nonrecovery among older adults seeking primary care for back pain
Authors: Vigdal Ørjan Nesse , Storheim Kjersti , Killingmo Rikke Munk , Rysstad Tarjei , Pripp Are Hugo , van der Gaag Wendelien , Chiarotto Alessandro , Koes Bart , Grotle Margreth
Published: July 2023

Prognostic prediction models for 3 different definitions of nonrecovery were developed in the Back Complaints in the Elders study in the Netherlands. The models' performance was good (optimism-adjusted area under receiver operating characteristics [AUC] curve ≥0.77, R

2
≥0.3). This study aimed to assess the external validity of the 3 prognostic prediction models in the Norwegian Back Complaints in the Elders study. We conducted a prospective cohort study, including 452 patients aged ≥55 years, seeking primary care for a new episode of back pain. Nonrecovery was defined for 2 outcomes, combining 6- and 12-month follow-up data: Persistent back pain (≥3/10 on numeric rating scale) and persistent disability (≥4/24 on Roland–Morris Disability Questionnaire). We could not assess the third model (self-reported nonrecovery) because of substantial missing data (>50%). The models consisted of biopsychosocial prognostic factors. First, we assessed Nagelkerke R
2, discrimination (AUC) and calibration (calibration-in-the-large [CITL], slope, and calibration plot). Step 2 was to recalibrate the models based on CITL and slope. Step 3 was to reestimate the model coefficients and assess if this improved performance. The back pain model demonstrated acceptable discrimination (AUC 0.74, 95% confidence interval: 0.69-0.79), and R
2 was 0.23. The disability model demonstrated excellent discrimination (AUC 0.81, 95% confidence interval: 0.76-0.85), and R

2
was 0.35. Both models had poor calibration (CITL <0, slope <1). Recalibration yielded acceptable calibration for both models, according to the calibration plots. Step 3 did not improve performance substantially. The recalibrated models may need further external validation, and the models' clinical impact should be assessed.
Brain-predicted age difference estimated using DeepBrainNet is significantly associated with pain and function—a multi-institutional and multiscanner study
Authors: Valdes-Hernandez Pedro A. , Laffitte Nodarse Chavier , Johnson Alisa J. , Montesino-Goicolea Soamy , Bashyam Vishnu , Davatzikos Christos , Peraza Julio A. , Cole James H. , Huo Zhiguang , Fillingim Roger B. , Cruz-Almeida Yenisel
Published: July 2023

Brain age predicted differences (brain-PAD: predicted brain age minus chronological age) have been reported to be significantly larger for individuals with chronic pain compared with those without. However, a debate remains after one article showed no significant differences. Using Gaussian Process Regression, an article provides evidence that these negative results might owe to the use of mixed samples by reporting a differential effect of chronic pain on brain-PAD across pain types. However, some remaining methodological issues regarding training sample size and sex-specific effects should be tackled before settling this controversy. Here, we explored differences in brain-PAD between musculoskeletal pain types and controls using a novel convolutional neural network for predicting brain-PADs, ie, DeepBrainNet. Based on a very large, multi-institutional, and heterogeneous training sample and requiring less magnetic resonance imaging preprocessing than other methods for brain age prediction, DeepBrainNet offers robust and reproducible brain-PADs, possibly highly sensitive to neuropathology. Controlling for scanner-related variability, we used a large sample (n = 660) with different scanners, ages (19-83 years), and musculoskeletal pain types (chronic low back [CBP] and osteoarthritis [OA] pain). Irrespective of sex, brain-PAD of OA pain participants was ∼3 to 4.7 years higher than that of CBP and controls, whereas brain-PAD did not significantly differ among controls and CBP. Moreover, brain-PAD was significantly related to multiple variables underlying the multidimensional pain experience. This comprehensive work adds evidence of pain type–specific effects of chronic pain on brain age. This could help in the clarification of the debate around possible relationships between brain aging mechanisms and pain.
Entecavir versus tenofovir on the recurrence of hepatitis B–related HCC after liver transplantation: A multicenter observational study
Authors: Kim Deok-Gie , Choi YoungRok , Rhu Jinsoo , Hwang Shin , You Young Kyoung , Kim Dong-Sik , Nah Yang Won , Kim Bong-Wan , Cho Jai Young , Kang Koo Jeong , Yang Jae Do , Choi Donglak , Joo Dong Jin , Kim Myoung Soo , Ryu Je Ho , Lee Jae Geun ,   Korean Organ Transplantation Registry Study Group
Published: July 2023

Considerable controversy exists regarding the superiority of tenofovir disoproxil fumarate (TDF) over entecavir (ETV) for reducing the risk of HCC. This study aimed to compare outcomes of ETV versus TDF after liver transplantation (LT) in patients with HBV-related HCC. We performed a multicenter observational study using data from the Korean Organ Transplantation Registry. A total of 845 patients who underwent LT for HBV-related HCC were divided into 2 groups according to oral nucleos(t)ide analogue used for HBV prophylaxis post-LT: ETV group (n = 393) and TDF group (n = 452). HCC recurrence and overall death were compared in naïve and propensity score (PS)-weighted populations, and the likelihood of these outcomes according to the use of ETV or TDF were analyzed with various Cox models. At 1, 3, and 5 years, the ETV and TDF groups had similar HCC recurrence-free survival (90.7%, 85.6%, and 84.1% vs. 90.9%, 84.6%, and 84.2%, respectively, p = 0.98) and overall survival (98.4%, 94.7%, and 93.5% vs. 99.3%, 95.8%, and 94.9%, respectively, p = 0.48). The propensity score-weighted population showed similar results. In Cox models involving covariates adjustment, propensity score-weighting, competing risk regression, and time-dependent covariates adjustment, both groups showed a similar risk of HCC recurrence and overall death. In subgroup analyses stratified according to HCC burden (Milan criteria, Up-to-7 criteria, French alpha-fetoprotein risk score), pretransplantation locoregional therapy, and salvage LT, neither ETV nor TDF was superior. In conclusion, ETV and TDF showed mutual noninferiority for HCC outcomes when used for HBV prophylaxis after LT.
Developmental Feeding Stages and Their Impact on Child Feeding Behavior
Authors: Sdravou Katerina , Printza Athanasia , Emmanouilidou-Fotoulaki Elpida , Michou Emilia , Sotiriadou Fotini , Fotoulaki Maria
Published: July 2023

Objectives:

Previous research has shown that critical periods of feeding skills development exist and feeding problems can arise in children due to delays in attaining feeding developmental milestones. This study aims to delineate the transitional process of feeding development in healthy children and children with gastrointestinal diseases (GIDs) and to examine the relationship between feeding milestones and the appearance of later feeding problems.

Methods:

A cross-sectional case–control study among 711 healthy Greek children and 119 children with GID, aged 2–7 years. Parents completed the Greek version of the Behavioral Pediatrics Feeding Assessment Scale and “self-reported” questionnaires assessing child’s feeding history.

Results:

Differences in feeding behavior of preschoolers between the 2 groups were found concerning the time of introduction of complementary (pureed), lumpy, and table foods as well as finger feeding and regular cup-drinking. Age-specific milestones as proposed by guidelines were not reached. Late introduction of complementary and lumpy foods (>6 months and >9 months, respectively) as well as finger feeding (>9 months) were predictive of more problematic feeding behaviors later on.

Conclusions:

The trajectory of feeding development, including less studied feeding milestones, both in healthy children and children with GIDs, indicates that there are discrepancies between current feeding practices and infant feeding guidelines, and a tendency to delay the acquisition of all assessed feeding milestones.
A Successful Treatment Approach in 2 Patients With Type 1 Plasminogen Deficiency: Intratracheal Application of Fresh Frozen Plasma and Tissue Plasminogen Activator
Authors: Al Serdar , Ulusoy Oktay , Asilsoy Suna , Uzuner Nevin , Kangalli Ozge , Atay Ozge , Odaman Al Isik , Ates Oguz
Published: July 2023

Background:

Respiratory system involvement is common in congenital plasminogen deficiency. Although many treatment approaches have been tried, there is still no definitive treatment for respiratory system involvement.

Observation(s):

We report 2 congenital plasminogen deficiency cases, who presented with severe respiratory symptoms, for whom a novel treatment modality was tried. After intravenous administration of FFP (fresh frozen plasma), tissue plasminogen activator and FFP were administered intratracheally, and respiratory system findings improved.

Conclusions:

Intratracheal administration of tissue plasminogen activator and FFP is an available treatment modality for patients with lung involvement. Fibrin plaques should be carefully removed and new lesion formation should be prevented.
A Standardized Protocol for the Safe Retrieval of Infectious Postmortem Human Brain for Studying Whole-Brain Pathology
Authors: James Ranjit Immanuel , Verma Richa , Johnson Latif Rajesh , Manesh Abi , Jayakumar Jaikishan , Sen Mousumi , Joseph Jayaraj , Kumarasami Ramdayalan , Mitra Partha P. , Sivaprakasam Mohanasankar , Varghese George M.
Published: July 2023

We describe a safe and standardized perfusion protocol for studying brain pathology in high-risk autopsies using a custom-designed low-cost infection containment chamber and high-resolution histology. The output quality was studied using the histological data from the whole cerebellum and brain stem processed using a high-resolution cryohistology pipeline at 0.5 μm per pixel, in-plane resolution with serial sections at 20-μm thickness. To understand the pathophysiology of highly infectious diseases, it is necessary to have a safe and cost-effective method of performing high-risk autopsies and a standardized perfusion protocol for preparing high-quality tissues. Using the low-cost infection containment chamber, we detail the cranial autopsy protocol and ex situ perfusion-fixation of 4 highly infectious adult human brains. The digitized high-resolution histology images of the Nissl-stained series reveal that most of the sections were free of processing artifacts, such as fixation damage, freezing artifacts, and osmotic shock, at the macrocellular and microcellular level. The quality of our protocol was also tested with the highly sensitive immunohistochemistry staining for specific protein markers. Our protocol provides a safe and effective method in high-risk autopsies that allows for the evaluation of pathogen-host interaction, the underlying pathophysiology, and the extent of the infection across the whole brain at microscopic resolutions.
Preliminary Prospective Preoperative and Postoperative Evaluation of Median Nerve Stiffness by Using Sonoelastography
Authors: Liao Kuan-Hao , Lin Yu-Te , Wu Chen-Te , Lin Cheng-Hung , Chen Shih-Heng , Hsu Chung-Chen
Published: July 2023

Carpal tunnel syndrome is the most common peripheral nerve entrapment syndrome. No previous studies have compared preoperative and follow-up sonoelastography results or investigated the correlation of median nerve stiffness with the subjective/objective outcomes. Therefore, the aim of this study was to compare the preoperative and postoperative elastography after carpal tunnel release and find the correlation with associated subjective/objective outcomes.

From May 2017 to March 2020, 32 patients (6 males, 26 females; 34 hands) with carpal tunnel syndrome were enrolled in this prospective study. Demographic data, QuickDASH score (Chinese version), Boston Carpal Tunnel Questionnaire (Chinese version), nerve conduction velocity/electromyography, and median nerve stiffness by sonoelastography were recorded.

Comparisons of preoperative and average sonoelastography findings 1.5 years postoperatively showed a significant decrease in stiffness presented by velocity (Vs) (preoperative Vs, 4.63 ± 1.27 m/s, vs postoperative Vs, 3.39 ± 0.59 m/s; P < 0.001). Changes in subjective functional outcomes also showed the same significant trend. Based on the neurophysiologic study, the improvement of nerve conduction study and elastography have the significant correlation.

The same trend of preoperative and postoperative changes in median nerve stiffness and subjective questionnaires/objective neurophysiologic studies may imply that sonoelastography can be used to assess the response to surgery in patients with carpal tunnel syndrome.
Expanding Our Role in Headache Management
Authors: Shaffrey Ellen C. , Seitz Allison J. , Albano Nicholas J. , Israel Jacqueline S. , Afifi Ahmed M.
Published: July 2023

Background

Chronic postcraniotomy headache (PCH) is common and debilitating. Unfortunately, the literature on this topic is sparse without clear management algorithms. Possible etiologies of PCH include nerve injury and/or entrapment, hardware, dural adhesions, or musculoskeletal injury. The purpose of this study was to present the results of both a systematic review of the literature and a single-center case series, both of which informed the development of a novel treatment algorithm that may be applied to this patient population

Methods

Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we performed a systematic review of the literature, identifying articles describing the surgical management of PCH. A retrospective chart review was performed to identify patients who met the criteria for PCH treated at our institution. A patient's history and physical examination determined the etiology and management, and pain severity scores were the primary outcome measured.

Results

Nineteen articles encompassing 131 patients described surgical management techniques for PCH. 83 patients (63.3%) had complete resolution of pain (χ
2 = 52.1, P < 0.0001). At our institution, 19 patients underwent surgical management for PCH. A significant reduction in pain scores from 7.57 to 2.16 (P < 0.001) was demonstrated, and 84 percent of patients achieved complete or significant pain reduction.

Conclusions

Through a literature review and our own case series, we demonstrate that surgical management of PCH can achieve remarkable results. Plastic surgeons, with their expanding role in treating migraine and headaches, are well suited to manage these patients. We present an algorithmic approach to simplify the management of this common and debilitating condition.